CHEST nov 2005

INTERLEUKIN 2 INCREASES ALVEOLAR FLUID CLEAR-ANCE IN ISOLATED RAT LUNGSMakoto Sugita MD* Zheng Wang MD Sumiko Maeda MD MotoyasuSagawa MD Jin Xu MD Toshishige Shibamoto MD Tsutomu Sakuma MDKanazawa Medical University, Ishikawa, Japan

PURPOSE: Clinical and basic studies have suggested that interleukin 2(IL-2) plays an important role for the development of pulmonary edema.However, its precise mechanism is still undetermined. For the resolution ofpulmonary edema, alveolar fluid clearance is essential, and this clearance isknown to be dependent of ion transport ability of alveolar epithelial cells. Inthis study, we determined the effects of IL-2 on alveolar fluid clearance.

METHODS: Isotonic 5% albumin solutions with pharmacologicaltreatments were instilled into the distal airways in the isolated rat lungs.The lungs were inflated with 100% oxygen at 8cm H2O and placed in ahumid incubator at 37°C. Alveolar fluid clearance was estimated by theprogressive increase in the albumin concentration over 1h.

RESULTS: Seven male S-D rats were used in each group. IL-2stimulation caused dose-dependent increase in alveolar fluid clearance(Control, IL-2 (50U/ml), IL-2 (5000U/ml), vs. IL-2 (10000U/ml):15.8�1.8%, 15.3�1.5%, 21.8�1.0%, vs. 24.6�1.7: P�0.05). Terbutaline(� adrenergic receptor agonist) caused significant increase in alveolar fluidclearance (27.8�1.1%), and this increase was inhibited by propranolol (�adrenergic receptor blocker). In contrast, propronolol did not inhibit theIL-2 stimulation.

CONCLUSION: This study indicates that IL-2 increases alveolar fluidclearance in the isolated rat lungs. Because the stimulatory effect by IL-2is not inhibited by propranolol, IL-2 may increase alveolar fluid clearancevia non-� adrenergic receptor mediated pathway.

CLINICAL IMPLICATIONS: Intravenous administration of IL-2 hasbeen shown to cause pulmonary edema. However, our results suggest thatIL-2 stimulates transalveolar fluid transport for clearance of excess edemafluid. This study was supported by Grant for Promoted Research fromKanazawa Medical University (S2003-8).

DISCLOSURE: Makoto Sugita, None.

LONG PENTRAXIN 3, A NEW INFLAMMATORY MEDIATOR INACUTE LUNG INJURYDaisuke Okutani MD* Bing Han MD Marco Mura MD Thomas K.Waddell MD Shaf Keshavjee MD Mingyao Liu MD Thoracic SurgeryResearch Laboratory, Toronto General Hospital, U of Toronto, Toronto,ON, Canada

PURPOSE: Acute respiratory distress syndrome (ARDS) is a seriousform of acute lung injury (ALI), and has a high mortality of 30-50%.Understanding of ALI at molecular level may provide insights and lead tonew therapies. PTX3 is a newly identified acute-phase protein, which canbe induced from a variety of tissue cells on pro-inflammatory stimulations,such as LPS, IL1� and TNF�. In this study we sought to define the PTX3expression patterns in multiple ALI models in rats and its relationshipwith the lung injury.

METHODS: Rats were randomized to receive hemorrhagic (HS) orendotoxic shock (LPS) followed by resuscitation, or sham operation. Thenthe animals were subjected to either high (HV) or low (LV) volumeventilation for 4 hours. Blood gas, lung elastance, and wet/dry ratio weremeasured. PTX3, IL1�, and TNF� were assayed by quantitative real timePCR and ELISA. Distribution of PTX3 in the lung tissue was determinedby immunohistochemistry.

RESULTS: After 4 hours of mechanical ventilation, the PTX3 expres-sion in both mRNA and protein levels in the lung tissues were significantlyenhanced by HS, or LPS, which is further increased by HV. In fact, HValone also increased PTX3 expression significantly. In contrast, the serumlevel of PTX3 was found no obviously increase by HV and HS, but onlyslightly enhanced by LPS. Immunohistochemistry showed a profoundpositive staining of PTX3 on the epithelial layer of alveolar walls,indicating a major local response of PTX3 during ALI. The local PTX3expression was well correlated with IL-1� and TNF�. Furthermore, thePTX3 expression was highly correlated with changes in wet/dry lung ratios,elastance, and PaO2, respectively (p � 0.0001).

CONCLUSION: PTX3 is an important inflammatory mediator whoseexpression can be increased by the inflammatory responses in thepathogenesis of ALI.

CLINICAL IMPLICATIONS: PTX3 might serve as a sensitivebiomarker for local inflammatory responses during ALI.

DISCLOSURE: Daisuke Okutani, None.

EFFECT OF ENTERAL NUTRITION WITH EICOSAPENTA-ENOIC ACID (EPA), GAMMA-LINOLENIC ACID (GLA), ANDANTIOXIDANTS REDUCES ALVEOLAR INFLAMMATORY ME-DIATORS AND PROTEIN INFLUX IN PATIENTS WITH ACUTERESPIRATORY DISTRESS SYNDROME (ARDS)Elamin M. Elamin MD* Larry F. Hughes PhD Diane Drew RNUniversity of South Florida, Tampa, FL

PURPOSE: Two previous studies showed that ARDS patients fed anenteral diet containing EPA�GLA and elevated antioxidants (Oxepa) hadsignificantly increased oxygenation, and improved clinical outcomes. Weinvestigated the potential benefits of the same diet in patients with ARDSin addition to Multiple Organ Dysfunction (MOD) which correlatesstrongly with the risk of intensive care unit (ICU) mortality.

METHODS: We enrolled 16 ICU patients with ARDS (as defined bythe American-European Consensus Conference) as a prospective, multi-center, double-blind, randomized controlled trial. Patients meeting entrycriteria were randomized and continuously tube-fed EPA�GLA or anisonitrogenous, isocaloric standard diet at a minimum caloric delivery of90% of basal energy expenditure for at least 4 days.

RESULTS: Ventilator settings were recorded and arterial blood gaseswere measured, at baseline and study days 4 and 7 to enable calculationof PaO2/FIO2, a marker for gas exchange and part of the Modified LungInjury Score (LIS). Significant improvements in oxygenation (PaO2/FIO2) from baseline to study day 4 with lower ventilation variables (FIO2,positive end-expiratory pressure, and minute ventilation) occurred inpatients with higher APACHE scoring at enrollment who were fedEPA�GLA compared with controls (p�.01). In addition, patients fedEPA�GLA had a decrease in their APACHE score 4 days after initiationof the enteral nutrition with decreased in length of stay in the intensivecare unit (12.8 vs. 17.5 days; p � .016) compared with controls. Over all,patients fed EPA�GLA had a significant decrease in MOD score at 28days after initiation of their tube feeding (p�.05).

CONCLUSION: This preliminary report support the previously re-ported benefits of EPA�GLA diet on gas exchange, and length of ICUstay. In addition, patients fed EPA�GLA had reduction of their APACHEscore within 4days of initiating of the enteral nutrition with decreasedMOD scores 28 days after initiation of their tube feeding.

CLINICAL IMPLICATIONS: Enteral nutrition of ARDS patientswith EPA�GLA diet can improve their gas exchange, in addition todecrease length of ICU stay and 28 days mortality.

DISCLOSURE: Elamin Elamin, None.

OPTIMIZATION OF VENTILATION-PERFUSION MATCHINGDURING PROTECTIVE LUNG VENTILATIONChin-Pyng Wu PhD* Kun-Lun Huang PhD Wann-Cherng Perng MDHung Chang PhD Chien-Wen Chen MD Chien-Ling Su MA Hsien-LiangChuang MA Horng-Chin Yan PhD Yuh-Chin Huang MPH Departmentof Critical Care Medicine, Tri-Service General Hospital, Taipei, TaiwanROC

PURPOSE: The primary purpose of this study was to determine theeffects of different positive end-expiratory pressure in the lung protectivestrategy on ventilation-perfusion distribution measured by the multipleinert gas elimination technique.

METHODS: All patients were on pressure-controlled mode with theinspiratory pressure, FiO2 and PEEP adjusted to provide a tidal volumeof 6-8 ml/kg, an oxygen saturation � 90% and a plateau pressure � 35 cmH2O. Six levels of PEEP were studied in an incremental manner: 0cmH2O (ZEEP), PLIP-4, -1 ,�2 ,�5 ,�8 cmH2O. All physiologicalparameters were measured at the end of each 30-min PEEP trial. If thepatient showed signs of hemodynamic instability or desaturation to � 88%during trials at lower PEEP, that trial was terminated and PEEP wasincreased to the next higher level.

RESULTS: Eleven patients were ventilated with low tidal volume andPEEP from 0 to 8 cmH2O above the lower inflection point pressure.These patients had a large intrapulmonary shunt and dead space with anadditional mode at the high ventilation-perfusion regions. Intrapulmonaryshunt and dead space improved with increasing positive end-expiratorypressure up to 2-5 cmH2O above the lower inflection point pressure.Higher positive end-expiratory pressure increased dead space withoutfurther reduction in intrapulmonary shunt.

CONCLUSION: The dispersion of ventilation and perfusion alsofollowed a similar trend. Other endpoints commonly used for titratingpositive end-expiratory pressure, such as oxygenation, alveolar recruit-

Wednesday, November 2, 2005

Acute Lung Injury and ARDS12:30 PM - 2:00 PM

CHEST / 128 / 4 / OCTOBER, 2005 SUPPLEMENT 225S

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ment and lung compliance, all increased with increasing positive end-expiratory pressure while hemodynamic parameters were unaffected.Thus based on ventilation-perfusion matching, positive end-expiratorypressure of 2-5 cmH2O above the lower inflection point pressure appearsoptimalduring protective lung ventilation.

CLINICAL IMPLICATIONS: We determined PEEP effects duringprotective lung ventilation using ventilation-perfusion (VA/Q) distributionas an endpoint.This method of adjusting PEEP was used because it hasbeen shown that the recruiting potential of lung tissues with PEEP variedsignificantly among individual ARDS patients. Our goal was to determineif there was a PEEP level that gave the most optimal VA/Q distribution.

DISCLOSURE: Chin-Pyng Wu, None.

RISK FACTORS FOR FAILURE OF NON-INVASIVE VENTILA-TION IN PATIENTS WITH ACUTE LUNG INJURYSameer Rana MD* Milie M. Tolentino MD Rolf D. Hubmayr MD PeterC. Gay MD Ognjen Gajic MD Mayo Clinic, Rochester, MN

PURPOSE: Non Invasive Positive Pressure Ventilation (NIPPV) is theaccepted initial treatment for exacerbation of chronic obstructive lungdisease and cardiogenic pulmonary edema. Its role in Acute Lung Injury(ALI) is controversial. We sought to assess the outcome of ALI initiallytreated with NIPPV and to identify specific risk factors for NIPPV failurein this patient population.

METHODS: In this observational cohort study,consecutive patientswith ALI initially treated with NIPPV were identified. ALI was definedaccording to standard American European Consensus Conference Defi-nition. Patients with do not resuscitate orders were excluded. NIPPVfailure was defined as the need to intubation or death while on NIPPV.Data on demographics, APACHE III scores, degree of hypoxemia(PaO2/FIO2), presence of shock, sepsis, aspiration, transfusion, metabolicacidosis, time to intubation, as well as NIPPV parameters (tidal volume,minute volume, inspiratory and expiratory pressure) were recorded.Univariate and multivariate regression analysis was performed to identifyrisk factors for NIPPV failure.

RESULTS: 79 patients met the inclusion criteria. 23 were excludedbecause of do not resuscitate order and 2 denied research authorization.34 of the remaining 54 patients (62.9%) had a primary diagnosis ofpneumonia. 38 (70.3%) patients failed NIPPV, including all 19 patientswith shock. ALI patients successfully treated with NIPPV had lowerApache-3 scores (55.5 vs 81.5; p�0.004), were less likely to havemetabolic acidosis (base deficit: 0.52 vs -4.01; p�0.017) and severehypoxemia (PaO2/FIO2: 147 vs 112; p�0.020). Multivariate logisticregression analysis identified higher base deficit (p� 0.04) and lowerPaO2/FIO2 ratio (p�0.008) but not APACHE III scores (p�0.105) assignificant predictors of NIPPV failure. In patients who failed NIPPV theobserved mortality was higher than APACHE predicted mortality (68.4%vs 38.6 %).

CONCLUSION: The presence of septic shock, low PaO2/FIO2 ratioand metabolic acidosis in patients with Acute Lung Injury predicts failureof NIPPV .

CLINICAL IMPLICATIONS: NIPPV should not be used in patientswith Acute Lung Injury who have shock, metabolic acidosis or profoundhypoxemia.

DISCLOSURE: Sameer Rana, None.

A MULTICENTER RETROSPECTIVE STUDY OF THE IMPACTOF THE 2000 ARDS NETWORK TRIAL ON MECHANICALVENTILATOR SETTING IN QUEBEC ICUSYannick Poulin MD* Marc-Andre LeClair MD Olivier Lesur MD MICUCHUS, CHU Sherbrooke, PQ, Canada

PURPOSE: Mechanical ventilation (MV) with low tidal volumes (Vt:8-6 cc/kg of IBW) has become a standard of care for patients with ARDSsince mid-2000 (NEJM 2000, 342: 1301). To analyze MV setting’s habitsfor ARDS patients by Quebec ICU physicians, before and after the ARDSnetwork report.

METHODS: i) files of 71 ARDS patients from 5 Quebec ICUs studiedfrom January 2000 to March 2002, ii) 2 groups arbitrarily defined tocompare the period up to 6 months (i.e November 2000) following theARDS network report, with the period after this landmark.Outcomesprimary: the change of Vt over-time between the groups, secondary:mortality, number of days without organ failure, PEEP level, respiratoryrate, PaCO2 .

RESULTS: 21/71 patients were enrolled before the landmark and50/71 after the landmark. Vt normalized to real or IBWs were reducedafter Nov 2000 (7.8 �/- 0.2 vs 6.8 �/- 0.1 p�0.0001 and 9.3 �/- 0.2 vs 8.1�/- 0.1 p�0.0001 respectively). There was no significant difference ofmortality between the two groups (48% vs 36%, NS). PEEP (10.6 �/- 0.4vs 13.9 �/- 0.2 p�0.02), respiratory rate (20 �/- 1.2 vs 29 �/- 0.6p�0.0001), PaCO2 (47 �/- 1.4 vs 50 �/- 0.7 p�0.02) significantlychanged. A trend towards higher number of days without organ dysfunc-tion was found after November 2000 (all organs: 14.8 vs 20.5; p�0.08,renal: 19.5 vs 24.4; p�0.06, cardiovascular: 15.4 vs 22.4; p�0.07, hepatic18.8 vs 22.4, p�0.2, coagulation; 18.4 vs 24.1; p�0.07).

CONCLUSION: Knowledge translation regarding on ventilation set-ting of ARDS patients has moved nearer standard practice in QuebecICUs after the 2000 ARDS Net release. Morbidity was affected in thissmall cohort of patients.

CLINICAL IMPLICATIONS: Standard practice regarding on me-chanical ventilation of ARDS patients has changed with time following theARDS Net release, with trends toward lower secondary organ dysfunctionrate.

DISCLOSURE: Yannick POULIN, None.

LOW VS HIGH TIDAL VOLUME THROUGH EXTRA-TRA-CHEAL CONTINUOUS GAS INSUFFLATION � NITRIC OXIDEIN PATIENTS WITH ACUTE RESPIRATORY DISTRESS SYN-DROME AND REFRACTORY HIPOXEMIASantiago M. Herrero PhD* Joseph Varon MD Robert E. Fromm MPHHospital Cabuenes, Gijon, Spain

PURPOSE: Mechanical ventilation (NCMV) using extra-tracheal con-tinuous gas insufflation (ETCGI) and nitric oxide (NO) has been used forpatients with ALI(1).The purpose of this preliminary study was to comparethe conventional mechanical ventilation (CMV) through lung protectiveventilation versus the effect of ETCGI using NO mixture, on oxygenationand ventilation parameters in patients with ARDS and refractory hypox-emia.

METHODS: Five patients (four women) with severe systemic inflam-matory response syndrome, multiple organ system failure (ApacheII:26,88,5�2,99) and ARDS (LIS:3,75�0,3) with refractory hipoxemia(PaO2/FiO2:52,06�2,14 torr and SatO2:65,2�4,20 cmH2O) were stud-ies. The sequential ventilatory support protocol was: 1.Protocol CMV:Initial PRVC:Pressure regulated volume control or PCV: Pressure con-trolled ventilation to 6,28�0,38 ml/kg tidal volume (protective ventila-tion), optimizing best Peep (17,4�1,81 cmH2O) and NO. 2.ProtocolNCMV: Subsequently changes ventilation mode to PRVC or PCV, withPeep (2,4�0,54 cmH2O), ETCGI (9,0�2,64 liters/minute) and NitricOxide (3,92�0,83 ppm). The tidal volume, finaly was: 11,97�1,89 ml/kgand the volume minute was 15654�3050 ml/minute (range:12400-19600).The peak pressure (PIP) values in ETCGI mode, were obtained throughtracheal level monitoring. All patients, the informed consent was obtained,less in two patients that was obtained differed.

RESULTS: See table: t-Student for comparative samples (95% CI).

CONCLUSION: 1.- NO�ETCGI optimal application appears toimprove oxygenation and ventilation substantially. 2.- All patients survivedthe refractory hypoxemia. 3.-One patient died due to refractory septicshock, after a new episode of sepsis. 4.- No high levels of NO2 (�1,0ppm). 5.- No barotrauma episodes, in spite use high tidal volume (twopatients development barotrauma previous and were treated withNO�ETCGI without ventilatory problems). REFERENCE: 1.Herrero S,


Acute Lung Injury and ARDS, continued

226S CHEST 2005—Poster Presentations

Varon J, Fromm RE. “Nitric Oxide and Extratracheal continuous gas flowin the acute respiratory distress syndrome. Crit Care Med. December2004. Vol. 32, No. 12 (Suppl.) P400.

CLINICAL IMPLICATIONS: 1.- In life-threatening ARDS withrefractory hypoxemia, it is possible to maintain an adequate PaO2 with theapplication of NO and ETCGi (considered as ”rescue treatment“) 2.-ETCGi can be performed even in presence of previous barotrauma.

DISCLOSURE: Santiago Herrero, None.

LACTATE DEHYDROGENASE ISOZYMES AS A MARKER OFVENTILATOR-RELATED LUNG INJURYGregory H. Howell MD* Mark Yagan MD Betty Herndon PhD Univer-sity of Missouri-Kansas City, Kansas City, MO

PURPOSE: Mechanical ventilation as a life-sustaining procedure is abenefit to medicine and usually safe for the patient. When performed overextended periods, it is known to cause lung injury. Various methods ofassessing lung injury have been utilized. An objective measure, lactatedehydrogenase (LDH) isozyme profiles, changed significantly after ven-tilation in lung-healthy rats. Human studies using LDH 4/5 ratio inbronchoalveolar lavage (BAL) have assisted in diagnosing pulmonaryinfection. We hypothesized that BAL LDH isozymes would relate to lungchanges induced by mechanical ventilation.

METHODS: With IRB approval and individual signed consent, 30patients with healthy lungs undergoing elective surgery were enrolled ina prospective non-randomized trial to determine levels of LDH isozymesin BAL fluid, and to correlate these levels to time on mechanicalventilation. Bronchoscopy was performed and a BAL was obtained atintubation. After surgery a second BAL was done in the contralateral lung.Total LDH and LDH isozymes were measured by protein electrophoresison BAL concentrates. Using pre-surgical BAL LDH isozymes as individ-ual baseline, change in each LDH isozyme as a function of time onmechanical ventilation was plotted.

RESULTS: Mechanical ventilation averaged 2 hr 20 minutes (range:15-509 minutes). All 5 LDH isozymes increased in the post-surgical BAL,isozyme 4 significantly so (p�0.05). Ventilator time was compared withthe change in each LDH isozyme; no statistical significance was found.

CONCLUSION: This study demonstrated an elevated LDH isoen-zyme 4 in BAL fluid during surgical mechanical ventilation with anaverage time of approximately 2 hours. LDH isozyme measurements,which have historically emphasized cardiac and skeletal muscle metabo-lism, showed that isozyme 4 is usually remarkably stable, with exercise andtraining affecting the other isozymes.

CLINICAL IMPLICATIONS: The significant increase in BALisozyme 4 in the present study suggests a potential target for investigatinglung injury in patients who are subjected to prolonged mechanicalventilation.

DISCLOSURE: Gregory Howell, University grant monies We workfor the University of Missouri-Kansas City. The study was funded by theUniversity.

FACTORS AFFECTING SUCCESSFUL TRANSITION FROMHIGH FREQUENCY OSCILLATION TO CONVENTIONAL ME-CHANICAL VENTILATION IN ADULT PATIENTSSatomi Shiota MD* Stephen E. Lapinsky MB, BCh Rod MacDonald RRTRobert Fowler MD Sangeeta Mehta MD Thomas E. Stewart MD MountSinai Hospital and University of Toronto, Toronto, ON, Canada

PURPOSE: High frequency oscillation (HFO) is increasingly used tosupport adults with ARDS. Little data are available to guide the transitionto conventional mechanical ventilation (CMV); commonly this occurswhen mean airway pressure has been weaned below 24 cmH2O. Thisstudy aimed to identify predictive factors for successful transition fromHFO to CMV.

METHODS: Retrospective chart review of all patients receiving HFOin our institutions from 2000 to 2005. Data are presented as mean � SD.Student’s t-test was used for comparisons.

RESULTS: 117 patients received HFO, with a mean age 50.9 � 18.8years. We excluded from analysis patients who died on HFO (n�10), orwho were transitioned for withdrawal of care (n�25) or other reasons (e.g.hemodynamic compromise or deterioration on HFO, n�17). The remain-ing 65 patients were transitioned to CMV with a view to weaning. Ofthese, 24 (37%) died a mean of 19.1 � 24.1 days after transition(“non-survivors”) and 41 (63%) survived to discharge (“survivors”). Com-

paring non-survivors with survivors, no differences were noted in illnessseverity when HFO was initiated (APACHE II 19.1 � 6.8 and 21.1 � 8.3,p�0.20; PaO2/FiO2 ratio 105 � 43.3 and 120 � 74.0, p�0.49; oxygen-ation index 32.1 � 13.6 and 34.4 � 16.4, p�0.39). At the time of transitionto CMV, no difference was noted between non-survivors and survivors inmean airway pressure (23.6 � 2.6 cmH2O and 24.6 � 3.9 cmH2O,p�0.062) or ventilator frequency (4.90 � 1.59 Hz and 4.93 � 1.84 Hz,p�0.43). However, non-survivors had significantly worse oxygenation attransition than survivors (PaO2/FiO2 ratio 191 � 74.3 and 224 � 72.3,p�0.05; OI 14.4 � 6.1 and 12.0 � 3.3, p�0.05).

CONCLUSION: Despite similar severity of illness and oxygenation atinitiation of HFO, patients who did not survive following successfultransition to CMV demonstrated worse oxygenation parameters at thetime of transition.

CLINICAL IMPLICATIONS: These finding may suggest a role foroxygenation indices in the decision to transition from HFO to CMV.

DISCLOSURE: Satomi Shiota, Consultant fee, speaker bureau, advi-sory committee, etc. Speakers fees

THE EFFECTS OF INOS ON PULMONARY CHEMOKINE PRO-DUCTION AND POLYMORPHONUCLEAR LEUKOCYTE SUR-FACE EXPRESSION OF ADHESION MOLECULES DURINGSEPSISCedrin S. Law BSc* Ravi Taneja MD Lefeng Wang PhD El-BdaouiHaddad PhD George De Sanctis PhD David G. McCormack MD SanjayMehta MD Lawson Health Research Institute, London, ON, Canada

PURPOSE: Previous work has shown that inducible nitric oxidesynthase (iNOS) derived from inflammatory cells plays a particularlyimportant role in the development of high-protein pulmonary edema andincreased oxidative stress in sepsis-induced acute lung injury (ALI).Interestingly, iNOS-/- animals show increased pulmonary polymorphonu-clear leukocyte (PMN) infiltration despite decreased lung injury. Thepurpose of this study was to test the hypothesis that iNOS reducespulmonary production of CXC chemokines and increases surface expres-sion of adhesion molecules on PMN.

METHODS: Experiments were performed using iNOS�/� andiNOS-/- C57BL/6 mice. Sepsis was induced via cecal ligation andperforation (CLP), the lungs were removed and homogenized for analysisof the CXC chemokine macrophage inflammatory protein-2 (MIP-2).Alveolar macrophages (AM) were cultured, stimulated with LPS�IFN-�and the culture medium was analyzed for MIP-2 production. Surfaceexpression of CD11b and CD62L was measured via flow cytometry inbone marrow PMN after LPS�IFN-� stimulation.

RESULTS: MIP-2 levels in lung homogenate were increased in septicmice vs control and were significantly lower in septic iNOS�/� vsiNOS-/- mice (35.8�12.3 vs 67.4�14.2 ng/mL). AM MIP-2 productionincreased following LPS�IFN-� stimulation but there was no differencebetween iNOS�/� and iNOS-/- AM. Bone marrow PMN stimulated withLPS�IFN-� showed increased expression of CD11b and decreasedexpression of CD62L vs control but there was no difference betweeniNOS�/� and iNOS�/� PMN.

CONCLUSION: iNOS inhibits septic pulmonary, but not AM produc-tion of MIP-2. PMN iNOS has no apparent effect septic PMN surfaceexpression of CD11b and CD62L on PMN.

CLINICAL IMPLICATIONS: A better understanding of the mech-anisms by which iNOS affects PMN infiltration and sequestration maylead to new therapeutic options for patients with ALI.

DISCLOSURE: Cedrin Law, None.

APPLICATION OF LUNG PROTECTIVE MECHANICAL VENTI-LATION (USING LOWER TIDAL VOLUMES) MANDATES THEUSE OF PREDICTED BODY WEIGHT INSTEAD OF ACTUALBODY WEIGHTEsther K. Wolthuis MD Rogier M. Determann MD Marcus J. SchultzPhD* Academic Medical Center, Amsterdam, Netherlands

PURPOSE: Use of lower tidal volumes (VT) is recommended forpatients suffering from ALI/ARDS. We previously reported on a simple’intervention’ aiming at lowering VT in our institution (goal: VT 6-8ml/kg): this intervention existed of feedback and education on the use oflower VT, during which special attention was paid to the importance ofclosely adjusting VT to predicted body weight (PBW) in stead of actualbodyweight (Wolthuis, Intensive Care Med 2005).




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METHODS: To determine the longstanding effects of the above-mentionedintervention, we (a) compared data on VT-settings of mechanically ventilatedpatients before feedback and education (June 2003, N � 30) with VT-settings 15months later (September 2004, N � 103); in addition, we (b) collected data onVT-settings of patients recruited in two consecutive randomized controlledALI/ARDS- trials: the first trial was performed in 10-month period before theintervention (March 2002 – December 2002, N � 12), the second wasperformed in a 10-month period after the intervention (July 2003 – May 2004,N � 8). Statistical analysis: Mann-Whitney U test. P-value � 0.05 was consideredto represent a significant difference.

RESULTS: (a) Before intervention, VT was 9.6 � 1.8 ml/kg PBW; VTdeclined shortly after the intervention (8.0 � 1.8 ml/kg PBW), andremained low (7.8 � 1.3 ml/kg PBW) 15 months after the intervention. (b)VT in the second randomized controlled trial was significantly lower ascompared with VT in the first study on ALI/ARDS-patients: while in themajority of patients in the first study VT was � 10 ml/kg at all times, in thesecond study almost all VT were between 6 and 8 ml/kg.

CONCLUSION: Feedback and education caused a sustained declinein VT in mechanically ventilated patients in our institution.

CLINICAL IMPLICATIONS: These results possibly underscore theimportance of the use of PBW, instead of actual bodyweight, to adjust VT.

DISCLOSURE: Marcus Schultz, None.

SHORT TERM ANALYSIS OF PULMONARY MECHANICS DUR-ING MECHANICAL VENTILATION FOR ARDSWilliam D. Marino MD* Mary O’Connell-Szaniszlo MS Our Lady ofMercy Medical Center, Mount Kisco, NY

PURPOSE: Current practice employs low tidal volumes (Vt) in theventilation of patients with ARDS. Studies supporting this approach alsosuggest that plateau alveolar pressures (Pplat) associated with such tidalvolumes (25 cmH2O) are much lower than Pplat values (�35 cmH2O)previously demonstrated to be safe. These studies assume that Pplatduring mechanical ventilation remains constant. We have observed fluc-tuating airway pressures during positive pressure ventilation of patientswith ARDS. The “snapshot” measurements of mechanics in the abovestudies could thus misrepresent the actual Pplat, explaining the studies’discrepancies. We have measured serial pulmonary mechanics and pres-sures during short periods of ventilation of patients with ARDS in orderto evaluate this possibility.

METHODS: In each of 20 patients using mechanical ventilation forARDS, clinical and ventilator data were extracted from the chart.Subsequently compliance, airway resistance (Raw), peak airway pressure(Ppeak) and Pplat were measured every 30 minutes for 6 hours. Thesemeasurements were performed in the absence of any spontaneousbreathing effort or change in ventilator settings. Mean values and therange of values of each parameter were measured in each patient.

RESULTS: 7 males and 13 females, aged 72�/-17 years were studied. Allutilized volume ventilation with a Vt of 9�/-2.6ml/kg and inspired oxygenconcentration of 48�/-21%. Compliance was 32�/-10ml/cm with an intrain-dividual variation of 12�/-6ml/cm. Raw was 18�/-6.6l/s/cm with a variation of12�/-6.6l/s/cm. Pplat was 23.8�/-8.9cmH2O with ranges of values from 5 to18 cmH2O. Ppeak was 32 �/-11cmH2O with ranges from 7 to 17.

CONCLUSION: There is substantial short term variation in airway andalveolar pressures during mechanical ventilation of lungs with ARDS. Thismay expose such lungs to barotrauma if initial ventilator settings causealveolar pressures at the high end of the safe pressure range, since thesepressures may be exceeded during continued mechanical ventilation.

CLINICAL IMPLICATIONS: When optimizing ventilation and lungexpansion of patients with ARDS, Pplat should be monitored serially toprevent exposure of the lung to traumatic pressures.

DISCLOSURE: William Marino, None.

Advances in Obstructive Sleep Apnea12:30 PM - 2:00 PM

REPETITIVE INSPIRATORY OCCLUSIONS ACUTELY IMPAIRMYOCARDIAL CONTRACTILITYColleen Lynch BSc* Jeremy Simpson PhD Steve Iscoe PhD Queen’sUniversity, Kingston, ON, Canada

PURPOSE: Obstructive sleep apnea (OSA) adversely affects ventric-ular function, increasing the incidence of nocturnal death of cardiac origin

and contributing to the pathogenesis of congestive heart failure. The largeswings in intrathoracic pressure caused by airway occlusion increasecardiac transmural pressure, decrease preload, and increase afterload,augmenting metabolic demand at the same time as arterial oxygen contentdecreases. We hypothesized that repeated inspiratory occlusions, mimick-ing OSA, cause myocardial dysfunction and injury.

METHODS: We subjected anesthetized male Sprague-Dawley rats to3 h of repeated airway occlusion (30 s occlusion every 2 min); results werecompared to sham rats.

RESULTS: Following occlusions, left ventricular function de-creased; the peak rates of pressure generation (�dP/dt) and relaxation(-dP/dt) fell from 7820 � 271 (SEM) to 6310 � 623 and from -8851 �502 to -7121 � 381 mmHg/s (p � 0.05), respectively. Myofibrilproteins were isolated from the left ventricle for determination ofCa2�-activated myosin ATPase activity. Compared to shams, inspira-tory occlusion significantly reduced maximum (97 � 5 vs. 137 � 9, p �0.01) and minimum (35 � 6 vs. 76 � 9 nmol/min/mg, p � 0.01)ATPase activity. We detected release of cTnT into the blood in 4 of 9occluded rats but none of the shams.

CONCLUSION: These results demonstrate for the first time thatrepeated inspiratory occlusions acutely impair left ventricular contractility,reduce ATPase activity of myofibril proteins, and, in some rats, causemyocardial necrosis. The mechanism(s) underlying the decrease in AT-Pase activity is unknown but probably reflects a post-translational modi-fication(s) to one or more myofibril proteins.

CLINICAL IMPLICATIONS: Collectively, these results may accountfor the acute pathological effects of OSA.

DISCLOSURE: Colleen Lynch, None.

FUNDAMENTAL FREQUENCY MEASURES WITH MORPHEUSOF HUMAN SLEEP ELECTROENCEPHALOGRAPHY(EEG) INSEVERE SLEEP APNEA WITH EARLY INTERVENTION OFCONTINUOUS POSITIVE AIRWAY PRESSURE (CPAP)Richard K. Bogan MD* Jo Anne Turner MSN Alex Novodvorets MS KobyTodros BS Baruch Levy BS SleepMed, Columbia, SC

PURPOSE: To evaluate a new measure of EEG synchrony or stabilityusing fundamental frequency analysis provided by Morpheus in subjectswith severe obstructive sleep apnea (OSA) adequately treated with CPAPusing a split night protocol.

METHODS: A total of 27 adults were selected with a primarydiagnosis of obstructive sleep apnea and who were treated with CPAPduring their initial study. Each individual had a baseline and treatmentperiod. Only those individuals with a respiratory disturbance index(RDI) � 10 episodes per hour and oxygen saturation greater than 85%during the ideal CPAP titration period were selected. When there wasmore than one CPAP level that this occurred, the multiple levels wereincluded. Fundamental frequency values below 4 Hz are believed torepresent increased EEG synchrony. The percentage of fundamentalfrequency below 4 Hz was calculated during the baseline period andideal CPAP titration period (total sleep time).

RESULTS: Means with standard deviations are reported. There were24 males (ages 25-77) and 3 females (ages 46-52). Body mass index was35(7); Epworth Sleepiness Scale 12(5), and SleepMed Insomnia Index16(8). Low oxygen saturation at baseline was 81%(6); oxygen saturation atideal CPAP level 91%(2); RDI at baseline 71(26); and RDI at ideal CPAPlevel 3(3). Fundamental frequency under 4Hz during the baseline periodwas 12%(13) and at the ideal CPAP pressure 31%(13). Independentt-tests comparing % of fundamental frequency below 4Hz at the baselineperiod with the ideal CPAP period were significant p�0.001.

CONCLUSION: Early intervention with CPAP in OSA improvessleep quality. Automated analysis that calculates modal frequency ofadaptive segmentation and fuzzy logic segments in sleep EEG dem-onstrates EEG synchrony that is believed to reflect improvement insleep quality.

CLINICAL IMPLICATIONS: Enhanced resolution by automatedanalysis offers improved efficiencies, reproducibility, and insights intosleep states and processes.




DISCLOSURE: Richard Bogan, Shareholder SleepMed Inc.

CLINICAL UTILITY OF BIOELECTRIC SIGNALS IN THE DI-AGNOSIS OF OBSTRUCTIVE SLEEP APNEA (OSA) IN UNAT-TENDED SETTINGSPierre Mayer MD* Vincent Jobin MD Francois Bellemare PhD Hotel-Dieu of CHUM, Montreal, PQ, Canada

PURPOSE: The standard diagnostic test of OSA, i.e. overnight poly-somnography (PSG), is complex and difficult to perform outside the sleeplaboratory. However, the value of electrophysiological and respiratorymonitoring has not been assessed critically in unattended settings. In thisstudy we evaluated whether full PSG is necessary to establish a diagnosisof OSA in unattended studies.

METHODS: Full unattended PSG studies were conducted in thehome place (25 tetraplegic patients)or in the hospital (25 surgical patientsstudied preoperatively)using a standard montage. Installation of thebiosensors was performed by a trained sleep technician. Recording wasinitiated at a preset time and all signals stored on a digital storage media(Flash card) and subsequently downloaded to a desktop computer foranalysis. No overnight monitoring was possible. The PSGs were firstscored using standard criterions by one of 3 trained sleep technicians andan apnea/hypopnea index (AHI) calculated as the number of respiratoryevents per hour of sleep as determined by sleep staging. The analysis wasthen repeated on a separate day and in a blind fashion using respiratoryvariables only (i.e. without EEG and EMG signals) and a respiratorydisturbance index (RDI) calculated as the number of respiratory eventsper hour of recording time.

RESULTS: Sleep efficiency was 77.1�13.8%. Recording time ex-ceeded sleep time by 117�79 minutes (p�.03) but RDI (20.5�21.3) wasnot �significantly different from AHI (22.9�24.2; p�.116). Both werehighly correlated (r2�.82). Using a AHI diagnostic cutoff value �15events/h, the diagnostic sensitivity and specificity of RDI were both 86%.If a RDI cutoff value of �10 events/h was adopted instead, sensitivitywould be 100%.

CONCLUSION: Because of frequent arousal, the Rechtschaffen andKales method for scoring sleep markedly underestimate sleep time as well

as the number of respiratory events. We conclude that bioelectric signalsare not necessary for the diagnosis of OSA.

CLINICAL IMPLICATIONS: Because PSGs are much simpler toperform without bioelectric signals, this simplified approach shouldimprove access to and cost/benefit of diagnosis and treatment of OSA.

DISCLOSURE: Pierre Mayer, None.

EVALUATION OF ANATOMIC BREATHING PATTERNS RE-LATED TO OBSTRUCTION AT NASOPHARYNX AND ORO-PHARYNXFlorence M. Sekito MS* Lucas N. Lemes MD State University of Rio deJaneiro, Rio de Janeiro, Brazil

PURPOSE: The objective was to evaluate the clinical prevalence ofnasal breathing mode, the most frequent one, and the presence of nasalobstruction. The obstruction sites (naso and oropharynx) and frequency inthe oral-breathing mode and mixed-breathing mode were also evaluated.

METHODS: The study design was transversal, analyzing 145 consec-utive healthy patients enrolled at UERJ Faculty of Dentistry, without anyprevious history of smoking or respiratory disease. They were classified byclinical examination in 3 groups according their mode of breathing:nasal-breathing, oral-breathing, mixed-breathing (turns nasal or oralmode). Their respiratory airflow were measured by the Forced OscillationTechnique (FOT), Oscilab-version 2.0, from nose and from mouth at afrequency of 5 Hz, to determine the obstruction in naso and oropharynx.

RESULTS: The Fisher exact test was used, with significant associationbetween breathing mode and the obstruction level (p � 0,003). Theoral-breathing occurred when there were obstruction (p�0,001) in naso-pharynx (33.33%), and/or oropharynx (44.44%). The nasal and mixedmode were more frequent with the obstruction absence (68.54% and53.19%, respectively).

CONCLUSION: The breathing pattern had positive correlation withthe obstruction site. The nasal and the mixed-breathing, may occur withsome obstruction degree. The naso or oropharynx obstruction contributedsignificantly to oral-breathing mode.

CLINICAL IMPLICATIONS: In the literature review, there wasn’tany reference about quantitative or qualitative methods to verify therelationship between the type of breathing and obstruction. This tech-nique could testify this correlation significantly.

DISCLOSURE: Florence Sekito, None.

A STUDY ON PREVALENCE ESTIMATES OF OBSTRUCTIVESLEEP APNEA IN INDIAN POPULATIONRajendra Prasad MD* Rajiv Garg MD Ram K. Verma MD S. P. AgarwalMS R. C. Ahuja MD King George’s Medical University, Lucknow, India

PURPOSE: To know prevalence estimates for key symptoms andfeatures that can indicate the presence of obstructive sleep apnea(OSA) inIndian population.

METHODS: Single centre cross sectional study done from August2003 to July 2004 in consecutive apparently healthy attendants of 25-64years age group coming to outdoor of Department of Pulmonary Medi-cine, King George’s Medical University, Lucknow, India. We recorded

Evaluation of the Clinical Concepts of NormalBreathing, Types of Breathing and the Obstruction in

Nasopharynx and Oropharynx

Frequency%

Nasal-Breathing

Oral-Breathing

Mixed-Breathing Total

No obstruction n 6168.54%

111.11%

2553.19%

87

Nasopharynxobstruction

n 1516.85%

444.44%

817.02%

27

Oropharynxobstruction

n 66.74%

333.33%

1021.28%

19

Naso and Oropharynxobstruction

n 77.87%

111.11%

48. 51%

12

Total 89 9 47 145


Advances in Obstructive Sleep Apnea,continued


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data on a pre-designed proforma and took interview on the basis ofpre-tested Berlin Questionnaire with some relevant modifications.

RESULTS: Out of 816 subjects approached, 702 responded. Out of702, 452(64.4%)were males. Mean age was 42.7 � 10.4 years; mean neckcircumference was 13.6 � 1.2 inch, mean BMI was 23.8 � 4.2 kg/m2.31.1%(218/702) were snorers. The loud snorers were17.4%, and 60.5% ofthem were at high risk for OSA. Among snorers 22.9% bothered otherpeople and 46.0% of them were at high risk for OSA. Out of 702, 6.0% hadmorning tiredness or sleepy awakening (� 3-4 times /wk) and 52.4% ofthem were at high risk for OSA, 5.1% had wake time tiredness and 61.1%of them were at high risk for OSA. Out of 702, 45.3% either did not knowto drive or never needed driving and only 54.7 % used to drive. Amongpersons who use to drive 2.1% had drowsiness behind the wheel (� 3-4times/wk) and 75% of them were at high risk for OSA. Out of 702, 13.0%were obese and 19.8% of them were at high risk for OSA. Overall therewere 3.7% (26/702) were at high risk for OSA(qualified for 2 or morecategory symptoms of Berlin questionnaire) .

CONCLUSION: Obstructive sleep apnea is a common disease andthere is high demand of its awareness, evaluation, diagnosis and manage-ment in countries like India.

CLINICAL IMPLICATIONS: There is need of relevant modificationof Berlin Questionnaire for countries like India as half of our populationeither do not know to drive ored not to drive.

DISCLOSURE: Rajendra Prasad, University grant monies Receivedno grants; Grant monies (from sources other than industry) Nil; Grantmonies (from industry related sources) Nil

SLEEP APNEA IN SARCOIDOSISMajid M. Mughal MD* Joseph Golish MD Mani Kavuru MD OlurantiAladesanmi MD Nancy Ivansek Daniel A. Culver DO Cleveland ClinicFoundation, Cleveland, OH

PURPOSE: The main purpose of this study is to estimate theprevalence of sleep related breathing disorders in patients with sarcoidosisby using Sleep Apnea/Sleep Disorders Questionnaire (SA/SDQ) andEpworth Sleepiness Scale (ESS).

METHODS: 70 consecutive patients with diagnosis of biopsy provensarcoidosis seen at the sarcoid clinic were screened for sleep relatedbreathing disorders using SA/SDQ and ESS. The SA/SDQ consists of 8questions and 4 other items related to weight, smoking status, age, andbody mass index, which are calculated to generate a raw score. Totalscores range from 0-60. To suspect sleep apnea, cutoffs of 32 for womenand 36 for men were used as a criteria for sleep study referral.

RESULTS: 70 patients with sarcoidosis completed the questionnaires.There were 42 females and 28 males with a mean age of 48 � 10 years.34% of pateints were African American. Mean duration of diagnosis was78 months. 60% of patients had 2 or more organs involved. Approximately2/3rd of patients were actively treated with steroids or other immunosu-pressive agents (mean prednisone dose was 7 mg/day). 39 patients hadpositive questionnaires (25 with positive SA/SDQ while 14 with positiveESS). Considering the reported 81% specificity of SA/SDQ for sleepapnea in general population, 39% of patients will most likely have sleepapnae syndrome by polysomnography.

CONCLUSION: The prevalence of sleep apnea syndrome in patientswith sarcoidosis is significantly high. In this study, we persented ourexperience with SA/SDQ as a screening instrument for sleep disorderedbreathing in a sample of patients with sarcoidosis.

CLINICAL IMPLICATIONS: Screening tools such as the SA/SDQ aregaining increasing importance because of high prevalence of sleep disorderedbreathing in chronic diseases and the high cost of polysomnography. Sleepdisordered breathing is highly prevalent in our sarcoid population and SA/SDQmay be a useful test in identifying patients at risk for sleep apnea syndrome.

DISCLOSURE: Majid Mughal, None.

THE ACCURACY OF NON-RESTRICTIVE SENSING SYSTEMFOR EVALUATING SLEEP APNEA SYNDROME UNDERTHREE-DIMENSIONAL FIBER-GRATING SENSORSHisashi Takaya MD* Toranomon Hospital, Tokyo, Japan

PURPOSE: Nasal flow sensors are utilized for diagnosis of sleep apneasyndrome (SAS). Discomfort and fluctuation in sensitivity caused by bodymovements are problems when patients wear nasal flow sensors duringpolysomnography (PSG) tests. The aim of this study was to clarify the

accuracy of non-restrictive sensing system for diagnosing SAS usingthree-dimensional Fiber-Grating (FG) sensors.

METHODS: Twenty patients with SAS were enrolled in the study[M:F�19:1, age 50.0�26 years old, BMI 26.2kg/m2, apnea-hypopneaindex (AHI): 25.6]. Three-dimensional FG measurement and PSG testswere conducted simultaneously. AHI determined by using pressure flow,and the movement of thoracic and abdominal walls during PSG werecompared to those by FG sensors in the supine and lateral positions.

RESULTS: AHI determined by FG sensors and PSG tests were wellcorrelated (r�0.973, P�0.0001; supine position: r�0.974, P�0.0001,lateral position: r�0.965, P�0.0001, respectively). All twenty patientsunderwent these tests with no trouble and good compliance.

CONCLUSION: The accuracy of non-restrictive sensing system fordiagnosing SAS was clarified.

CLINICAL IMPLICATIONS: Since the non-restrictive system usingFG sensors is more comfortable and convenient for making diagnosis ofSAS than the conventional one, it may be widely introduced.

DISCLOSURE: Hisashi Takaya, None.

THE INCIDENCE OF POSSIBLE OBSTRUCTIVE SLEEP AP-NEA SYNDROME IN SUBJECTS WITH ACUTE MYOCARDIALINFARCTION AND NORMAL CORONARY ANGIOGRAPHYMichael Chalhoub MD* Marwan Elia MD Mohammed Zgheib MDTheodore Maniatis MD Staten Island University Hospital, Staten Island,NY

PURPOSE: The purpose of this study is to compare the incidence ofpossible obstructive sleep apnea syndrome (OSAS) in patients with acutemyocardial infarction (AMI) and normal coronary angiography to theincidence of possible OSAS in patients with MI and abnormal coronaryangiography.

METHODS: All patients admitted to a university hospital with thediagnosis of AMI were evaluated. AMI was defined as having 2 out of 3criteria: Chest pain, ST elevation of � 1 mm in two contiguous leads, orelevated cardiac enzymes. Patients who underwent coronary angiographywere included in the study. The subjects were asked a set of questions.The questions were scored from 1 to 3. The questions addressed thefollowing: Epworth sleepiness scale (ESS). ESS�10 (score 1), ESS�18(score 2), snoring (score 1), witnessed apneas (score 3), falling asleep ininappropriate situations (score 2), unrefreshed sleep (score 1), and historyof OSA diagnosed by NPSG. The subjects were then classified into fiveclasses. Class I highly unlikely to have OSA (score � 1), class II unlikelyto have OSA (score 2), class III likely to have OSA (score 3), class IVhighly likely to have OSA (score �3), and class V definite OSA (OSAdiagnosed by nocturnal polysomnography (NPSG)). The subjects weredivided into two groups. Group I included patients with normal coronar-ies, whereas group II included patients with abnormal coronaries onangiography.

RESULTS: A total of 55 patients were included in the final dataanalysis. 22 subject in group I, and 33 in group II.The results aresummarized in the following table.

CONCLUSION: The incidence of possible OSAS was significantlyhigher in patients with AMI and normal coronaries compared to patientswith AMI and abnormal coronaries on angiography. 28.5% compared to6% p value 0.035.

CLINICAL IMPLICATIONS: Patients with AMI and normal coro-nary angiography should be investigated for the possibility of OSAS. Thosefound to have high likelihood of having OSAS should be sent for NPSGand adequate treatment offered.

DISCLOSURE: Michael Chalhoub, None.

Age(years)

BMI(Kg/m2)

Male(%)

Female(%)

ClassIII/IV (%)

Group1n�22

57.1�13.1 39.6�10 41 59 28.6

Group 2n�33

66.2�11.8 31.1�8 69 31 6

P value NS NS 0.029 0.029 0.035

Results are mean�standard deviations unless otherwise specified.BMI� Body Mass Index.




THE IMPACT OF SLEEP DISORDERS ON THE ATTENTIONDEFICIT DISORDER IN THE ADULT PART I: THE PATIENTWITH OBSTRUCTIVE SLEEP APNEAClifford G. Risk MD* Clifford Risk, MD, Marlborough, MA

PURPOSE: Patients with obstructive sleep apnea (OSA) report exces-sive daytime sleepiness and attention impairment. This study assesses theimpact of continuous positive airway pressures (CPAP) treatment ofattention deficit.

METHODS: We studied 41 adult patients who presented at anationally accredited sleep center for evaluation of OSA. Severity of OSAis evaluated using the Epworth Sleepiness Scale (ESS) a self reportquestionnaire designed to assess daytime sleepiness on a scale of 0 to 24;and by the respiratory disturbance index (RDI) measured during theirsleep study. Attention impairment was evaluated using the adult self-report scale (ASRS) symptom checklist, a validated scale assessing atten-tion impairment on a scale of 0 to 36. A score of 17 or greater indicatespossible or probable attention deficit. Patients completed both question-naires at baseline and following CPAP treatment; the RDI was measuredduring their baseline sleep study and during a subsequent CPAP titrationstudy.

RESULTS: The average baseline score on ESS was 11.6 (4.2) and 2.7(3.3) at 3 months post-treatment (t�11.8,p�.0001). The average RDI onthe baseline PSG was 29.9 (16.8) and 2.2 (3.6) on the subsequent CPAPstudy (t�10.5,p�.0001). The ASRS score was 16 (8) at baseline and 11 (8)at 3 months post-treatment (t�6.0,p�.0001). Of 41 patients at baseline,19 demonstrated an ASRS score of 17 or greater; at 3 months post-treatment, 11 showed an ASRS that had decreased to the normal range,while 8 did not. These patients were subsequently diagnosed with ADDdue to a comorbid psychological or neuromuscular diagnosis, hearing orreading deficit, or memory or executive function impairment. Mostsuffered from concurrent insomnia and non-restorative sleep.

CONCLUSION: This study demonstrated a high comorbidity betweenADD and OSA. Forty-six percent showed significant attention impair-ment at baseline; with treatments, 58% reported substantial improvement,but 42% reported persistent serious attention deficit, and required furtherevaluation and treatment.

CLINICAL IMPLICATIONS: OSA is a significant factor contribut-ing to ADD. In patients with persisting deficits after CPAP treatment,further evaluation and treatment is required.

DISCLOSURE: Clifford Risk, None.

IS OBSTRUCTIVE SLEEP APNEA (OSA) IN NON-OBESE PA-TIENTS A LESS SERIOUS DISEASE THAN IN OBESE PA-TIENTS?Ammar Ghanem MD* Syed Mahmood MD Marshall University, Hun-tington, WV

PURPOSE: OSA occurs in non-obese patients,but they may exhibitdifferent characteristics than obese patients with OSA. To elucidate thispoint,we investigated several physiological and clinical parameters amongnon-obese and obese OSA patients.

METHODS: Of 254 patients referred to sleep clinic,we identified 102patients with OSA(Apnea Hypopnea Index�5). We classified OSA pa-tients with Body Mass Index(BMI)�30 as non-obese and those with aBMI�30 as obese. We conducted a retrospective evaluation that includeddemographic,physiological and clinical data and compared the non obeseand obese groups. For statistical comparisons, continuous variables wereanalyzed by student’s t-test and categorical variables by chi-square.Fisher’s exact test was used for analysis when a variable contained lessthan 5 observations.

RESULTS: Of 102 patients with OSA,17(16.7%)were non-obese and85(83.3%)were obese. The groups of non-obese and obese OSA patientsdiffered significantly in four parameters. Mean AHI was 13.5 in thenon-obese group and 27.6 in the obese group(P� 0.03). Non-obesepatients were older(average age 57.1 years compared to 48.3 years amongobese patients)(t-test,p� 0.01);used more sedatives(usage of one or moresedatives by 52.9% in non-obese group compared to 24.7% in the obesegroup)(Chi-square,p� 0.02);and,exhibited less upper airway narrow-ing(23.5% of the non-obese group compared to 55.1% in the obesegroup)(Chi-square,p� 0.02). Only one non-obese patient(5.9%) wasyounger than 50,compared to 48 patients(56%)in the obese group(Chi-square,p�0.0001). There were no significant differences between non-obese and obese OSA patients in gender,family history of OSA,facial

malformations,adenoid or tonsillar enlargement,smoking,co-morbid con-ditions and use of narcotics.

CONCLUSION: In our study,about 1 in 5 patients with OSA wasnon-obese,suggesting OSA is not limited to obese persons. Non-obesepersons differed from obese persons in several important characteristics.We report for the first time that excess use of sedatives occurred innon-obese OSA patients compared to obese patients.

CLINICAL IMPLICATIONS: OSA is milder in non-obese patientsand is unlikely in non-obese patients who are less than 50 years old.

DISCLOSURE: Ammar Ghanem, None.

OBESITY HYPOVENTILATION SYNDROME: AN UNDERREC-OGNIZED ENTITYFarooq Sattar MD* Alex Duarte MD Luigi Terminella MD GulshanSharma MBBS University of Texas Medical Branch, Galveston, TX

PURPOSE: Obesity is epidemic in the United States and is a majorcause of morbidity and mortality. In addition to obstructive sleep apnea,obesity is associated with obesity hypoventilation syndrome (OHS),characterized by daytime hypercapnia. OHS is associated with significantmorbidity and mortality. In order to initiate therapy with non invasivepositive pressure ventilation (NIPPV), a sleep study is required. Weperrformed a study to determine the prevalence of daytime hypercapniain morbidly obese patients referred for evaluation of dyspnea and toevaluate if body mass index or pulmonary function test help distinguishsimple obesity from OHS.

METHODS: All subjects who underwent pulmonary function test(PFT) at our institution from January 2003 to December 2004 werescreened. Inclusion criteria was a BMI � 35 kg/m2, � 20 pack yearshistory of smoking, an FEV1 � 50%, an FEV1 / FVC �70, and absenceof neuromuscular disorder. Simple Obesity (SO) was defined as a BMI �35 kg/m2 in the absence of daytime hypercapnea. OHS was defined as aBMI � 35 Kg/m2 and daytime hypercapnia (arterial PaCO2 � 45 mmHg). Data on subjects age, gender, height, weight, smoking history,pulmonary function tests (PFT’s), arterial blood gas (ABG), polysomnog-raphy and use of NIPPV were collected by chart review.

RESULTS: 1904 PFT’s were performed during the study period. 122patients met the inclusion criteria. Seventy six (62%) patients hadcomplete PFT’s and an ABG available for review. Twelve (16%) subjectshad daytime hypercapnia.

CONCLUSION: OHS is common in morbidly obese patients. Clinicalparameters such as BMI and pulmonary function test do not helpdistinguish OHS from SO. Arterial blood gas measurements are necessaryto establish a diagnosis of OHS.

CLINICAL IMPLICATIONS: Morbidly obese individuals with un-explained dyspnea should have arterial blood gas measurements toexclude daytime hypercapnia. Polysomnography should be considered inpatients with daytime hypercapnia to determine the presence of sleepdisordered breathing and to initiate noninvasive positive pressure venti-lation.

DISCLOSURE: Farooq Sattar, None.

USE OF A SIX POINT QUESTIONNAIRE TO CATEGORIZESTABLE HEART FAILURE PATIENTS TO HIGH AND LOWRISK FOR SLEEP DISORDERED BREATHINGJohn D. Roehrs MD* Anselmo Garcia MD Cynthia K. Scott RN Carl T.Hayden VA Medical Center, Phoenix, AZ

PURPOSE: We evaluated the efficacy of an abbreviated sleep ques-tionnaire, desgined to recognize sleep disordered breathing (SDB)in acohort of patients assigned to a VA heart failure clinic.

METHODS: A 6 point data set consisting of (1)Excessive DaytimeSleepiness,(2) Snoring, (3)Observed Apneas,(4) Non-restorative sleep,(5)BMI, (6)and Neck Circumference were collected. Each positive re-sponse was given one point. BMI�30 and Neck Circumference�17.5 inwere given one point each. Scores of 3 or more points were placed in thehigh probability category and were assigned high priority for SDBevaluation. Two or less point scores were assigned to the Low probability.All were scheduled for Attended Polysomnography.

RESULTS: Of the 40 heart failure clinic patients evaluated 25 hadscores of 3 or more points on the screening questionnaire. 15 patients had2 or less points and were referred to the VA sleep clinic for confirmatoryexamination. Four of those 15 patients were referred for polysomnogra-phy while the remainder were felt unlikely to have significant SDB. All




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high probablity patients were scheduled for polyomnography. SleepDisordered Breathing was identified in 70 per cent of those patients.

CONCLUSION: The 6 point screening questionnaire appeared todelineate a higher risk group for sleep disordered breathing in this cohortof patients with known heart failure. Less than 30 per cent of the lowprobability cohort were ultimately studied.

CLINICAL IMPLICATIONS: SDB is present in approximately 50percent of patients with known stable CHF. A short simplified 6 pointdata set appeared to be sensitive in selecting patients with a highprobability for SDB. Use of the questionnaire should identify patients atrisk for SDB earlier, and could prioritize their early evaluation and shouldresult in earlier treatment.

DISCLOSURE: John Roehrs, None.

THE IMPACT OF PHYSICAL CHARACTERISTICS AND POLY-SOMNOGRAPHIC FINDINGS TO HEALTH RELATED QUAL-ITY OF LIFE (QOL) IN A PATIENT WITH OBSTRUCTIVESLEEP APNEA (OSA)Asegid M. Kebede MD* Amao Olusegun MD Samir Fahmy MD SUNYDownstate Medical Center, Brooklyn, NY

PURPOSE: OSA is a relatively common condition with a prevalence of5%. Significant reduction in QOL is the major complication OSA.Con-tinuous positive airway pressure (CPAP) titrated to eliminate Apnea andHypoapnea significantly improve quality of life. Previous study indicatesthere is no correlation between QOL and severity of sleep apnea. Thereare various physical and polysomnographic finding that associated with thedecrease in health related QOL in this cohort study. The purpose of thisstudy is to evaluate the impact of polysomnographic features and physicalcharacteristics to health related QOL in a patient with OSA.

METHODS: The Study was conducted in sleep laboratory of KingsCounty medical center, Brooklyn, New York. We studied 34 adult (22male and 12 female) patients with mean age of 45 (19-72), a body massindex (BMI) of 41.99 and diagnosis of OSA (apnea-hypoapnea index morethan 5). Patients with major medical and psychiatric illness were excluded.Baseline physical and polysomnographic characteristics were obtained.The health related QOL was assessed by administering medical outcomesshort-form ( MOS SF-36), a 36-item questionnaire that summarizes healthrelated QOL using eight subscales and two summary scores. The resultswere analyzed using Pearson correlation statistics.

RESULTS: The was significant negative correlation between BMI andSF-36 physical score ( p�0.001). Subclass analysis also showed significantcorrelation between BMI and all components. There was also positivecorrelation between sleep efficiency and physical functioning and mental

health. It is of note that there was no significant correlation betweenapnea-hypoanea index (AHI), arousal index, nocturnal oxygen desatura-tion (NOD) and the SF-36 physical and mental health scores.

CONCLUSION: AHI factor that define OSA may not determine theseverity of disease outcome with respect to health related QOL.The studyshowed the significant impact of obesity on QOL in patients with OSA.

CLINICAL IMPLICATIONS: weight reduction measures shouldaggressively be incorporated in management of OSA to improve theirQOL. The positive association in sleep efficiency and QOL may indicatepossible mechanism of improvement of QOL with CPAP.

DISCLOSURE: Asegid Kebede, None.

EFFECTS OF A HEATED TUBE ON SLEEP QUALITY, WITHACTIVE HEATED HUMIDIFICATION DURING CPAP THER-APY IN A COOL SLEEPING ENVIRONMENTGeorg Nilius MD* Ulrike Domanski PhD Karl-Josef Franke MD Kral-Heinz Ruhle MD Klinik-Ambrock, Hagen, Germany

PURPOSE: Active heated humidification improves the side-effects ofCPAP therapy for patients with sleep-breathing disorder (SAS) in theupper airways.In a cool ambience temperature, however, condensationwill form and the patients feel disturbed in their sleep.The object of thisstudy was to examine the effects of condensation on sleep quality duringcontinuous CPAP. Furthermore, a comparison of sleep quality achievedwith an active heating breathing tube versus conventional heated humid-ification was intended to be gained in a prospectively random study.

METHODS: 19 patients with a first diagnosis of obstructive sleepapnoea syndrome, median age 55.2 (�/- 10.4) years, median BMI 32.8(�/- 6.3) kg/m2 and median ESS score 10.8 (�/- 5.0) were treated withCPAP (HC 602, Fisher & Paykel) with conventional heated humidifica-tion (integrated humidifier and tube heater turned off, humidification viaHC100, temperature 32°C) and on another night with an active heatedbreathing tube (level 8, heating humidifier 32°C) in the sleep lab.

RESULTS: The results of the poysomnography data.CONCLUSION: If condensation forms in the CPAP tubing system,

sleep quality is considerably reduced. This can be eliminated almostentirely by a heated breathing tube.

CLINICAL IMPLICATIONS: We suggest that patients needingactive heated humidification during CPAP, who wish to sleep in a coldbedroom ambience, should use a system with a heated breathing tube.

DISCLOSURE: Georg Nilius, Grant monies (from industry relatedsources) The study was fianced by gift from fisher and Paykel healthcare

A RANDOMISED SINGLE-BLINDED CROSS-OVER TRIAL OFSESAME OIL (“NOZOIL™”) FOR THE TREATMENT OF NASALSYMPTOMS ASSOCIATED WITH CPAPJohn F. Feenstra MBBS* Kelli Rixon BSc Craig Hukins MBBS SleepDisorders Centre, Princess Alexandra Hospital, Brisbane, Australia

PURPOSE: Nasal symptoms are a common side effect of CPAPtherapy. Although most patients experience self-limiting nasal congestion,at least 10% complain of persistent nasal problems to some degree after6 months of therapy. Nasal symptoms can be treated in a variety of ways(inhaled nasal steroids, antihistamines, topical saline sprays and heatedhumidification); there is limited trial data of their effectiveness. The idealand best treatment is heated humidification. Unfortunately heated hu-

Variable (mean � SD)

SimpleObesity(n�64)

ObesityHypoventilation

Syndrome(n�12)

Age 54.2�12.9 52.5�13.4Body mass index

(kg/m2)Pulmonary Function(% predicted) FEV-1 FVC FEV-1/FVC TLC ERV DLCO

43.5�9.3 48.3�10.2

FEV-1 81�16 77�15FVC 82�15 7715FEV-1/FVC 80�5 81�5TLC 88�12 87�13ERV 48�37 37�21DLCO 85�22 85�14

Arterial blood gasespHPaO2

PaCO2

7.41�0.0376�9

39.5�3

7.39�0.02*69�12*

48.4�6.6*Polysomnogram n (%)

Apnea-hypopnea index � 5 (n)20 (31)

131 (8)

1

*p-value � 0.05




midification is expensive and many patients cannot afford this treatment.Nasal sesame oil (“Nozoil™”) has been shown to be superior to NormalSaline when used in patients with nasal symptoms associated with drywinter months in the northern hemisphere. The aim of the study was toassess the effect of “Nozoil™” on nasal symptoms and objective compli-ance.

METHODS: Randomised, single-blinded, cross-over trial of subjectswith obstructive sleep apnoea on CPAP with nasal symptoms, recruitedfrom a tertiary referral Sleep Disorders Centre. Subjects were assessedwith visual analogue scales of nasal symptoms, anterior rhinomanometry,and objective compliance at enrolment and at the end of each 2 weekintervention period. Patients were randomised to normal saline (NS) or“Nozoil™” for 2 weeks then crossed over for a further 2 weeks.

RESULTS: 17 subjects have completed the protocol. Compliancesignificantly improved on “Nozoil™” from baseline (5.50�2.05 hours/dayimproving to 6.50�1.35, p�0.007) and also when compared to NS(6.50�1.35 vs. 5.97�1.55, p�0.002). There was no statistically significantdifference with nasal resistance between the baseline and interventionmeasurements. Significant subjective improvements in nasal crustiness(p�0.05), nasal and sinus discomfort on CPAP (p�0.001) and CPAPtolerance (p�0.001) were seen with the use of “Nozoil™”. Subjects alsoreported “Nozoil™” was superior to NS in making it easier to breathethrough the nose (p�0.001).

CONCLUSION: The use of “Nozoil™” in subjects with nasal sideeffects with CPAP results in improvements in objective compliance withCPAP and subjective improvement in nasal symptoms.

CLINICAL IMPLICATIONS: “Nozoil™” is a potential alternativetreatment for patients with nasal symptoms on CPAP.

DISCLOSURE: John Feenstra, None.

DETERMINANTS OF THE EFFECTIVE LEVEL OF CONTINU-OUS POSITIVE AIRWAY PRESSURE (CPAP) IN OBSTRUCTIVESLEEP APNEA (OSA)Octavian C. Ioachimescu MD* Joseph Lamont RRT Charles Bae MDNancy Foldvary-Schaefer DO Joseph Golish MD Cleveland Clinic Foun-dation, Cleveland, OH

PURPOSE: CPAP is the established treatment of moderate/severeOSA. The parameters capable to influence the level of effective CPAP inthese patients are yet unknown. Previous predictive equations for CPAP(hereafter called eCPAP) included body mass index (BMI), neck circum-ference (NC) and baseline apnea-hypopnea index (AHI. None of theseequations included arousal index (AI) or desaturation index (DI).

METHODS: Fifty consecutive patients (20 females and 30 males) withmoderate/severe OSA, who underwent a split-night or a CPAP titrationpolysomnographic study in our Sleep Center, were retrospectively ana-lyzed. We used multiple regression analysis to compute a predictiveequation of the effective level of CPAP and we analyzed the correlationbetween eCPAP and the prescribed CPAP (pCPAP).

RESULTS: The derived predictive equation for pCPAP was: pCPAP �6.8 � 0.001AHI � 0.10BMI - 0.08NC � 0.06AI - 1.14DI (p�0.0001,R2�0.45, SD�2.0). The mean pCPAP was 10 (�2.6 SD); the meaneCPAP was 8 (�2.3 SD); mean difference was 2 cmH2O. The meandifference was slightly smaller in split-night vs. titration studies (2.0 vs.2.6), in males vs. females (2.0 vs. 2.8), and in severe OSA vs. moderateOSA (2.0 vs. 3.0) cmH2O. The derived equation is distinct from previouslypublished equations, which estimated eCPAP. There was a weak corre-lation between pCPAP and eCPAP [R2�0.48, p�0.0001]. This could beexplained by the fact that our CPAP prescription protocol takes intoaccount not only normalization of AHI, but also near-normalization of AIand DI.

CONCLUSION: We determined an equation for pCPAP based onseveral clinical parameters. The correlation between eCPAP and thepCPAP was weak, warranting new studies to explore the lack of correla-tion and the role of additional predictive parameters.

CLINICAL IMPLICATIONS: This is a pilot phase of a larger studyfor derivation and validation of the best predictive equation for effectiveCPAP in OSA. The predictive value of OSA severity parameters such asAHI, AI, DI, and body habitus characteristics such as NC and BMI will beevaluated extensively in the main study.

DISCLOSURE: Octavian Ioachimescu, None.

PREDICTORS OF IMPROVEMENT WITH CONTINUOUS POS-ITIVE AIRWAY PRESSURE (CPAP) IN PATIENTS WITHCHRONIC FATIGUE SYNDROME AND OBSTRUCTIVE SLEEPAPNEAMarcel A. Baltzan MD* Osama Elkhouli MD Laura Creti PhD SallyBailes PhD Catherine Fichten PhD Norman Wolkove MD Eva LibmanPhD Mount Sinai Hospital Center, Montreal, PQ, Canada

PURPOSE: Patients with chronic fatigue syndrome (CFS), as definedby Centers of Disease Control criteria, often have a potentially treatablesleep disorder. However, even when obstructive sleep apnea (OSA) isidentified in these patients, improvement with treatment is not predict-able. We sought to determine whether any parameters of the diagnostic ortitration sleep study were associated with improvement in symptoms ofCFS after a subsequent trial of home CPAP.

METHODS: We reviewed the clinical and polysomnographic (PSG)findings of 78 patients with CFS. Thirty-nine (50%) were found to haveOSA and underwent a CPAP titration night. Thirty-seven pts subse-quently agreed to a therapeutic CPAP trial lasting up to 6 months. Theythen rated their CFS symptoms as “improved” or “not-improved”.

RESULTS: In the diagnostic PSG, patients with CFS who reportedimprovement to later CPAP had a higher mean arousal index 67.6 (70.1)vs. 26.1 (12.1) in those who did not improve (p � 0.037). The followingtable compares several PSG variables in patients who improved with theCPAP trial compared with those who did not. Each value represents thechange between the diagnostic and CPAP titration nights (mean andstandard deviation).

CONCLUSION: Patients with CFS and OSA are more likely toimprove with CPAP if they have higher arousal indices in the diagnosticPSG and show improved sleep efficiency during CPAP titration. Changesin REM latency and stage 1 and 2 sleep may also predict improvement.

CLINICAL IMPLICATIONS: The above mentioned PSG variablesmay be clinically useful in predicting which patients with CFS and OSAare more likely to improve with CPAP use.

DISCLOSURE: Marcel Baltzan, None.

COMPLIANCE IN CHINESE PATIENTS WITH OBSTRUCTIVESLEEP APNEA SYNDROME (OSAS): A SINGLE NURSE-CON-DUCTED EDUCATIONAL SESSION WOULD MAKE A DIFFER-ENCEMaggie P. Lit RN* C.K. Ng MBBS W.H. O MBBS H.W. She MBBS W.L.Law MBBS Samuel Lee MBBS Johnny W. Chan MBBS Queen ElizabethHospital, Kowloon, Hong Kong PRC

PURPOSE: CPAP is the cornerstone treatment for OSAS, yet itscompliance was unsatisfactory. Attempt is made to look at the factorsassociated with compliance.

METHODS: A retrospective study evaluating CPAP compliance in agroup of newly diagnosed OSAS Chinese patients in a regional hospitalover a 6-month period (August 2003 - February 2004). Objective andself-reported compliance was obtained 6 months after commencingCPAP. Acceptable compliance was defined as CPAP usage for at least 4hours/day in at least 70% of the night. Suboptimal treatment was defined

Diagnostic vs. TitrationImprovement

with CPAPNo Improvement

with CPAP p Value

Change in SleepEfficiency (%)

13.1 (27.8) 9.6 (14.2) 0.010

Change in Latencyto REM-sleep (min)

40.8 (108) 48.9 (75.8) 0.023

Change in Stage 1Sleep (%)

4.8 (8.9) 2.9 (12.1) 0.050

Change in Stage 2Sleep (%)

5.0 (10.3) 7.5 (18.2). 0.023

Change inApnea-hypopneaindex (per hour)

21.7 (50.7) 3.3 (19.5) 0.094




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as either refusal of CPAP treatment or unsatisfactory CPAP compliance.Newly diagnosed patients are invited to attend a specialty-nurse con-ducted educational session on OSAS before physician assessment.

RESULTS: One hundred and six subjects were diagnosed to haveOSAS. Only 58 patients (54.7%) accepted CPAP treatment. Fifty patients(86.2%) fulfilled the criteria of acceptable compliance (mean5.9�1.3hours/day) and 8 had unsatisfactory compliance (mean 3.0�1.7 hours/day). Attendance of the education class (p�0.007) and number of sideeffects experienced by patients (p�0.007) were independent predictors ofsatisfactory compliance. Fifty-six (52.8%) either declined or failed tocomply to CPAP satisfactorily. There were no significant differences inage, sex distribution, presenting symptoms, degree of sleepiness, level ofCPAP pressure, and type of side effects experienced between the 2groups. Univariate analysis suggested associations of optimal treatmentwith greater body weight (p�0.05) and body mass index (p� 0.01), higherrespiratory disturbance index (p� 0.05), higher desaturation index(p�0.01), higher arousal index (p� 0.05), having hypertension (p� 0.01),attendance of an education session (p� 0.001). Using logistic regression,CPAP education was the only independent predictor of both goodacceptance and compliance (p� 0.001).

CONCLUSION: CPAP acceptance rate was fair (54.7%). A singleeducational session could improve CPAP acceptance and compliance innewly diagnosed OSAS patients.

CLINICAL IMPLICATIONS: Since augmented CPAP education hasnot been shown to offer additional benefits (Hui DSC et al. Chest 2000),basic education appears a cost-effective intervention in improving accep-tance and compliance rate.

DISCLOSURE: Maggie Lit, None.

EFFECT OF TREATMENT BY UVULOPALATOPHARYNGO-PLASTY ON CARDIOPULMONARY EXERCISE TEST IN OB-STRUCTIVE SLEEP APNEA SYNDROMEChing C. Lin MD* Chest Division, Mackay Memorial Hospital, Taipei,Taiwan ROC

PURPOSE: To evaluate the effects of successful uvulopalatopharyn-goplasty (UPPP) on cardiopulmonary exercise testing (CPET) in patientswith obstructive sleep apnea syndrome (OSAS).

METHODS: 25 subjects with moderately severe or severe OSAS whodesired UPPP were enrolled. All patients had an overnight sleep study andCPET before and 3 months after LAUP. Patients were divided into 2groups based on the success (group I) or failure (group II) of UPPP toimprove their sleep apnea.

RESULTS: The results showed that successful UPPP in group I wasfollowed by improvement in right ventricular ejection fraction, maximalwork rate (WRmax), VO2max/kg, anaerobic threshold, oxygen pulse and alower breathing reserve. CPET results were unchanged after UPPP ingroup II subjects.

CONCLUSION: Patients with OSAS before UPPP had abnormalCPET as reflected by low VO2peak/kg, WRmax, anaerobic threshold andoxygen pulse. All of these variables improved after UPPP that successfullyameliorated OSAS.

CLINICAL IMPLICATIONS: Patients with OSAS before UPPP hadabnormal CPET. CPET improved after UPPP that successfully amelio-rated OSAS.

DISCLOSURE: Ching Lin, None.

ORAL APPLIANCE THERAPY FOR OBSTRUCTIVE SLEEPAPNEAVidya Krishnan MD* Steven C. Scherr Nancy A. Collop MD JohnsHopkins University, Baltimore, MD

PURPOSE: Oral appliance therapy (OAT) is an alternative therapy forobstructive sleep apnea (OSA). It is most often recommended for patientswho have mild OSA, or who have moderate-severe OSA and are unwillingor unable to comply with continuous positive airway pressure. We soughtto identify the subset of patients most likely to benefit from OAT.

METHODS: Patients of a sleep disordered breathing dental clinic withnocturnal polysomnography date before OAT initiation and during OATtitration. The main outcome variable was success of OAT (post-treatmentAHI�10/hr). Secondary outcome measures included average nocturnaloxygen saturation (SpO2) and subjective symptoms. Independent vari-ables available for analysis included patient demographics (age, sex), bodyanthropomorphic measurements (body-mass index (BMI), neck circum-

ference, canine classification, facial skeletal classification), sleep charac-teristics (apnea-hypopnea index, average nocturnal oxygen saturation),and intervention (type of oral appliance, posture change during PSG andoverall). Comparisons of patients by treatment success were performedusing Student’s t-tests and chi-squared tests.

RESULTS: Twenty-nine patients were identified for analysis, with age54.7�13.3years, 62.1% male, and BMI 30.1 kg/m2. Most patients (76%)had moderate to severe OSA (AHI�20/hr) at baseline. OAT resulted intotal posture change of 6.5�3.1mm, with 66.8�32.7% reduction in AHI(p�0.001), 6.8�7.5% absolute increase in SpO2 (p�0.001), improvementof subjective symptoms of 86%, and overall success of 69.0%. In thebivariate analysis, patients with post-treatment success were no differentby age, sex, anthropomorphic measurements, or intervention characteris-tics compared to patients with post-treatment failure, but had higheraverage baseline SpO2 (82.4% vs. 76.2%, p�0.061). SpO2 remainedsignificantly different after therapy (89.1% vs. 82.1%, p�0.001).

CONCLUSION: OAT improves AHI, SpO2, and subjective symptomsin most patients with OSA, regardless of severity. Baseline hypoxia maypredict failure of OAT monotherapy.

CLINICAL IMPLICATIONS: OAT may be appropriate for treat-ment of OSA patients without baseline hypoxemia. Further studies areneeded to evaluate the role for OAT in adjuvant therapy with CPAP andto determine the degree of baseline oxygen saturation that will predictOAT success.

DISCLOSURE: Vidya Krishnan, None.

LONG-TERM EFFECTS OF BILEVEL NONINVASIVE POSI-TIVE PRESSURE VENTILATION ON SLEEP APNEA ANDHEART RATE VARIABILITY IN STABLE CONGESTIVE HEARTFAILUREHitoshi Koito MD* Keiko Kohna MD Satoshi Morita MD Hiroshi YutakaMD Kansai Medical University, Otokoyama Hospital, Yawata, Japan

PURPOSE: The purpose of this study is to evaluate the long-termeffects of domiciliary bilevel noninvasive positive pressure ventilation(NPPV) on sleep apnea, cardiac function, sympathetic nervous activity andheart rate variability in stable congestive heart failure.

METHODS: We examined 6 patients with stable congestive heartfailure who completed 1 year of domiciliary NPPV with pulsed oxymeter,chest and abdominal wall motion sensor, nasal air flow sensor andelectrocardiographic monitoring system (TEIJIN, Morpheus C) duringsleep at night under a room air and NPPV before (Control; C) and after1 month (1M), 4 month (4M) and 1 year (1Y) of NPPV. Urinarynoradrenaline level at night and next morning mood index were alsoexamined. Chest rentogenogram, electrocardiography, doppler echocar-diography and serum noradrenaline level were measured befor and after1M, 4M and 1Y of domiciliary NPPV.

RESULTS: Apnea hypopnea index (/h) improved from 23 (C; Air) to 9(C; NPPV), 9 (1M; NPPV), 10 (4M; NPPV) and 10 (1Y; NPPV). Centrlapnea index (/h) improved from 11 (C; Air) to 2 (C; NPPV), 2 (1M;NPPV), 3 (4M; NPPV) and 1 (1Y; NPPV). The left ventricular systolicdimension (mm) by echocardiography decreased from 50 (C) to 46 (1M),43 (4M) and 43 (1Y). Percent fractional shortening (%) of the left ventricleincreased from 21 (C) to 28 (1M), 29 (4M) and 32 (1Y), and the leftventricular ejection fraction (%) increased from 42 (C) to 51 (1M), 53(4M) and 56 (1Y). Heart rate (bpm) decreased from 65 (C) to 59 (4M),and SDNN increased from 86 (C) to 98 (4M) and 108 (1Y). Serumnoradrenaline level had decreased tendency in 1M and 1Y.

CONCLUSION: The long-term domiciliary bilevel NPPV improved asleep apnea, cardiac function, sympathetic nervous activity, heart rate andheart rate variability in patients with stable congestive heart failure.

CLINICAL IMPLICATIONS: The long-term domiciliary bilevelNPPV might be a useful complementary therapy for stable congestiveheart failure.

DISCLOSURE: Hitoshi Koito, None.

EFFECT OF OBSTRUCTIVE SLEEP APNEA ON LIPID PRO-FILE IN CHINESE SUBJECTSJamie C. Lam MBBS* Sidney C. Tam MD Clara S. Yan MBBS Agnes LaiKaren S. Lam MD Mary S. Ip MD The University of Hong Kong, HongKong, PRC

PURPOSE: Dyslipidemia has been reported to be common in subjectswith obstructive sleep apnea (OSA), but this may be comorbid with




obesity or visceral obesity which are highly prevalent in those with OSA.This prospective cohort study investigated the relationship of OSA to lipidprofile in Chinese subjects.

METHODS: Consecutive Chinese subjects of male sex, with nohistory of cardiovascular disease, diabetes mellitus, hyperlipidemia orsignificant chronic illness or medications, were recruited from oursleep laboratory. Their demographic and anthropometric data, fastinglipid profile (cholesterol, triglycerides, low density lipoprotein-choles-terol (LDL-cholesterol) & high density lipoprotein-cholesterol (HDL-cholesterol), apolipoproteins A1 & B (Apo A1 & B), and polysomno-graphic findings were collected. The relationships between apnea-hypoapnea index (AHI) and each lipid parameter were examined withmultiple linear regression, adjusted for obesity (body mass index orwaist circumference).

RESULTS: 98 subjects were recruited, aged between 21 and 65. OSAwas defined as AHI�5. 73 subjects had OSA. Significant linear relation-ships were present between AHI and waist circumference, body massindex (BMI), LDL-cholesterol, HDL-cholesterol, Apo B, LDL-cholester-ol:HDL-cholesterol and Apo B:Apo A1 (all p�0.05). On multiple linearregression analysis, with lipid parameters as dependent variables, adjustedfor BMI, AHI was associated with Apo B (p�0.05), total cholesterol:HDL-cholesterol (p� 0.01), LDL-cholesterol:HDL cholesterol (p�0.05)and Apo B:Apo A1 (p�0.05).

CONCLUSION: In this cohort of Chinese subjects, AHI was associ-ated with apolipoprotein B, apolipoprotein and cholesterol fraction ratios,controlled for obesity.

CLINICAL IMPLICATIONS: OSA may have an independent effecton adverse lipid profile, and thus confer independently to cardiovascularrisks.

DISCLOSURE: Jamie Lam, University grant monies This project wassupported by the Hong Kong Research Grants Council, The University ofHong Kong, HKU7307/00M

SUBJECTIVE SLEEP PERCEPTIONS FROM POST-TEST QUES-TIONNAIRE AND OBJECTIVE SLEEP PARAMETERS AMONGAFRICAN AMERICAN AND CAUCASIAN POPULATION WITHOBSTRUCTIVE SLEEP APNEACynthia R. Crowder MD* Houman Dahi MD Narong SimakajornboonMD Denise Sharon Tulane University Health Sciences Center, NewOrleans, LA

PURPOSE: Currently, there are controversies about the relationshipbetween OSA and subjective sleepiness. Recent study has shown thecorrelation between subjective sleep complaints and respiratory arousal.However, there is limited information on the relationship betweensubjective sleep perceptions and objective sleep parameters in differentpatient populations.

METHODS: A retrospective study was performed in patients withobstructive sleep apnea. All patients completed post-test questionnaireafter sleep study as part of our routine procedure. Any patients withsignificant neurological diseases, psychiatric disorder, central sleep apnea,severe periodic leg movements (PLMI�50) or incomplete records wereexcluded from the study.

RESULTS: 79 patients met the criteria for entry into analysis; 41African American (B) and 38 Caucasian (W). The average age is47.5�10.1 years and the mean apnea-hypopnea index (AHI) is25.9�19.5 per hour. There was no difference between age, sex, BMIor AHI between two groups. The subjective feeling upon awakening(Question 15 (Q15); scale 1-6) correlated with the arousal index(r�0.27, P�0.019), AHI (r�0.3, P�0.008), and apnea-hypopnearelated arousal (r�0.24, P�0.038). There is a tendency towardsignificant correlation between subjective sleep quality (Question 7(Q7), scale 1-4) and arousal index (r�0.22, P�0.054) as well asbetween Q7 and AHI (r�0.22, P�0.056). The subgroup analysisrevealed a significant correlation between Q15 and arousal index onlyin African American population (r�0.36, P�0.02 [B] versus r�0.17,P�NS [W]). However, Q15 correlated with AHI only with Caucasianpopulation (r�0.20, P�NS [B] versus r�0.46 P�0.01 [W]).

CONCLUSION: It is concluded that subjective perception frompost-sleep questionnaire correlates significantly with severity of apnea andfrequency of arousals especially respiratory arousals. The subjectiveperception correlates only with the frequency of arousals in AfricanAmerican population, while subjective perception of Caucasian popula-tion correlates directly with severity of apnea.

CLINICAL IMPLICATIONS: It is speculated that other factors inaddition to apnea may play a role in sleep disruption in African Americanpopulation with sleep apnea. However, more studies are needed.

DISCLOSURE: Cynthia Crowder, None.

EFFECT OF ZOLPIDEM ON THE EFFICACY OF NASAL CON-TINUOUS POSITIVE AIRWAY PRESSURE AS TREATMENT OFOBSTRUCTIVE SLEEP APNEAPrakash B. Patel MD* Richard B. Berry MD University of Florida,Gainesville, FL

PURPOSE: Obstructive sleep apnea (OSA) patients using CPAP(Continuous Positive Airway Pressure) are frequently prescribed BZRA-(Benzodiazepine receptor agonist) hypnotics. However, no prior studieshave evaluated the effect of BZRAs on the efficacy of CPAP. CPAP worksas a pneumatic splint so upper airway muscle tone is much reduced.Therefore, further reduction in muscle tone by BZRAs should be minimal.For this reason, we hypothesize that Zolpidem (selective BZRA withgreater hypnotic than muscle relaxant properties)should not cause achange in the level of required CPAP to maintain an open airway.

METHODS: To test this hypothesis, we conducted a double blindplacebo controlled cross-over study in patients with OSA currently beingtreated with CPAP. Patients were studied on three nights in the sleeplaboratory over three consecutive weeks (one night per week). On nightone, the pressure level required to prevent apnea, hypopnea, and snoringwas determined (optimal pressure). On the second night and third nights,either Placebo or Zolpidem 10 mg was given and subjects slept on theCPAP level determined by first night (optimal pressure).

RESULTS: For our initial four patients, there was no significantdifference in Total Sleep Time (TST), REM sleep, AHI overall, or AHINREM sleep (see table).

CONCLUSION: Study of a limited number of OSA patients suggestsZolpidem 10 mg does not significantly increase the AHI in a patienttreated with an appropriate level of CPAP. We plan to study at least 20patients to confirm this preliminary result.

CLINICAL IMPLICATIONS: If further study confirms our prelim-inary findings this would suggests Zolpidem can be used safely in OSApatients with insomnia who are on CPAP. This may improve tolerance ofCPAP in these patients.

DISCLOSURE: Prakash Patel, None.




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COMPARISON OF MEDICAL UTILIZATION IN THE YEARPRECEDING AND ANTECEDING LARYNGOSCOPIC DIAGNO-SIS OF VOCAL CORD DYSFUNCTIONJeffrey A. Mikita MD* Joseph Parker MD Walter Reed Army MedicalCenter, Washington, DC

PURPOSE: Patients with vocal cord dysfunction (VCD) have highmedical utilization. This has been attributed to somatization, but mayreflect a lack of understanding and recognition of the VCD diseaseprocess. The effect of laryngoscopic diagnosis of VCD on medicalutilization has never been evaluated and results from this study will addinsight into the benefit of laryngoscopy evaluation and treatment of VCD.Furthermore, the role of somatization in the pathogenesis of VCD may bebetter understood.

METHODS: Subjects were obtained thru retrospective review of alllaryngoscopies conducted in our clinic from January 2002 to March 2004.Patients with laryngoscopy confirmed VCD had their medical utilizationevaluated. Inclusion required subjects to have evidence of medicalutilization one year predating and one year postdating diagnosis andexclusion occurred if their diagnosis could not be confirmed by chartreview. Medical utilization information for the preceding year andanteceding year were compiled from a computerized medical record.t-test analyses was utilized to compare differences between the group’smedical utilization before and after diagnosis of VCD. This study wasapproved by the Institutional Review Board.

RESULTS: Forty three ambulatory patients with VCD with a mean ageof 45 (range 21-81) yearsmet inclusion criteria. Total physician visits andprimary care visits were found to reduce significantly after diagnosis ofVCD. These patients were also found to have comparable frequency ofhospitalizations, urgent care visits, and prescriptions.

CONCLUSION: Total physician visits and primary care visits amongambulatory VCD patients are significantly reduced after diagnosis of VCDby laryngoscopic criteria.

CLINICAL IMPLICATIONS: Aggressive diagnosis of ambulatoryVCD patients has a significant impact on healthcare utilization.

DISCLOSURE: Jeffrey Mikita, None.

REAL-TIME ANALYSIS OF EXHALED BREATH WITH MPLI-MS: OBSERVED NITRIC OXIDE PROFILELuke C. Short PhD* Thorsten Benter PhD Bergische Universitat Wup-pertal, Wuppertal, Germany

PURPOSE: An elevated concentration of nitric oxide (NO) in alveolarventilation indicates inflammatory stress within the lung. Trace-gas anal-ysis using mass spectrometers (MS) have been used extensively within theatmospheric community with great success. We present here the firstdescription of time-resolved NO measurement in breath using photoion-ization MS, providing new capabilities for the medical investigator, such asisotopic tracing.

METHODS: For NO measurement, we use resonance enhancedmultiphoton ionization (REMPI) coupled with a time-of-flight MS with amedium pressure laser ion source. A single male subject breathes NO-freeair for several minutes, and then the exhaled breath is monitored for NO.

RESULTS: The ability of REMPI to differentiate among three differ-ent isotopomers of NO is demonstrated, and then the concentrationprofile of NO in exhaled breath is measured. A similar time-dependenceconcentration is found as observed by previous techniques.

CONCLUSION: This study presents MPLI-MS as a new techniqueavailable for the time-resolved measurement of NO in breath. Theresulting system can be made portable and brought into the medicalsetting using newer-generation, broad-bandwidth lasers. When measuring

NO via REMPI, we found a concentration profile in agreement with thatof research groups using different techniques (chemiluminescence andLMRS). Sampling the breath from a person without respiratory ailments,we found a dead-space air NO concentration of 20 ppbV and an alveolarventilation concentration of 5 ppbV. In contrast to the chemical-basedtechnique chemiluminescence, MPLI-MS can also selectively measureisotopically-labeled NO, as demonstrated with REMPI of 14N16O,15N16O and 14N18O. Further, MPLI-MS can be used to measure otherbiologically-significant molecules, such as the aldehydes. In forthcomingstudies, we will explore the application of MPLI-MS for the measurementof other biologically-significant molecules.

CLINICAL IMPLICATIONS: (1) ppbV mixing ratios of NO can bemeasured on a sub-second time scale, (2) other biologically significant gasmolecules can be measured on a similar time scale and (3) since thetechnique operates optically as well as mass-resolved, isotopomers of NOare discernable, permitting the use of isotopic tracing.

DISCLOSURE: Luke Short, None.

HIGH RESOLUTION COMPUTED TOMOGRAPHY EVALUA-TION OF AIRWAY DISTENSIBILITY IN ASTHMATIC ANDHEALTHY SUBJECTSAntonio Castagnaro MD* Alfredo Chetta MD Emilio Marangio MDPanagiota Tzani MD Marina Aiello MD Raffaele D’ippolito MD NicolaSverzellati MD Maurizio Zompatori MD Dario Olivieri MD Dept ofClinical Sciences, Respiratory Disease Section, University of Parma,Parma, Italy

PURPOSE: In bronchial asthma, airway wall remodeling may result inreduced airway distensibility. In this study, we assessed in asthmaticpatients both the baseline airway caliber and distensibility by means ofHigh Resolution Computed Tomography (HRCT).

METHODS: We studied 7 patients (2 M, age range: 36-69 yrs)affected by chronic asthma (FEV1 range: 30-87 % of predicted; FEV1/VCrange: 48-75 % of predicted) in stable clinical conditions and 6 healthysubjects (3 M, age range: 29-50 yrs), as a control group. In all subjects,HRCT scanning, obtained at suspended end-espiratory volume, wasperformed at rest and during ventilation with 6 and 12 cmH2O by nCPAP,both at baseline and after the inhalation of 200 mcg oxitropium bromideMDI.. External and lumen diameter (mm) of the right apical upper lobebronchus were measured in all HRCT scans.

Health Care Measure

Year precedingVCD diagnosis

n�43

Year antecedingVCD diagnosis

n�43 p

Total Physician Visits 796 603 0.049*Primary Care Visits 265 137 0.0005*Urgent Care Visits 77 49 0.084Hospitalizations 12 5 0.068Total Prescriptions 767 767 ns


Asthma Evaluation I12:30 PM - 2:00 PM


RESULTS: Results (means�SD) are listed in the table.CONCLUSION: Our results showed that in asthmatic patients the

airway distensibility, assessed by HRCT, could differ as compared to thatof healthy controls.

CLINICAL IMPLICATIONS: HRCT can provide useful informationon airway distensibility.

DISCLOSURE: Antonio Castagnaro, None.

EXHALED NITRIC OXIDE IS INCREASED IN RESPONSE TOSTRESS IN ADULT ASTHMATICSJonathan S. Ilowite MD* Mary Bartlett RN Winthrop University Hospital,Mineola, NY

PURPOSE: Nitric oxide in exhaled air (FENO) is a marker of airwayinflammation in asthma. This study was undertaken to determine whetherFENO increases as a result of stress.

METHODS: This study was a prospective, unblinded study in an officesetting. 20 adult asthmatics were recruited to participate. Subjects wereinitially put into a relaxed state using a progressive relaxation technique.They were then put into a stressful state by asking them to completecomplicated mathematical problems.

RESULTS: FENO was measured using standard techniques afterrelaxation and after stress. Pulse was monitored during the stressfulintervention. FENO significantly increased after stress. Mean �/-Stan-dard Deviation (SD) for baseline FENO was 2.9 �/- 2.1. After stress,mean �/- SD FENO rose to 3.1 �/- 2.1. This was significant by pairedtest. (p� 0.03).

CONCLUSION: A stressful situation can cause an immediate increasein the inflammatory state of the airways in adult asthmatics, as measuredby FENO.

CLINICAL IMPLICATIONS: This study provides insight into themechanism in which a psychological stress could lead to worseningasthma.

DISCLOSURE: Jonathan Ilowite, None.

THE DIFFERENCES IN ASTHMA SEVERITY BETWEEN PRE-MENOPAUSAL AND POSTMENOPAUSAL AFRICAN AMERI-CAN WOMENCelia Maxwell MD Reverly M. John MBBS* Alicia Thomas MBBSHoward University Hopsital, Washington, DC

PURPOSE: Prolonged hormonal exposure has been linked to anincreased severity of asthma among Caucasian women. Our aim is todetermine if the same is true or are there differences in the severity ofasthma among premenopausal(PREM) vs postmenopausal(PM)AfricanAmerican(AA)women.

METHODS: We enrolled 37 women ages 18-82, who were admittedthrough the emergency department over a 2-year period with asthmaexacerbation. In this retrospective chart review, asthma severity wasdefined by the National Heart Lung and Blood Institute guidelines.Menopause was defined as cessation of the menstrual cycle by natural orsurgical means.Additionally, body mass index (BMI), age of onset ofmenarche and number of cigarette pack years (CPY) of smoking wererecorded.

RESULTS: Twenty (58.5%)of the women were PM, and 17(41.5%)were PREM. The mean ages were 35�/-8.2 for PREM and60�/-10 for PM women. There was no significant difference in population

demographics except for CPY, that was statistically greater in PM womenP�0.003. Multivariate analysis was used to control for BMI, CPY, numberof pregnancies, highest educational level and onset of menarche. Eightypercent of PM and 55.8% of PREM women had a BMI �30, (40% of PMvs 29%of PREM had BMI’S � 40). P � 0.68 between the groups. Averageonset of menarche in the PREM vs PM group was 11.2�/-2.8 and 13.4�/-2.7, P � 0.9. Chi-Square test was used in the analysis of the asthmaseverity. Although there was a percentage trend to more severe asthma inthe PM group, it was not statistically significant P � 0.189.

CONCLUSION: Women in the PM group had shorter duration ofhormonal exposure, however an increased severity of asthma. While notexplained by population characteristics except CYP and BMI that werenot statistically significant , nonetheless, severe obesity rather thanhormonal changes may be the primary factor in asthma severity amongPREM and PM AA women.

CLINICAL IMPLICATIONS: Asthma severity in PREM vs PM AAwomen may need to be evaluated using different parameters. Furtherstudies are required.

DISCLOSURE: Reverly John, None.

DOES BODY MASS INDEX OF PATIENTS EFFECTS SEVERITYOF DISEASE IN HOSPITALIZED ASTHMATICS?Esra Uzaslan MD* Oktay Gozu MD Funda Coskun MD Dane EdigerMD Mehmet Karadag MD Ercument Ege MD Uludag UniversityMedical Faculty, Bursa, Turkey

PURPOSE: In this study, we aimed to analyze the effects of obesity to theseverity of the disease, by investigating the correlation between body massindex (BMI) and characteristics of asthma in hospitalized asthma patients.

METHODS: Characteristics of asthma related factors and BMI of patientsanalyzed retrospectively from the data obtained from the clinic files of 160hospitalized patients (41male,119female, mean age 46.5�1.1years)who werefollowed in our department.Body mass index was calculated as body weight/height (kg/m2).Patients were divided and evaluated in three groups accordingto their BMI; Group1: BMI�22.5 thin, Group2: 22.5� BMI�30 normal oroverweight,Group3: BMI�30 obese.

RESULTS: The mean BMI of the whole patients was 28.3�0.5, whilstthe mean BMI of patients in Group 1 was 32.9�2.9,in Group 2 was 46.6 �1.6,and in Group 3 was 49.2 � 1.5. The 20% of patients in Group 1, 47%of patients in Group2 and 33% of patients in Group3 were atopic The33%of the asthmatic patients was also diagnosed to have allergic rhinit-es.The 8.4% of patients (n:13)had a history of childhood asthma (54% inGroup1, 31% in Group2 and 15% in Group3).The percentage of patientswith the history of childhood asthma was significantly higher in Group1than in Group2 and Group 3.Although there was not any significantdifference in the mean eosinophiles counts and mean serum ECP levelsof patients, those values were lower in Group3 than in other groups.Therewas not any significant difference in mean outdoor and indoor allergensensitivity scores of patients among groups. Mean medication score(number of controller drugs) of patients in Group1 was significantly lowerthan in Group2 and Group3.The lung function parameters of FEV1 andPEF were not significantly different among groups, but predicted value ofFVC was significantly higher in Group1 than Group2 and Group3 .

CONCLUSION: According these results we came to the conclusionthat obesity was a severity factor in hospitalized asthmatic patients.

CLINICAL IMPLICATIONS: Asthma outcomes was effected badlywith increasing body weight in asthmatics.

DISCLOSURE: Esra Uzaslan, None.

RHINOSINUSITIS CONTROL DECREASES SEVERITY OFASTHMARamon Figueroa -Lebron MD* Asthma Management Center, San Juan,PR

PURPOSE: Chronic non allergenic Rhinosinusitis accounts for 1/3 ofvisits to physicians offices.In many of our asthmatics, cough is thepresenting symptom. This study is to evaluate benefits of daily nasalsteroids and HT1 blockers in decreasing severity of bronchial inflamation,improvement of disease control and quality of life.

METHODS: Study is a retrospective observational based on BlueShield Puerto Rico expenditures of all services and medications paid in2004 for the population of this study and the control patients. The subjectwere 358 patients referred to center because of refractioness to manage-ment. Control population consisted of 12,070 asthmatics treated by the

Asthmatics Patients

Baseline After Oxitropium

At rest 6 cmH2O 12 cmH2O At rest 6 cmH2O 12 cmH2O

external Ø (mm) 6.2�0.9 6.3�0.9 6.7�0.8* 7.3�1 6.9�0.7 7.1�0.9

lumen Ø (mm) 3.3�0.7 3.5�0.6 3.8�0.6* 4.4�0.6 3.8�0.4 4�0.4

Healthy Controls

external Ø (mm) 7.3�1.8 7.9�1.7 7.8�2 8�1.6 8�1.8 9�1.7

lumen Ø (mm) 4.0�1.6 4.8�1.6* 4.7�1.7* 5�1.5 5�1.4* 6�1.6*

* p� 0.05 vs at rest


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neumologists in the community. Inclussion criteria were: an age of 12-70years, presence of Rhinosinusitis, cough as prominent symptons, severeairway obstruction shown by spirometry and low peak flow (PEF)readings,prior visits to emergency department and or hospital admissions in2003.Upon entry patients received instructions in the use of PEF andlogging, nasal steroids, inhaled bronchial medication, emergency albuterolinhalations.The use of daily nasal steroids was continous for 4 weeks.

RESULTS: Asthma complex with Bronchial Obstruction decreased as evi-denced by peak flow redings and controller medications and by dollars paid forthem.The shift in cost occurs in favor use of nasal steroids and HT1 blockers .Theemergency dept visits and admissions decreased to the lowest levels. In 2004 2out of 176 ptswere admitted for 0.4% lower than in 2003that was 1 %.

CONCLUSION: The study showed dramatical improvement in severity ofairway obstructions and symptoms complex with 88% less hpspital admissionsand a dramatic decrease in the use and cost of controller medications. Use of dailynasal steroids is of great benefit in the majority of patients.

CLINICAL IMPLICATIONS: Daily nasal steroids and HT1 blockersshould be part of the management of moderately severe and severeasthmatic. Study showed the benefit of this practice for patients and forthe economy. This study may improved the asthma management.

DISCLOSURE: Ramon Figueroa -Lebron, None.

TOTAL IGE AND STIMULATED T CELL CYTOKINE PRODUC-TION IN A COHORT OF ETHNICALLY DIVERSE PREGNANTWOMEN BY ASTHMA HISTORYChristine C. Johnson* M Maliarik SL Haystad DR Ownby EL Peterson GWegienka LK Williams M McCabe EM Zoratti CL Joseph Henry FordHealth Systems, Detroit, MI

PURPOSE: Little is known about the relationships between total IgEas a marker for Th2 phenotype, T cell production of interferon _ (IFN-_)and IL4 as markers of Th1 and Th2 phenotypes, respectively, and IL10 asa marker of immune regulation, in a population of racially diverse femalescategorized by history of asthma diagnosis.

METHODS: We analyzed blood samples taken during pregnancy from themothers of urban and suburban African American and Caucasian children in ageographically defined Detroit area birth cohort (WHEALS). Total IgE wasmeasured using the Pharmacia CAP low range with a detection limit of 0.1 IU/ml.IFN-_, IL4 and IL10 production by PMA stimulated lymphocytes was detectedby antibody staining and flow cytometry. Results are expressed as the percentageof CD4� cells positive for these cytokines. Wilcoxon rank sum tests were used tocompare mean IgE and mean IFN-_, IL4 and IL10 percentages by history ofphysician diagnosed asthma and race.

RESULTS: Blood samples from 443 women were tested; 65% wereAfrican American and 21.0% had a history of asthma. Total IgE was higherin women with asthma (155.7 vs 71.2 IU/mL, p� .001) and higher inAfrican American women vs Caucasian women with asthma (185.8 vs114.7 IU/mL, p� .001). IFN-_ positive cells tended to be lower in womenwith an asthma history (8.0% vs 9.4%, p�0.065), and lower in AfricanAmerican vs Caucasian asthmatics (7.4% vs 9.2%, p�0.097). There wereno differences in IL4 or IL10.

CONCLUSION: Total IgE is higher in women with a history of asthmaand African American women, while IFN-_ was lower, following theTh1-Th2 paradigm. NIAID.

CLINICAL IMPLICATIONS: Total IgE is higher in women with ahistory of asthma and African American women, while IFN-_ was lower,following the Th1-Th2 paradigm. NIAID.

DISCLOSURE: Christine Johnson, None.

Asthma Evaluation II12:30 PM - 2:00 PM

CHARACTERISTICS OF PATIENTS WITH REPEAT ATTEN-DANCE AT EMERGENCY DEPARTMENT FOR ASTHMA EXAC-ERBATIONSLee Lan Phoa MBBS* Lathy Prabhakaran RN Wee Yang Pek MBBSSeow Yian Tay MBBS Eillyne Seow MBBS Alan W. Ng MBBS Tan TockSeng Hospital, Singapore, Singapore

PURPOSE: To identify demographic characteristics of patients withrepeat Emergency Department (ED) attendance for asthma exacerbation.

METHODS: Analysis of computer database records of all patients thatwere treated and discharged from the ED of a tertiary hospital over 6

months in year 2004 for asthma. Data analyzed included demographiccharacteristics such as age, sex, ethnicity and ED attendance in the past 40days and past 24hrs for acute asthma.

RESULTS: 750 patients with Male: Female of 1:1 was seen at the EDfor asthma exacerbation and 195 had previous attendances. Out of these195 patients, 132 had past attendance within 40 days, 64 had pastattendance within last 24 hrs and 1 had past attendance in the last 40 daysand within last 24 hrs. The median age for our patients was 32 years (range2 to 92 years). 42% of the patients were Chinese, 29% were Malays, 23%were Indians and 7% were of other ethnicity. Male patients had asignificantly higher repeat ED attendance compared to female patients(34.3% vs 13.8%, p � 0.0001).There was also a significantly higherproportion of Malay patients with repeat attendance when compared toChinese, Indians and other ethnicity (35.3% vs 23.3% vs 22.2% vs 16.4%respectively, p � 0.002).Patients of age 21 years and below were alsofound to have higher repeat attendance for asthma when compared tothose above 21 years of age (39.3% vs 21.3%, p � 0.0001). Multivariateanalysis showed that male sex (OR 3.03, p � 0.0001), Malay ethnicity (OR2.30, p � 0.04) and age 21 years and below (OR 1.61, p � 0.015) wereassociated with increased risk of repeat ED attendance.

CONCLUSION: Male sex, Malay ethnicity and young age of 21 yearsand below were associated with higher risk of repeat ED attendance inour asthmatic patients.

CLINICAL IMPLICATIONS: Further studies should be conductedon this high risk group to identify factors which contribute to theirfrequent ED visits in order to optimise their asthma control.

DISCLOSURE: Lee Lan Phoa, None.

DOES OBESITY EFFECTS ASTHMA OUTCOMES IN FEMALEASTHMATIC PATIENTS?Esra Uzaslan MD* Funda Coskun MD Dane Ediger MD MehmetKaradag MD Oktay Gozu MD Uludag University Medical Faculty, Bursa,Turkey

PURPOSE: In this study we aimed to investigate the correlationbetween body mass index and characteristics of asthma in female asth-matic patients of our clinic.

METHODS: Characteristics of asthma related factors and body massindex (BMI) analyzed from the data obtained out-patients files of 900female patients, who were followed in our department between the yearsof 1992-2004.Patients were divided and evaluated in four groups accord-ing to their BMI; Group1: BMI�18.5 thin,Group2:18.5�BMI�25 nor-mal, Group3: 25�BMI�30 overweight, Group4: BMI �30 obese.

RESULTS: The number of patients in Group1 was 23, was 336 inGroup 2, was 302 in Group3, and was 239 in Group4. The mean BMI ofpatients was 26.9�0.2. The mean age of patients was 37.4� 0.4 and thepatients in Group4 was significantly older than patients in other groups.The 42.6% of patients were atopic and 50.9 % was also diagnosed to haveallergic rhinites. The 53.8 % of patients in Group1, 72.9 % of patients inGroup2, 63.5 % of patients in Group3, 58.2 % of patients in Group4 wereatopic . The mean serum IgE levels of patients in Group4 was significantlylower than others. Although there was not any significant difference in themean eosinophiles count of patients, those values were lower in Group4than in other groups. The mean asthmatic years of patients in Group4 wassignificantly longer than others. The mean and predicted values of lungfunction parameters of Group4 were generally lower than other groups,especially the means FEV1 and FVC values was significantly lower inGroup4 than Group1, Group2 and Group3. The mean medication score(number of controller drugs) of patients in Group4 was significantlyhigher than in patients of other groups.The hospitalization rate of patientsin Group4 (19%) was significantly higher than patients in patients Group2(9%) and Group3 (12) (p�0.05).

CONCLUSION: In conclusion, obesity was a severity factor forasthmatic female patients.

CLINICAL IMPLICATIONS: Asthma outcomes are effected badlydue to obesity in females.


GENDER AND ASTHMA: WHAT DO WE KNOW? (A SURVEY)Wendy A. Lopez BSc* Sunnybrook & Women’s College Health SciencesCentre, Toronto, ON, Canada

PURPOSE: There appear to be gender differences in the prevalence,morbidity and severity of asthma, with variations across the lifespan.


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Asthma is a chronic obstructive airway disease that occurrs more fre-quently in adult females. The objective of the survey was to determinewhether respiratory therapy students (SRT) and registered respiratorytherapists (RRT) who may deal with adult asthmatic patients are aware ofthe sex and gender differences that exist in this disease.

METHODS: A survey was conducted with 175 subjects. Four differentgroups were surveyed: first-year, second-year, and third-year SRTs fromthe Michener Institute for Applied Health Sciences and RRTs fromhospitals in Toronto.

RESULTS: There was a 78% response rate. Out of all the respondents,25.3% thought that asthma was the same in males and females, 24.7%thought that more males had asthma, 21.4% thought that more femaleshad asthma, and 28.6% did not know. The second year SRTs and RRTshad the majority choosing males as having asthma more than females. Thethird year SRTs were the only group that identified women as havingasthma more than males.

CONCLUSION: Sex and gender differences of asthma in adulthoodare still relatively new areas of research. SRTs and RRTs may not be awareof these differences, which may lead to misdiagnosis, and sub-optimaltreatment and management plans for the female asthmatic population.

CLINICAL IMPLICATIONS: More research in this area is needed.Updated school curricula should reflect emerging issues to provide thebest treatment possible.

DISCLOSURE: Wendy Lopez, None.

COMPARISON BETWEEN 3.5 LITER SINGLE BREATH COL-LECTIONAND DEAD-SPACE DISCARD TECHNIQUES INMEASUREMENT OF EXHALED NITRIC OXIDE IN ADULTSJamson S. Lwebuga-Mukasa MD* Paulette M. Wydro MPH TiffanyKolniak BS SUNY at Buffalo, Buffalo, NY

PURPOSE: Increased levels of fraction exhaled nitric oxide (FENO)have been found among individuals with atopic asthma and are believedto reflect on going airway inflammation. However, routine use of FENOin health care diagnosis and treatment is limited by the expense of therequired equipment. Two offline methods are currently available forobtaining FENO namely, the American Thoracic Society (ATS) FENO350cc/sec recommended method and the Dead Space Discard (DSD)FENO 50cc/sec kit method. However, there have not been publishedstudies comparing the two techniques in the field. In the current study wesought to compare the FENO levels obtained by the ATS method and theDSD method and to investigate the utility of FENO levels in detectinginflammation is persons with diagnosed asthma.

METHODS: Cross-sectional study. A convenient sample of 45 subjectsages 17 to 82 years, mean age 44.26 � 16.71 years. There were 19 femalesand 26 males. Paired exhaled samples were collected from the subjects intriplicate using ATS and DSD techniques and analyzed offline usingSievers 280i Nitric Oxide Analyzer.

RESULTS: Comparison of the two methods was performed usingcorrelations, regression analysis and ANOVA. 33.3% had health careprovider diagnosed asthma, 8.9% had other respiratory problems, theremainders were healthy individuals with no known respiratory condi-tions; 11.1% were current cigarette smokers. FENO levels obtained byDSD technique were consistently higher than those obtained by the ATStechnique. The two techniques were highly correlated r� 0.691, p�0.000,2df and r2 � 0.48.

CONCLUSION: FENO levels obtained by the ATS and DSD tech-nique are highly and positively correlated.

CLINICAL IMPLICATIONS: The DSD technique is well suited forfield studies when replicate samples are to be collected from manysubjects. Furthermore, the smaller bags are more cost efficient and easierto transport than the high flow bags.

DISCLOSURE: Jamson Lwebuga-Mukasa, None.

COAL-DUST EXPOSURE AND THE PREVALENCE OFASTHMA, ALLERGIC DISEASES AND ATOPYZdenka Hajdukova MD* Daniela Pelclova MD Milena Menzlova MDClinic of Occupational Diseases, University Hospital of Ostrava1, CzechRepublic

PURPOSE: Find out whether workplace exposures to coal mine dustcontribute to the development of allergic diseases and if atopy in minersis more frequent than in general population. Atopy is an important riskfactor for asthma. Latest epidemiological studies in Czech Republic

estimate, that prevalence of allergic diseases in Czech population is 24 %,the prevalence of asthma 5 % and atopy 40-50 %.

METHODS: In the cross-sectional study (2004/2005) we studied thefrequency distribution of airway diseases(spirometry including non-spe-cific bronchoprovocation test, if indicated, examination by physician),allergic disease in personal history (mucosal and cutaneous) and atopy(presence of specific IgE to common inhalation allergens in blood byPhadiatop) in 548 coal miners (mean age 49) and 315 subjects of controlgroup (mean age 43). Controls where recruited from men, who have neverbeen exposed to dust in their occupational environment. Subjects wheredivided into cohorts according to age and lengh of exposure; statisticalanalysis was by x-square testing using contingency tables.

RESULTS: Atopy and allergic diseases after mean exposure to coaldust lasting 3 years, 14 years, and 29 years was 38 % and 22 %; 31 % and26 %, and 17 % and 19 %, respectively. Atopy and allergic diseases inminers age 27-31 years, 32-40 years, and 54-65 years was 37 % and 25 %;30 % and 23 %, and 22 % and 20 %, respectively. Controls ind the sameage group had atopy and allergic diseases in 48 % and 51 %; 37 % and 40%, and 22 % and 19 %, respectively. Statistical analysis has shown, noinfluence of either coal-mine dust or of smoking status on the prevalenceof atopy, rhinitis and asthma. Prevalence of chronic bronchitis and COPDincreased with age and exposure to coal-dust.

CONCLUSION: Coal mining does not seem to represent a risk factorof atopy and respiratory allergic disorders.

CLINICAL IMPLICATIONS: In occupational medical care atopy inminers should not represent contra-indication for mining occupation.

DISCLOSURE: Zdenka Hajdukova, None.MORPHOLOGY OF TISSUES USED FOR CILIARY STUDIESThorsten Stein MD* Mohamed Abdel-Aziz MD Inge Wissen-Siegert MDChristine Eidner MD Hans L. Hahn MD Deutsche Klinik fur Diagnostik,Wiesbaden, Germany

PURPOSE: We have shown previously that the allergic reaction doesnot change the beat frequency of nasal cilia (Europ. Respir. J., Vol. 22,Suppl. 45, 291s). Increasing allergen dose and length of exposure did notchange this (CHEST, Vol. 124, Suppl. 4, 140s). It might be argued thatsignificant components of the allergic reaction were lacking in our biopsyspecimens.

METHODS: We obtained surgical specimens during turbinate sur-gery. All patients (n � 17, 10M, 7F, age 35 � 14) had allergic rhinitis(allergy testing and clinical history). From each specimen we obtained atleast five biopsies with a bronchoscopy forceps. We processed thesebiopsies histologically and stained them with H.E. and Giemsa. Thesections were 3 � thick with a distance of 10 � in between; we analyzeda total of 8 sections. We overlaid them with a grid (integration plate I,Zeiss) and counted hits over the different tissue structures. We alsocounted single cells (mast cells, eosinophils, and polymorphonuclearleukocytes attached to the vessel wall [marginating PMN]) and expressedthem per total grid area.

RESULTS: Tissue composition derived from percent hits over eachstructure was as follows: epithelium 20,65%, blood vessels 10,32%,connective tissue 55,59%, serous glands 10,34%, mucous glands 3,10%,mast cells 47/mm2, marginating PMN 210/mm2, eosinophils 13/mm2.

CONCLUSION: We conclude that all tissue components of theallergic reaction were contained in even the smallest of our biopsyspecimens. Similarly, isolated blood or tissue cells that are known to beinvolved in the allergic reaction were present in our specimens insufficient numbers.

CLINICAL IMPLICATIONS: We suggest that a full blown allergicresponse with mediator release and mucosecretion was possible in ourspecimens and must have taken place following allergen challenge.Equivalence of mediator release from specimens challenged in vivo and invitro has been shown (Nakamura et al., J. Allergy Clin. Immunol.2000;105:1146-52). Nevertheless ciliary beating was unchanged and thusappears to be remarkably resistant to effects of the allergic reaction.

DISCLOSURE: Thorsten Stein, None.

GENETIC POLYMORPHISM OF GLUTATHIONE-S-TRANS-FERASE M1,T1 AND SUSCEPTIBILITY TO PREMENSTRUALASTHMA IN UKRAINIAN POPULATIONNatalia Gorovenko MD* Mohammad Ebrahimi MD Svetlana PodolskayaPhD Kiev Medical Academy of Post-Graduate Education, Kiev, Ukraine

PURPOSE: About one-third of women with asthma (A) have anincrease in asthma symptoms during in menstrual period. Patients


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affected by premenstrual asthma (PA) in comparison to asthmatic womenwithout premenstrual asthma (WPA), generally have more sever symp-toms and more frequently hospitalization. Hormonal fluctuations andchanges during the menstrual cycle may be responsible for PA occurring.GSTT1, GSTM1 genes take part in detoxification and excretion ofxenobiotics from organism, and also in metabolism of prostaglandins,leukotreine and sexual hormones. Allergy also is a major risk factor forasthma. To evaluate the role of GSTT1 and GSTM1 genotypes and allergyin susceptibility to PA, we conducted the given study.

METHODS: We survey 74 asthmatic women, 9 (12.16%) with PA,average age 44.95�1.50 years and 65 (87.84%) WPA, average age44.47�1.22 years. All subjects were interviewed using a special question-naire, which allowed taking into account presence or absence of symptomsof asthma related to menstrual cycle and allergy. Allergy is also assessed byskin prick test. GSTT1 and GSTM1 genotypes were identified bymultiplex polymerase chain reaction.

RESULTS: We found that the frequency of GSTT1 functional allele inwomen with PA was 100% and in asthmatic women WPA was 68.96%(p�0.0001).The frequency of allergy in patients WPA was 83.07% and inwomen with PA was 44.45% (�2 �4.37, P�0.027).

CONCLUSION: We concluded that:1) The patients with PA have asignificantly higher frequency of GSTT1 functional genotype as comparedto those WPA.2) The frequency of allergy in patients WPA is significantlyhigher, then in cases with PA.

CLINICAL IMPLICATIONS: The diagnosis of premenstrual asthma asone form of sever asthma in related to GSTM1 and GSTT1 genotypes in women.

DISCLOSURE: Natalia Gorovenko, None.

Asthma Guidelines12:30 PM - 2:00 PMDO RESTRICTIVE REIMBURSEMENT PROCESSES INHIBITPHYSICIANS FROM ADOPTING AND IMPLEMENTINGGUIDELINES INTO THEIR PRACTICE: THE CANADIANASTHMA EXPERIENCEAndrew R. Mc Ivor MD* Laureen Rance PharmD Dalhousie University,Bedford, NS, Canada

PURPOSE: Provincial drug programs are increasingly listing pharma-ceutical products with restrictions. This may be to ensure appropriate useof a drug or serve as a cost containment strategy to control the provincialformulary budget. To determine if physicians treat asthma patients whoare beneficiaries of the provincial drug plan differently than patients whohave private drug plan.

METHODS: On-line market research was conducted using a structuredquestionnaire with 284 general practitioners (GPs) from across Canada. Thesample was weighted by province. Physicians were provided scenario-basedquestions to determine their preferences for treating patients. They werepresented with two scenarios for patients uncontrolled on moderate doses ofinhaled corticosteroids (ICS), provincial plan beneficiary vs. private drug planbeneficiary. These asked whether they would increase the dose of ICS or addadditional therapy.

RESULTS: Physicians ranked asthma symptoms, treatment guidelinesand insurance coverage (public versus private) as the three most impor-tant factors impacting drug therapy choice. Eighty percent of physicians(80%) reported that they ask patients about drug coverage (private vs.public) before making a prescribing decision. 37% of physicians reportedthat they would increase the dose of ICS for public versus 22% forprivately insured patients uncontrolled on moderate doses of ICS. Thistrend remained consistent across the regions, however in Atlantic Canadathere was no difference at 35%.For provincial drug plan patients, themajority reported adding a long acting beta agonist (LABA) via a separateinhaler vs. those with private drug plans where the physicians opted for acombination of ICS � LABA in one inhaler.

CONCLUSION: Asthma treatment approaches differ for patients withpublic vs. private drug plans. Patients uncontrolled on ICS alone withpublic drug coverage, physicians continue to increase the dose of ICS,despite the fact that this approach is misaligned with current guidelinerecommendations.

CLINICAL IMPLICATIONS: Patients with private drug coverageare treated more closely to national guidelines developed to improveoutcomes. The market research used to prepare this document wasperformed by PSL Inc.,Toronto, Ontario, Canada.

DISCLOSURE: Andrew Mc Ivor, None.

THE 2005 ASTHMA ACTION STUDY IN CANADAAndrew R. Mc Ivor MD* Mark Greenwald MD Melva BellefountaineMeyer Balter MD Dalhousie University, Bedford, NS, Canada

PURPOSE: To obtain current 2005 information to determine theunmet needs of Canadians with asthma.

METHODS: Telephone survey of patients with physician diagnosedasthma was performed during March 2005 in Canada. The authors developeda study questionnaire and ethics approval was obtained. The telephoneinterview was performed by a prominent Canadian Market Research Firm.The sample was weighted to obtain a representative sample of adult patientswith asthma in Canada with respect to age, gender and geographical location(10 Provinces and 1 Canadian Territory).

RESULTS: 997 patients with physician diagnosed asthma re-sponded to the complete survey. Age ranges 18% (18-34 years old),52% (35-54 years old), and 39% (55� years old). 60% of therespondents were female. 10% of patients had been treated in theemergency room in the last year and 12% missed work or school; 97%of patients said that asthma effected their work or school performanceover the previous year. 28% were experiencing daily daytime symptomsand 67% reported daytime symptoms at least weekly. 6% experiencednocturnal wakening from their asthma on a daily basis with 29%wakening at least once a week with asthma.Only 50% of the sample hadobjective tests of pulmonary function performed (peak flow/spirome-try). 70% of patients stated that they had not had their inhalertechnique checked. Only 15% had been referred for asthma education.Significant misconceptions of medications were identified including39% of patients using short acting bronchodilators as their most oftenused “controller” medications and a further 11% were unsure as towhich of their medications were “controller” medications.

CONCLUSION: This March 2005, nationwide Canadian survey iden-tifies significant asthma care gaps, patient and physician misconceptionsaround knowledge transfer of asthma guidelines to patient care. Thesehave not reduced from previous surveys.

CLINICAL IMPLICATIONS: Guideline groups should integratemethods of dissemination and implementation strategies to change prac-tice, reduce care gaps and improve asthma outcomes.Funding via unre-stricted grant from Novartis through the Asthma Society of Canada.Telephone survey conducted by Pollara Inc., Toronto, Canada.

DISCLOSURE: Andrew Mc Ivor, None.

ASTHMA CARE PERCEPTIONS AND PRACTICES AMONGASTHMA SPECIALISTS IN LEBANONHani M. Lababidi MD* Mazen AbuAkl MD Makassed General Hospital,Beirut, Lebanon

PURPOSE: Asthma is a common chronic condition. Despite publishedguidelines for the diagnosis and treatment of asthma, the real medicalpractices for this condition vary among different care providers. Thepurpose of this study is to evaluate the current perceptions and practicesof asthma among asthma specialists in Lebanon.

METHODS: A cross sectional survey was conducted on asthmaspecialists in Lebanon in November 2004. The studied parametersincluded asthma diagnosis, follow-up, treatment, patient education, use ofasthma guidelines, demographic characteristics of providers and theirinvolvement in continuous medical education.

RESULTS: Out of 125 practicing pulmonolgists and allergistsregistered in Lebanon, 70 filled out the questionnaire (56%). Thesewere 20 females (29%) and 50 males (71%). The average age was42.6�8.5 years. There were 55 pulmonolgists (78.5%), 5 allergists(7.1%) and 10 with double specialty in pulmonary and allergy (14.3%).81.4% of responders performed spirometry on newly diagnosed sub-jects with asthma, while 74.3% monitored peak flows. The frequency ofuse of different treatment modalities for asthma was 94.1% for inhaledsteroids, 95.4% for long acting beta-agonists (LABA), 60.6% forLeukotriene antagonists, 32.8% for theophylline, 25.8% for oralanti-histamines and 5.2% for cromolyn sodium. The inhaler techniqueis often monitored by 65.2% and sometimes by 24.6%, while peakflow diary is often reviewed by 29.9% and sometimes by 34.3%.About 87.9% of the responders indicated that they follow asthmapractice guidelines, 84.6% of them reported using the GINA guide-lines. Around 92.6% of asthma specialists in Lebanon attendedcontinuous medical education (CME) program on asthma in the pastyear.


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CONCLUSION: This survey characterizes the pattern of asthmatreatment by specialists in Lebanon. The overall performance of theresponders meets the international guidelines.

CLINICAL IMPLICATIONS: This study provides data for improvingthe performance of asthma treatment in Lebanon.

DISCLOSURE: Hani Lababidi, None.

DOES ASTHMA KNOWLEDGE OF INTERNSHIP YEAR STU-DENTS DIFFER THAN PHYSICIANS IN SPECIALIZATIONTRAINING?Esra Uzaslan MD* Esref Erdem Funda Coskun MD Beril Erdogan MDDane Ediger MD Mehmet Karadag MD Oktay Gozu MD UludagUniversity Medical Faculty, Bursa, Turkey

PURPOSE: The goal of this survey was to assess the knowledge,attitudes and beliefs of interns (students in internship year of medicalfaculty)about asthma and its management and to compare the correctresponse rate of interns with physicians in specialization training (PST) inteaching hospitals.

METHODS: An asthma questionnaire including 33 items was appliedto interns (n:209,40% female and 60 % male) and PST (n:202,49% femaleand 51% male)of Uludag Medical Faculty in July 2004.

RESULTS: The 89% of interns believed that asthma can be cured,whilst 84 % of PST believed so(p�0.05).The 13% of interns thoughtthat when acute asthma attacks resolved, the disease can be cured,whilst 15% of thought so (p�0.05).The 76% of interns believed thatasthma runs in families whilst 53% of PST believed so (p�0.001).The99% of interns and 97% of PST knew that animal feathers were one ofthe triggers of asthma ((p�0.05).The 76% of interns and 47% of PSTknew that cockroach was one of the triggers of asthma (p�0.001). The57% of interns and 46% of PST thought that nutritional conditions cantrigger asthma (p�0.05).There was not any significant difference oncorrect response rate to questions on about asthma signs. The 97% ofinterns believed that asthmatics can be treated without hospitalization,whilst 96% of PST believed so (p�0.05).The 19% of interns and 18%of PST thought that asthma medication should be sold withoutprescription (p�0.05).The 9% of interns and 9% of PST believed thatasthma medication was addictive (p�0.05). The 90% of interns and85% of PST thought that inhaler (vaporizer) was a good treatment(p�0.05).The 64 % of interns and 61% of PST believed that asthmacare was expensive (p�0.05).

CONCLUSION: The interns knowledge about asthma was generallybetter than the PST, but by the time passing this compact knowledge maydecrease as we observed in PST.

CLINICAL IMPLICATIONS: Postgraduate education about asthmashould be offered every physician whatever their specialization is, whenplanning to improve asthma outcomes in society.


HOSPITAL-BASED PHYSICIAN ASSESSMENT OF KNOWL-EDGE, ATTITUDES AND PRACTICE IN THE DIAGNOSIS ANDMANAGEMENT OF ASTHMA GUIDELINESOgee Mer A. Panlaqui MD* Eloisa S. De Guia MD Veterans MemorialMedical Center, Quezon City, Philippines

PURPOSE: To determine the knowledge, attitude and practice ofhospital based physicians in the diagnosis, management and prevention ofasthma.

METHODS: The study was conducted in a tertiary governmenthospital involving physicians in practice of Family Medicine, InternalMedicine, Pediatrics and Pulmonary Medicine. A 31 point question-naire was distributed consisting eight subject areas: assessment,asthma diagnosis, education, pathology, prevention, pharmacology,severity and therapy. The score for each of the subjects and the totalscore were calculated and grouped according to the level of training ofthe physicians and specialties. The mean score for each group ofphysicians were compared using the one way analysis of variance withlevel of significance set at p� 0.05 with 95% CI.

RESULTS: A total of 144 (75.8%) physicians out of the 190responded.The mean score is 45.8 �/- 13.4 (mean, SEM) performingbest in asthma diagnosis and scored poorly in prevention of asthmatriggers. The pulmonary fellows in training got the highest mean score

(59.7 SEM 12.3). The physicians performed least in asthma assess-ment, education, prevention, severity classification and therapy. Sig-nificant differences were noted in physician understanding of theguidelines concerning:diagnosis(p� .001),pathology(p�.001), pharma-cology (p � .001), severity (p � .001) and therapy(p� .001). Acrossdifferent specialties,pulmonary specialists got the highest mean score(61.7 SEM 11.6).Significant differences in understanding of theguidelines were observed in asthma diagnosis (p � .001), assessment(p � .026), pathology (p � .001), pharmacology (p � .001), prevention(p �.001) and therapy (p � .001).

CONCLUSION: The results of the study showed that there is aneed for further improvement in the knowledge and understanding ofthe NHLBI Global Initiative for Asthma among physicians at theVMMC.Subject areas that should be emphasized in asthma guidelinesdissemination are proper assessment, asthma education, prevention ofasthma triggers, proper severity classification and choice of appropri-ate therapy.

CLINICAL IMPLICATIONS: Proper diagnosis and management ofasthma will reduce its fatal consequences. This can be achieved byensuring physicians’ understanding of existing guidelines through continu-ing medical education.

DISCLOSURE: Ogee Mer Panlaqui, None.


Asthma Guidelines, continued


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A CLINCAL DIAGNOSIS OF ASTHMA DOES NOT CORRELATEWELL WITH ATS FEV1 BRONCHODILATOR CRITERAJohn A. Gjevre MD* Thomas S. Hurst DVM Regina M. Taylor-GjevreMD Donald W. Cockcroft MD University of Saskatchewan, Saskatoon,SK, Canada

PURPOSE: The ATS has developed criteria suggesting that a signifi-cant post-bronchodilator FEV1 response is 200 ml and 12% improvement.To our knowledge, the ATS criteria never been validated versus theclinical diagnosis of asthma.

METHODS: All spirometry tests done from Sept 1999 to Sept 2004were analyzed for meeting the ATS criteria for FEV1 improvement Therewere a total of 1862 tests meeting the ATS FEV1 criteria with a total of644 individual non-duplicate records. A total of 311 individual patientrecords were analyzed for staff respirologists.

RESULTS: 311 patients were found who met ATS FEV1 criteria andwhose complete physician records were available. There were 170 menand 141 women with a median age of 62.8 years. Of the 311 patientsmeeting a 12% FEV1 change, there were 170 (54.7%) diagnosed by thestaff respirologist with asthma. Of the 208 patients meeting a 15% FEV1improvement, there were 120 (57.7%) diagnosed with asthma. Of the 98patients meeting a 20% FEV1 improvement, there were 62 (63.3%)patients diagnosed by the staff respirologist with asthma. For the diagnosisof asthma versus not asthma, there was a statistically significant differencein the post-bronchodilator FEV1 % improvement with p�0.02 (CI0.256-3.02). Of the 170 patients with asthma (for 12% FEV1 response),there was a mean improvement in FEV1 of 19.4% (SD 6.87), while the140 not asthma patients had a mean improvement in FEV1 of 17.8% (SD5.53).

CONCLUSION: While the ATS FEV1 criteria are a help in asthmadiagnosis, relying on spirometric criteria alone is inadequate in asthmadiagnosis. Only 170 patients (54.7%) meeting ATS bronchodilator im-provement criteria were felt to clinically have asthma.

CLINICAL IMPLICATIONS: The diagnosis of asthma requires aclinical history and physical examination. Spirometry changes are helpfulbut the level of bronchodilator significance remains unclear.

DISCLOSURE: John Gjevre, None.

CLASSIFICATION OF ASTHMA SEVERITY AMONG STEROID-NAIVE ADULT SUBJECTS PREVIOUSLY RECEIVING SHORT-ACTING BETA2-AGONISTS: IS MILD REALLY MILD?Paul M. Dorinsky MD* Steve Yancey MS John Stauffer MD AmandaEmmett MS Laura Sutton PharmD GlaxoSmithKline, Research TrianglePark, NC

PURPOSE: Current guideline criteria for mild asthma are based onsymptomatology or rescue use which are quite broad, suggesting that theymay not define a distinct group of patients. Furthermore, the results of arecent study suggested that patients with mild persistent asthma may notrequire regular maintenance treatment with an inhaled corticosteroid(ICS).1.

METHODS: This analysis evaluated subjects (n�85) previously re-ceiving short-acting beta2-agonists alone from two completed 12-wk trialsin which subjects received placebo. Subjects were initially stratified bybaseline PEF �80% or �80% predicted and further stratified bysymptoms and/or albuterol use on �2 days/wk, 3-6 days/wk or 7 days/wk.

RESULTS: For subjects with PEF �80% and symptoms/albuterol useon �2 days/wk, the majority of weeks (78%) were spent in the intermit-tent or mild categories. However, for subjects with PEF �80% andsymptoms/albuterol use on 3-6 days/wk, subjects who could be guideline-classified as having mild persistent asthma, approximately 54% of weekswere spent in the moderate or severe categories. In addition, for subjectswith PEF �80% and daily symptoms or albuterol use (i.e., the type ofsubject often recruited into mild asthma studies1), 77% of weeks werespent in the moderate category. Furthermore, when only those pts withPEF �80% and symptoms/albuterol use on �2 days/wk were considered,approximately 67% of weeks were spent in the moderate or severecategories.

CONCLUSION: This analysis clearly demonstrates that asthma sever-ity cannot be determined in many patients by discrete, point-in-timeassessments of lung function, albuterol use or symptoms. More impor-tantly, these observations suggest that the current classification system forpersistent asthma needs to be re-evaluated as many patients who meetcurrent guideline criteria for mild persistent asthma would appear to bemore appropriately classified as having moderate or severe disease.

CLINICAL IMPLICATIONS: Using current guidelines to definemild asthma may underestimate the true severity of the underlyingdisease. In light of recent publications, this underestimation may lead toinadequate therapy for patients with mild asthma. 1. Boushey, et al.NEJM 2005;352:1519-28.

DISCLOSURE: Paul Dorinsky, Shareholder I am a GSK shareholder;Employee I am a GSK employee

RELATIONSHIP BETWEEN MEASURED LUNG FUNCTIONAND SELF-REPORTED SYMPTOMSJamson S. Lwebuga-Mukasa MD* Tiffany Kolniak BS Paulette M. WydroMPH SUNY at Buffalo, Buffalo, NY

PURPOSE: This study investigates the relationship between responsesto a lung health questionnaire and measured pulmonary function usingspirometry.

METHODS: Community-based, cross-sectional study design using aconvenient sample of adults. A total of 567 adults, ages from 18 to 86years, mean age of 45 � 15.48; 36.5% males and 63.5% females; 24.3%African American, 53.8% Caucasian, 14.6% Latino/Hispanic, and 5.5% ofother race/ethnicity. Lung function was measured by spirometry; an18-item questionnaire was administered to adults attending health fairs inWestern New York State over a period of two years (2003-2005).

RESULTS: Asthma prevalence was 19.6%. Persons who reported threeor four symptoms, namely: wheeze, night cough, wheezing with exercise,and long-lasting colds, in the preceding 12 months had a lower percentpredicted value for the forced expiratory volume in the first second(FEV1) (F�5.92, p�.015 and p�.001, respectively) than persons who didnot report any symptoms of asthma. Persons who had health careutilization for asthma in the preceding 12 months had lower percentpredicted FEV1 values (�75%) than persons who had not (p�.000,OR�3.62, CI�2.18-6.02). The same relationship was seen for mid-expiratory flow rate (MEFR 25/75) (p�.000, OR�2.62, CI�1.66-4.15).As the frequency of self-reported health care utilization increased,abnormal FEV1 measurements increased (B�-1.250, p�.001), and theratio of FEV1 to the forced vital capacity (FEV1/FVC) decreased by -.131standard deviations, S.E.�.001, p�.017.

CONCLUSION: These results indicate that self-reported symptoms ofasthma in thelung health questionnaire are associated with decreasedpulmonary function and increased health care utilization.

CLINICAL IMPLICATIONS: The results demonstrate that self-reported symptoms may be used as a cost-effective method for actualpulmonary function where spirometry is unavailable.

DISCLOSURE: Jamson Lwebuga-Mukasa, None.

A SECONDARY CARE PERSPECTIVE ON THE STEPPING-DOWN OF INHALED CORTICOSTEROID THERAPY IN PA-TIENTS WITH STABLE ASTHMADaniel K. Lee MD* Prashant S. Borade MD Graeme P. Currie MD D. A.Promnitz MD Department of Respiratory Medicine, Ipswich Hospital,Ipswich, Suffolk, England, United Kingdom

PURPOSE: Current guidelines advocate stepping-down inhaled corti-costeroid (ICS) therapy at 3-monthly intervals once asthma control hasbeen achieved. Despite this, there are no data describing how widespreadthe practice of reducing ICS therapy is, especially in secondary care.

METHODS: We assessed patients with asthma being followed up in asecondary care respiratory clinic for a minimum period of 6 months.Patients who were actively receiving or had received either oral orparenteral corticosteroids, or immunosuppressive therapy within a 12-month period were excluded. Patients were also required to be exacer-bation-free during this period. A retrospective study was performed overthe preceding 12 months in order to evaluate whether ICS therapy hadbeen reduced or not following a prolonged period of stability.

RESULTS: 60 consecutive patients with asthma were assessed in clinic.12 patients with mean age of 56 years and forced expiratory volume in 1second of 1.97L (73% predicted) completed the study. The meanbeclomethasone dipropionate (BDP) equivalent ICS daily dose was1267�g and patients had either moderate (n � 6) or severe (n � 6)asthma. Only two patients had step-down in ICS therapy. One patient hada 33% reduction in ICS dose from an initial daily dose of BDP 1500�g,having had stable asthma for 11 months. The other patient had a 50%reduction in ICS dose from an initial daily dose of fluticasone propionate1000�g, having had stable asthma for 8 months. The remaining 10




patients continued on the same dose of ICS despite having had stableasthma during the preceding 12 months. There were no significantdifferences in any outcomes according to whether patients had ICStherapy reduced or not.

CONCLUSION: Our preliminary data have shown that stepping-downICS therapy in patients with stable asthma is being poorly implemented.

CLINICAL IMPLICATIONS: If this is reflective of practicesthroughout the United Kingdom, many patients with stable asthma maybe exposed to unnecessary high doses of ICS.

DISCLOSURE: Daniel Lee, None.

NO HISPANIC ASTHMATIC LEFT BEHINDRamon E. Figueroa-Lebron MD* Asthma Management Center, San Juan,PR

PURPOSE: Medical literature and government (Federal & State)reports that Hispanics suffer greater morbidity and mortality from asthmathan the general population. This study compares the efficacy between agoal oriented management with the current NAEPP guidelines in thispopulation since there is not a Spanish version of them and are inaccesibleto patients.

METHODS: A retrospective observational study based on expendi-tures paid by Blue Shield Puerto Rico for the years 2003-04 for servicesprovided for the treatment of asthma. The services compared were officevisits, ED admissions, ICU admissions, medications,readmissions and alldiagnostic & therapeutic procedures per patient/year.Population wasdivided in two groups:A- 24,320 patients treated by 108 pneumologistswith presumed knowledge of NAEPP guidelines in private offices.B-1,094 patients treated by a team of a physician, therapist, nurse, andassistant. The management followed faithfully the Asthma Patient Bill ofRights (APBOR)Spanish version. Each person received a copy of thedocument.Patients were of low middle and middle class and Spanish wastheir principal language. On February Blue Shield provided the expensespaid for the previous year in U.S. dollars.

RESULTS: Data showed huge differences between groups. The goaloriented had lowest expenses when compared to the standard therapygroup saving $3 millions. No deaths in the goal oriented group and manyin the standard group. Deaths occurred more at home or in route tohospital than in the ICU admissions. Readmissions were 20% within 15days after discharge in the standard therapy group.There were noreadmissions in the goal oriented group.

CONCLUSION: Results were positive beyond expectations. No mor-tality and less morbidity in the goal oriented treatment group with greatsavings in resources. Current NAEPP guidelines are ignored by physicianscreating inadequate prescriptions patterns and no patient education andsupport.

CLINICAL IMPLICATIONS: A goal oriented management based onSpanish language guidelines (APBOR) generate commitment in patients,relatives, physicians with an unexpected positive outcome in Hispanicsasthmatics.

DISCLOSURE: Ramon Figueroa-Lebron, None.

Asthma Treatment12:30 PM - 2:00 PM

OMALIZUMAB IMPROVES SYMPTOMS AND REDUCES RES-CUE BETA-AGONIST USE IN OLDER PATIENTS WITH UN-CONTROLLED ASTHMARobert J. Maykut MD* Marc Massanari PharmD Farid Kianifard PhDYamo Deniz MD Colin Reisner MD Robert Zeldin MD Gregory P. GebaMD Novartis Pharmaceuticals Corporation, East Hanover, NJ

PURPOSE: Asthma in older adults is under-diagnosed, under-treated,and the role of immunoglobulin E (IgE) in asthma is under-appreciated inthis population . Therapy with omalizumab (OMA), an anti-IgE antibody,is indicated in patients with moderate to severe IgE-mediated asthmawhose remain symptomatic despite inhaled corticosteroids. We conducteda pooled analysis of all double-blind placebo-controlled trials to evaluatethe effect of OMA on asthma symptom score and rescue beta-agonist usein patients 50 years and older.

METHODS: Data were combined from 5 randomized double blindplacebo-controlled (PBO) trials of patients with moderate to severeIgE-mediated asthma; 4 were of 28 weeks and 1 was 32 weeks in duration.From the pooled study population comprised of 2236 patients, 601were � 50 years of age (296 OMA, 305 PBO). The change from baselinein mean total asthma symptom score [range 0 (symptom free) to 9], andin mean beta-agonist rescue puffs was assessed using an analysis ofcovariance. Least-squares mean treatment differences were calculatedand 95% confidence intervals were constructed.

RESULTS: The mean age of the older subgroup was 58 years; 61%were female; median IgE level was 132 IU/dl; mean percent predictedFEV1 64.6% � 17.0%; baseline mean total asthma symptom score was3.35 (OMA) and 3.40 (PBO), and baseline mean daily rescue beta-agonistuse was 4.48 puffs (OMA) and 4.37 puffs (PBO). In this subpopulation,least-squares mean difference (OMA-PBO) for change from baseline inmean asthma symptom score was -0.26 (95% CI -0.51, -0.01; p�0.0411)and least-squares mean difference for change from baseline in rescuebeta-agonist puffs was -0.47 (95% CI -0.92, -0.02; p�0.0414). Thetolerability profile of OMA in the � 50 year age subgroup was generallysimilar to that of the overall study population.

CONCLUSION: Treatment with omalizumab significantly improvedasthma symptoms and reduced beta-agonist use in older patients withmoderate to severe persistent IgE-mediated asthma.

CLINICAL IMPLICATIONS: IgE-mediated asthma is important torecognize and manage in older patients.

DISCLOSURE: Robert Maykut, Employee I am an employee ofNovartis Pharmaceuticals Corporation.

PILOT STUDY OF ANTI-IGE ANTIBODY IN THE TREATMENTOF SEVERE OBSTRUCTIVE PULMONARY DISEASE: UPDATEAFTER ONE YEARClifford G. Risk MD* John L. Ohman, Jr. MD Clifford Risk, MD,Marlborough, MA

PURPOSE: To report on the continued experience with the use ofomalizumab in patients with obstructive lung disease who may also havea comorbid asthmatic component mediated by IgE antibody.

METHODS: All patients were drawn from the original pool of 250patients in a pulmonary practice who had asthma or chronic bronchitisand qualifying levels of IgE (�30 IU/ml). Seventeen patients have beenstudied. Eleven completed 12 months of therapy (4 completed 4 to 9months of therapy). Age range was 48 to 82 years. Nine were females.Fifteen have heavy primary or secondary cigarette exposure. Sixteen hadpositive skin tests to relevant indoor allergens. Baseline FEV1 was below60% predicted in 11 patients. IgE ranged from 32 to 496 IU/ml. Endpoints were reduction in number of acute exacerbations requiring hospi-talizations or unscheduled office visits, reduction in inhaler use andimprovement in dyspnea or cough indices. A 12 month baseline periodwas compared was compared with treatment intervals after the first monthof omalizumab therapy.

RESULTS: Comparing the year before therapy to the treatmentperiod, the average monthly exacerbation rate decreased from 0.20 to0.11. Comparing the month before therapy with the final treatmentmonth, the average daily number of inhalations of asthma inhalersdecreased from 13.5 to 7.4. The average daily Fletcher dyspnea scoredecreased from 1.35 to 0.53. The average daily cough severity scaledecreased from 1.12 to 0.59. Of the six patients that were prednisonedependent at baseline the average daily prednisone requirement de-creased from 37 to 10 mg.

CONCLUSION: Continued experience with the use of omalizumab inpatients with severe chronic obstructive lund disease confirms the initialimpression of effectiveness. The role of IgE in these patients may besignificant in disease severity. This pilot study suggests that furthercontrolled studies in this group of patients would be warranted.

CLINICAL IMPLICATIONS: A patient population with chronicobstructive lung disease should be screened for the use of omalizumabtherapy. Skin test reactivity to indoor allergens was common.





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THE VIRTUAL ASTHMA CLINIC: MANAGING ASTHMA PA-TIENTS ONLINEIrvin Mayers MD* Arto Ohinmaa PhD Dilini Vethanayagam MD HeatherM. Sharpe MSN Cindy O’Hara RN Carina Majaesic MD Philip JacobsPhD University of Alberta, Edmonton, AB, Canada

PURPOSE: Asthma continues to be a major health concern internationallydespite improvements in treatment and the introduction of internationalasthma guidelines. Asthma education and action plans are essential toenhancing asthma knowledge, adherance, quality of life, and control ofasthma and these form the basis for all treatment strategies recommended.There are over 90 Internet websites that provide asthma education. Thesesites did not provide interactive asthma management and the majority did noteven meet acceptable educational standards. This study aimed to assess theimpact of providing asthma management by a Certified Asthma Educator(CAE) to patients with asthma via the Internet.

METHODS: The Virtual Asthma Clinic (VAC) was created to allow aCAE to communicate with patients, and assist patients with asthmamanagement. Patients initially had spirometry testing, an asthma educa-tion session, and completed Asthma Quality of Life Questionnaire(AQLQ), symptoms questionnaire and SF-36. The site provided access totheir personalized action plan, and asthma information. Data was com-pared between those who actively participated in the program and thosewho dropped-out.

RESULTS: A total of 16 physicians referred 63 patients to the clinic. Theactive participants have taken part for a mean of 107.4 days (ongoing), whilethe dropouts participated for a mean of 140.6 days. The dropouts wereyounger (p�0.01) and both groups were predominantly female (60.5% activeparticipants, 75.0% dropouts, NS). There were no differences in history ofsmoking. Participants had a mean of 41.4 hits to the website, compared to14.8 for the dropouts (p�0.01). Participants were more likely to email thenurse (p�0.01), enter peak flow data (p�0.01), complete the weekly survey(p�0.05), the AQLQ (p�0.01), the SF-36 (p�0.01).

CONCLUSION: Active participants in the VAC were older and whilethey were enrolled for fewer days, participated more actively.

CLINICAL IMPLICATIONS: It is feasible to provide asthma man-agement to patients online. Through this study we are able to identify aspecific demographic of older patients who appear to participate morereadily in the program than young adults.

DISCLOSURE: Irvin Mayers, Grant monies (from sources other thanindustry) Capital Health Regional Telehealth, Alberta Health & Wellness;and The Alberta Strategy to Help Manage Asthma; Grant monies (fromindustry related sources) AstraZeneca Canada Inc.

THE EFFECTS OF ADDITIONAL CARE BY A PULMONARYNURSE FOR ASTHMA AND COPD PATIENTS AT AN OUTPA-TIENT CLINIC: RESULTS FROM A DOUBLE BLIND, RAN-DOMIZED TRIALGeert N. Rootmensen MD* Anton R. van Keimpema PhD Elske E.Looysen Letty van der Schaaf RN Rob J. de Haan PhD Henk M. JansenPhD Academic Medical Center, Amsterdam, Netherlands

PURPOSE: To determine the effects of additional nursing care in thetreatment of asthma and COPD patients at a pulmonary outpatient clinic.

METHODS: In a randomized, double blind clinical trial, 191 patientswere allocated to an additional care (ACG) or control group (CG).Patients were masked for the trial objectives. Patients in the ACG groupreceived an extra education program on individual basis provided by apulmonary nurse. Between initial and final assessments was a six monthsinterval.

RESULTS: 97 patients were randomized to the additional care groupand 94 to the control group of which 157 finished the trial. Small albeitsignificant differences were found for the outcomes knowledge andexacerbation rate in favour of the additional care group. No differenceswere found for self-management scores, inhalation technique, health-related quality of life and satisfaction with provided care.

CONCLUSION: for the outcomes knowledge and exacerbation ratepatients in the additional care group had significant better results. Nodifferences were found for the outcomes self-management scores, inha-lation technique, health-related quality of life and satisfaction withprovided care.

CLINICAL IMPLICATIONS: additional care by a pulmonary nurseis easy to implement, provides patient tailored care, is easy accessible andmight reduce the workload of the pulmonary physician. Since we foundthat some aspects were effective we conclude that it is worthwhile to

consider providing additional nursing care to asthma and COPD patientsin a pulmonary outpatient clinic.

DISCLOSURE: Geert Rootmensen, None.

CLINICAL EFFICACY OF AEROSOLIZED FLUTICASONETHERAPY IN THE EARLY MANAGEMENT OF ACUTE MODER-ATE EXACERBATIONS OF ASTHMA BY PMDI AND ZERO STAT‘V’ SPACERSudhir K. Agarwal MD* Institute of Medical Sciences, Banaras HinduUniversity, Varanasi, India

PURPOSE: To assess the utility of inhaled corticosteroids for the earlymanagement of acute exacerbations of asthma in the emergency room.

METHODS: This randomized, double-blind, placebo-controlled studywas conducted to evaluate the efficacy of high dose inhaled fluticasonewith frequent beta-2-agonist therapy in patients of acute moderateexacerbations of asthma. Eighty patients between 15 and 45 years of agewith acute moderate exacerbations of asthma were put on aerosolized 500�g of fluticasone at half hourly intervals for three doses with metered doseinhaler and zero stat ‘V’ spacer. All patients received humidified oxygenand nebulized salbutamol (0.15 mg/kg in 3 ml saline) prior to fluticasoneadministration. The control group received placebo instead of inhaledfluticasone. Patients who had received corticosteroids in the preceding72 h were excluded from the study. If there was an inadequate responseor no response to treatment at the end of 2 hour, oxygen and salbutamoltherapy were continued and given one dose of intravenous hydrocortisoneand was started on an aminophylline infusion.

RESULTS: Both fluticasone and control group showed a significantimprovement in respiratory status at the end of 2 h. However, patients inthe fluticasone group showed greater improvement in PEFR (P � 0.05)and significantly lower proportion of patients required oxygen improve-ment in PEFR (P � 0.01). The length of stay was significantly shorter inthe fluticasone group than in the placebo group (P � 0.01).

CONCLUSION: Aerosolized fluticasone therapy with MDI and spacertogether with salbutamol in the treatment of acute exacerbations ofasthma helped in early recovery and decreased hospital stay.

CLINICAL IMPLICATIONS: Inhaled fluticasone may be given withMDI and spacer in the treatment of acute exacerbations of asthma.

DISCLOSURE: Sudhir Agarwal, None.

Primary outcomes: knowledge, self management,inhalation technique and exacerbation frequencyincidences. Differerences between additional care

(ACG) and control group (CG)

ACG

(n�80)

median#

CG

(n�77)

median# p-value

knowledge* initial 55 (33-73) 55 (41-73)

final 64 (38-77) 59 (45-70)

change score 5 (-5-14) 0 (-5-9) 0,02

inhalation

technique**

initial 78 (68-83) 70 (63-80)

final 83 (68-90) 72 (63-83)

change score 0 (-5-10) 0 (-8-12) 0,84

self management initial 36 (25-56) 36 (25-48)

final 38 (25-63) 38 (25-53)

change score 3 (-12-19) 6 (-10-13) 0,85

exacerbation

frequency?

incidence rate‡ 1,46 3,65 0,40 (0,24-0,67)

� exacerbation*? 11% 24% 0,68 (0,49-0,94)


Asthma Treatment, continued


ZILEUTON PROVIDED SIGNIFICANT IMPROVEMENT INPULMONARY FUNCTION COMPARED TO PLACEBO IN MOD-ERATE AND SEVERE ASTHMATICSWilliam Berger MD* Daniel J. Stechschulte MD Karen Walton-BowenAllergy and Asthma Associates, Mission Viejo, CA

PURPOSE: Zileuton Provided Significant Improvement in PulmonaryFunction Compared to Placebo in Moderate and Severe Asthmatics.

METHODS: This was a randomized, placebo-controlled, double-blind, par-allel, multicenter study of the safety and efficacy of zileuton in patients withasthma. Asthma patients on no chronic asthma treatment other than inhaledbeta-agonists were randomized to one of three treatment groups: zileuton, 600mg QID, zileuton, 400 mg QID, or placebo for six months. Efficacy assessmentsincluded forced expiratory volume (FEV1) and peak expiratory flow rate (PE-FR).In an exploratory secondary analysis, 231 asthma patients randomized totreatment were stratified by baseline (BL) percent predicted normal FEV1 intotwo subgroups: moderate (�60%-�80%; n�133) and severe (�60%; n�98).Pulmonary function measurements were obtained on asthmatics on 600 mgzileuton and compared to placebo.

RESULTS: Moderate and severe patients on zileuton experiencedsignificant improvement in FEV1 and A.M. PEFR. This difference wasdemonstrated as early as 30 minutes post-dose and was sustained through-out the duration of the study. Improvements in P.M. PEFR were alsodemonstrated.

CONCLUSION: Zileuton, 600 mg QID, provided rapid and sustainedimprovement in pulmonary function in moderate and severe asthmaticpatients versus placebo.

CLINICAL IMPLICATIONS: Zileuton, a 5-lipoyxgenase inhibitorapproved for chronic asthma, may improve pulmonary function via itsmechanism of action in moderate and severe asthmatics.

DISCLOSURE: William Berger, None.

ZILEUTON PROVIDED CLINICALLY RELEVANT REDUC-TIONS IN THE NEED FOR RESCUE MEDICATION AND ORALCORTICOSTEROIDS COMPARED TO PLACEBO IN MODER-ATE AND SEVERE ASTHMATICSMark C. Liu MD* Malcolm N. Blumenthal MD Karen Walton-BowenJohns Hopkins Bayview Medical Center, Baltimore, MD

PURPOSE: Zileuton Provided Clinically Relevant Reductions in theNeed for Rescue Medication and Oral Corticosteroids Compared toPlacebo in Moderate and Severe Asthmatics.

METHODS: This was a previously published, randomized, placebo-controlled, double-blind, parallel, multi-center six-month study of thesafety and efficacy of zileuton (400 or 600 mg QID) in 373 patients withasthma on no chronic asthma treatment other than beta-agonists (J AllergyClin Immunol 1996; 98(5):859-71). Assessments included beta-agonistuse, acute asthma exacerbations requiring alternative treatment or oralcorticosteroids, and daily and nocturnal symptoms, as well as mean FEV1and other pulmonary function tests.In an exploratory secondary analysis ofpatients in the high dose zileuton 600 mg QID group, patients werestratified by baseline (BL) percent predicted FEV1 into two subgroups ofasthma severity: moderate (�60%-�80%) and severe (�60%).

RESULTS: Moderate and severe zileuton patients reported reduced dailynumber of occasions of beta-agonist use. Fewer zileuton patients experiencedasthma exacerbations requiring alternative treatment and oral corticosteroidtreatment. Improvements in daily and nocturnal symptoms were also reported.These differences were sustained throughout the six-month study.

CONCLUSION: In severe asthmatic patients, Zileuton, 600 mg QID,provided significant improvement versus placebo in markers of asthmacontrol including reductions in daily number of occasions of beta-agonistuse, asthma exacerbations.

CLINICAL IMPLICATIONS: Zileuton, a 5-lipoyxgenase inhibitorapproved for the treatment of chronic asthma, may reduce the need forbeta-agonists and oral corticosteroids and improve other markers ofasthma control, especially in severe asthmatics.

DISCLOSURE: Mark Liu, None.

EVALUATION OF POST-TREATMENT EFFECTS OF LEUKO-TRIENE RECEPTOR ANTAGONISTSEsra Uzaslan MD* Funda N. Coskun MD Dane Ediger MD ErkanRodoplu MD Mehmet Karadag MD Ercument Ege MD Oktay Gozu MDUludag University Medical Faculty Chest Disease Department, Bursa,Turkey

PURPOSE: The aim of this study to evaluate the of post-treatment effects ofLeukotriene Receptor Antagonists (LTRA) in persistent asthmatic patients whohave been treated with inhaler steroid and LTRA, by investigating clinical andlaboratory parameters before addition of LTRA, end of treatment with LTRAand at least three months after ending of LTRA treatment.

METHODS: We retrospectively investigated clinical data of 19 asth-matic patients (16 females, 3 males, mean age 33.3�2.5 years) beforeLTRA treatment,last day of LTRA treatment and at least three monthsafter ending of LTRA treatment and compared symptom score, medica-tion score (number of controller drugs for asthma), total dose of inhalersteroid and lung function tests of patients for each visits.

RESULTS: We found decreases in symptom score (p�0.01), medica-tion score (p�0.05), total dose of inhaler steroid (p�0.05),and increaseslung function tests (p�0.05) at the end of the treatment.When weevaluated same parameters at least three months after the ending ofLTRA treament, we observed continuation of increases in FEV1 and PEFvalues (p�0.05) comparing to beginning and ending of treatment and alsoa significant decrease in total dose of inhaler steroid comparing tobeginning of treatment (p�0.05).

CONCLUSION: We come to the conclusion that in persistent asth-matic who use LTRA in addition to inhaler steroids,the improvement inlung function tests, symptom scores and medication scores are protectedand the total dose of inhaler steroids needed for control of asthma isdecreased,even 3 months after the ending of treatment.

CLINICAL IMPLICATIONS: The post-treatment effects of LTRA contin-ues three months after the discontinuation of the treatment in asthmatics.


Severity

Group

Difference From Placebo

in Mean Change From

BL to Post-Dose in FEV1 (L)Difference From Placebo in

Mean Change From BL in

A.M. PEFR (L/Min)Month 3 Month 6

30

Mins

60

Mins

120

Mins

30

Mins

60

Mins

120

Mins Days 2-22 Days 163-190

Moderate 0.19* 0.26** 0.16�� 0.11 0.12 0.18�� 17.76** 11.47

Severe 0.35* 0.30* 0.28�� 0.27�� 0.33* 0.32�� 15.93* 30.24*

**p�0.010; *p�0.050; ��p�0.100; Mins�Minutes

Severity

Group

Mean Change From BL to Days 163-

190 in Beta-Agonist Use

(Number of Occasions/Day)

Patients With Exacerbations

Requiring Alternative

Treatment (%)

Patients Requiring

Oral Corticosteroids

(%)

Zileuton Placebo Zileuton Placebo Zileuton Placebo

Moderate

(n�133)

-0.70 -0.40 13.6%� 26.5% 9.1% 17.7%

Severe

(n�98)

-0.85** �0.16 7.8%* 23.4% 5.9%** 25.5%

Baseline Post-treatment 3 months later

Symptom score 1.3�0.8 0.5�0.6 0.9�0.8Medication score 1.4�0.9 1.2�0.7 1.3�0.2Inhaled steroid

dose (mcg)875�583 695�391 445�216

FEV1 (L) 2.62�0.9 2.66�0.9 2.75�0.8PEF (L/sec) 5.68�1.7 6.27�1.8 6.77�1.8




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ELECTROLYTES DISTURBANCE: THE EFFECT OF DIFFER-ENT FORMS OF B-STIMULANTSEmad H. Ibrahim MD* Ahmed Yousery MD Alexandria Faculty ofMedicine, Alexandria, Egypt

PURPOSE: To determine the electrolyte disturbances in chronicstable asthma patients receiving outpatient therapy including differentforms of beta stimulants.

METHODS: Consecutive out patients with chronic, stable airwayobstruction of bronchial asthma. Once diagnosed patients were subjectivefull clinical data collection including: age, gender, duration of asthma,severity of illness, details of therapy, and serum levels of potassium,sodium, calcium, and magnesium were measured.

RESULTS: Sixty consecutive patients with chronic, stable airwayobstruction of bronchial asthma were included in the study.Age37.7�12.8 and females were 53.3% of patients. Electrolyte disturbanceswere found in 58.3% of patients; of those patients 51.4% had oneelectrolyte disturbance, 31.4% had two electrolytes disturbance, and17.1% had three electrolyte disturbance. The majority (45%) had lowerpotassium levels, followed by magnesium in 31.7% of patients. Lowerincidence of hyponatremia was found in 18.3% of patients. We did notfound hypocalcemia in those patients. Logistic regression analysis showedstatistically significant correlation between inhaled steroids and thepresence of electrolyte disturbance. Beta long acting inhalers wereassociated with significant correlation for hypokalemia whereas the use oftheophyline was significant for the presence of hypomagnesmia.

CONCLUSION: Hypokalemia and hypomagnesemia were the mostcommon electrolyte disturbance in patients with chronic, stable bronchialasthma. Inhaled steroids and long acting beta agonist seems to have aneffect on the electrolytes serum levels. Mechanisms are needed to beclarified.

CLINICAL IMPLICATIONS: The use of different inhalers should becarefully monitored in patients with long term therapy. Especially, if thosepatients are relectant to consult their doctors about their illness.

DISCLOSURE: Emad Ibrahim, None.

HOSPITAL ECONOMIC IMPACT IN THE TREATMENT OFACUTE ASTHMA: A COMPARISON OF RACEMIC ALBUTEROLVERSUS LEVALBUTEROLDavid M. Schreck MD* Stephen Babin RN Summit Medical Group,Summit, NJ

PURPOSE: To quantify the hospital economic impact comparingracemic albuterol (ALB) versus levalbuterol (LEV) in the emergencydepartment (ED) treatment of patients presenting with acute asthma.

METHODS: ED patients with acute asthma were retrospectivelyreviewed over a 9 month consecutive period. Outcome measures includedED admission rate, length of stay (LOS), arrival acuity, payer status, andtreatment costs. Patients were excluded for age less than 1 year or if notreatment for acute asthma was rendered.

RESULTS: A total of 736 consecutive cases were reviewed, including608 patients treated with ALB and 128 patients treated with LEV. Theindigency rate was approximately 25%. There were 92 (15.1%) admittedpatients treated with ALB and 6 (4.7%) admitted patients treated withLEV(p�0.0016; Chi-square). The number-needed-to-treat (NNT) toachieve ED discharge benefit was 9.58 patients. No significant differencesin age, gender, LOS in ED, or arrival acuity were noted between thegroups (p�NS; ANOVA). The drug costs were $0.25 and $1.50 per dosefor ALB and LEV respectively. The average ED charge for dischargedpatients receiving ALB was $422.30 � 230.61 and $404.56 � 192.56 forthose patients receiving LEV. The average LOS for admitted patients was3.8 days. The per diem rate for admitted patients was $945 and the perdiem cost of care was $780. Based on these data, a financial risk:benefitratio of approximately 1:80 favoring LEV was determined for EDtreatment. The hospital revenue loss for admitted patients was $40,600 forRAC and $13,500 for LEV.

CONCLUSION: Patients treated with LEV had a better pharmaco-economic outcome and ED discharge rate. The hospital sustained less ofa financial loss for admitted patients using levalbuterol. This study mayindicate beneficial economic and clinical effects of levalbuterol in patientswith acute asthma.

CLINICAL IMPLICATIONS: Levalbuterol use is controversial dueto its perceived negative financial impact. This study demonstrates in largeretrospective series that there are both financial and clinical benefits tousing levalbuterol in patients presenting to the ED with acute asthma.

DISCLOSURE: David Schreck, None.

COMPARATIVE EVALUATION OF CARDBOARD VERSUSRIGID SMALL VOLUME VALVED HOLDING CHAMBERS FORTHE DELIVERY OF A BETA-2 AGONIST FORMULATION: DE-LIVERY TO THE UNCOORDINATED USERDominic Coppolo RRT* Jolyon Mitchell PhD Kimberly Wiersema BAValentina Avvakoumova BSc Mark Nagel BSc Monaghan Medical Corp.,Syracuse, NY

PURPOSE: VHCs are prescribed for patients that have difficultycoordinating pressurized metered-dose inhaler (pMDI) use, frequentlyresulting in delayed inhalation following inhaler actuation. Our studyintroduced a realistic 2-second delay, comparing delivery of a beta-2agonist via VHCs of similar size (n�5/group), one manufactured fromcardboard (LiteAire™, Thayer Medical, Tucson, AZ – 160-ml) the otherfrom rigid polymer (AeroChamber Plus®, Monaghan Medical Corp.,Syracuse, NY – 150-ml).

METHODS: The AeroChamber Plus® VHCs were pretreated bywashing in water containing a mild ionic detergent, rinsed and drip-dried,as recommended prior to use. The LiteAire™ VHCs were assembled andused in accordance with manufacturer’s instructions. Each VHC wastested using an Andersen 8-stage impactor with USP Induction Portoperated at 28.3�0.5 L/min, representative of flow rates seen with adultpatients. A shutter that interfaced between the VHC mouthpiece andinduction port entrance was used to simulate a 2-s delay interval betweenpMDI actuation and the onset of sampling. The shutter moved to allowflow from the VHC to the impactor only after the defined delay.5-actuations of albuterol (Ratiopharm, Mississauga, Canada, 100 �g/dosealbuterol base equivalent ex metering valve) were delivered from apre-primed and shaken pMDI canister at 30-s intervals. The inductionport and stages of the impactor were subsequently assayed for albuterol byHPLC-UV spectrophotometry. Benchmark measurements were alsomade with the pMDI alone.

RESULTS: Fine particle mass/actuation ((FPM) �4.7 �m aerody-namic diameter (mean (95% CI)) was 27.8 (4.2) �g (pMDI alone), 21.7(5.0) �g (AeroChamber Plus® VHC) and 13.9 (4.2) �g (LiteAire™ VHC).

CONCLUSION: FPM(pMDI-alone) represents delivery with perfectinhaler technique. The AeroChamber Plus® VHC delivered nearly 80%FPM(pMDI-alone) with a 2-s delay, but the corresponding delivery viathe LiteAire™ VHC was only 50% FPM(pMDI-alone).

CLINICAL IMPLICATIONS: Dosing may have to be adjusted totake into account the poorer efficiency of the cardboard VHC, consideringthe likelihood of imperfect coordination.

DISCLOSURE: Dominic Coppolo, Employee All of the authors areemployees of companies in the Trudell Medical Group. These companiesmanufacture the AeroChamber Plus® VHC

A SINGLE DOSE OF FORADIL PROVIDES SIGNIFICANTLYGREATER BRONCHODILATION THAT MULTIPLE DOSES OFALBUTEROL OVER 12 HOURS IN OLDER ASTHMATICSUmit Yegen MD* Denise Till MS Gregory P. Geba MD NovartisPharmaceuticals Corporation, East Hanover, NJ

PURPOSE: The efficacy of beta-agonists in elderly patients has notbeen extensively studied. We conducted a pooled analysis conductedacross two 12-week, randomized, double-blind, double-dummy multi-center clinical trials to assess the efficacy of Foradil® (FOR) in an elderlysubgroup population.

METHODS: Forty patients �65 years of age with mild to moderateasthma had been randomized to receive formoterol (Foradil® dry powderinhalation capsules) 12�g b.i.d. (FOR12) or 24�g b.i.d. (FOR24) via theAerolizerTM, albuterol MDI 180�g q.i.d. (ALB) or placebo. FEV1measurements were performed pre-dose, and 5, 15, 30 and 60 minutesand hourly through 12 hours post AM dose on the first day and every 4weeks up to 12 weeks of treatment.

RESULTS: Effect on FEV1 in the elderly subgroup receiving 12 or24�g formoterol b.i.d. were similar to the general population, showingclinically significant bronchodilation (� 15% increase in FEV1) through-out the 12-hour interval, [area under the FEV1 curve (AUC; primaryendpoint)].

CONCLUSION: These results show that elderly patients with asthmaachieved significantly greater and sustained bronchodilitation (�12 hours)with FOR than with multiple doses of ALB.




CLINICAL IMPLICATIONS: The elderly population is a growingsubgroup of patients that need to be further studied. This small sample ofdata investigates the efficacy and safety of formoterol in an elderlysubgroup.

DISCLOSURE: Umit Yegen, Employee

COPD Evaluation12:30 PM - 2:00 PM

ANALYSIS OF TH1 AND TH2 CYTOKINES IN EXHALEDBREATH CONDENSATE OF EXACERBATED CHRONIC OB-STRUCTIVE PULMONARY DISEASE PATIENTSJuan A. Mazzei MD* Nancy Tateosian Paulo Maffia BS Catalina K.Wilson MD Eduardo Chuluyan PhD Hospital de Clinicas, Buenos Aires,Argentina

PURPOSE: Chronic obstructive pulmonary disease (COPD) is char-acterised by chronic inflammation of the respiratory tract. Thus, Th1/Th2cytokines could be a useful tool to monitor exacerbations of COPD. Theaim of the present study was to investigate Th1 and Th2 cytokines inexhaled breath condensate (EBC) of exacerbated COPD patients.

METHODS: The study population consisted of 20 patients withexacerbated COPD. The inclusion criteria were as follows: FEV1/vitalcapacity �70%, FEV1 �80% predicted value and stage 3 or 4 of GOLD.EBC samples were collected within 24 hours after admittance to hospitaland three months later. Cytokines were measured simultaneously in asingle EBC sample of exacerbated COPD patients by using a HumanCytokine kit II BD. This kit allowed us to quantitatively measure IL-2,IL-4, IL-6, IL-10, IFN� and TNF� protein levels.

RESULTS: The concentration of cytokines in the EBC of patients was closeto the detection limits of the assay. The mean concentration of IFN�, TNF�,IL-10, IL-6, IL-4 and IL-2 at admittance to hospital was 40�5.1, 15�0.5,23�1.0, 24�0.6, 34�1.1 and 15�0.4 respectively; while the concentration atthree months after admittance was 39�2.5, 18�1.7, 27�1.6, 30�3.3, 44�6.2;20�2.7 respectively. Although the parameters did not change significantly twomonths after admittance, there was a tendency to increase the concentration ofIL-10(p�0.06) and IL-2(p�0.08). Remarkably, by analyzing mainly IFN� andIL-4, two clearly differentiated groups of patients appeared: those whose EBCconcentration of cytokines had increased (Figure A) and those whose EBCconcentration of cytokines had decreased (Figure B) two months after admit-tance.

CONCLUSION: Considering the sample population as a whole, thisstudy showed no significant changes in cytokine concentration in EBCthree months after admittance to hospital. However, two different groupsof patients could be identified based on the pattern of cytokine.

CLINICAL IMPLICATIONS: Perhaps the presence of two group ofpatients may correlate with outcome of patients and will define a newperspective in the treatment of these patients.

DISCLOSURE: Juan Mazzei, None.

UBIQUITIN EXPRESSION IS UP-REGULATED IN PERIPERALMUSCLE IN PATIENTS WITH CHRONIC OBSTRUCTIVE PUL-MONARY DISEASEYi Ming Yuan MD* Yang Hu Jiang MD Xiao Jing Liu PhD West ChinaHospital of Sichuan University, Chengdu, Peoples Rep of China

PURPOSE: Peripheral skeletal muscle dysfunction is observed in manypatients with chronic obstructive pulmonary disease(COPD).A significantnumber of patients with normal weight also suffer muscle wasting.Fur-thermore,some investigators have found an association between reducedmuscle mass and survival in COPD patients,independent of a reduction ofFEV1.The molecular mechanisms of muscle wasting remains as yetunknown.Our study was to explore the role of ubiquitin-proteasomepathway(UPP) in the loss of muscle mass.

METHODS: 11 consecutive COPD patients(aged 67.7�8.1 years-,FEV1 percentage of predicted of 49.6�10.2%) and 6 healthy age-matched control subjects were enrolled in the study.All subjects wereunderwent 6 minute walk test.Health-related quality of life(HRQL) wasmeasured using St. George’s Respiratory Questionnaire(SGRQ).Whole-body and extremity fat free mass(FFM) were assessed by dual-energyX-ray absorptiometry.Samples of peripheral muscle were collected fromthe quadriceps by microbiopsy procedure(Bard,USA.).The extent ofubiquitin expression in skeletal muscle was determined by immunohisto-chemistry.

RESULTS: Whole-body and extremity FFM were significantly lowerin the COPD patients than in healthy control(whole body 50.1�8.4kg vs53.9�10.5kg,p�0.05;extremities 21.4�4.6kg vs 25.2�5.2kg,p�0.01).Theintensity of ubiquitin immunostaining in quadriceps muscle fibers inCOPD patients was significantly higher than in control(110.1�2.0 densityunits vs 85.8�0.4 density units,p�0.01).Whole-body FFM was positivelycorrelated with 6 minute walk distance(r�0.63,p�0.05).There was signif-icantly negative correlation between extremity FFM and expression levelsof ubiquitin(r�-0.78,p�0.05),SGRQ total score(r�-0.54,p�0.05).

CONCLUSION: Depletion of FFM is associated with a decline inHRQL and exercise capacity in COPD patients.The ubiquitin expresionlevels is up-regulated in these patients.Therefore,the UPP might beinvolved in peripheral skeletal muscle wasting of COPD patients.

CLINICAL IMPLICATIONS: Drug development targeting UPP mayprovide novel strategies for treating skeletal muscle abnormalities inCOPD.

DISCLOSURE: Yi Ming Yuan, None.

SINGLE MEASUREMENTS OF INSPIRATORY CAPACITY ARENOT BETTER THAN FEV1 IN PREDICTING SYMPTOMSCORES IN COPDShirley F. Jones MD* John A. Cooper MD Mark T. Dransfield MDBirmingham VA Medical Center, Birmingham, AL

PURPOSE: Chronic obstructive pulmonary disease (COPD) is thefourth leading cause of death in the United States. Although the forcedexpiratory volume (FEV1) is an accurate marker of mortality in populationstudies it has only shown a weak correlation with dyspnea and quality oflife. It has been shown that changes in inspiratory capacity (IC), a measureof hyperinflation, correlate well with improvements in these outcomes.The aim of this study is to determine whether a single, baselinemeasurement of IC is a better predictor of measures of dyspnea andquality of life than FEV1.

METHODS: We enrolled veterans with COPD from two pulmonaryclinics. Demographic data was obtained and enrollees completed threequestionnaires, the Medical Research Council Dyspnea Scale (MRC), theUniversity of California San Diego (UCSD) Shortness of Breath Ques-tionnaire and the St. George’s Hospital Respiratory Questionnaire(SGRQ). Spirometry was performed according to ATS standards andFEV1 and IC measurements were recorded. Correlation coefficientsbetween FEV1, IC, and questionnaire scores were then determined andcompared.

RESULTS: 36 patients were enrolled. The mean age of our partici-pants was 66 with the majority being Caucasian males (95%). The meannumber of pack-years smoked was 71. The mean IC among enrollees was68% predicted. The mean FEV1 was 40% predicted indicating severeairflow obstruction. The mean scores for the MRC, UCSD and SGRQwere 3.3, 67.5, and 46.5 respectively. Both FEV1 (r�-0.58, p�0.001) andIC (r�-0.47, p�0.004) correlated with the UCSD score though neithermeasure was superior (p�0.53). Neither FEV1 (r�-0.24, p�0.15) nor IC

AUC of FEV1 (L x hours)

FOR12 vPlacebo

FOR24 vPlacebo

FOR12v 24

ALB vPlacebo

After first dose 4.50* 4.71* -0.21 2.53After 12 weeks 4.02 4.17 -0.15 1.54

* Indicates statistical significance at the 0.05 level




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(r�-0.28, p�0.10) correlated with the MRC. FEV1 correlated with theSGRQ (r�-0.37, p�0.02) while IC (r�-0.24, p�0.15) did not.

CONCLUSION: In patients with severe COPD, a single baselinemeasurement of IC does not appear to be better predictor of dyspnea orquality of life scores than FEV1.

CLINICAL IMPLICATIONS: Clinicians should be mindful that nospirometric measure is reliably predictive of symptoms and quality of lifein COPD.

DISCLOSURE: Shirley Jones, None.

DETECTION OF CHRONIC OBSTRUCTIVE PULMONARY DIS-EASE BY SPIROMETRIC SCREENINGAshok K. Janmeja MD* Kiran Jit MBBS Government Medical CollegeChandigarh, Chandigarh, India

PURPOSE: COPD is a progressive disease but its advanced stages canbe averted if noxious agents are removed early. Often, patients seek advicewhen they become dyspneic, but by then half of their ventilation isirreparably lost. By far smoking cessation is most rewarding interventionin prevention of COPD. If harnessed adequately for control of COPD, itwould prevent alarming future predictions. COPD currently ranks 6th inglobal impact scale and is predicted to number 3 by 2020. Recent studiesindicate that COPD could be detected early by spirometry. High preva-lence, morbidity and cost involved prompt early identification of suchcases to obviate progression. So far no such study has been conducted inIndia. Present study evaluated role of spirometric screening in earlydetection of COPD in smokers.

METHODS: Study was conducted at Medical College Hospital since2003 to 2005. Initially for 3 months, a COPD awareness campaign wasenacted through mass media viz. articles in papers, radio and televisioninterviews, posters in hospital etc. Thus, smokers with smoking index [SI]above 100 were motivated for spirometry. Finally, 307 subjects wereenrolled. Spirometry performed comprised estimation of FVC, FEV1 andFEV1 / FVC ratio. COPD was diagnosed and staged as per GOLDguidelines. Non- COPD pulmonary cases were excluded through clinicalexamination and investigations.

RESULTS: Of 60 asymptomatic smokers 12% had COPD while 47% of240 symptomatic subjects suffered COPD. Incidence of COPD insubjects with SI of 100-200, 200-400, and above 400 was 33, 38 and 42 %respectively. Incidence of severe disease i.e. stage III and IV was higher[14%] in subjects with SI above 400 than the incidence [9%] in subjectswith SI below 400, [P�0.01].

CONCLUSION: COPD detected in 40% of all smokers and 12% ofasymptomatic smokers. Positive association existed between amount ofsmoking with incidence and severity of COPD, [P�0.01].

CLINICAL IMPLICATIONS: The preliminary data thus generatedwill make useful contribution towards concept of spirometric screeningfor early detection and prevention of COPD in country.

DISCLOSURE: Ashok Janmeja, None.

USE OF SPIROMETRY IN CLINICAL PRACTICE FOR OB-STRUCTIVE AIRWAYS DISEASE IN INDIASundeep S. Salvi MD* Liesel D’Silva MD Sushmeeta Chhowala MS BillBrashier MBBS Trupti Bal MS Jaideep Gogtay MD Chest ResearchFoundation, Pune, India

PURPOSE: Office Spirometry is essential for the diagnosis andmanagement of asthma and COPD. However, it remains an underutilizedtool in clinical practice. In this study we aimed to investigate the use ofSpirometry by General Practitioners, General Physicians, Chest Physi-cians and Pediatricians from different cities across India.

METHODS: 3750 doctors from 20 centers across India were randomlyselected and invited to fill in a one-page questionnaire.

RESULTS: 1715 doctors returned the completed questionnaire (256general practitioners, 717 general physicians, 458 chest physicians, 209pediatricians and 74 others) (response rate: 45.7%). The mean duration ofclinical practice was 15.2 years and on average 32 asthma patients and 17.5COPD patients were seen per week by each clinician. The table shows theuse of spirometry by different groups of clinicians in their practice. Thecommonest cause for not using Spirometry was lack of access to Spirom-etry (41.6%), and non-affordability of the test by the patients (36.2%).

CONCLUSION: Spirometry is underutilized by clinicians in India.CLINICAL IMPLICATIONS: Clinicians in India need to be moti-

vated to perform spirometry in clinical practice.

DISCLOSURE: Sundeep Salvi, Grant monies (from industry relatedsources) Cipla Ltd.

COMPARISON OF BRONCHODILATOR RESPONSE IN PA-TIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DIS-EASE AND BRONCHIAL ASTHMAG. Gandev MD* K. Gupta MD J. Williams MD K. Kanagarajan MDConey Island Hospital, Brooklyn, NY

PURPOSE: The response to bronchodilators is often used to distin-guish chronic obstructive pulmonary disease (COPD) and bronchialasthma (BA). Numerous studies have shown that many patients withCOPD exhibit significant bronchodilator response while some patientswith BA may not. Our study compares the bronchodialator response inpatients with COPD and BA.

METHODS: Retrospective analysis of PFT’s in patients referred withdiagnosis of COPD and BA was done. Positive bronchodialator responseusing ATS criteria were noted in both groups. The patients were furtherstratified into those under the age of 55 and those over 55. The data wasanalyzed using independent t-test for the mean and chi square test for anyvariables with percentage.

RESULTS: 78 patients with COPD and 76 patients with BA wereidentified. In the group younger than 55 years, there were 6 patients withCOPD and 47 patients with BA. 20 patients with COPD had significantbronchodilator response (25.6%), and 34 patients with BA had significantbronchodilator response (44.7%). The overall difference in bronchodilatorresponse between the two groups was statistically significantly (p�0.01).In the group younger than 55, 50% (n�3) of patients with COPD hadsignificant bronchodilator response versus 42.6% (n�20) of patient withBA. For the age above 55, 23.6% (n�17) of patient with COPD hadsignificant bronchodilator response versus 48.3% (n�14) of patient withBA and the difference in bronchodilator response for this age group wasstatistically significant (p�0.01).

CONCLUSION: Even though patients with BA were more likely tohave bronchodilator response a significant number of patients withCOPD, exhibit the same. Bronchodilator response was observed in theolder cohort of COPD patients as well.

CLINICAL IMPLICATIONS: Bronchodialator response cannot reli-ably distinguish between BA and COPD.

DISCLOSURE: G. Gandev, None.

CHANGES OF DIFFUSION CAPACITY IN PATIENTS WITHCHRONIC OBSTRUCTIVE PULMONARY DISEASES (COPD)Yaling Zhu MD* Haoyan Wang MD Xiaohong Chang Chaoyang Hospital,Beijing, Peoples Rep of China

PURPOSE: To assess the changes of diffusion capacity in differentstages of COPD patients.

METHODS: 95 stable COPD patients were divided into 4 groups:Stage I, II, III and IV according to EFV1/FVC% and FEV1% values, eachwith 8, 47, 34, 6 patients respectively. The transfer factor of the lung forcarbon monoxide (TLco), pulmonary membrane diffusion capacity (Dm)and pulmonary capillary blood volume (Vc) were measured with singlebreathing method.

RESULTS: TLco,Dm and Vc were decreased in all COPD groups,significant differences were found in stage II to Stage IV groups incomparison with those of the normal subject group. TLco and Dm wereprogressively decreased from stage I to stage IV while Vc were compara-ble among all stage groups.

CONCLUSION: Diffusion capacity was progressively impaired withthe severity of COPD.

Category

% Of patients asked to performSpirometry

Asthma COPD

General Practitioner 9.36 11.11General Physician 19.99 22.83Chest Physician 54.92 56.70Pediatrician 5.42 Not applicable


COPD Evaluation, continued


CLINICAL IMPLICATIONS: Diffusion capacity measurement isalso a valuable approach for further understanding the entity of COPD.

DISCLOSURE: Yaling Zhu, None.

PREVALENCE OF CHRONIC OBSTRUCTIVE PULMONARYDISEASE IN PATIENTS ATTENDING CHEST CLINIC IN ATERTIARY CARE HOSPITALArul Vigg MBBS* Ajit Vigg MD Avanti Vigg MBBS Sumanth Mantri MDChest Clinic-Hyderabad, Hyderabad, India

PURPOSE: To assess the true prevalence of COPD in the communityin South India and to estimate the burden of disease.

METHODS: Three year retrospective analysis of all subjects whounderwent Pulmonary Function Tests between January 1999 to Decem-ber 2001. The cohort included individuals who underwent spirometry aspart of routine health checkup and patients attending hospital for electivesurgery or for non-respiratory medical problems and those patientsreferred from the chest clinic for Spirometry. History of more than 10pack years of smoking was noted in all relevant cases.

RESULTS: Out of 13,860 patients who underwent pulmonary functiontesting during the 3 years period, there were 9702 males and 4164females. 946 patients (6.8%) were diagnosed to have COPD according toGOLD guidelines of which 811 were males (86%) & 135 were females(14%). More than 10 pack years of smoking was seen in 830 patients(87.7%) & 116 patients were non-smokers (12.3%). Mean age was 44.65 �4.15 years. Out of 946 patients, 284 had mild COPD (30%),286 hadmoderate disease (30%) and the remaining 387 patients (40%) had severeCOPD. The overall prevalence of COPD in the present study was 6.85%with prevalence of disease in males being 7.4% and in females 4.64%.

CONCLUSION: There is a significant burden of COPD as a disease inthe community with overall prevalence of 6.85% in South India.

CLINICAL IMPLICATIONS: The burden of COPD in south India ishuge as shown by our study there is an urgent need to reconize this in fieldconditions so as to treat them appropriately.

DISCLOSURE: Arul Vigg, None.

RADIOGRAPHIC ABNORMALITIES PREDICT FUNCTIONALIMPAIRMENT IN PATIENTS WITH CHRONIC OBSTRUCTIVEPULMONARY DISEASETarek A. Dernaika MD* Jean I. Keddissi MD Walid G. Younis MD GaryT. Kinasewitz MD University of Oklahoma Health Sciences Center,Oklahoma City, OK

PURPOSE: To examine the hypothesis that abnormalities on chestroentogram (CXR) will predict physiologic impairment on pulmonaryfunction tests (PFTs) in patients with chronic obstructive pulmonarydisease (COPD).

METHODS: The CXRs of 108 consecutive patients with COPD werescored 0-4 with 1 point being awarded for the presence of each of thefollowing: 1) flattening of the diaphragm, 2) increased retrosternal air, 3)hyperlucency, and 4) bullous changes. Demographic characteristics,absolute and percent of predicted (%) values of forced expiratory volumein one second (FEV1), forced vital capacity (FVC), total lung capacity(TLC), residual volume (RV), single breath carbon monoxide diffusingcapacity (DLCO) and corrected for alveolar volume (DLCO/VA) werecorrelated with the CXR score. Data are presented as mean � SD.

RESULTS: Radiographic signs of emphysema (CXR score �1) wereseen in 67 patients (62%). Diaphragmatic flattening was the mostcommon (n�46; 68%), followed by bullous disease (n�40; 59%) and

retrosternal air (n�31; 46%). Patients with a CXR score �1 were older(63.5�10.3 vs. 58.1�11.1 years, p�0.01) and had more pack-years(48.5�20.8 vs. 36.7�18.9; p�0.01). Hyperinflation (increased TLC%),air-trapping (decreased FVC% and increased RV%) and gas exchange(decreased DLCO%) were all worse with increasing CXR scores asindicated in Table 1. A normal CXR score � 0 virtually excluded thepossibility of hyperinflation (negative predictive value � 0.98). In contrast,a CXR score �1 was a good marker of functional hyperinflation (increasedTLC% sensitivity � 0.96) and air trapping (increased RV/TLC% sensitiv-ity � 0.81) while a score �2 was highly specific indicator of air trappingand decreased DLCO% (positive predictive values of 0.93 and 0.83respectively).

CONCLUSION: The CXR score is an accurate predictor of the degreeof functional impairment in patients with COPD. A normal CXR scoreobviates the need to measure lung volumes.

CLINICAL IMPLICATIONS: Disagreement between the CXR scoreand results of PFTs in the patient with COPD should prompt a search fortechnical errors in measurement.

DISCLOSURE: Tarek Dernaika, None.

PATIENT-REPORTED SYMPTOMS OF CHRONIC OBSTRUC-TIVE PULMONARY DISEASE (COPD) IN CLINICAL TRIALSSteven Kesten MD* Shailendra Menjoge PhD Boehringer Ingelheim,Ridgefield, CT

PURPOSE: Several respiratory symptoms are associated with COPD.We sought to determine the symptom most frequently perceived bypatients to be the first symptom and the most troublesome of COPD andto identify patient characteristics associated with these perceptions.

METHODS: An evaluation of pooled data was conducted from threeclinical trials of tiotropium in COPD (205.264, 205.266, 205.284) in whichpatients reported the features of their disease at baseline. The trials hadcommon inclusion criteria (age �40 years, diagnosis of COPD, no historyof asthma, FEV1/FVC �70%, FEV1 �60 to 65% predicted, smoking �10pack-years). Data are expressed descriptively as means or proportions.

RESULTS: There were 2,678 patients. Dyspnea was the most com-monly reported first and most troublesome COPD symptom. In patientsalso reporting chronic bronchitis, the first symptom and most troublesomesymptom was dyspnea (71% and 86%, respectively) followed by cough(19% and 8%, respectively). In patients also reporting emphysema, thefirst symptom and most troublesome symptom was dyspnea (77% and90%, respectively) followed by cough (14% and 5%, respectively). Base-line data are displayed below according to the patient-reported first ormost troublesome symptom:.

CONCLUSION: Dyspnea is the first symptom and the most trouble-some symptom of COPD and is reported as such irrespective of demo-graphics and diagnoses of either chronic bronchitis and/or emphysema. Ingeneral, baseline demographic characteristics are unable to adequatelydistinguish which symptom patients will report as their most troublesome.

CLINICAL IMPLICATIONS: The focus of clinical research inCOPD should include evaluations of dyspnea as this appears to be the firstand most troublesome symptom to COPD patients with differing demo-graphic features.

Group

nml/min/mm Hg Dm

TLcoPred

Vcml

Normal subject 43 13.82�4.92 100.25�16.26 79.40�28.44COPD stage I 8 11.97�4.01 99.32�23.48 56.68�16.54COPD stage II 47 9.76�4.54** 69.39�19.43** 52.38�20.76**COPD stage III 34 8.26�3.27** 62.29�13.62** 45.13�18.29**COPD stage IV 6 4.74�1.66** 43.60�10.24** 53.62�34.64*Normal subject 43 13.82�4.92 100.25�16.26 79.40�28.44

* P�0.05 ** P�0.01 compared with normal subject group

Table 1

CXR Score

0 (n�41) 1 (n�27) 2 (n�22) � 3 (n�18)

FEV1 % 65�12a 51�8b 43�14 45�15FVC % 75�13.5c 70�13 64�16 60�18TLC % 96�10a 111�12 112�15 118�21RV % 125�25a 179�46 187�34 200�58RV/TLC % 44�8a 54�14d 60�9 65�8DLCO % 80�26a 73�29e 58�22 49�19

a� p � 0.05; 0 vs. 1, 2, 3; b� p � 0.05; 1 vs. 2; c� p � 0.05; 0 vs.2, 3; d� p � 0.05; 1 vs. 3; e� p� 0.05; 1 vs. 2,3




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DISCLOSURE: Steven Kesten, Employee S. Kesten and S. Menjogeare employees of Boehringer Ingelheim.; Grant monies (from industryrelated sources) Study 205.264 and 205.266 were funded by BoehringerIngelheim and Pfizer. Study 205.284 was funded by Boehringer In-gelheim.

RELATIONSHIP OF SPIROMETRY RESULTS AND REASONFOR MECHANICAL VENTILATION (MV) TO HOSPITAL SUR-VIVAL IN PATIENTS WITH CHRONIC OBSTRUCTIVE PULMO-NARY DISEASE (COPD)Thomas B. Zanders DO* David G. Bell MD Ethan E. Emmons MDBrooke Army Medical Center, San Antonio, TX

PURPOSE: In general, the mortality of COPD patients requiringhospital admission and MV is high. Many physicians rely on a patient’sspirometry results in guiding advance directive discussions and deter-mining prognosis. There is unclear data to support that pre-morbidspirometry helps predict outcomes in mechanically ventilated COPDpatients.

METHODS: We conducted a retrospective chart review of 33 admis-sions of 29 patients with COPD requiring MV for acute respiratory failure(ARF) for whom preadmission spirometry data was available. Additionaldata obtained included age, sex, comorbidities, outpatient therapies, andreason for MV. The primary outcome was in-hospital mortality.

RESULTS: Nineteen (58%) of the patients were male. The meanage was 69.2 years (range 56-85). There were 16 (49%) currentsmokers and 18 (55%) patients on home oxygen. The mean percentpredicted forced expiratory volume in one second (FEV1) was 44.1%and percent predicted forced vital capacity (FVC) was 53.6%. A COPDexacerbation necessitated MV in 51.5% of the admissions, pneumoniain 21.2%, cardiac reasons in 12.1%, and other etiologies in 15.2%.Overall in-hospital mortality was 21.2% (7 of 33). Survivors andnon-survivors had no statistically significant difference in preadmissionFEV1, FVC, or FEV1/FVC ratio values (Table 1). Multivariate analysisdemonstrated significantly lower in-hospital mortality for patientsintubated due to COPD exacerbations as compared to other etiologiesof ARF (Figure 1).

CONCLUSION: We conclude that pre-morbid spirometry data doesnot correlate to in-hospital mortality in COPD patients requiring MV forARF. It appears that patients with COPD requiring mechanical ventila-

tion for reasons other than a COPD exacerbation have a significantlyincreased risk of death.

CLINICAL IMPLICATIONS: Pre-morbid spirometry data does notappear to aide in discussions of advance directives or prognosis regardingthe use of MV in patients with COPD.

DISCLOSURE: Thomas Zanders, None.

MECHANISM OF EXPIRATORY CRACKLESRaymond L. Murphy MD* Andrey Vyshedskiy PhD Ruqayyah M.Alhashem BS Rozanne Paciej BS Margo Ebril Brigham and Women’s /Faulkner Hospitals, Boston, MA

PURPOSE: Crackles are intermittent explosive sounds that are asso-ciated with a number of pulmonary disorders including InterstitialPulmonary Fibrosis (IPF), Congestive Heart Failure (CHF), and Pneu-monia (Pn). The mechanism underlying expiratory crackles generation isnot very well understood. Some authors think that airway closing isresponsible for expiratory crackles. Others claim that intermittent airwayreopening during expiration is responsible for the crackling sounds. Thegoal of this research was to gain insights into crackle generation mecha-nism by systematic examination of the relationship between inspiratoryand expiratory crackle characteristics and by testing the crackle patterns,as recorded by multiple microphones, against the predictions of thestress-relaxation quadrupole crackle generation model as developed byFredberg and Holford.

METHODS: Fifty five patients with over 2 inspiratory crackles perbreath and over 2 expiratory crackles per breath were selected for thisstudy from a pool of nearly 1000 patients who were examined using amultichannel lung sound analyzer (Stethographics, STG1602). Cracklecharacteristics such as frequency, amplitude, transmission coefficient, andpolarity were calculated for each crackle.

RESULTS: The frequency, amplitude, and transmission coefficients ofexpiratory crackles were very similar to those of inspiratory crackles. Themajority of patients had predominantly positive polarity of inspiratorycrackles (98% of patients) and predominantly negative polarity of expira-tory crackles (81% of patients). Crackle polarity was also found to bedependent on the observation angle, consistent with predictions by thestress-relaxation quadrupole crackle generation model.

CONCLUSION: The reported findings are consistent with the hypoth-esis that expiratory crackles are caused by events that are identical inmechanism and opposite in direction to that of inspiratory crackles. Theexpiratory crackle data can be explained by the closing of airways duringexpiration in accordance with the stress-relaxation quadrupole cracklegeneration model.

CLINICAL IMPLICATIONS: While there are no immediate clinicalbenefits to knowing the mechanism of crackles, a clearer understanding ofthe mechanism of production of lung sounds offers the promise ofimproving noninvasive diagnosis of lung disorders.

DISCLOSURE: Raymond Murphy, Grant monies (from industryrelated sources) The research was supported in part by a grant fromStethographics, Inc.; Shareholder Dr. Murphy is founder and CMO ofStethographics, Inc.

First Symptom

% of total

DyspneaN�2033

75.9%

CoughN�40014.9%

WheezeN�113

4.2%

SputumN�431.6%

OtherN�893.3%

% women/% men 12/88 17/83 12/89 7/93 12/88FEV1 (L) 1.03 1.06 1.04 1.06 1.04FEV1 predicted (%) 36.0 37.9 36.6 12.0 13.1COPD duration (yrs) 10.9 12.4 12.6 12.9 13.2Former smoker (%) 69.7 63.0 65.5 67.4 73.0Smoking history

(pack-yrs)65.2 66.6 58.9 58.4 68.5

Most Troublesome Symptom

% of total

DyspneaN�2376

88.7%

CoughN�168

6.3%

WheezeN�461.7%

SputumN�602.2%

OtherN�281.0%

% women / % men 12/88 16/84 15/85 10/90 25/75FEV1 (L) 1.02 1.19 1.21 1.22 1.07FEV1 predicted (%) 35.7 42.1 42.0 42.8 37.9COPD duration (yrs) 11.3 11.0 14.1 11.5 9.6Former smoker (%) 70.0 54.2 50.0 66.7 67.9Smoking history

(pack-yrs)65.5 62.2 69.1 67.8 57.8




PROLONGATION OF THE EXPIRATORY PHASE IN CHRONICOBSTRUCTIVE LUNG DISEASERaymond L. Murphy MD* Andrey Vyshedskiy PhD Rozanne Paciej BSAnna Wong-Tse RN Dhirendra Bana MD Brigham and Women’s /Faulkner Hospitals, Boston, MA

PURPOSE: The expiratory phase of respiration is commonly describedas prolonged in patients with Chronic Obstructive Pulmonary Disease(COPD). The goal of this study was to quantify the degree of thisexpiratory sound prolongation in patients with COPD as compared tonormals.

METHODS: We studied 38 patients with COPD and 43 normals usinga multichannel lung sound analyzer (Stethographics, STG1602) as previ-ously reported. The ratio of the duration of inspiration to expiration (R1)was measured on the time-amplitude plots from the microphone placedover the trachea.

RESULTS: R1 averaged 0.67�0.16 in the COPD patients and0.83�0.16 in the normals (p�0.0001). The frequency distribution of R1 isshown in Figure 1. R1 equal to or less than 0.6 was observed in 39% ofCOPD patients, but only in 9% of normals. R1 equal to or less than 0.5was observed in 18% of COPD patients, but only in 2% of normals. Thesensitivity of R1 equal to or less than 0.6 was 0.39, the specificity was 0.91,and the positive predictive value was 0.79.

CONCLUSION: As expected a relatively prolonged expiratory phasewas more common in COPD than normals. Values of R1 less than 0.6were particularly more common in COPD than normals. However, low R1values were seen in some normals and relatively high values were seen insome COPD patients.

CLINICAL IMPLICATIONS: A simple test using a lung soundanalyzer that requires little patient cooperation can identify the presenceof prolonged expiration consistent with COPD. Although the test hasrelatively low sensitivity, the relatively high specificity can help guide theselection of patients for further evaluation.

DISCLOSURE: Raymond Murphy, Grant monies (from industryrelated sources) The research was supported in part by a grant fromStethographics, Inc.; Shareholder Dr. Murphy is founder and CMO ofStethographics, Inc.

USING DISTRIBUTION-BASED STANDARD ERROR OF MEA-SUREMENT (SEM) METHOD TO DETERMINE MINIMAL IM-PORTANT DIFFERENCE (MID) FOR THE SYMPTOM STATUSINDEX (SSI)Rohit D. Borker PhD* Michael Watkins PharmD Kate Knobil MDAmanda Emmett MS Chris Kalberg PhD GlaxoSmithKline, ResearchTriangle Park, NC

PURPOSE: To assess the minimal important difference (MID) of theSymptom Status Index (SSI) using the distribution-based standard errorof measurement (SEM) method.

METHODS: The SSI is a diary-based index comprised of 4 VAS items:shortness of breath, tiredness, activity limitation, and frustration withsymptoms. It has been shown to be a reliable, valid, and a responsive toolin COPD population. Individual item scores are summed to obtain theSSI total score. Patients record the severity of their symptom status on a0mm (none/not at all) to 100mm (worst it has ever been/as bad as it canbe) VAS. The SEM method was used to determine the MID because ofits sample independent properties. This results from simultaneous incor-poration of sample reliability and variability in its determination. The

one-SEM criterion has been shown to represent MID and was used in thisanalysis as MID criterion. Data from 3 sets of twin trials (Study sets A, B,& C) in patients with COPD was used in this analysis. Internal consistencyreliability (Cronbach’s �) and the standard deviation of the summated SSIscores, which are required for computation of the SEM, were determinedfor the SSI.

RESULTS: SEM based MID for SSI based on 3 study sets areillustrated in the Table.

CONCLUSION: Consistent results across the 3 sets of trials point toabout 5 to 6 unit change on the SSI (0 to 100 scale) as MID.

CLINICAL IMPLICATIONS: Once this MID has been validatedusing different approaches, it can serve as an useful anchor to assessmeaningful changes in patient’s symptom status.

DISCLOSURE: Rohit Borker, Employee GlaxoSmithKline

FACTORS THAT REFLECT CLINICAL STABILITY OF COPDPATIENTSJee-Hong Yoo MD* Myung Jae Park MD Hong Mo Kang MD Kyung HeeUniversity Medical Center, Seoul, South Korea

PURPOSE: Chronic obstructive pulmonary diseases (COPD) is one ofthe leading cause of death and is increasing in incidence. The forcedexpiratory volume in one second (FEV1) is usually used to grade theclinical severity of COPD. However, assessment of functional capacity isalso important to understand clinical state of patients. The aim of thisstudy was thus to retrospectively examine what factors reflects clinicalstability in patients with COPD.

METHODS: Twenty-six patients with COPD volunteered and com-pleted the test sequence, which included pulmonary function tests,6-minute walk distance (6-MWD), complete blood count, blood chemis-try, blood pressure, and body mass index. The patients were divided intotwo groups, stable and unstable group, according to the presence of acuteexacerbation history during last one year. After dividing, we retrospec-tively validated factors that reflect clinical stability of patients.

RESULTS: At presentation, Mean age of 26 patients was 65.3 � 9.0years (mean � SD). Sixteen patients were included in stable group and 10patients in unstable group. FEV1 was 63.3 � 20.6% for stable group and46.9 � 9.4 for unstable group (p�0.02). Mean 6-MWD was 461.9 � 88.3meter and 298.0 � 72.1 meter respectively (p�0.01). The number ofpatients in each stage based on Global Initiative of Obstructive LungDiseases (GOLD) showed significant difference between two groups(p�0.03) and number of patients who walked more than 400 meter was 13out of 16 for stable group and no one for unstable group (p�0.001).6-MWD and stage of COPD showed significant correlation (p�0.01).

CONCLUSION: 6-MWD, a simple test to evaluate clinical status,showed significant correlation with GOLD stage of COPD. Multidimen-sional approach should be done to evaluate clinical stability.

CLINICAL IMPLICATIONS: For the evaluation of severity ofCOPD, not only the degree of airflow limitation but also functional statussuch as 6-MWD should be included.

DISCLOSURE: Jee-Hong Yoo, None.

WORLD COPD DAY EXPERIENCE IN ZONGULDAK PROV-INCE OF TURKEYMeltem M. Tor MD* Tacettin Ornek MD Hakan Tanriverdi MDMuhammed E. Akkoyunlu MD Yalcin Dutkun MD Zonguldak KaraelmasUniversity Hospital Department of Pulmonary Medicine, Zonguldak,Turkey

PURPOSE: Chronic Obstructive Pulmonary Disease (COPD) is animportant public health problem both in developed and developingcountries. In Turkey too, COPD is an important lung health burden.Public education and early diagnosis are crucial in the prevention ofCOPD.We hereby present the results of our “World COPD Day”

Study SetsSSI Mean

(SD)rxx

(Cronbach’s �) 1-SEM

Study set A (SCO40011 & 12) 50.82(16.93) 0.910 5.08Study set B (SMS40314 & 15) 58.07(14.08) 0.858 5.31Study set C (SMS40320 & 21) 52.10(17.01) 0.906 5.21




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experience in the spirometry tent built in Zonguldak city center (popula-tion: 115000)on this occasion on 17 November 2004.

METHODS: On World COPD Day, 305 persons over 18 years of age( 197 males and 108 females, mean age 41.7�11.97(18-82), %38.7smokers, %17.4 exsmokers, %43.9 nonsmokers) underwent spirometricanalysis.

RESULTS: Of 305 persons, 28 (9.2%) had FEV1/FVC below 70%, and26 of 28 had %pred FEV1 below 80%. Overall, 52 (17%) had %predFEV1 below 80%. Of 174 persons who were above 40 years of age, 14(8%) had FEV1/FVC below 70%, and 13(7,4%) had %pred FEV1 below80%. Of 14 with diagnosed with airway obstruction , spirometric analysisrevealed %pred FEV1 �80% in one(7%), between 50 and 80% innine(%64), and below 50% in four(%29). At the end of this activity, 9.2%of adult population tested (age�18) and 8% of tested population above 40years of age had airway obstruction.Tested population with a confirmedCOPD had been referred to hospitals.

CONCLUSION: In conclusion, obstructive pulmonary diseases in-cluding COPD are prevalent in central Zonguldak province.

CLINICAL IMPLICATIONS: Wide scale epidemiologic studies areneeded to reveal the real problem in this polluted region of Turkey.

DISCLOSURE: Meltem Tor, None.

COPD Non-Pharmacologic Treatment andOutcomes12:30 PM - 2:00 PM

UTILITY OF A HIGH-FREQUENCY CHEST WALL OSCILLA-TION (HFCWO) TRIAL PERIOD TO ASSESS TREATMENT SAT-ISFACTION, ADHERENCE AND BENEFIT IN PATIENTS WITHCOPDDiane L. Kachel BA* Cynthia S. Davey MS Timothy C. Kennedy MDVictor L. Marchione MD Mark W. Rolfe MD Mark J. Rumbak MDHill-Rom, St Paul, MN

PURPOSE: To evaluate the utility of a short-term therapy trial toassess individual use and potential benefit of HFCWO in patients withCOPD prior to extending therapy for long-term use.

METHODS: Consenting patients with COPD, FEV1%�70%, re-tained secretions, dyspnea and reduced physical functioning were trainedto use an HFCWO airway clearance device twice daily at home (N�94, 3centers). Medical history, physical exam, spirometry, dyspnea, functionalcapacity, and quality of life (QOL) assessments were taken at baseline andafter 90-days of therapy. Periodic symptom assessments and treatmentsatisfaction/adherence data were also collected.

RESULTS: Patients with moderate to severe COPD that completedthe trial demonstrated improvements in symptoms, 6-min walk distance(6-MWD, p�0.001) and role-physical domain (SF-36, p�0.004). Analysisof inter-group differences between patients who continued or discontin-ued HFCWO after trial completion indicated a higher, sustained level oftreatment satisfaction and adherence within the group that continuedHFCWO long-term. Improvements in dyspnea (Borg, p�0.009; BDI/TDI, p�0.003), 6-MWD (p�0.001) and QOL (general health, vitality andphysical functioning, p�0.05) were also significantly higher. Compared tobaseline, a clinically significant improvement in 6-MWD (182�34 ftfurther) was demonstrated. Patients with moderate COPD demonstratedgreater improvements in functional capacity after 90 days of HFCWOtherapy than those with severe disease. Baseline predictors of success forspecific outcomes are being assessed.

CONCLUSION: In this prospective, cohort study, COPD patientscompleting a 90-day trial of HFCWO demonstrated improvements insymptoms, functional capacity and QOL. Patients who did not perceivetreatment benefit were less adherent and more likely to discontinue.Patients who reported a higher level of treatment tolerance and effective-ness within the first week were more likely to demonstrate significantimprovements after 90 days of therapy.

CLINICAL IMPLICATIONS: Select patients with COPD adherewell to daily HFCWO therapy and may benefit from regular airwayclearance therapy. A HFCWO therapy trial can help identify patients whoare more likely to be adherent and satisfied with this therapy. Improve-

ments in functional capacity and QOL may warrant consideration forlong-term use.

DISCLOSURE: Diane Kachel, None.

CHEST PHYSIOTHERAPY CHANGED VENTILATORY ME-CHANICS IN PATIENTS WITH SEVERE COPDKayomi Matsumoto MS* Hajime Kurosawa MD Yuko Sano MS NaokiMori MS Yoko Goto PhD Masahiro Kohzuki MD Tohoku. Univ. Grad.Sch. of Med. Dep. of Int. Med. and Rehab., Sendai, Miyagi, Japan

PURPOSE: As one of chest physiotherapy (CPT) techniques, manualstretching of intercostal and other respiration related muscles to mobilizethoracic cage had been frequently performed in patients with airflowlimitation, especially in Japan. Purpose of those techniques is supposed toimprove chest flexibility and alleviate dyspnea. To examine hypothesis thatCPT techniques in patients with chronic obstructive pulmonary disease(COPD) may change the mechanical properties of the chest.

METHODS: Eight patients with COPD (mean age: 67.0 � 4.4 years,M:F�8:0) were studied. We performed physiological measurements includingspirometry, oxygen consumption during quiet breathing at sitting position (VO2),maximal voluntary ventilation (MVV), and maximal inspiratory and expiratorypressures (MIP, MEP). Thoracic gas volume and specific airway conductance(sGaw) were also measured using body plethysmography. After those baselinemeasurements, the CPT described above including manual breathing supporttechniques were performed for about total 40 minutes. Immediately after theCPT, pulmonary function tests were repeated.

RESULTS: Inspiratory capacity (IC) and vital capacity (VC) signifi-cantly increased (p�0.05, p�0.01). Forced expiratory volume in 1 second(FEV1) was unchanged. Functional residual capacity (FRC) and residualvolume (RV) significantly decreased (p�0.01) after CPT. Both sGaw andVO2 were tended to decrease, but it could not reach to the statisticsignificance. MEP, MIP, and MVV were not significantly change.

CONCLUSION: After CPT, lung volume decreased, and IC increasedin patients with COPD.

CLINICAL IMPLICATIONS: Decreased lung volume and increasedIC by CPT possibly contribute to improve breathlessness in patients withCOPD. Further research is needed to elucidate how long this effects last.

DISCLOSURE: Kayomi Matsumoto, None.

SELF-MANAGEMENT EDUCATION PROGRAM FOR PA-TIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DIS-EASE HAS LONG TERM EFFECT ON QUALITY OF LIFEIMPROVEMENTManon Labrecque MD* Khalil Raby PhD Marcel Julien MD HopitalSacre-Coeur, Montreal, PQ, Canada

PURPOSE: Purpose of this study was to investigate the effects onhealth related quality of life (HRQoL), and disease knowledge’s of aSelf-management education programme(SMEP) for patients with chronicobstructive pulmonary disease (COPD).

METHODS: The programme lasted 4 weeks (3 hours/week) andincluded teaching of how to use an action plan for self-treatment ofexacerbations.Patients were evaluated at time 0 , at 3 months and 12months. 61 COPD with a mean age of 70(53-84)and FEV1 48.8% ofthe predicted(SD:18.2%) that was stable on a standard medicalregimen. OUTCOME MEASURES: The SF-36 Quality of Life Ques-tionnaire (SF-36), St George’s Respiratory Questionnaire (SGRQ) anda Disease Knowledge’s Questionnaire (DKQ) based on the teachingprogramme .

RESULTS: SGRQ total scores and domain scores were all lower(indicating a better HRQoL) 3 months, and 12 months after the pro-gramme comparing to before. These differences reach clinical significancefor the SGRQ impact domain who was at (35.2�17.2) at time 0 ,(28.2�19) at 3 months (P� .001) and (24.2�17.8) at 12 months (P�.001).For the SGRQ total score the value was (44.1�17.0) before, (39.8�15.3)at 3 months (p� 0.006) and (35�17.4) at 12 months (p�.001). For theSF-36, physical activity domain showed no significant difference;(33.8�8.6) before , (35.7�9.4) at 3 months and (36.8�11.3) at 12 months(NS). Psychological domain resulted in a score of (45.3�11.6) before , (50.8 �10.7) at 3 months ( P�.003) and (49.5�11.3) at 12 months (P�.03)Concerning the DKQ, the pre- programme score was (59.4 %�11.4),(73.6%�13.4)(P�0.0001) at one month and 74.5�15.5 at 12months,(P�0.0001).




CONCLUSION: A(SMEP) significantly improved HRQoL in COPDpatients probably by increasing patients’ knowledge of disease and hencetheir ability to manage themselves. The Improvement in HRQoL last atleast one year.

CLINICAL IMPLICATIONS: This approach of care is interestingbecause it does not require specialized resources and could easily beimplemented within normal practice by health professionals.The presentstudy supports its use as an integral part of the long-terme care of patientswith COPD.

DISCLOSURE: Manon Labrecque, None.

EFFECTIVENESS OF A REHABILITATION PROGRAM INMORBIDLY OBESE SUBJECTS WITH SLEEP DISTURBANCIESSasa Lucic MD Francesco Prato MD Daniela Lugli BSc Barbara SerriRRT Giuseppe Cirelli MD Manuela Nobile BSc Enrico M. Clini MD*Fondazione Villa Pineta, University of Modena, Pavullo (MO), Italy

PURPOSE: To assess the clinical effectiveness of a hospital-basedmultidisciplinary rehabilitation program (MRP), in a selected populationof morbidly obese subjects.

METHODS: An observational study was undertaken in a population of59 morbidly obese patients (18 M, 60�10 years, BMI 47�8) withdisability and sleep disturbancies (Epworth scale score �6). Assessmentand correction of OSAS, improvement of exercise tolerance, body weigthand associated psychological features were aims of this MRP. Calibrateddietary intake, twice daily sessions of moderate intensity exercising, twiceweekly sessions of psychotherapy have been carried out over 1 month.Polisomnographic assessment and correction of apnea/hypopnea index(AHI) have been performed according to the current guidelines. Lungfunctions, AHI, 6-minute walked distance (6MWD), boby weight (BW),serum metabolic data (cholesterol, triglicerides, uric acid and glicatehaemoglobin), and the quality of life by means of the Sat-P questionnairehave been recorded baseline (T0), at the end (T1) and 6 months after (T2)the MRP.

RESULTS: Overall, PaO2 improved over time (p�0.01), whereas AHIreduced at T1 and then remained stable at T2; in particular, thepercentage of patients with AHI�10 declined (from 65% at T0 to 20% atT1 and T2), despite 14 obese with AHI�20 were prescribed to havenCPAP at T1. At T1, 6MWD and BW significantly improved (p�0.005)and then maintained at T2; a significant relationship (r� 0.379, p�0.01)has been found between changes of BW and 6MWD (recorded inbetween T0 and T2). Sat-P item scores dealing with sleep efficiency,problem solving, and social interactions improved (p�0.01) at T1 andthen maintained at T2.

CONCLUSION: This conservative intervention provides useful shortand long-term benefits in morbidly obese subjects with disability andsleep disturbancies.

CLINICAL IMPLICATIONS: Comprehensive and multidisciplinaryrehabilitation could be a useful medical approach in the long-termmanagement of severely disabled morbidly obese subjects.

DISCLOSURE: Enrico Clini, None.

DOES COPD DISEASE STATE EDUCATION BY A HOMECAREPROVIDER [RESPIRATORY THERAPIST] AND EARLY IDENTI-FICATION OF NEED FOR LONG-TERM OXYGEN THERAPY(LTOT) REDUCE RELAPSES OF EARLY STAGE COPD PA-TIENTS? A MEASUREMENT OF SHORT-TERM CHANGES INDYSPNEA AND DISEASEVernon R. Pertelle RRT* James Dudley RRT Apria Healthcare, LakeForrest, CA

PURPOSE: We evaluated patients with COPD who were prescribedaerosolized respiratory medications; administered by homecare pro-vider to determine if assessment and education by homecare respira-tory therapist (RT)could decrease emergency room (ER) visits andhospitalization by identifying their need for LTOT before a relapse.

METHODS: Patients were evaluated retrospectively following win-ter months from April 2003 to April 2004. Inclusion criteria: (1)diagnosis of COPD, (2) chronic airflow obstruction (evidenced byCOPD diagnosis), (3) age �/� 65, (4) education by homecare RT (5)receiving LTOT. Patients recieved oximetry at rest, activity, noctur-

nally; nutritional status and activities of daily living assessed; LTOTbased on qualification by an independent testing facility (IDTF). Atotal of N�56 from a database of N�238 completed the chronicrespiratory disease index questionnaire (CRQ) and the transitionaldyspnea index (TDI) via phone interview upon entry into the programand again within 6 months to determine if they experienced a relapse(urgent hospital revisit within 6 months because of an acute exacer-bation).

RESULTS: Patients who did not relapse (n � 49) showed moderate-to-large improvements in disease-specific QOL across all four CRQdomains (p � 0.001) large positive changes in TDI (p � 0.0001). Patientswith a relapse (n � 7) did not have improved CRQ or TDI scores (p �0.02). Changes in the CRQ dyspnea score and TDI correlated with eachother (r � 0.78; p � 0.0001). A control of N�5 with COPD whoparticipated in the program and not prescribed LTOT showed no changesin the CRQ or TDI over 6 months.

CONCLUSION: The outcomes and magnitude of change in CRQ andTDI scores were correlated. Outpatients treated for a COPD exacerbationwith aerosolized medications and education with early identification ofneed for LTOT by a homecare RT experience significant short-termimprovements in QOL and dyspnea.

CLINICAL IMPLICATIONS: The use of a homecare RT for outpa-tient assessment and education of COPD patients can aid to identify theneed for LTOT early to prevent rehospitalization following acute exacer-bation.

DISCLOSURE: Vernon Pertelle, None.

IMPROVEMENT IN PHYSICAL PERFORMANCE COINCIDESWITH IMPROVEMENT IN ACTIVITIES OF DAILY LIVING PER-FORMANCE FOLLOWING PULMONARY REHABILITATIONMary K. Hart RRT* Cheri A. Duncan RRT Lucy A. Aguirre-Kelley BSAna M. Lotshaw MS Mark W. Millard MD Baylor Universtiy MedicalCenter, Dallas, TX

PURPOSE: Pulmonary rehabilitation (PR) has traditionally focused onimproving patient endurance and strength, in which outcomes are easilymeasured. However, documenting objective improvement in an individ-ual’s ability to perform activities of daily living (ADL) following PR has notbeen well established, despite the obvious utility of such a demonstration.We developed an observational functional assessment tool with threeprogressively more difficult levels of ADL tasks to evaluate ADL perfor-mance in patients with chronic lung disease. The purpose of this study wasto determine if improvements found in ADL performance following PRcoincided with concurrent improvements in physical performance.

METHODS: A retrospective chart review was performed for PRparticipants from 2003-2004. Thirty six patients who had participated ineither a land or water-based PR program and in whom data wascompletely available were included in this study. Charts were reviewed fordata on physical performance and observed ADL performance. The datawas analyzed with repeated measures, MANOVA, univariate analysis anda Wilcoxin Signed Ranks test.

RESULTS: Both land and water-based exercise PR participants dem-onstrated similar improvements in physical performance as measured bychanges in six minute walk test distance and six repetition maximumstrength tests for the shoulder, knee, and hip (p�.05). These improve-ments were mirrored by significant increases in observed ADL taskperformance measured across all three levels of tasks (p�.05).

CONCLUSION: The assessment tool developed at our facility wasfound to be effective in measuring changes in patient ADL performancefollowing PR. Both physical and ADL performance can now be demon-strated to improve after PR.

CLINICAL IMPLICATIONS: Usually, ADL function is obtained throughself-reporting patient questionnaires. The ADL assessment tool developed by ourfacility provides an objective measurement of ADL performance.

DISCLOSURE: Mary Hart, None.

TOLERANCE AND QUALITY OF LIFE IMPROVEMENT FOLLOW-ING AEROBIC AND STRENGTH TRAINING EXERCISE IN PA-TIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASEOgee Mer A. Panlaqui MD* Teresita O. Aquino MD Celestino S. DalisayMD Veterans Memorial Medical Center, Quezon City, Philippines

PURPOSE: To determine the efficacy of aerobic combined withstrength training exercise in the improvement of exercise tolerance and


COPD Non-Pharmacologic Treatment andOutcomes, continued


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quality of life of mild and moderate chronic obstructive pulmonarydiseases (COPD) patients.

METHODS: The study was conducted at the Pulmonary Rehabilita-tion Unit of Veterans Memorial Medical Center. Inclusions are (1)physician diagnosed COPD based on smoking history, cough of 3 monthsin 2 consecutive years (2) pulmonary function test compatible with COPD(i.e. FEV 1/FVC ratio of less than 70% and bronchodilator response lessthan 15%) (3) stable patients at the time of entry (4) patients havingexercise limitation manifested as shortness of breath or general fatigue.Exclusion criteria are clinical evidence of cardiovascular or neuromusculardiseases.

RESULTS: Nine patients completed the exercise program. Mean ageis 71 �/- 7, with seven males and 2 females. Pre-training lung functionstudies showed mild to moderate airflow obstruction. Anthropometricmeasurements revealed normal body mass indexes. There were significantincrease in the right arm and left thigh circumference with meandifference of 1.3cm �/- 0.32cm and 1.14 cm �/- 0.28 respectively. Therewas marginal improvement in lung function which is not significant. Sixminute walk test improved to 631 m �/- 148 m with significant meandifference of 218 meters post exercise training. Improvement in thequality of life showed significant change in the grading of patients frommoderate grade to no impairment at all in performing their activities ofdaily living.

CONCLUSION: Aerobic combined with strength training exerciseimproved patients exercise capacity and tolerance as shown by the changein the six minute walk test and increase in the upper arm extremitycircumference. No improvement seen in the pulmonary function test.Thegreatest benefit is the improvement in the baseline dyspnea index ofpatients during and after the exercise program.

CLINICAL IMPLICATIONS: Chronic obstructive pulmonary dis-ease patients can benefit from this combined exercise program. Patientscould perform daily activities and even help their households which is asignificant reversal from their dependency for care.

DISCLOSURE: Ogee Mer Panlaqui, None.

EFFECTS OF PULMONARY REHABILITATION ON EXACER-BATION RATE, HOSPITALIZATIONS, LENGTH OF HOSPITALSTAY AND PUBLIC HEALTH ECONOMICS IN PATIENTS WITHMODERATE-TO-SEVERE CHRONIC OBSTRUCTIVE PULMO-NARY DISEASEEpaminondas N. Kosmas MD* Helen Vey RPh Maria-Konstantina Frag-gou MD Irene Papaneofytou MD Zoi Athanassa MD Antonia KoutsoukouMD Ioannis Vogiatzis PhD Olga Georgiadou MS Nikolaos Koulouris MDDora Orfanidou MD Charis Roussos MD Pulmonary Rehabilitation Unit,Sotiria Chest Diseases Hospital, Athens, Greece

PURPOSE: Chronic obstructive pulmonary disease (COPD) exacerba-tions are a significant cause of morbidity and mortality and with asubstantially high cost worldwide. The objective of this study was toevaluate the impact of pulmonary rehabilitation (PR) on the exacerbationrate and on the frequency and duration of hospitalizations in patients withCOPD. A secondary aim was to estimate the annual cost savings/patient ofPR with respect to hospitalizations.

METHODS: We studied 32 ex-smoking patients (age 62�7 years) withmoderate-to-severe COPD (FEV1 38�6 %pred). Patients participated ina 12-week (36-session) program of PR consisting of education, nutritionalintervention, physiotherapy, exercise and psychologic support. They com-pleted a questionnaire for the previous year to assess the exacerbationswhile their emergency visits, admissions and length of hospital stay werefound from the hospital records. Patients were followed for the year afterPR with both scheduled and emergency visits and with telephonecontacts.

RESULTS: The total annual number of exacerbations reduced from112 pre-PR (3.5/patient) to 88 post-PR (2.8/patient)while the emer-gency visits decreased from 89 (2.8/patient) to 70 (2.2/patient). Thesignificant decreases were found in hospitalizations (from 54 or1.7/patient to 35 or 1.1/patient; p�0.05) and in hospital stay (from 648days or 20.2/patient to 357 days or 11.2/patient; p�0.01). Consideringthe costs of PR program and of hospital days, the overall result is thatthe cost-savings for the 32 patients amounted to 9627 € (300 €/patientin approximation).

CONCLUSION: A comprehensive pulmonary rehabilitation programresults to a significant reduction in frequency and duration of hospitaliza-tions in patients with moderate-to-severe COPD. There is also a trend

towards reducing the annual number of exacerbations and the emergencyhospital visits.

CLINICAL IMPLICATIONS: These effects of pulmonary rehabili-tation are very important, given that hospitalizations, among other detri-mental effects, are an important factor of impairment in health-relatedquality of life and the principal source of increasing direct costs of COPD.Our results justify the need for reimbursement of rehabilitation programsfor COPD patients by our National Public Health System.

DISCLOSURE: Epaminondas Kosmas, None.

A RANDOMIZED TRIAL OF STRATEGIES FOR ASSESSING ELI-GIBILITY FOR LONG-TERM DOMICILIARY OXYGEN THERAPYGordon H. Guyatt MD Mika L. Nonoyama RRT* Christina Lacchetti RonGoeree MA Diane Heels-Ansdell MS Roger Goldstein MB, ChB Respi-ratory Diagnostics & Evaluation Service, West Park Healthcare Centre,Toronto, ON, Canada

PURPOSE: To determine the impact of alternative strategies forassessing eligibility for domiciliary oxygen on funded oxygen use, quality oflife, and costs.

METHODS: Randomized controlled trial involving applicants for aGovernment sponsored home oxygen program (HOP). Comparisonswere an assessment system that relied on data collected and submittedby oxygen providers at the time of application and judgements by HOPpersonnel (conventional assessment) versus a system of data collectionby a respiratory therapist that included, in patients unstable at the timeof initial assessment, a repeat assessment after two months of stability,with judgements by the RT and a respiratory specialist (alternativeassessment). Main outcome measures included use of funded domicil-iary oxygen; quality of life; mortality; costs to the health care system.

RESULTS: 276 applicants were allocated to the conventional armand 270 to the alternative assessment. In the year following applica-tion, oxygen use was appreciably lower in the alternative arm with nobetween group differences in mortality, quality of life or resource usein the community. Although alternative assessment applicants had onaverage higher assessment costs by $155 per applicant, these costswere more than offset by decreased HOP costs of $596 per applicant.

CONCLUSION: Reassessment of applicants for domiciliary oxygenafter several months of stability identifies an appreciable portion ofinitially eligible patients who are no longer eligible, thus reducing programcosts to public funders without adverse consequences on quality of life,mortality, or other resource use.

CLINICAL IMPLICATIONS: Limiting assessment of patients for eligibilityfor long-term oxygen to the period immediately following an exacerbation willlead to many patients receiving long-term oxygen in whom the benefit isuncertain. Many patients improve, physiologically and with respect to their qualityof life, over the first three months following an exacerbation, and an appreciableadditional group improve further between 3 months and one year. Optimizingoxygen use requires that the patients be reassessed, both at 3 months and atapproximately one year after commencing oxygen.




DISCLOSURE: Mika Nonoyama, None.

VOLUME-REDUCING SURGERY FOR DIFFUSE EMPHYSEMA:EFFECT OF WAITING WITH OPERATIONGunnar N. Hillerdal MD* Kerstin Strom MD Karolinska Hospital,Stockholm, Sweden

PURPOSE: Volume-reducing surgery for diffuse emphysema: effect ofwaiting with operation.

METHODS: A Swedish study on Volume-reducing Surgery in diffuseEmphysema(EVRS)was performed during 1997 to 2000. Patients fulfillingstrict criteria and having participated in a training program were random-ized to either operation (Surgical Group, SG) or to continued training forone year (TG). After this year, patients in TG were offered surgeryprovided they were still fulfilling the criteria. 53 patients were randomizedto each group, and the results showed a significant improvement inHealth-related Quality of Life (QoL) and also lung function in the surgicalgroup (Article in Press). In the TG, after the first year, surgery wasperformed in 32 patients. We compared the results with those who wereoperated in the SG.

RESULTS: The QoL and Lung function was the same in both SG andTG at start (Total Score St Georges Respiratory Questionnaire 59; SF-36Physical function 22.2 and 22.9, respectively; FEV1 per cent predicted 26and 27, respectively, and RV % predicted 255 and 267, respectively).There were large improvements in the SG in these figures after 3 and 6months which then had a tendency to worsen again but at 1 year therewere still significant differences between the groups. After surgery in thetraining group, these patients also improved , but no to the same extent ashad those in the SG after their operation; and at two years afterrandomization, the patients in the SG and those in the TG who had beenoperated one year later had only non-significant differences both in QoLand lung function, but with a tendency to worse figures in the TG.

CONCLUSION: It seems that surgery should be performed early oncethe patient fulfills the criteria since this gives the patient a longer relief.

CLINICAL IMPLICATIONS: Of importance when deciding onoperation or postponing possible surgery.

DISCLOSURE: Gunnar Hillerdal, None.

QUALITY OF LIFE FOR 5 YEARS AFTER LUNG VOLUMEREDUCTION SURGERY IN PATIENTS WITH SEVERE COPDYoko Goto PhD* Hajime Kurosawa MD Nobuyoshi Mori MD MasahiroKohzuki MD Department of Occupational Therapy, School of HealthSciences, Sapporo Medical U, Sapporo, Japan

PURPOSE: Chronic obstructive pulmonary disease (COPD) ischaracterized by progressive airflow limitation leading to disability.Patients with severe COPD suffer from dyspnea, which can subse-quently cause a difficulty in performing routine activities of daily livingand affect their quality of life (QOL). Lung volume reduction surgery(LVRS) has been reported to be an effective treatment modality forselected patients with advanced COPD to improve pulmonary func-tion, lung mechanics, exercise tolerance, and dyspnea. However, thelong-term effects of LVRS on QOL and psychological states such asanxiety and depression have not been fully elucidated. We evaluatedQOL and psychological state before and after LVRS in patients withsevere COPD for 5 years.

METHODS: Eleven patients with severe COPD (Age: 66.1�5.9, VC:2.3�0.7L, FEV1: 0.75�0.21L, RV:4.5�1.0L) who underwent LVRS werestudied. QOL was assessed by Sickness Impact Profile (SIP). Psycholog-ical states (anxiety, depression) were measured by using the State TraitAnxiety (STAI) and the Self-Rating Questionnaire for Depression (SRQ-D). Serial measurements of QOL and psychological state were donebefore and 3, 12, 24, 36 and 60 months after LVRS.

RESULTS: The best scores in SIP were obtained at 36 months afterLVRS. Especially, physical-SIP scores at 12, 24, 36 months reached tonormal range. However, psychosocial-SIP score at 60 months was worsethan pre-LVRS. As for psychological state scores, STAI scores did notshow significant changes during 36 months, and indicated in the range ofhigh anxiety at 60 months after LVRS. The SRQ-D scores have been inthe suspected level of depression for 60 months.

CONCLUSION: It is difficult to maintain the beneficial effect ofLVRS on psychosocial QOL and psychological states up to 5 years.

CLINICAL IMPLICATIONS: It is important to evaluate not onlyphysiological functions but also psychological changes, when the totaloutcome should be assessed to determine the long-term benefit of LVRS.

DISCLOSURE: Yoko Goto, None.

COPARATIVE STUDY OF MANAGEMENT OF CHRONIC OB-STRUCTIVE PULMONARY DISEASE (COPD) AS PER GLOBALINITIATIVE ON OBSTUVTIVE LUNG DISEASE (GOLD)GUIDELINES AND ALTERNATE SYMPTOMS/DYSPNEABASED STRATEGYJai Kishan MD* Ashish Chawla MBBS Bal K. Kapoor MD TB & ChestDept/Hospital Govt. Medical College, Patiala, India

PURPOSE: GOLD guidelines emphasize the need of spirometery fordiagnosis and management of COPD.However, in developing countrieswho share the major burden of COPD spirometery is not universallyavailable hence an alternate strategy avoiding spirometery need to bedeveloped.

METHODS: 50 patients each in Group A & B were studied. Group Awere classified on spirometery and managed managed as per GOLDguidelines and Group B graded on symptoms/dyspnea based approach. Acomparision made of outcome measures like exacerbations,hospital visits/hosptallizaion.Group B was classified acording to no dyspnea, dyspnea onunaccustomed exercise, on accustomed exercise,on normal routines of lifeor on lying in the bed and also on basis of cyanosis, oedema feet or CCF.

RESULTS: Exacerbtion were equal (16%)in both the groups.12% ofGroup A & 16% of Group B patients were lost to folow up.Time forsymptomatic imrovement was delayed in Group B but was not statiticallysignificant.Patients when classified according to alternate strategy werefalling in lower grade of spirometery based Gold guidelines and thusreceived lower grade of treatment.

CONCLUSION: COPD can be graded and managed according tosymptoms/dyspnea based approach. Even GOLD guidelines based man-agement shoul be validated thoroughly.

CLINICAL IMPLICATIONS: In resource poor countries symptoms/dyspnea based COPD management can be employed.

DISCLOSURE: Jai Kishan, None.

Table: Cost analysis comparing alternative andconventional assessment process, by type of health

care expense, Canadian costing.

Alternative

Assessment

Conventional

Assessment Difference

Assessment and

Appeal Costs

$168 $13 $155

● HOP Coordinator

● Respirologist

● Resp. Therapist

● Secretary

● Travel Blood Gas

n/a

20

126

�1

6

16

4

n/a

n/a

n/a

n/a

9

HOP Oxygen Costs $2,501 $3,097 ($596) 95% CI

(-903,-291) p�0.0002

Health Care Follow-up Costs

● Hospitalizations

● GP visits

● Specialist Visits

● Emergency Room

● Clinic Visits

● Tests/procedures

● Other Professionals

$2,958

2090

263

136

44

10

193

222

$2,871

2158

273

118

36

5

121

160

$87

95% CI

(-1477, 1651)

p�0.94

Total Cost $5,627 $5,982 ($355) 95% CI

(-1968, 1259) p�.66




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GASTRO ESOPHAGEAL REFLUX SYMPTOMS IN PATIENTSWITH CHRONIC RESPIRATORY FAILURE DUE TO CHRONICOBSTRUCTIVE PULMONARY DISEASESnezana V. Raljevic MD* Marija M. Mitic-Milikic PhD LjudmilaNagorni-Obradovic PhD Institute for Pulmonary Diseases and TB,Belgrade, Serbia

PURPOSE: Gastro Esophageal Reflux (GER) is well described inpatients with Asthma and Chronic Obstructive Pulmonary Disease(COPD). The purpose of this study was to determine prevalence of GERsymptoms among patients with Chronic Respiratory failure (CRF) due toCOPD.

METHODS: The study included two groups of patients: Group I: 70patients with COPD and CRF and Group II: 50 patients with COPD andAcute Respiratory Failure (ARF). All patients were treated for exacerba-tion at Institute for pulmonary diseases in Belgrade. Pulmonary functiontests (PFT) and blood gas analysis (BGA) were performed in all patients.After collecting basic demographic and habit information, all patientsfilled out Mayo Clinic Gastro Esophageal Reflux Questionnaire.

RESULTS: In group I was 48 male and 22 female mean age 61�5years. PFT results were: FEV1 36�10%, FEV1/FVC 42�8%. BGAanalysis: PO2 6.8�10 Kpa, PCO2 8.1 �4Kpa, Sat 85�8%. In group II was35 male and 15 female, mean age 54 � 8 years. PFT results were FEV149�3.2%, FEV1/FVC 48�10%. BGA analysis were: PO2 7.1�5.5Kpa,PCO2 6.9�2Kpa, Sat 89�11%. GER symptoms in group I vs. group IIwere: acid regurgitation (68% vs. 55%), dysphagia (30% vs.19%), heart-burn (81% vs.70%), chronic cough (71% vs. 67%) and hoarseness (15% vs.8%). Both groups have significant GER symptoms, but difference did notreach statistical significance (p�0.05). Heartburn and acid regurgitationoccurs daily and it was described as hard or very hard. Average durationof heartburn and acid regurgitation was 10�4 years. All patients occa-sionally take anti reflux drugs mostly during exacerbation of disease.

CONCLUSION: GER symptoms are significantly present in patientswith CRF due to COPD. There was a trend toward higher prevalence ofGER symptoms among patients with CRF comparing to patients withARF, but the difference did not reach statistical significance.

CLINICAL IMPLICATIONS: Patients with respiratory failure due toCOPD (both acute and chronic) require further medical investigation andappropriate therapy with anti reflux drugs.

DISCLOSURE: Snezana Raljevic, None.

CLINICAL OUTCOME OF PATIENTS ADMITED WITH ACUTEEXACERBATION OF COPDAvanti Vigg MBBS* Ajit Vigg MD Arul Vigg MBBS Sumanth Mantri MDRoyal Preston Hospital, Preston, United Kingdom

PURPOSE: To identify risk factors related to Acute Exacerbation ofChronic Obstructive Pulmonary disease ( COPD ) in hospitalized patientsas a retrospective nested case control study.

METHODS: From Jan 2002 to June 2004, a total of 162 patients wereadmitted who satisfied the criteria for Acute Exacerbation of COPD. Ofthese, 26 patients died. They were compared with 136 discharged patients(controls)Acute Exacerbation of COPD was defined using the criteria ofAnthonisen et al : increased dyspnoea /sputum volume & sputumpurulence. Severity of lung disease was stratified based on FEV1 %predicted using GOLD guidelines (StageI:FEV1/ FVC � 70% withFEV1 � 80%, Stage IIa:FEV1 50-80% stage IIb:FEV1 30 – 50% & stageIII FEV1 �30%): Clinical outcomes were recorded in all patients.

RESULTS: Sixteen percent of deaths occurred in hospitalized patientsdue to acute exacerbation. The main risk factors with odds ratios (OR)were: use of ventilator OR � 3.46 ( 95% CI :1.22-9.28, P� 0.02),increased stage of severity OR � 4.35 (95% CI : 1.01-18.86, P� 0.05)prolonged length of stay in ICU OR 9.32 (95%,CI:4.27-87.3) (P�0.0001)prolonged length of stay in hospital OR �2.76 (95% CI : 1.02-7.51,P�0.04). Interestingly age, sex, type of respiratory failure, sputum culture/sensitivity and presence of one or more co-morbidities did not affect theultimate outcome.

CONCLUSION: The results of our study suggest that use of ventilator,prolonged length of ICU stay, hospital stay,decreased FEV1 determinetreatment outcomes. Prospective studies in appropriately stratified pa-tients are needed to validate these findings in Indian setup loco regionally.

CLINICAL IMPLICATIONS: Treatment outcomes in acute exacer-bations of COPD are determined by variable factors which need to beascertained in each center.

DISCLOSURE: Avanti Vigg, None.

OUTCOME AND SURVIVAL IN HYPERCARBIC RESPIRATORYFAILURE FROM COPD TREATED WITH NON-INVASIVE VEN-TILATION (NIV)Kwok Yim MS En-chia J. Liu MD Robert A. Fleming MD* TerenceBrady MD NYHQ, Manhasset, NY

PURPOSE: Objective: NIV in properly selected patients (non-ob-tunded with a pH�7.19) can result in improved tidal breath, minuteventilation and prevent endotracheal intubation in COPD patients withhypercarbic respiratory failure. This study explores the efficacy of NIV inavoiding endotracheal intubation and surviving to discharge.

METHODS: Method: a retrospective chart review was conducted on30 consecutive deployments of NIV in hypercarbic COPD patients in theyear 2003. Arterial blood gas. (ABG) Pre-NIV, post NIV, endotrachealintubation and survival to discharge were recorded.

RESULTS: Results: Demographics revealed 14 males, and 16 females;mean age was 74.4 years. ABG’s were all obtained within 24 hours ofdeployment. There were 25/30 (83%) responders with pre-NIV ABG ofpH 7.29, PCO2 63.3 mmHg. and mean post –NIV ABG’s were pH 7.38,PCO2 52.6mmHg,ŒpH was 0.0796, ŒPCO2 was10.7mmHg. Of thenon-responders 5/30 (17%) mean ABG’s pre-NIV were pH 7.29, PCO253.0mmHg, post-NIV mean ABG’s pH were 7.24, PCO2 60.6 mmHgŒpH -0.058 and ŒPCO2 0.7.6 mmHg. NIV success in avoiding EI was22/25 (88%) Patients surviving to discharge 22/25 in the responder group.

CONCLUSION: The non-responding group had a pre-NIV ABGrevealing a primary respiratory acidosis with no metabolic compensationor a concomitant metabolic acidosis that was predicted of failure on initialpresentation. This has not been previously reported. We demonstated thehigh rate of success of NIV at avoiding endotracheal intubation with lowmortality and high rate of discharge back to the community.

CLINICAL IMPLICATIONS: Further study is required to validatethe predictive value of NIV failure in uncompensated respiratory acidosison the initial arterial blood gas.

DISCLOSURE: Robert Fleming, None.

PREDICTORS OF SUCCESS AND OUTCOME OF NONINVA-SIVE VENTILATION IN ACUTE EXACERBATIONS OF COPDAT A UNIVERSITY HOSPITAL IN TURKEYMeltem M. Tor MD* Suna Akbulut MD Levent Kart MD Remzi AltinMD Figen Atalay MD Muhammed E. Akkoyunlu MD Zonguldak Karael-mas University Hospital Department of Pulmonary Medicine, Zonguldak,Turkey

PURPOSE: Non-invasive ventilation (NIV) is being used more fre-quently in the management of acute exacerbations of chronic obstructivepulmonary disease (COPD ). We hereby present our experience at auniversity hospital setting in Turkey.

METHODS: Twenty-two patients with a COPD exacerbation whomwere treated with NIV in the first place were enrolled in the study. Of 22patients(82% males, mean age of 63.4), eight (36%) had a mild , 10(46%)had a moderate and four(18%) had a severe exacerbation. Comorbiditieswere present in 82% of them, and 68% had previous hospitalizations forexacerbation. APACHE II score (mean�/-SD) was 18.09�/-4.02.

RESULTS: NIV was initiated in the emergency department in 9% ofpatients, in an ICU setting in 77% , on a general ward in 14% . The meanbaseline pH, pO2 and pCO2 at baseline were 7.39(9% with a pH of �7.30), 57�/-17 mmHg(63%with pO2�60mmHg),and 56�/-14 mmHg(87% with pCO2�45mmHg) respectively. Mean duration of NIV andtotal length of hospital stay were 9 and 18 days respectively. On follow-up,two patients (9%) required endotracheal intubation (ETI), and there wasonly one death (4.5%). Success of NIV was not correlated with APACHEscore, age, severity of exacerbation, number of previous hospitalizations,pCO2 and pH, although one failed patient had a pH�7.30. Baseline pO2(k�-0.470, p�0.027) and spO2 ( k�-0.491, p�0.020) were found asnegative predictors of NIV success. On discharge, home ventilators wereprescribed to three(13,5%) patients.

CONCLUSION: We have found that NIV was iniatiated and usedmostly inside of a critical care setting in our institution. Our outcomes ofETI and death were lower than those reported previously because lesssevere exacerbations were present in our series. Hypoxemia was found asthe main predictor of NIV success.

CLINICAL IMPLICATIONS: NIV should be considered early in thecourse of acute exacerbations of COPD and before severe hypoxemiaensues, in order to reduce the likelihood of ETI, treatment failure andmortality.




DISCLOSURE: Meltem Tor, None.

SYSTEMATIC REVIEW OF DISEASE MANAGEMENT INCHRONIC OBSTRUCTIVE PULMONARY DISEASESandra G. Adams MD* Paulla K. Smith RRT John E. Cornell PhDAntonio Anzueto MD Jacqueline A. Pugh MD University of Texas HealthScience Center at San Antonio and The South Texas Vet, San Antonio, TX

PURPOSE: The chronic illness care model (CICM) has been shown toimprove outcomes in diabetes mellitus and congestive heart failure, butdata regarding the effectiveness of a comprehensive model in patientswith chronic obstructive pulmonary disease (COPD) are lacking. Asystematic review of the literature was undertaken to determine theeffectiveness of the components of the CICM in patients with COPD.

METHODS: MEDLINE, CINAHL, and COCHRANE databaseswere searched from the earliest date available to January of 2005 toidentify English-language articles that evaluated outcomes of adults withan intervention of at least one of the components of the CICM in patientswith COPD.

RESULTS: A total of 514 abstracts were screened, but only 32 articleswere suitable for full abstraction and review. These studies were hetero-geneous (different interventions and outcomes) and only a few metstandard criteria for high quality. Outcomes such as symptoms, quality oflife, lung function, and functional status were not significantly differentbetween the intervention and control groups. However, the pooledrelative risk (RR) and 95% confidence intervals (CI) for the emergency/unscheduled visits for the group who received at least 2 components of theCICM was 0.575 (0.418, 0.790) and for the length of hospital stay was-0.522 (-0.721, -0.322). There was no significant change in healthcareutilization in the control groups or in patients who received only onecomponent (such as self-management alone) of the CICM.

CONCLUSION: Only limited data are available in the literatureevaluating interventions of any of the components of the CICM in patientswith COPD. However, the pooled data from the available studiesdemonstrated that patients with COPD who received interventionsincluding 2 or more components of the CICM had lower rates ofemergency/unscheduled visits and an overall shorter length of hospitalstay than patients who received only one component or those who were inthe control groups.

CLINICAL IMPLICATIONS: Implementation of multiple compo-nents of the CICM in patients with COPD has the potential to signifi-cantly reduce healthcare utilization.

DISCLOSURE: Sandra Adams, None.

EVALUATION OF HEALTHCARE RESOURCE UTILIZATION(HRU) AND COSTS OF ANEMIA AMONG CHRONIC OBSTRUC-TIVE PULMONARY DISEASE (COPD) PATIENTSMichael T. Halpern MD* Jordana K. Schmier MA Marya Zilberberg MDEdmund Lau MS Exponent, Alexandria, VA

PURPOSE: Anemia has been reported in 13-30% of patients diag-nosed with COPD1,2,3. However, little information is available on theincremental economic burden resulting from concomitant anemia. Weevaluated the impact of anemia on HRU and costs among COPD patients.

METHODS: Retrospective data analysis of the Medicare 5% benefi-ciary encrypted files (BEF) was performed. All individuals with a COPDdiagnosis code in the 1997-2001 BEF data were identified. COPDpatients with anemia (A�) were identified using ICD-9 diagnosis codes orreceipt of transfusion(s) in the absence of major GI bleeding, trauma, orsurgery. A 6-month control period preceding the 1st COPD diagnosis(index date) served to compare disease severity.

RESULTS: Of the 132,424 patients with COPD identified, 27,932(21%) had an anemia code. A� patients were more likely to be older,female and non-Caucasian (p�0.0001). Except for pre-dialysis chronickidney disease (22% A� vs. 9% without anemia [A-], p�0.0001), comor-bidity burden was similar between the 2 groups. Average total annualMedicare reimbursement was $855 for A� and $437 for A- before theindex date; after the index date it increased by 71% to $1466 in the A�group vs. 49% to $649 in the A- group. In both groups, the greatest costdriver before and after the index date was hospitalizations, accounting for�50% of the average payments. In regression models controlling fordemographics, disease severity, and comorbidities, anemia maintained anindependent and significant association with increased payments.

CONCLUSION: Presence of anemia is associated with a substantialincrease in resource utilization and costs among Medicare enrollees withCOPD, independent of demographic differences, higher disease severity,and comorbidity burden.

CLINICAL IMPLICATIONS: Prospective studies are needed toevaluate the effect of anemia correction on HRU in the COPDpopulation.1John M, et al. Chest. 2005;127:825-829.2Cote C, et al. AnemiaIs Associated with Increased Breathlessness and Decreased 6-MinuteWalk Distance in COPD Patients. Proc Am Thorac Soc 2005;2:A498.3Cote C, et al. Anemia Is a Predictor of Mortality in Patients withCOPD. Proc Am Thorac Soc 2005;2:A890.

DISCLOSURE: Michael Halpern, Grant monies (from industry re-lated sources) Supported by a grant from Ortho Biotech Clinical Affairs,LLC.; Employee Marya Zilberberg, MD is an employee of Ortho BiotechClinical Affairs, LLC.

COPD Pharmacologic Therapy12:30 PM - 2:00 PM

RISK OF HOSPITALIZATION/EMERGENCY VISIT IN PA-TIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DIS-EASE BY INITIAL MEDICATION REGIMENRohit D. Borker PhD* Cortney Hayflinger MS Richard Stanford MSGlaxoSmithKline, Research Triangle Park, NC

PURPOSE: To compare risk of all-cause & COPD-related emergencydepartment (ED) visit/hospitalization in patients with COPD receivinginitial maintenance therapy.

METHODS: Retrospective observational analysis was conducted usingdata from a large managed care database ( � 30 managed care plans).Patients � 40 years with a primary diagnosis of COPD within 1 year priorto initial treatment and at least 18 months of continuous eligibility wereidentified. Following cohorts were identified: ipratropium (IP), salmeterol(SL), inhaled corticosteroid (ICS), ICS plus SL in the same inhaler (FS),and IPR and albuterol (AL) in the same inhaler (IP/AL). Logisticregression analysis was performed that determined risk of all cause andCOPD-related hosp/emergency room (ER) visit. The model adjusted forbaseline differences in age, comorbities, COPD sub type, baseline oralcorticosteroid, theophylline and albuterol use.

RESULTS: In all, 14,368 patients were identified, 2122 IP, 1099 SL,3940 ICS, 3819 FS and 3388 IP/AL. Compared with IP, FS reduced therisk of all-cause ER/hosp by 46 % (OR 0.539, CI: 0.467 to 0.622). Inaddition, ICS and SL reduced the risk by 41 %, (OR 0.594, CI: 0.516 to0.683) and 36% (OR 0.640, CI: 0.529 to 0.774), respectively. IP/AL cohortwas associated with a 12% risk reduction (OR 0.877, CI: 0.770 to 0.999).FS was also associated with a 69% lower risk (OR 0.309, CI: 0.200 to0.475) of having a COPD related ER/hosp, while ICS and SL had 58%,(OR 0.419, CI: 0.287 to 0.611) and 61% (OR 0.387, CI: 0.216 to 0.694)lower risk, respectively. A 13% risk reduction, which was not statisticallysignificant, was also observed in the IP/AL cohort (OR 0.868, CI: 0.645 to1.167).

CONCLUSION: Treatment of COPD with SL or ICS containingmedications, especially when ICS and SL are used in combination (FS),may significantly decrease the risk of all-cause and COPD relatedED/hosp compared to treatment with IP alone.

CLINICAL IMPLICATIONS: These findings provide further evi-dence of clinical benefits for FSC in patients with COPD.

DISCLOSURE: Rohit Borker, Employee GlaxoSmithKline

POOLED CLINICAL TRIAL ANALYSIS OF THE SAFETY OFTIOTROPIUMSteven Kesten MD* Michele Jara PhD Charles Wentworth MS StephanLanes PhD Boehringer Ingelheim, Ridgefield, CT

PURPOSE: Marketing approval of pharmaceutical products is oftenbased on efficacy and safety data from several thousand subjects. Afterapproval, information may be obtained from larger numbers of patientsfrom Phase IV clinical trials enhancing the ability to detect rare adverseevents.




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METHODS: We pooled data on adverse events from 19 randomized,double-blind, placebo-controlled trials with tiotropium in patients withCOPD (17 studies) and asthma (2 studies) using data available in projectdatabase as of May 2004. Heterogeneity of incidence rate ratios wasexamined by trial prior to pooling. We computed incidence rates ofselected adverse events and Maentel-Haenszel incidence rate ratio esti-mates, and used 95% confidence intervals for precision of effect estimates.Patients were included while in the study until 30 days post-treatment(tiotropium, placebo) or until they had the event of interest, whichevercame first.

RESULTS: Pooled population includes 7,819 patients (4,435 tiotro-pium; 3,384 placebo), contributing 2,159 person-years of exposure totiotropium; 1,662 person-years of exposure to placebo. Dyspnea, drymouth, COPD exacerbation and upper respiratory tract infection were themost common events. There was decreased relative risk of dyspnea(RR�0.64, 95%CI�0.05, 0.81) and COPD exacerbation (RR�0.72,95%CI�0.64, 0.82) with tiotropium compared with placebo. Among heartrate and rhythm disorders, risk of tachycardia was slightly elevated withtiotropium (RR�1.68, 95%CI�0.69, 4.11). Serious cardiac conditions,such as cardiac arrest and myocardial infarction did not occur morefrequently with tiotropium. There was an elevated risk of urinary retention(RR�10.93, 95%CI�1.26, 94.88) with tiotropium. There was lower risk ofall cause mortality (RR�0.76, 95%CI�0.50, 1.16), cardiovascular mortal-ity (RR�0.57, 95%�0.26, 1.26) and respiratory mortality (RR�0.71,95%CI�0.29, 1.74) with tiotropium.

CONCLUSION: The benefit/risk profile of tiotropium is characterizedby decreased risk of dyspnea and COPD exacerbation and increased riskof dry mouth and urinary retention. Pooling of adverse event data fromtiotropium clinical trials supports the present safety profile of tiotropium.

CLINICAL IMPLICATIONS: Pooling of adverse event data frompre- and post-registration clinical trials has value in understanding thesafety of recently approved medications.

DISCLOSURE: Steven Kesten, Grant monies (from industry relatedsources) Funded by Boehringer Ingelheim and Pfizer.; Employee S.Kesten and S. Lanes are employees of Boehringer Ingelheim.; Consultantfee, speaker bureau, advisory committee, etc. M. Jara and C. Wentworthare consultants for Boehringer Ingelheim.

ADDITION OF FORMOTEROL TO TIOTROPIUM PRODUCESBETTER FEV1 AND FVC RESPONSES WHEN MEASUREDOVER 24 HOURS FOLLOWING SINGLE-DOSE ADMINISTRA-TION IN SUBJECTS WITH MODERATE-TO-SEVERE COPDBill Brashier MBBS Ashwini Jantikar MBBS Manisha Maganji MBBSAnchala Raghupathy MBBS Sapna Valsa MS Partha Gokhale MDPurnima Mahadik MS Jaideep Gogtay MD Sundeep S. Salvi MD* ChestResearch Foundation, Pune, India

PURPOSE: Tiotropium, a new long-acting anticholinergic drug isrecommended as first-line bronchodilator in the management of COPD.The aim of this study was to investigate whether addition of Formoterol,a long-acting b2-agonist produces a superior bronchodilator responsewhen compared to Tiotropium alone in subjects with moderate-to-severestable COPD.

METHODS: 23 male subjects (mean age: 59.6 � 7.6 yrs) diagnosedwith COPD and no histories of exacerbation over the previous 4 weeks,were recruited into this study. Single doses of Tiotropium (18mcg) and acombination of Tiotropium plus Formoterol [18 and 12 mcg respectively)administered through a single ihaler, were given with a pMDI plusnon-static spacer on two separate study days, 4-7 days apart, in arandomized, double-blind, cross-over manner. FEV1 and FVC weremeasured at baseline and 5min, 15min, 30min, 60min, 2hr, 3hr, 4hr, 6hr,8hr, 12hr and 24hr following the study drug administration with aVitalograph Gold Standard dry bellows Spirometer.

RESULTS: The mean baseline FEV1 value in this study populationwas 40.6 � 14.1% predicted. Tiotropium plus Formoterol produced asignificantly better mean difference in area under the curve change frombaseline to 24 hrs for both FEV1 (p � 0.001) and FVC (p � 0.02). Also,the mean difference in trough (24 hr) values from baseline weresignificantly better with the combination than Tiotropium alone [(FEV1 –289.6mL vs 185.7mL; p � 0.001)(FVC – 503.5mL vs 297mL; p � 0.007).The combination showed a faster onset of action for FVC, defined as anincrease of at least 150mL from baseline (5.0 mins vs 12.1 mins; p � 0.02)and tended to show a longer duration of action when compared toTiotropium alone (FEV1: p � 0.06; FVC: p � 0.05).

CONCLUSION: In patients with moderate-to-severe COPD, additionof Formoterol to Tiotropium (in a single inhaler) produces better FEV1and FVC responses than Tiotropium alone when measured over 24 hrs.

CLINICAL IMPLICATIONS: Combination of Tiotropium and For-moterol may produce better clinical response in patients with moderate-to-severe COPD.

DISCLOSURE: Sundeep Salvi, Grant monies (from industry relatedsources) Cipla Ltd.

HANDLING PERFORMANCE AND PATIENT SATISFACTIONOF A METERED DOSE INHALER(MDI) WITH INTEGRATEDDOSE COUNTER IN PATIENTS WITH COPDCourtney Crim MD* William R. Lincourt BS Nickolas W. Locantore PhDJ. R. Carranza-Rosenzweig PharmD GlaxoSmithKline Inc., Raleigh, NC

PURPOSE: Current methods that require patients to track inhalerdoses are unreliable and can lead to circumstances where medication isunavailable. This study examined patient satisfaction and handling perfor-mance of an MDI fitted with an integrated dose counter in 219 patientswith COPD.

METHODS: Data were collected using self-report questionnaires thatassessed previous MDI experience and overall satisfaction with the MDIwith counter. Counter performance was assessed during a 30 or 50 daytreatment period by measuring the discrepancies between the counterreadings and the actuations reported on a subject recorded diary card.

RESULTS: At baseline 65% of the patients reported feeling anxiousnot knowing the amount of medication left in their inhaler. Fifty-sevenpercent reported assessing the remaining quantity by shaking the inhalerand 43% reported waiting until it was completely empty. After usingfluticasone propionate/salmeterol HFA or albuterol HFA MDI withCounter, 93% of patients were satisfied with it based on its ease of use andconvenience. Ninety-one percent felt that it would allow them to monitortheir medication use while 93% agreed that the counter would help themavoid running out of medication. A total of 308 discrepancies betweensubject-reported use and counter readings occurred in 15,835 devicehandlings (31,667 MDI actuations), constituting a discrepancy rate of 0.97discrepancies per 100 actuations. Fifty-two percent of the subjectsreported no discrepancies. For subjects reporting a discrepancy, themajority (90%) were of 1 or 2 actuations.

CONCLUSION: These data support the need for a reliable, MDIactuation counting device and document the favorable patient perceptionsof the MDI with Counter. The results showed a high level of concordancebetween the MDI with Counter and the subject-recorded diary card.

CLINICAL IMPLICATIONS: The addition of an integrated dosecounter to an MDI will provide patients with a reliable indication ofremaining actuations in their inhalers and increase clinicians’ assurancethat patients are not using their inhalers beyond the recommendednumber of labeled doses, a situation that clearly impacts patient health.

DISCLOSURE: Courtney Crim, Grant monies (from industry relatedsources) Study supported by a grant from GlaxoSmithkline; Employee Allauthors are employees of GlaxoSmithKline Inc.; Product/procedure/technique that is considered research and is NOT yet approved for anypurpose. MDI dose counter is approved for Ventolin HFA in the US andfor Seretide in the UK

IMPROVEMENT OF DYSPNEA IN COPD PATIENTS BY COM-BINATION THERAPY WITH TIOTROPIUM PLUS SALMET-EROL (T�S) IN RESPONDERS AS WELL AS POOR RESPOND-ERS TO SALBUTAMOLJ.A. van Noord MD* J-L Aumann MD E. Janssens MD J.J. Smeets A.Mueller P.J.G. Cornelissen PhD Atrium Medisch Centrum, Heerlen,Netherlands

PURPOSE: Recommended mono- or combination therapy of long-acting bronchodilators in COPD is successful if relief of dyspnea isprovided.

METHODS: A retrospective analysis was conducted in 93 patients(FEV1: 1.09 L / 39% pred) who completed a 4-way, double-blind,crossover study of tiotropium 18 mcg (qd), salmeterol 50 mcg (bid), T(qd) � S (qd) or T (qd) � S (bid). Patients were characterized asresponder (R, � 12% increase in FEV1 45 min after 400 mcg salbutamol)or poor responder (PR, � 12%) on the basis of a single test. Effects ondyspnea (TDI, � 1 unit is clinically relevant), FEV1, FVC and need for


COPD Pharmacologic Therapy, continued


reliever medication were compared at the end of 6-week treatmentperiods.

RESULTS: Mean FEV1 at screening was 1.05 L (37% pred, N � 57)in the R-group and 1.16 L (40% pred, N � 36) in the PR group.

CONCLUSION: Treatment responses showed the same rank order inthe R and PR groups, with combination therapies superior to single agenttherapy.

CLINICAL IMPLICATIONS: Data confirm guidelines regardingpatient benefit of combination therapy of long-acting agents tiotropiumplus salmeterol over mono-therapy in moderate to severe COPD, even inpatients who fail to reach a pre-defined threshold response to salbutamol.

DISCLOSURE: JA van Noord, Grant monies (from industry relatedsources) First three authors received honorarium to conduct clinicalresearch

BREAKTHROUGH TREATMENTS RATES DURING A CONVER-SION TO LEVALBUTEROL, TIOTROPIUM AND BREATH AC-TUATED NEBULIZERSRobert S. Pikarsky RRT* Russell A. Acevedo MD Tracey Farrell RRTWendy Fascia RRT Crouse Hospital, Syracuse, NY

PURPOSE: In order to maximize therapist time, an auto-conversion toLevalbuterol (Lev) Q8h, Tiotropium (Tio) QD and AeroEclipse BreathActuated Nebulizer (BAN) usage in mouthpiece (MP) mode was evaluated.

METHODS: All patients assessed by Respiratory Therapists with the ability toperform aerosol treatments by mouthpiece were converted to Lev 0.63 mg Q8hby BAN MP. If ordered, Ipratropium (Ipra) 0.5 mg was converted to Tio 18 mcgQD. If unable to perform the MP treatment patients were converted to Lev 1.25mg Q8h delivered by mask. If ordered, Ipra 0.5 mg was converted to Ipra 0.25 mgQ8h. All protocol treatments, including breakthrough treatments deliveredbetween 10/04 and 4/05 were recorded. Treatment refusals and omitted treat-ments were recorded. The breakthrough data for Racemic Albuterol (Alb)wasfrom our previous studies.

RESULTS: The table shows the number of treatments(tx), the numberof prn breakthrough treatments and the per-treatment and daily rates ofbreakthroughs per 100 treatments. Lev 0.63 mg Q8h MP had significantlylower breakthroughs rates than the Alb 2.5 mg Q4h, both in per-treatmentand daily rates (p�0.05)* Alb/Ipra Q4h had significantly lower per-treatment rates when compared with Lev/Tio Q8h and Lev/Ipra Q8h(p�0.01)**; the daily breakthrough rates were not significantly different.Omitted treatments decreased from 2.28% to 1.95%. Patients refused3.81% of scheduled treatments.

CONCLUSION: The conversion from Alb Q4h to Lev Q8h allowed fora decreased frequency of daily medication administrations and a decrease

in breakthrough requirements. Ipratropium showed a significant benefitin breakthrough reduction for the Alb group. Lev 0.63 mg MP performedas well as Lev 1.25 mg via mask.

CLINICAL IMPLICATIONS: The efficiencies gained by decreasingthe daily frequency of aerosol administration can have a significant impacton resource utilization. The conversion to Lev allows for decreasedrespiratory therapy time or the re-allocating of workforce needs whilemaintaining, or improving, quality of aerosol administration, as evidencedby the decrease in breakthrough requirements. Smaller doses in the BANlead to shorter administration times.

DISCLOSURE: Robert Pikarsky, None.

ECONOMIC IMPACT RESULTING FROM A CONVERSION TOLEVALBUTEROL EVERY SIX TO EIGHT HOURSRobert S. Pikarsky RRT* Russell A. Acevedo MD Tracey Farrell RRTWendy Fascia RRT Crouse Hospital, Syracuse, NY

PURPOSE: Crouse Hospital approved an automatic conversion fromRacemic Albuterol (Alb) 2.5mg Q4h to either Levalbuterol (Lev) 0.63 mgQ6h or Lev 1.25 mg Q8h. To further maximize Respiratory Therapist timewe took the next step of automatic conversion of all Lev Q6h to Lev Q8h.

METHODS: All protocol treatments delivered between 10/04 and 4/05were recorded. Pre-conversion estimates for Alb Q4h were twice thecurrent Lev Q8h protocol. The ratio of Lev Q6h to Q8h deliveredbetween 1/04 and 4/04 (prior protocol) was 85%:15%. The cost for unitdose Alb was $0.22. The cost for unit dose Lev was $1.85. We used the0.26 hour per treatment time as reported in the AARC Uniform ReportingManual. The FTE average cost (salary/benefits) � $23.80/hr. All aerosoltherapy was provided with the use of the AeroEclipse Breath ActuatedNebulizer (BAN).

RESULTS: The table shows the drug and labor cost for the currentprotocol and the estimated number of treatments, with their respectivecosts, for the prior protocol and pre-conversion periods. For the currentprotocol, the drug cost of $16,482 is lower than the prior protocol andconsiderably higher than the pre-conversion period. Labor costs de-creased with each protocol as the number of treatments dropped. Thedrop in labor cost more than offset the increase drug costs in eachprotocol. The largest savings was seen with the current Lev Q8h protocol.The Respiratory Care Department’s total expenses for the first 3 monthsof this year was 8.6% under budget and 7.9% below the same time periodin 2004.

CONCLUSION: Hospital-wide conversion to Lev is cost-effectivewhen administered on both a Q6h and Q8h frequency with the maximumbenefit at the Q8h frequency. Therapist availability was enhanced withfewer scheduled treatments.

CLINICAL IMPLICATIONS: The conversion to Lev allows theability to meet our patient care demands and for the reallocation ofworkforce needs in an economically advantageous manner.

DISCLOSURE: Robert Pikarsky, None.

Mean* Tio (qd) Salm (bid) T(qd) � S(qd) T(qd) � S(bid)

R PR R PR R PR R PRTDI (focal score) 1.52 0.65 1.18 0.67 2.97

#�1.93# �3.15# �2.08#

FEV1 (0-12h) - ml 142 86 97 32 250 152 262 164FVC (0-12h) - ml 230 185 133 66 411 301 407 294Puffs salb (0-12h) 1.55 2.26 1.47 2.21 1.00 1.50 1.12 1.38

*Means are adjusted for centre, patient within centre and period.

Order CountBreak-

throughs

Break-throughs

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per day

DailyBreak-

throughsper 100 tx

Lev 0.63mg Q8h (MP)

3541 58 *1.64 3 *4.91

Lev 0.63 mgQ8h/Tio 18 mcgQday (MP)

1130 22 **1.95 3 5.84

Lev 1.25 mgQ8h (Mask)

3092 74 2.39 3 7.18

Pre-conversionPrior

ProtocolCurrentProtocol

Treatments Alb Q4h 17,818Treatments Lev Q6h 9,642Treatments Lev Q8h 1,678 8,909Total treatments 17,818 11,320 8,909

Drug cost (dollars) $ 3,920 $20,942 $16,482

Labor (hours) 4,633 2,943 2,316Labor cost (dollars) $110,258 $70,048 $55,129

Total cost (dollars) $114,178 $90,990 $71,611Savings compared with

current protocol$ 42,567 $19,380




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LEVALBUTEROL IN THE TREATMENT OF PATIENTS WITHCHRONIC OBSTRUCTIVE PULMONARY DISEASEJames F. Donohue MD* Merdad Parsey MD Charles Andrews MD TonyD. D’Urzo MD Satyendra Sharma MD Kendyl Schaefer MS RaymondClaus MS Rudolf Baumgartner MD University of North Carolina atChapel Hill, Chapel Hill, NC

PURPOSE: GOLD guidelines recommend short-acting �2-agonists(SABAs) for symptom control across all severities of chronic obstructivepulmonary disease (COPD) and state that exacerbations affect quality oflife and decrease health status. This study assessed the efficacy and safetyof levalbuterol in treatment of patients with COPD.

METHODS: This double-blind, placebo-controlled study evaluatedpatients with COPD who were �35 years of age, had FEV1 �65%predicted and �0.70 L, a �15 pack-year smoking history, and amedical research council dyspnea scale score of �2. Stable doses ofinhaled corticosteroids were allowed. Patients were randomized tonebulized levalbuterol 1.25mg (n�49), levalbuterol 0.63mg (n�53),racemic albuterol (RAC) 2.5mg (n�52), or placebo (n�55) TID for 6weeks. Patients returned to clinic every 2 weeks for serial spirometryand assessment of dyspnea and rescue medication use (MDI SABA andipratropium). COPD symptoms and exacerbations, adverse events(AEs), and dropouts were monitored throughout. At the 4-week visitonly, response to study drug added to ipratropium bromide wasassessed.

RESULTS: Mean time-normalized AUC percent change FEV1(AUC % FEV1) was significantly greater (p�0.001) following allactive treatments relative to placebo. Concomitant administration oflevalbuterol 1.25mg with ipratropium resulted in significantly greater(p�0.009) AUC % FEV1 than ipratropium with placebo. Rescuemedication use increased in the RAC and placebo groups, wasunchanged in the levalbuterol 0.63mg group, and significantly de-creased in the levalbuterol 1.25mg group (p�0.02 vs RAC). RAC-treated patients had the most COPD exacerbations and significantlymore study withdrawals due to COPD exacerbations when comparedwith placebo (p�0.01). AE rates and beta-mediated side effects werelowest in the levalbuterol 0.63mg group, although all active treatmentswere well tolerated.

CONCLUSION: In this study, levalbuterol was well tolerated, pro-duced significant bronchodilation, and reduced rescue medication use.RAC was associated with significantly more study withdrawals due toCOPD exacerbations compared with placebo.

CLINICAL IMPLICATIONS: Levalbuterol may offer advantages inthe treatment of patients with COPD.

DISCLOSURE: James Donohue, Consultant fee, speaker bureau,advisory committee, etc. I am a paid consultant for Sepracor and serve ontheir Advisory Board. I have also participated as an investigator in severalclinical trials for Sepracor, including the one presented here.

BRONCHODILATION IN ELDERLY PATIENTS WITH COPD: ASUB-GROUP ANALYSIS OF TWO RANDOMIZED CLINICALTRIALSUmit Yegen MD* Denise Till MS Gregory P. Geba MD NovartisPharmaceuticals Corporation, East Hanover, NJ

PURPOSE: The efficacy of beta-agonists in elderly patients hasreceived little attention to date. We performed an analysis based onpooled data from 2 large randomized, double-blind, multicenter clinicaltrials comparing Foradil® dry powder inhalation capsules 12�g b.i.d.(FOR12) and 24�g bid (FOR24) with placebo.

METHODS: Of a total of 1634 COPD patients randomized, 598 were �65years of age, comprising the elderly subgroup. Serial measurements of FEV1were performed pre-dose, and 5, 15, 30 and 60 minutes and hourly through 12hours post AM dose on the first day and after 3 months of treatment.

RESULTS: Elderly patients tended to have slightly lower FEV1 at baseline.Clinically and statistically significant bronchodilation (� 15% increase in FEV1)with both FOR doses compared to placebo was achieved throughout the 12 hourinterval as shown by the area under the FEV1 curve (AUC; primary endpoint).These results were similar to the total study population (shown below). Theincidence of adverse events (AEs) were also similar in the elderly subgroupcompared to the full study population.

CONCLUSION: FOR provided clinically significant and sustainedincreases in airflow in elderly patients with COPD that was similar inmagnitude to the total study population with a similar tolerability profile.

CLINICAL IMPLICATIONS: The elderly is a growing patientpopulation that will have to studied carefully in the future, especially inthe area of COPD. This study will give insight as to the efficacy and safetyof formoterol in this subgroup.

DISCLOSURE: Umit Yegen, Employee

HIGH SATISFACTION WITH FLUTICASONE PROPIONATE/SALMETEROL VIA DISKUS REPORTED DURING EXPERI-ENCE PROGRAM IN PATIENTS WITH COPDStuart Stoloff MD* Steven Samuels MD Sidney Braman MD ChristyBrown PharmD Donna Kerney PhD Michael Cicale MD University ofNevada School of Medicine, Reno, NV

PURPOSE: An initial experience program was conducted in patientswith COPD to collect patient reported feedback about newly initiatedtherapy with fluticasone propionate/salmeterol 250/50 (FSC).

METHODS: Patients completed 2 surveys; one at baseline (beforeinitiating therapy with FSC 250/50) and one targeted for 30 days afterstarting therapy with FSC 250/50). The first survey collected patientdemographics, duration of COPD diagnosis, smoking history, and satis-faction with prior treatment. The second survey assessed patient per-ceived impact of FSC 250/50 on breathing, and convenience and satis-faction with FSC therapy.

RESULTS: A total of 973 patients completed both surveys. Completerswere mostly female (62%), and 87% were � 45 years of age. Two-thirds ofthe completers had been diagnosed with COPD for � 1 year. At baseline,58% of the population used prescription medications prior to starting FSC250/50. The most common medications were ipratropium/albuterol (37%)and salmeterol (27%). Patients reported satisfaction with their prior therapy(5.52 on a 9 point scale), but 22% of patients were quite dissatisfied (1-3 ona 9 point scale). The second survey, completed an average of 51 days afterstarting FSC 250/50, showed that patients perceived improvement in theirbreathing overall (6.82 on a 9 point scale) and had a high level of satisfactionwith FSC 250/50 (7.76 on a 9 point scale). Less than 4% of patients were quitedissatisfied (�3 on a 9 point scale). FSC 250/50 was regarded as a veryconvenient medication (8.12 on a 9 point scale).

CONCLUSION: Patients with COPD reported a high level of satis-faction with their treatment an average of 51 days after initiating therapywith FSC 250/50.

CLINICAL IMPLICATIONS: High patient satisfaction with therapymay encourage increased compliance with therapy and therefore mayresult in improved outcomes.

DISCLOSURE: Stuart Stoloff, Grant monies (from industry relatedsources) Received research grants from GlaxoSmithKline; Consultant fee,speaker bureau, advisory committee, etc. Received consultant fees fromGlaxoSmithKline and serve on speaker bureau and advisory board forGlaxoSmithKline

AUC of FEV1 (L x hours)

ElderlyPatientsTrial 1

ElderlyPatientsTrial 2

ElderlyPatientsPooled

All AgeGroupsPooled

Contrast N�394 N�397 N�598 N�1158**FOR24 vs

Placebo1.701* 2.753* 2.251* 2.430*

FOR12 vsPlacebo

2.127* 2.459* 2.358* 2.475*

FOR24 vsFOR12

-0.426 0.294 -0.108 -0.045

* Indicates statistical significance at the 0.05 level




EFFECT OF THE BRONCHODILATOR INHALATION ON DIF-FUSION CAPACITY IN PATIENTS WITH CHRONIC OBSTRUC-TIVE PULMONARY DISEASES (COPD)Yaling Zhu MD* Haoyan Wang MD Xiaohong Chang Chaoyang Hospital,Beijing, Peoples Rep of China

PURPOSE: To evaluate the effect of bronchodilator inhalation on thediffusion capacity in patients with COPD.

METHODS: 58 COPD patients were tested with bronchodilatorinhalation (Albuterol 200ug) and divided into 2 groups according to theresponse of FEV1 : Positive if FEV1 increase �15% and �200ml,Negative if FEV1 increase �15% and �200ml. The transfer factor of thelung for carbon monoxide (TLco), pulmonary membrane diffusion capac-ity (Dm) and pulmonary capillary blood volume (Vc) were measured inbaseline and after Albuterol inhalation and compared subsequently ineach group.

RESULTS: 40 COPD patients were found positive and 18 werenegative in the Albuterol inhalation test. No significant differences werefound in Dm, TLco and Vc between baseline and after Albuterolinhalation in either group.

CONCLUSION: Bronchodilator inhalation did not affect diffusioncapacity in COPD patients.

CLINICAL IMPLICATIONS: Bronchodilator inhalation improvessymptoms of COPD patients mainly by way of the improvement ofventilation rather than the improvement of diffusion capacity.

DISCLOSURE: Yaling Zhu, None.

LOWER RESPIRATORY TRACT BIOCHEMICAL EFFICACY OFINTRAVENOUS ADMINISTRATION OF A NEW FORM OFHIGHLY PURIFIED ALPHA1-ANTITRYPSINL T. Spencer MD* David P. Pollock MD James M. Stocks MD Mark L.Brantly MD University of Florida College of Medicine, Gainesville, FL

PURPOSE: To evaluate the biochemical efficacy and safety of a newsource of highly purified, plasma derived alpha1-proteinase inhibitor(A1-PI) in individuals with alpha1-antitrypsin (AAT) deficiency.

METHODS: A randomized, double-blind study compared Zem-aira® (ZLB Behring LLC) [Z] with Prolastin® (Bayer Corporation)[P]. Patients received either Z or P (randomized 2:1) for 10 weeks byintravenous infusion (60 mg/kg functionally active A1-PI weekly). TheP group was then crossed over to an open-label phase where allsubjects received Z for 14 weeks. A subset of 15 patients with forcedexpiratory volume in 1 second �50% predicted underwent bronchoal-veolar lavage. Antigenic AAT levels and AAT:neutrophil elastase(AAT:NE) complexes in the epithelial lining fluid (ELF) betweenbaseline and Week 11 were measured by ELISA.

RESULTS: Increases in ELF AAT levels were statistically significant inboth treatment groups. Subjects receiving Z A1-PI had ELF values of197.1 nM at baseline, increasing to 1125.5 nM after 10 weeks of treatment(p�0.0001), and those receiving P increased from 261.5 nM to 1192.5 nM(p�0.0121). Z A1-PI remained functionally active when delivered to thelung from the systemic circulation, as indicated by significant increases inELF AAT:NE complexes from baseline to 11 weeks [2.8 nM to 66.8 nM(p�0.0012)]. Both Z and P were safely tolerated.

CONCLUSION: The results indicate that both protein preparationsare delivered to the lung in an equivalent manner after intravenousadministration and that the exogenous protein is in a functional statecapable of forming complexes with NE in the lung.

CLINICAL IMPLICATIONS: Z intravenous augmentation therapy isassociated with reconstitution of lower respiratory protease-anti-proteasehomeostasis similar to P.

DISCLOSURE: L Spencer, Consultant fee, speaker bureau, advisorycommittee, etc. LTS and MB have been scientific advisors to AventisBerhing and Bayer Healthcare.; Other DPP and JMS have no financialdisclosures.

COMPARABLE PHARMACOKINETIC PROPERTIES OF TWOALPHA1-PROTEINASE INHIBITORS AFTER SINGLE THERA-PEUTIC DOSESJames M. Stocks MD* Mark Brantly MD Alan Barker MD FriedrichKueppers MD Charlie Strange MD James F. Donohue MD RobertSandhaus MD University of Texas Health Center at Tyler, Tyler, TX

PURPOSE: This study evaluated the bioavailability of a new prepara-tion of alpha1-proteinase inhibitor (A1-PI), Zemaira® (ZLB BehringLLC, [Z(A1-PI)]), with that of Prolastin® (Bayer Corporation, [P(A1-PI)])after single intravenous infusions.

METHODS: This was a double-blind, randomized, controlled, 2x2crossover study comparing a single dose of Z(A1-PI) and P(A1-PI) (60 mgper kg bodyweight). Patients with AATD were randomized (n�9 pergroup) to Z(A1-PI) followed by P(A1-PI), or P(A1-PI) followed byZ(A1-PI), with a washout period between infusions of 35 days. Bioavail-ability was measured by two baseline-adjusted area-under-the-curve(AUC) variables: area-under-the observed data up to Day 21 (AUD0-21)and AUD0-�. The ratio of mean AUC variables (Z(A1-PI):P(A1-PI)) with90% confidence intervals (CI) was calculated. Standard pharmacokinetic(PK) parameters Cmax, tmax, terminal t1⁄2, mean residence time, totalclearance, and steady-state volume of distribution were also compared.

RESULTS: The bioavailability of Z(A1-PI) was statistically non-inferior toP(A1-PI) as shown by the lower limit of the 90% CI for the mean AUC ratio(Z(A1-PI):P(A1-PI)) being greater than 80% for AUD0-21 and also for AUD0-�(Table). Furthermore, the PK profile of functional A1-PI levels followingZ(A1-PI) and P(A1-PI) administration showed no clinically relevant differences interms of mean (SD) Cmax (39.9�5.3 vs. 41.6�8.0 �M), tmax (0.7�0.3 vs.1.5�1.4 hours), terminal t1⁄2 (4.5�3.1 vs. 4.8�1.2 days), mean residence time(5.9�3.3 vs. 6.1�1.3 days), total clearance (636�115 vs. 583�108 mL/day) orsteady-state volume of distribution (3.6�1.3 vs. 3.5�0.8 L). The PK profile wasreflected by that of antigenic A1-PI levels.

CONCLUSION: A single therapeutic dose of Z(A1-PI) was compara-ble and statistically not inferior to P(A1-PI) in bioavailability. There wereno differences between Z(A1-PI) and P(A1-PI) in standard pharmacoki-netic parameters.

CLINICAL IMPLICATIONS: Since Z(A1-PI) is statistically notinferior to P(A1-PI) in bioavailability, a weekly infusion of Z(A1-PI) 60mg per kg body weight is expected to augment and maintain A1-PIserum levels above the protective threshold of 11 �M, and increaseA1-PI levels in the lower lung, to a similar extent to that reported withP(A1-PI).

DISCLOSURE: James Stocks, None.

HEALTH-RELATED QUALITY OF LIFE (HRQOL) IN PA-TIENTS WITH ALPHA1-ANTITRYPSIN (AAT) DEFICIENCYAND EFFECT OF AUGMENTATION THERAPY: PRELIMINARYRESULTSKaren C. Chung PharmD Matthew E. Borrego PhD Jennifer Short BS*Loretta Kristofek RN Nancye Buelow David M. Gelmont MD Universityof New Mexico Health Sciences Center, Albuquerque, NM

PURPOSE: AAT deficiency (AATD), a common genetic disorderwhich predisposes subjects to early onset emphysema, has been associated

Bronchodilatorinhalation N

Dmml/min/mm Hg

TLco%Pred

Vcml

Positive groupBaseline 40 9.87�4.71 67.49�19.47 50.08�20.82After 11.10�5.34 67.87�20.02 50.71�24.32

Negative groupBaseline 18 8.05�4.34 61.99�21.10 47.46�18.18After 18 7.47�3.77 58.62�18.25 53.10�25.41

AUC variable(�M*day)

Median (range) Ratio ofZ(A1-PI):P(A1-PI) 90% CIZ(A1-PI) P(A1-PI)

AUD0-21 129 (93 – 171) 140 (101 – 194) 92.4% 88.5% - 96.5%AUD0-� 134 (96 – 190) 147 (104 - 214) 92.0% 84.9% - 99.7%




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with significant decrease in HRQoL over time. Chronic AAT augmentationtherapy slows the progression of emphysema, however, its effect on HRQoL hasnot been clearly delineated. The purpose of our study is to evaluate HRQoL inAAT deficient patients receiving augmentation therapy and to compare theHRQoL scores of AAT deficient patients to the general population.

METHODS: To date, 68 patients with AATD receiving AATaugmentation therapy have been enrolled in this longitudinal obser-vational patient outcomes study. Interviewer-administered question-naires, which collected demographic, clinical outcomes, healthcareresource utilization, and HRQoL [Short Form-36 Health Surveyversion 2 (SF-36)] data were administered at baseline (start ofaugmentation therapy), and at 6-month intervals. Six-month data hasbeen collected on 36 patients.

RESULTS: Analysis of 6-month HRQoL scores indicate no clinicallyimportant differences in the eight SF-36 scales and Physical and MentalComponent Scores (Figure). Patients with AATD demonstrated clinicallyimportant decreases in HRQoL Physical Functioning scores compared tothe general population, changes in HRQoL mental health scale scoreswere not clinically important.

CONCLUSION: SF-36 scale scores remain stable from baseline to 6-monthfollow-up indicating a lack of significant disease progression during that time-frame. Trends toward improved HRQoL mental health scores from baseline to 6months may be indicative of satisfaction with AAT augmentation therapy,resilience in this group of patients with regard to coping strategies and theirdisease, and/or Hawthorne effect. Overall, AAT deficient patients are dispropor-tionately affected with regard to HRQoL Physical Functioning compared to thegeneral population.

CLINICAL IMPLICATIONS: Results suggest patients with AATDhave significantly compromised physical health. Although HRQoL ap-peared stable from baseline to 6-month follow-up, additional longitudinaldata are needed to assess the long-term stability of the HRQoL scores.HRQoL assessment can be used as an additional measure of diseaseseverity and progression in AAT deficient patients.

DISCLOSURE: Jennifer Short, Grant monies (from industry relatedsources) MEB and JS received a grant from Baxter BioScience to conductdata entry and analysis.; Employee KCC and DMG - Baxter BioScience.

DIFFERENCES IN MICROHETEROGENEITY AND NON-THERAPEUTIC PROTEIN CONTENT OF THREE COMMER-CIAL PREPARATIONS OF PURIFIED HUMAN ALPHA1-PRO-TEINASE INHIBITORFriedrich Kueppers MD* Utpal Patel MS Temple University School ofMedicine, Philadelphia, PA

PURPOSE: Three commercially available preparations of alpha1-proteinase inhibitor (A1-PI) are derived from human plasma but differ inthe purification steps employed during manufacture, leading to differ-ences in purity. As little is known about the effect of purification onbiochemical composition of the final active substance, we compared theirmicroheterogeneity and non-therapeutic protein content.

METHODS: Zemaira® (ZLB Behring LLC) [Z], Prolastin® (BayerCorporation) [P] and Aralast® (Baxter Inc) [A] were evaluated. Isoelectricfocusing (Am J Hum Genet 1978; 30: 359-65) was performed to evaluatethe relative proportion of different isoforms (M2, M4, M6) of A1-PIrelative to historical values for normal serum (Scand J Clin Lab Invest1969; 23: 97-103). Double diffusion experiments were performed todetect non-therapeutic serum proteins.

RESULTS: The relative protein concentrations (SD) of the M2, M4and M6 isoforms of Z were: 31.1 (4.2), 40.0 (5.0) and 19.8 (3.3) comparedwith 11 (2.3), 48.7 (1.5) and 40.4 (2.4) for normal serum. The correspond-ing values for P were: 12.6 (2.3), 39.1 (4.8), 48.3 (5.5) and those for Awere: 13.0 (3.1), 48.0 (5.2) and 38.5 (4.2). Non-therapeutic serum proteinsin all three preparations included alpha1-antichymotrypsin and antithrom-bin III. Albumin and transferrin were detected in A and P but not Z.Alpha1-acid glycoprotein was detected in Z but not A or P.

CONCLUSION: Different purification processes appear to affect themicroheterogeneity of A1-PI preparations: Z and P, but not A, displayedsimilar isoform content to that in normal serum. The absence of albuminin Z may account for its known high purity and solubility.

CLINICAL IMPLICATIONS: The biochemical difference betweenisoforms of A1-PI is thought to reside in the carbohydrate portion, butother unidentified biochemical differences may lead to changes inisoelectric point. A1-PI glycoforms contain side chains with varying ratiosof terminal moieties that could affect A1-PI tissue distribution andhalf-life. Long-term exposure to non-therapeutic proteins in A1-PI prep-arations may induce immune-mediated adverse events, as suggested by aprevious study (Chest 2003; 123: 1425-34). Both findings warrant furtherinvestigation.

DISCLOSURE: Friedrich Kueppers, Grant monies (from industryrelated sources) FK and UP have received funding from the Arlene MethFund, Baxter and ZLB Behring.

EFFICACY AND ANTI-INFLAMMATION ACTIVITY OF A SE-LECTIVE PHOSPHODIESTERASE-4 INHIBITOR CILOMILASTIN TREATMENT OF COPDChangzheng Wang PhD* Yunxi Song PhD Xuiqing Liao BA Qi Li PhDJingping Wang Zhiqiang Zhao Xinqiao Hospital,, Chongqing, Peoples Repof China

PURPOSE: To study the efficacy and anti-inflammation action of aselective phosphodiesterase-4 inhibitor cilomilast in treatment of COPD.

METHODS: 38 patients were randomized into a double-blind, place-bo-controlled, parallel-group trial. Twenty-four patients were randomizedto treat by cilomilast 15mg b.i.d., for 24 weekd, and fourteen patients toplacebo b.i.d.. Pulmonary function tests and symptoms such as cough,sputum, breathlessness were assessed at every visit. The levels of IL-8,TNF-�, LTB4 and IL-6 induced sputum were assessed using ELISA.

RESULTS: After treatment, the score of dyspnea, cough and sputumin the cilomilast group improved significantly, but there no difference inthe control group.Though there was no significant change in FEV1 andFEV1% predicted after treatment in the cilomilast group. But comparedwith baseline, significant decrease in FEV1 was observed in the controlgroup after 24 weeks of treatment (p�0.01). Also, no significant change inRV and FRC was observed in the control group after treatment. However,RV and FRC was significantly improved in the cilomilast group (p�0.01).After the treatment, significant decrease was observed for the level ofIL-8, TNF-�, LTB4 and IL-6 in induced sputum in cilomilast group(p�0.01) and there was no significant difference in control group.

CONCLUSION: Cilomilast has clinical efficacy on COPD and couldmodify decline of pulmonary function for COPD, which effects may bedue to its anti-inflammation activity.

CLINICAL IMPLICATIONS: Cilomilast as a new selective phosphodi-esterase-4 inhibitor might be an effective long-term treatment for COPD.

DISCLOSURE: Changzheng Wang, Grant monies (from industryrelated sources).

COPD: Assessment of Comorbidity12:30 PM - 2:00 PM

NOSOCOMIAL INFECTIONS AND CHRONIC OBSTRUCTIVEPULMONARY DISEASEPrashant S. Borade MD* Daniel K. Lee MD Department of RespiratoryMedicine, Ipswich Hospital, Ipswich, Suffolk, England, United Kingdom

PURPOSE: Chronic obstructive pulmonary disease (COPD) predis-poses an individual to community-acquired infections. However, therelationship between COPD and nosocomial infections is less clear.




METHODS: A prospective study was conducted in 499 consecutivepatients admitted to the intensive care unit without clinical or laboratoryevidence of community-acquired infections over a 6-month period.

RESULTS: The incidence of nosocomial infections was not signifi-cantly different comparing patients with COPD (26%) and without COPD(20%). Mortality was 47% in ventilated patients.

CONCLUSION: Patients with COPD are no more susceptible todevelop nosocomial infections than patients without COPD.

CLINICAL IMPLICATIONS: The acquisition of nosocomial infec-tions is independent of COPD.

DISCLOSURE: Prashant Borade, None.

DOPPLER TISSUE IMAGING IN THE EVALUATION OF RIGHTVENTRICULAR FAILURE IN PATIENTS WITH CHRONIC OB-STRUCTIVE PULMONARY DISEASEVasiliy Pyankov MD* Yulia Chuyasova MD Kirov Medical Academy,Kirov, Russia

PURPOSE: Right ventricular (RV) failure associated with pulmonaryartery hypertension (PAH) in patients with chronic obstructive pulmonarydisease (COPD) has important prognostic implications. The noninvasiveevaluation of the RV failure in patients with COPD still represents aproblem. The purpose of this study was to evaluate RV failure in patientswith COPD using pulsed wave Doppler tissue imaging (DTI).

METHODS: 46 males with COPD (mean age 57�8 years; mean FEV130�8%) were studied. All patients underwent clinical and laboratoryexaminations. RV wall thickness, RV end-diastolic diameter, RV systolicand diastolic functions were evaluated with two-dimensional echocardi-ography. The tricuspid inflow profile (E, A, E/A, DT) and hepatic veinflow velocity (S, D, A) were measured with pulsed Doppler. Peakvelocities of the tricuspid annular motion (Sa, Ea, Aa, Ea/Aa) were derivedfrom pulsed DTI.

RESULTS: RV systolic dysfunction (RV ejection fraction � 45% andSa � 11.5 sm/s) was detected in 13% of cases. RV diastolic dysfunctionwas detected in 100% of cases. Impaired relaxation pattern of tricuspidinflow (E/A�1.0 and Ea/Aa�1.0) was detected in 69.6%, pseudonormalpattern - in 17.4% (2.0�E/A�1.0 and Ea/Aa�1.0), restrictive pattern - in13% (E/A�2.0). There were significant correlations between tricuspidannular motion (Ea/Aa) and tricuspid inflow profile (E/A) (r�-0.56;p�0.019), RV wall thickness (r�0.72; p�0.001), RV end-diastolic diam-eter (r�0.70; p�0.001) and RV ejection fraction (r�0.70; p�0.001);between systolic pulmonary artery pressure and hepatic vein flow velocity(retrograde A velocity) (r�0.60; p�0.007).

CONCLUSION: Our study confirmed high prevalence of RV systolicand diastolic dysfunction in patients with COPD. Physicians should detectRV failure in patients with COPD.

CLINICAL IMPLICATIONS: The complex echocardiography eval-uation with DTI provides a simple, rapid and noninvasive tool fordiagnosis of RV failure in patients with COPD.

DISCLOSURE: Vasiliy Pyankov, None.

CHRONIC OBSTRUCTIVE PULMONARY DISEASE INDUCEDRIGHT VENTRICULAR DIASTOLIC DYSFUNCTION AND/ORFAILURE: FACT, FICTION OR A DILEMMA FOR NEW THER-APEUTIC INTERVENTIONS?Nestor J. Angomachalelis MD* Eva Serasli MD Alex Hourzamanis MDJohn N. Angomachalelis MD Nikos Salem MD Aristotle University ofThessaloniki, “George Papanikolaou” General Hospital, Thessaloniki,Greece

PURPOSE: Up-to-date right ventricular diastolic function in ChronicObstructive Pulmonary Disease (COPD) patients (pts)has not beenthoroughly investigated. Thus, there is always a great dilemma to berecognised, whether right ventricular diastolic dysfunction (RVVD)and/orfailure, related to COPD pathophysiology, is, indeed, a fact, fiction or adilemma for new therapeutic interventions.

METHODS: Fourty three consecutive pts with COPD and 14 age andheart rate-matched controls underwent M-Mode and Acoustic Quantifi-cation (AQ) echocardiographic evaluation of right ventricular systolic(RVS) and diastolic function, Doppler transtricuspid flow estimation andlung function tests (spirometry and blood gases analysis), as well asradionuclide ventriculography with Technetium-99m-pyrophosphate(Multigated Acquisition, MUGA).Pts were classified in three groups:

Group A (mean FEV1�70% predicted), Group B (50%�FEV1�69%),Group C (FEV1�50%), according to the ERS Consensus Statement.

RESULTS: It was resulted that right ventricular systolic dysfucntion(RVSD)in COPD pts was found in 16/43 pts(37.2%) by AQ(FAC�39%)and in 13/43 pts (30.23%) by MUGA(RVEF�45%).Transtricuspiddiastolic flow evaluation by Dopper showed diastolic abnormalities of relax-ation type in 23 pts (53.4%), whereas AQ diastolic indices indicated the samepattern of RVDD in 20 pts (43.5%).Correlations of diastolic AQ and Dopplerindices with lung function tests and blood gases abnormalities as well as withM-Mode indices of cor pulmonale were statistically significant.

CONCLUSION: We conclude, that, altough RVS function remainsnormal in the first two stages of COPD, RVDD becomes evident earlierin the progress of the second and mainly the third stage of the disease inconjunction with the development of respiratory impairment and chroniccor pulmonale, followed very frequently by clinical symptoms and signs ofright ventricular failure. Furthermore, RVDD is statistically proven toplay an important role in the pathophysiology of right ventricular failure.

CLINICAL IMPLICATIONS: Is it consequently the time for estab-lishing new therapeutic interventions targeting the early asymptomaticand symptomatic stages of the disease, including the RVDD itself?.

DISCLOSURE: Nestor Angomachalelis, None.

PREVALENCE AND RISK FACTORS OF LEFT VENTRICULARDIASTOLIC DYSFUNCTION IN COPD PATIENTSParthasarathi Bhattacharyya MD* Sushmita RoyChowdhury MD DipabaliGhosh (Acharya) PhD Saikat Nag MD Dipankar Sarkar MD Institute ofPulmocare and Research, Kolkata, India

PURPOSE: Left ventricular diastolic dysfunction, though known inCOPD patients, is quite frequent in advanced COPD sufferers to ourexperience. We studied the presence of diastolic dysfunction in 43(GOLD stage IIb and III) patients and its association with several clinicalvariables that appeared important from our experience in an OPD basedstudy.

METHODS: This was a cross sectional survey of patients in a tartiaryclinic using the following variables: easy fatiguability, disproportionatetachycardia, poor clinical response to treatment, poor exercise tolerence,FEV1, cardiothoracic ratio, and cardiomegaly. The known predisposingfactors for diastolic dysfunction as ischemic heart disease and hyperten-sion were recorded. Thereafter, the patients underwent 2D dopplerechocardiography to detect the presence of diastolic dysfunction. Finally,the association of diastolic dysfunction was evaluated with the variables ofinterest.

RESULTS: Cardiothoracic ratio greater than 0.4, cardiomegaly andsubjective easy fatiguability were found to be significantly associated withdiastolic dysfunction. Low FEV1 (less than 35% predicted) and dispro-portionate tachycardia were the other two risk factors though they couldnot achieve statistical significance in explaining diastolic dysfunction.

CONCLUSION: Diastolic dysfunction appear in about 70 % ofadvanced COPD patients independent of the presence of ischemia orhypertension. Cardiothoracic ratio greater than 0.4 and easy faiguabilityare the two independent predictors of diastolic dysfunction in advancedCOPD sufferers. However, further evaluation is necessary to unveil theCOPD-diastolic dysfunction association.

CLINICAL IMPLICATIONS: Intervention of diastolic dysfunctionin advanced COPD patients may help in ameliorating symptoms asdyspnoea or easy fatiguability with improvement in the functional ability.

DISCLOSURE: Parthasarathi Bhattacharyya, None.

INTENSIVISTS’ PERCEPTIONS OF ANEMIA IN INTENSIVECARE UNIT (ICU) PATIENTS WITH CHRONIC OBSTRUCTIVEPULMONARY DISEASE (COPD): A SURVEYMarya Zilberberg MD* Michele Pisano PharmD Ortho Biotech ClinicalAffairs, LLC, Bridgewater, NJ

PURPOSE: To understand the hemoglobin (Hb) thresholds US Inten-sivists (ICUMDs) use to assess and manage anemia in critically ill COPDpatients (ICU-COPD).

METHODS: A survey was conducted to identify Hb thresholdsrepresenting presence and severity of anemia in ICU-COPD.

RESULTS: Ninety-nine ICUMDs, who care almost exclusively foradult patients, completed the survey at a specialty society meeting in 2005.All were either certified or eligible in Critical Care, with the specialty ofPulmonology in 31%, Internal Medicine 45%, Surgery/Trauma 20%,


COPD: Assessment of Comorbidity,continued


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Anesthesia 18%, and other 8%. 30% have been in practice for �5 years,with 41% and 29% in practice for 5-15 years and �15 years, respectively.48% work in a university-affiliated hospital, and 42% and 34% areaffiliated with hospitals with �500 total and �50 ICU beds, respectively.Over 70% of responders see �80% of their patients in a hospital setting,and �1/3 spend �80% of their time in the ICU. Of the mean 36�27 ICUpts seen/week, on the average 13�14 (36%) are estimated to have COPD,with 9�9 (69%) on mechanical ventilation (MV). Over 2/3 of theresponders didn’t consider even mild anemia to be present above an Hbthreshold of 10g/dL, and nearly 3/4 deemed severe anemia to be presentonly at Hb�7g/dL. Despite this, over 50% utilize Hb�8g/dL as atransfusion threshold for ICU-COPD, regardless of their MV status.Interestingly, 58% and 59% of the responders identified Hb�10g/dL asthe optimal Hb level in these patients off and on MV, respectively.

CONCLUSION: Despite the accepted WHO definition of anemia(men, Hb�13g/dL; women, Hb�12g/dL), the majority of ICUMDssurveyed do not consider anemia to be present in ICU-COPD until theHb is �10g/dL, and consider severe anemia to be present only atHb�7g/dL.

CLINICAL IMPLICATIONS: Consistent with the findings of therecent Canadian survey by Hebert et al (Crit Care Med 2005), in the USmuch like in Canada, utilization of 7g/dL as the transfusion threshold(Hebert et al, NEJM 1999) is far from ubiquitous.

DISCLOSURE: Marya Zilberberg, Employee Marya Zilberberg, MDis an employee of Ortho Biotech Clinical Affairs, LLC. Michele Pisano,PharmD, is an employee of Ortho Biotech Products, LP.

ANEMIA IN CHRONIC OBSTRUCTIVE PULMONARY DISEASE(COPD): ASSOCIATION WITH SUPPLEMENTAL O2 USE ANDHOSPITALIZATIONSMarya Zilberberg MD* Claudia Cote MD Samir H. Mody PharmDBartolome Celli MD Ortho Biotech Clinical Affairs, LLC, Bridgewater, NJ

PURPOSE: We recently demonstrated that anemia in COPD patientsis associated with diminished 6MWD and increased breathlessness andmortality1,2. A substantial percentage of annual expenditure in COPD isdue to O2 utilization and hospitalizations. It is not known if anemia isassociated with increased O2 utilization or hospitalization. We character-ized the association of anemia with O2 utilization and hospitalization rateand duration in COPD.

METHODS: A retrospective analysis of data collected prospectively on683 patients between 1/97 and 6/02 in a VA Pulmonary clinic for BMI,airflow obstruction, dyspnea, and exercise capacity (BODE) index valida-tion3 was conducted. Anemia was defined as Hb �13g/dL. All values areexpressed as mean (SD). P values were derived using a 2-sided Student’st-test or Chi-square statistic where appropriate.

RESULTS: In this sample of 677 patients with known Hb values,anemia (A�) was present in 116 (17%) patients. The Table below

compares A� to non-anemic (A-) patients. There was no differencebetween the groups with regard to the prevalence of O2 utilization or the

mean O2 flow. There was a trend toward increased incidence of hospi-talizations in the A� group, and A� patients had statistically significantlymore hospitalizations per patient, as well as a longer hospitalization timeover similar follow-up period.

CONCLUSION: Although there was no difference between thegroups in their supplemental O2 utilization, hospital utilization wassignificantly higher in the A� than the A- group.

CLINICAL IMPLICATIONS: Economic impact of anemia in COPDpatients needs to be evaluated. 1Cote C, et al. Anemia Is Associated withIncreased Breathlessness and Decreased 6-Minute Walk Distance inCOPD Patients. Proc Am Thorac Soc 2005;2:A498. 2Cote C, et al. AnemiaIs a Predictor of Mortality in Patients with COPD. Proc Am Thorac Soc2005;2:A890. 3Celli BR, et al. N Engl J Med. 2004;350:1005-1012.

DISCLOSURE: Marya Zilberberg, Grant monies (from industry re-lated sources) These analyses were supported by Ortho Biotech ClinicalAffairs, LLC.; Employee Marya Zilberberg, MD and Samir H. Mody,PharmD are employees of Ortho Biotech Clinical Affairs, LLC.

THE PREVALENCE OF POLYCYTHEMIA IN A CHRONIC OB-STRUCTIVE PULMONARY DISEASE (COPD) COHORTClaudia Cote MD* Marya Zilberberg MD Samir H. Mody PharmDBartolome Celli MD Bay Pines VAMC, Bay Pines, FL

PURPOSE: Although thought to occur frequently, the actual preva-lence of polycythemia among patients with COPD and its effect onoutcomes in the current treatment environment is unknown. We charac-terized polycythemia prevalence and its association with outcomes inCOPD.

METHODS: We retrospectively analyzed data collected prospectivelyon 683 patients between 1/97 and 6/02 in a VA Pulmonary clinic for BMI,airflow obstruction, dyspnea, and exercise capacity (BODE) index valida-tion1. Polycythemia (P�) was defined as Hb�17 g/dL in men and �15g/dL in women2. All values are expressed as percentages or mean (SD). Pvalues were derived using a 2-sided Student’s t-test or Chi-square statisticwhere appropriate.

RESULTS: In this sample of 677 patients with known Hb values,polycythemia was present in 36 (5.3%) patients. The Table belowcompares P� to non-polycythemic (P-) patients.

CONCLUSION: Polycythemia is uncommon in COPD, occurring in�5% of patients, and is not associated with greater hypoxemia or anyother important clinical expression of the disease.

CLINICAL IMPLICATIONS: Additional studies are warranted toevaluate the prevalence and effects on outcomes of polycythemia inCOPD patients.1Celli BR et al. N Engl J Med 2004;350:1005-12 2Harri-son’s online, accessed 11-12-04 http://www3.accessmedicine.com/content.aspx?aID�58150&searchStr�polycythemia.

DISCLOSURE: Claudia Cote, Grant monies (from industry relatedsources) These analyses were supported by Ortho Biotech Clinical Affairs,LLC.; Employee Marya Zilberberg, MD and Samir H. Mody, PharmDare employees of Ortho Biotech Clinical Affairs, LLC.

A�(n�116)

A-(n�561) p Value

Age (yrs) 72.8 (9.3) 69.5 (8.8) 0.0003FEV1%predicted 43.17 (16.95) 42.07 (17.26) 0.5PaO2 (torr) 72.1 (13.3) 71.9 (11.9) 0.9BMI (kg/m2) 27.1 (6.7) 26.3 (5.8) 0.2Charlson Comorbidity

index, points6.5 (3.5) 4.8 (2.4) �0.0001

BODE index, points 5.3 (2.6) 4.7 (2.4) 0.0128Supplemental O2% on any 38 34 0.37Flow (L/min) 2.6 (0.7) 2.6 (0.9) 0.97Hospitalizations% hospitalized 47 38 0.06# hospitalizations/pt 1.3 (2.2) 0.9 (1.7) 0.03Days hospitalized/pt 13.4 (30.3) 7.8 (21.7) 0.02Follow-up (mos) 33.9 (21.7) 37.2 (22.1) 0.1511

P� (n�36) P- (n�641) p Value

Hb (g/dL) 17.5 (0.8) 14.3 (1.5) �0.0001On supplemental O2 (%) 31 34 0.62Age (yrs) 68.7 (9.5) 70.2 (9.0) 0.35F/U time (mos) 34.3 (20.4) 36.7 (22.2) 0.52FEV1% 42.7 (18.3) 42.2 (17.2) 0.88Room air PaO2 (torr) 70.4 (11.3) 72.0 (12.2) 0.446MWD (m) 339.1 (131.1) 313.5 (125.6) 0.24MRC dyspnea 2.4 (0.8) 2.6 (0.9) 0.21Charlson co-morbidity 4.8 (2.1) 5.1 (2.7) 0.56BMI (kg/m2) 27.8 (4.6) 26.4 (6.0) 0.16BODE index 4.4 (2.4) 4.9 (2.5) 0.302-year respiratory mortality (%) 31 27 0.822-year all-cause mortality (%) 36 35 0.93




THE PENETRATION/ASPIRATION RISK IN PATIENTS PRE-SENTING WITH AN ACUTE EXACERBATION OF CHRONICOBSTRUCTIVE PULMONARY DISEASE (COPD)Laura J. Carney MA Suzanne Sheppard PhD Karen F. Laframboise MD*University of Saskatchewan, Saskatoon, SK, Canada

PURPOSE: To determine the incidence of penetration/aspiration inpatients presenting with a COPD exacerbation. Is there a relationshipbetween the severity of tracheal penetration or aspiration and spirometryin patients with a COPD exacerbation?.

METHODS: Prospective study of twenty-one consecutive andeligible patients with the diagnosis of an acute COPD exacerbationadmitted to a university based tertiary care hospital. Patients under-went a videofluroscopic evaluation of swallowing and spirometry.consistencies were administered, for purposes of diet recommendationonly, analysis was done only with thin liquid consistency (100 mls totalvolume swallowed). Spirometry and the swallowing assessment werecarried out during the acute hospital admission. An eight-pointPenetration/Aspiration Scale developed by Rosenbek et al (1996) wasused to quantify the presence and severity of tracheal penetration oraspiration. Spirometry measures included FEV1, FVC and the FEV1/FVC, all values met ATS standards.

RESULTS: Penetration (contrast entering the trachea but not passingthe vocal cords) was seen in 10/21 patients. Aspiration or silent aspirationoccurred in 10/21 patients. One patient had no contrast enter the trachea.There was no obvious relationship between the severity ratings ofpenetration/aspiration and the severity of the airflow obstruction seen onspirometry.

CONCLUSION: The incidence of penetration/aspiration in patientspresenting with COPD exacerbation is of significance. There does notappear to be a correlation between the severity of the airflow obstructionand the degree degree of penetration or aspiration of thin fluids in thepopulation.

CLINICAL IMPLICATIONS: This study implies that a significantnumber of patients presenting with a COPD exacerbation have evidenceof unrecognized penetration/aspiration. Consideration of the implicationson dietary recommendations may need to be considered in this patientpopulation.

DISCLOSURE: Karen Laframboise, None.

SEX DIFFERENCES IN THE PREVALENCE OF PSYCHIATRICDISORDERS AND PSYCHOLOGICAL DISTRESS IN PATIENTSWITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE IN ACANADIAN SAMPLECatherine Laurin BSc* Kim L. Lavoie PhD Simon Bacon PhD Philippe R.Stebenne BSc Gilles Dupuis PhD Andre Cartier MD Guillaume LacosteBA M Julien MD Manon Labrecque MD Sacre-Coeur Hospital, Pneu-mology Research, Montreal, PQ, Canada

PURPOSE: Research has documented a high prevalence of psychi-atric disorders in patients with chronic obstructive pulmonary disease(COPD). In general, psychiatric disorders are more common in womenthan in men. However, few studies have evaluated sex differences inthe prevalence of psychiatric disorders in COPD patients. The presentstudy evaluated the prevalence of mood and anxiety disorders in 62women and 54 men with documented, stable COPD.

METHODS: Patients (n�116) underwent a sociodemographic andmedical history interview, followed by a structured psychiatric inter-view (ADIS-IV). All patients underwent spirometry and completed abattery of questionnaires measuring psychological distress and qualityof life.

RESULTS: A total of 57% of women vs. 35% of men met criteria forone or more anxiety disorder (Chi-Square�5.70, p�.01), and 31% ofwomen vs. 14% of men met criteria for one or more mood disorder(Chi-Square �4.03, p�.05). The most common anxiety disorder amongpatients was panic disorder, affecting 27% of women and 11% of men(Chi-Square �4.83, p�.05). The most common mood disorder was majordepression, affecting 18% of women and 6% of men (Chi-Square �6.70,p�.05). Women had significantly higher anxiety sensitivity and depressionscores compared to men (p’s �.01). Women also reported being lessconfident in their ability to control respiratory symptoms compared tomen (p�.05) and perceiving themselves as more limited in their activitiesas a result of their disease (p�.01), despite having comparable dyspneascores (p�.08).There were no differences in exacerbation rates (last year)

or forced expiratory volume in 1 second (FEV1, % predicted) betweenwomen and men.

CONCLUSION: Compared to prevalence rates in the general popu-lation (1-13%), results indicate that psychiatric disorders are at least threetimes higher in COPD patients, and that rates are nearly three times ashigh in women than in men. Women also show greater psychologicaldistress, worse perceived control of symptoms and worse disease-relatedquality of life.

CLINICAL IMPLICATIONS: Greater efforts should be made toidentify and treat psychiatric disorders in COPD patients, particularly inwomen.

DISCLOSURE: Catherine Laurin, None.

INDEPENDENT CONTRIBUTIONS OF CHRONIC OBSTRUC-TIVE PULMONARY DISEASE AND ABDOMINAL AORTIC AN-EURYSM TO MORTALITY RISKDmitry Lvovsky MD* Ashok Fulambarker MD Mark E. Cohen PhDSinan A. Copur MD Sunita Kumar MD Rosalind Franklin University ofMedicine and Science, Chicago Medical School, North Chicago, IL

PURPOSE: To determine mortality in patients with aortic abdominalaneurysm (AAA) and chronic obstructive pulmonary disease (COPD) ascompared to patients with only AAA.

METHODS: A retrospective cross-sectional study evaluated mor-tality for the four combinations of AAA (� or -) and COPD (� or -),using patient hospital records identified by ICD-9 codes. Other factorsrecorded and considered for predictive modeling included: coronaryartery disease, peripheral arterial occlusive disease, hypertension,smoking, pulmonary function tests, hypercholesteremia, size andrepair status of AAA.

RESULTS: Data were available for 460 subjects (455 males), with115 subjects in each of four groups defined by the presence or absenceof COPD and AAA. Mean ages (SD) were 75.12 (6.41), 76.49 (6.61),77.70 (5.64), and 76.60 (5.92) for COPD-/AAA-, COPD�/AAA-,COPD-/AAA�, and COPD�/AAA� groups, respectively (P�0.018,ANOVA, with only the oldest and youngest groups being significantlydifferent, Tukey). Among these groups, mortality rates were 6.96,66.96, 34.78, and 69.57 percent, respectively.Preliminary analysis,using logistic regression, found that COPD and AAA (P�0.0001) andtheir interaction (P�0.0002) were significant predictors of the binarymortality outcome. These effects were consistent when other factorswere included in the model. The Table shows odds ratios for variousgrouping arrangements. The group-wise comparisons suggest thatCOPD had a significant effect on mortality in the absence (OR�27.10)or presence of AAA (OR�4.29), while AAA had a significant effect onmortality in the absence of COPD (OR�7.13) but not in its presence(OR�1.13).

CONCLUSION: Among patients positive for AAA, the risk of death issignificantly greater when COPD is present. Among patients positive forCOPD, the risk of death is not significantly raised by AAA. This outcomemight due to a mortality ceiling effect observed for COPD but not forAAA.

CLINICAL IMPLICATIONS: Patients with AAA should be screenedfor COPD, because of the latter’s profound effect on mortality. Futurestudies on recognition and management of concurrent COPD and AAAseem warranted, with a potential to extend survival in this high-riskpopulation.

DISCLOSURE: Dmitry Lvovsky, None.




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NITRIC OXIDE DONOR-INDUCED, PERSISTENT INHIBI-TION OF CELL ADHESION MOLECULE EXPRESSION ANDNUCLEAR FACTOR KAPPAB ACTIVATION IN ENDOTHELIALCELLSThomas Waldow MD* Wolfgang Witt PhD Elvis Weber Michael KnautMD Klaus Matschke MD Herzzentrum Dresden, Dresden, Germany

PURPOSE: Our previous studies using a porcine model have shownthat inhalation of NO for a brief period just before the onset of ischemiacan protect the lung against ischemia/reperfusion (I/R) injury later on.The protection persisted throughout 90 min ischemia of the left lung anda reperfusion phase of up to 5 h. Here we present first results of theattempt to investigate the underlying mechanisms of “NO precondition-ing” by an in vitro approach using endothelial cells. Since NO pretreat-ment was especially effective in blocking I/R-induced inflammation, thestudy aims at the cytokine-dependent and NFkappaB-mediated expres-sion of cell adhesion molecules (CAM).

METHODS: Human umbilical vein endothelial cells (HUVEC) wereexposed to the NO donor, SNAP, for 5 min to 60 min. After washout, cellswere cultured in reagent-free medium for up to 16 h before the CAM -ICAM, VCAM, and E-selectin - were induced by exposure to TNFalphaor IL-1beta. The CAM on the cell surface were quantified by cell ELISA,and the level of the inhibitor of NFkappaB activation, IkappaBalpha, byWestern blotting. The relevance of the cGMP pathway was tested by usingthe guanylyl cyclase inhibitor, ODQ, and the cGMP analogue, 8-Br-cGMP. The dependence on NFkappaB was verified by the inhibitor ofNFkappaB activation, BAY 11-7082.

RESULTS: Preincubation with SNAP (1 mM) for 30 min was sufficientto reduce the cytokine-induced expression of CAM to less than 10 % ofcontrols. This “refractory” state persisted for 6 h after washout of the NOdonor in the combination TNFalpha/VCAM. The SNAP effect was notmediated by the cGMP pathway. The TNFalpha-dependent induction ofCAM was strictly dependent on the activation of NFkappaB. AfterTNFalpha exposure, a high level of IkappaBalpha was persistentlydetected in SNAP-treated HUVEC, while the inhibitor was immediatelydegraded in controls.

CONCLUSION: Persistent blocking of NFkappaB-dependent CAMexpression by SNAP pretreatment in endothelial cells may be causallyrelated to the stabilization of IkappaBalpha.

CLINICAL IMPLICATIONS: Results may be relevant to clinicalsituations of I/R-induced inflammation.

DISCLOSURE: Thomas Waldow, None.

OFF-PUMP CORONARY ARTERY BYPASS SURGERY IN A LOWCASE LOAD CENTER: MID-TERM FOLLOW-UP OF THEFIRST 107 PATIENTSParwis Massoudy MD* Matthias Thielmann MD Julia Schafer MS EvaAssenmacher MD Christian Losch Axel Schmermund MD Ivan AleksicMD Jarowit A. Piotrowski MD Walter O. Schuler MD Peter KienbaumMD Raimund Erbel MD Heinz Jakob MD West German Heart Center,Department of Thoracic and Cardiovascular Surgery, Essen, Germany

PURPOSE: Off pump coronary artery bypass (OPCAB) grafting is stilldiscussed controversially in the cardiac surgical community. Early peri-operative results are encouraging. Only few reports have focused onmid-term recurrence of angina and freedom from death or re-interven-tion.

METHODS: 107 OPCAB patients (mean age 63�1 years, 77 male,mean additive EuroScore 4.1�0.3, mean logistic EuroScore 5.6�0.7%,number of distal anastomoses 2.0�0.1), operated on between January1999 and December 2003, were systematically followed up comparingpre- and post-operative NYHA- and CCS-classifications and assessingfreedom from death and re-intervention. 52 of 107 patients underwentpostoperative angiography or multi-slice computed tomography (MSCT).24 of the latter 52 patients were symptomatic, 21 with stable angina, 3with unstable angina, the others underwent follow-up studies having giventheir informed consent.

RESULTS: Perioperative 30 day mortality was 3%. Freedom fromdeath or re-intervention at 5.5 years was 91% and 80%, respectively. Onlythree patients required re-intervention in an OPCAB-related vessel. CCSclassification was 2.8�0.1 before surgery and 1.8�0.2 (p�0.01) atfollow-up (3.3�0.3 years). NYHA classification was 2.7�0.1 and 2.2�0.1(p�0.01), respectively. 52 patients (24 for cardiac symptoms) underwentcoronary angiography or MSCT at a mean follow-up of 2.2�0.3 years. Left

internal thoracic artery was patent in 91%, venous graft patency rate was83%.

CONCLUSION: In this small but consecutive OPCAB populationwith a considerable perioperative risk according to the EuroScore,freedom from death and re-intervention at 5.5 years is acceptable andgraft patency rate at 2.2�0.3 years is in the expected range. Significantreduction in both CCS and NYHA classification indicate sustained clinicalimprovement at mid-term.

CLINICAL IMPLICATIONS: Even with a low case load, reservingOPCAB to selected indications, surgery can be performed at low operativemortality and acceptable mid-term results.

DISCLOSURE: Parwis Massoudy, None.

CORONARY ARTERY BYPASS GRAFTING USING SKELETON-IZATION OF THE RADIAL ARTERY: EXPERIENCE OF 500CASESHitoshi Hirose MD* Atsushi Amano MD Juntendo University Hospital,Tokyo, Japan

PURPOSE: To optimize graft flow and graft patency of arterialgraft, all arterial conduits including the internal mammary artery (sinceJanuary 1999), radial artery (since September 1999) and gastroepiploicartery (since September 2002) have been harvested in skeletonizedtechnique. Currently, in Japan, the “standard” technique of radialartery harvesting has been completely changed from pedicle harvestingtechnique (the artery, associated veins, adventitia, and surroundingfascia harvested as an en-block using an electrocautery) to skeletonizedharvesting technique (removal of all adventitia from the main trunk ofthe radial artery using a ultrasonic scalpel). Here we report ourexperience of more than 500 cases of skeletonized radial arterygrafting.

METHODS: Between September, 1999 and April, 2004, isolatedcoronary artery bypass grafting (CABG) was performed in a total of 893patients at Shin-Tokyo – Juntendo Hospital Group. Of these, 557 patientsunderwent skeletonized radial artery grafting, and their perioperative,early angiographic, and follow-up results were analyzed.

RESULTS: Study group was consisted of 417 male and 138 femalewith mean age of 66.2 � 9.1, and preoperative EuroSCORE of 3.7 �2.7. The details of the perioperative data are shown in Table 1. Noperioperative myocardial infarction, bleeding related to the radialartery graft or graft harvesting site complication was observed. Earlyangiography within 3 month after surgery was performed in 291patients demonstrated radial artery anastomosis patency rate of 97.0%(458/472) and stenosis-free anastomosis patency rate of 92.8% (458/472). Distant angiography beyond 6 months after surgery performed inadditional 37 patients, revealed stenosis-free anastomosis patency rateof 92.4% (61/66). Follow-up was completed all hospital survivors witha mean follow-up of 1.0 � 0.5 years and found 3 patients (0.5%)developed radial artery related cardiac events.

CONCLUSION: The early clinical outcome and angiographical resultsof radial artery grafting using “new standard” skeletonized harvestedtechnique were excellent and comparable to previous reports of thosewith “classical” pedicle harvesting technique.

CLINICAL IMPLICATIONS: This new standard skeletonizationtechnique may replace the classical pedicle harvesting technique.

DISCLOSURE: Hitoshi Hirose, None.

POSTOPERATIVE CREATINE KINASE MB LEVEL IS ASSOCI-ATED WITH IN-HOSPITAL MORTALITY AFTER CORONARYSURGERYLi Zhang MD Kathleen Petro MD Peter Hill MD* Elizabeth Haile MSJorge Garcia MD Ammar Bafi MD Steven Boyce MD Paul Corso MDWashington Hospital Center, Washington, DC

PURPOSE: Cardiac enzymes are widely used for evaluation of peri-operative myocardial injury. This study was to investigate the potentialrelationship between postoperative creatine kinase MB (CKMB) level andclinical outcomes in the patients after isolated coronary artery bypassgrafting (CABG).

METHODS: Seven thousand and ninety-five patients who under-went isolated CABG between January 2000 and June 2004 at theWashington Hospital Center were included in this study. CKMB levelwas measured in the morning of the first post-operative day. Threegroups were created according to CKMB level: Group I: CKMB � 5.2


Cardiac Surgery12:30 PM - 2:00 PM


ng/ml; Group II: 5.2 � CKMB � 13 ng/ml; Group III: CKMB � 13ng/ml.

RESULTS: CKMB level above normal upper limit was relativelycommon after isolated CABG. Patient with CKMB � 13 ng/ml (5 timesof normal upper limit) were more frequently those with history ofmyocardial infarction (MI), left main disease and poor left ventricularfunction (EF � 35%), preoperative IABP support, having a repeatedprocedure (Table 1). Difference of in-hospital mortality, morbidities(stroke, MI) and length of hospital stay was statistically significantbetween the three groups (Table 2). Based on multivariable analysis,patients with CKMB � 13 ng/ml were more likely at risk for isolatedCABG than those with CKMB � 5.2 ng/ml (2 times of normal upper

limit), in terms of in-hospital mortality, postoperative MI, and pro-longed hospitalization (p � 0.01).

CONCLUSION: This is the largest retrospective study on the prog-nostic value of postoperative CKMB level in patients undergoing CABG.We conclude that an extremely high CKMB level is an indicator ofin-hospital mortality and morbidities.

CLINICAL IMPLICATIONS: CKMB levels should be measuredroutinely after CABG, to identify high-risk patients.

DISCLOSURE: Peter Hill, None.

C1-ESTERASE INHIBITOR TREATMENT DURING EMER-GENCY CORONARY ARTERY BYPASS SURGERY IN PATIENTSWITH ACUTE ST-ELEVATION MYOCARDIAL INFARCTIONMatthias Thielmann MD* Guenter Marggraf MD Parwis Massoudy MDMarkus Neuhauser PhD Stephan Knipp MD Markus Kamler MD JarowitPiotrowski MD Heinz Jakob MD Thoracic and Cardiovascular Surgery,West-German Heart Center Essen, University, Essen, Germany

PURPOSE: Myocardial inflammatory response including complementactivation was demonstrated as an important mechanism of ischemia-reperfusion injury and complement inhibition by C1-esterase-inhibitor(C1-INH) has recently shown cardioprotective effects in experimental andclinical settings.

METHODS: The effects of C1-INH on complement activation, peri-operative myocardial cellular damage and patients outcome were studiedin patients undergoing emergency CABG due to acute ST-elevationmyocardial infarction (STEMI) with (group 1,n�25) and without (group2,n�25) bolus administration of C1-INH (40 IU.kg -1) during reperfusionand 6 hours (hrs) postoperatively (20 IU.kg-1) besides the same studyprotocol. Complement activation fragments (C4), C1-INH, and cardiactroponin I (cTnI) were measured preoperatively, and at 6, 12, 24, and 48hrs postoperatively. Clinical data, adverse events and patients outcomewere recorded prospectively.

RESULTS: Patient characteristics were not different betweengroups. No drug-related adverse events could be observed in group 1.Constant plasma levels of C1-INH and a reduction of C4 fragmentswere found in group 1. Preoperative cTnI levels were elevated but notdifferent between the groups. The postoperative release of cTnI wassignificantly lower (P�0.05;ANOVA) in group 1 with �6hrs betweensymptom onset and reperfusion compared to group 2 at 12 (38.5�22.1versus 75.7�24.6 ng/mL), 24 (65.5�24.5 versus 95.2�28.3 ng/mL),and 48hrs (58.3�37.5 versus 87.5�41.2 ng/mL) after surgery, butremained unchanged between the groups among patients with atreatment delay of more than 6hrs. Adverse events, ICU and hospitalstay, and in-hospital mortality (13.4% versus 14.3%) were not differentbetween the groups.

CONCLUSION: The present study is the first to evaluate the effectsof complement inhibition during emergency CABG with STEMI. C1-INH effectively inhibited complement activation and did not causeadverse effects. The reduced release of cTnI was only observed in

Table 1. Univariate Comparisons of Demographic andClinical Characteristics Between the Three Groups.

Group I

(CKMB �5.2

ng/ml)

(N�3,531)

Group II

(5.2�CKMB

�13ng/ml)

(N�2,197)

Group III

(CKMB�13

ng/ml)

(N�1,367) p value

Age (y) 64.4�10.6 64.6�10.6 65.1�10.7 0.05*

Female Gender 1020(28.9) 583 (26.5) 434 (31.8) 0.23

Diabetes 1308 (37.0) 783 (35.6) 482 (35.3) 0.19

Hypertension 2465 (69.8) 1587 (72.2) 977 (71.5) 0.12

Congestive Heart

Failure

281 (8.0) 215 (9.8) 98 (7.2) 0.92

Myocardial Infarction

within 24 hrs

6 (0.2) 11 (0.5) 28 (2.1) �0.01

History of Myocardial

Infarction

1259 (35.7) 891 (40.6) 633 (46.3) �0.01

Previous CVA 4 (0.1) 7 (0.3) 1 (0.1) 0.81

Carotid Artery Disease 60 (1.7) 32 (1.5) 28 (2.1) 0.58

Renal Failure 123 (3.5) 87 (4.0) 62 (4.5) 0.08

Preoperative Hemodialysis 62 (1.8) 44 (2.0) 35 (2.6) 0.08

COPD 18 (0.5) 20 (0.9) 9 (0.7) 0.31

Left Main Disease 458 (13.0) 336 (15.3) 224 (16.4) �0.01

Ejection Fraction �0.01*

� 45% 1951 (55.3) 1055 (48.0) 579 (42.4)

35% - 45% 945 (26.8) 623 (28.4) 445 (32.6)

25% - 34% 506 (14.3) 388 (17.7) 276 (20.2)

� 25% 129 (3.7) 131 (6.0) 67 (4.9)

Preoperative IABP

Insertion

38 (1.1) 42 (1.9) 33 (2.4) �0.01

Peripheral Vascular

Disease

397 (11.2) 288 (13.1) 188 (13.8) 0.01

Parsonnet Risk Score 11.0 (6.0–17.0) 12.0 (6.5–19.0) 13.5 (9.0–20.5) �0.01*

Northern New England

CVA Risk Score

1.1 (0.7–1.9) 1.5 (0.7–2.8) 1.5 (0.7–2.8) �0.01*

Off-pump CABG 2864 (81.1) 798 (36.3) 545 (39.9) �0.01

Redo CABG 82 (2.3) 110 (5.0) 122 (8.9) �0.01

Urgent CABG 763 (21.6) 559 (25.4) 405 (29.6) �0.01

Number of Grafts �0.01*

1 221 (6.3) 42 (1.9) 32 (2.3)

2 704 (19.9) 192 (8.7) 147 (10.8)

3 1254 (35.5) 656 (29.9) 391 (28.6)

4 924 (26.2) 793 (36.1) 505 (36.9)

5 357 (10.1) 414 (18.8) 241 (17.6)

6 57 (1.6) 81 (3.7) 41 (3.0)

7 13 (0.4) 17 (0.8) 9 (0.7)

8 1 (0.03) 1 (0.1) 1 (0.1)

9 0(0.0) 1(0.1) 0(0.0)

*Values are expressed as N (%), mean � std or median (25th – 75th

percentile).

Table 2. Univariate Comparisons of PostoperativeOutcomes Between the Three Groups.

Group I

(CKMB �5.2

ng/ml)

(N � 3,531)

Group II

(5.2 �CKMB �13

ng/ml)

(N � 2,197)

Group III

(CKMB �13

ng/ml)

(N � 1,367) p Value

In-Hospital Operative

Mortality

13 (0.4) 27 (1.2) 24 (1.8) �0.01

Stroke 46 (1.3) 40 (1.8) 36 (2.6) �0.01

Myocardial Infarction 13 (0.4) 36 (1.6) 90 (6.6) �0.01

Prolonged Ventilation 126 (3.6) 142 (6.5) 146 (10.7) �0.01

Need of Hemodialysis 3 (0.1) 6 (0.3) 3 (0.2) 0.17

Length of Hospital

Stay (day)

4 (4–6) 5 (4–7) 5 (4–7) �0.01*

*Values are expressed as N (%) or median (25th – 75th percentile).


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patients, who were treated within the first 6hrs from symptom onset toreperfusion.

CLINICAL IMPLICATIONS: C1-INH administration during emer-gency CABG with acute STEMI is safe and effective to inhibit comple-ment activation and may reduce myocardial ischemia-reperfusion injury inpatients undergoing CABG within 6hrs between symptom onset andreperfusion.

DISCLOSURE: Matthias Thielmann, None.

RISK STRATIFICATION AND CLINICAL OUTCOME IN PA-TIENTS WITH ACUTE ST-ELEVATION MYOCARDIAL IN-FARCTION UNDERGOING CORONARY ARTERY BYPASS SUR-GERYMatthias Thielmann MD* Parwis Massoudy MD Guenter Marggraf MDIvan Aleksic MD Markus Kamler MD Ulf Herold MD Jarowit PiotrowskiMD Heinz Jakob MD Thoracic and Cardiovascular Surgery, West-German Heart Center Essen, University, Essen, Germany

PURPOSE: Treatment strategies for ST-elevation myocardial infarc-tion (STEMI) have undergone great evolution since introduction of acutepercutaneous coronary intervention (PCI) therapy. The purpose wastherefore to evaluate in-hospital mortality, clinical outcomes, and predic-tors of survival among patients who underwent surgical revascularizationwith coronary artery bypass grafting (CABG) due to STEMI unresponsiveto maximal non-surgical therapy.

METHODS: Between 01/2000 and 01/2005 eighty-four patients un-derwent CABG due to STEMI at our institution. Preoperative, intraop-erative and postoperative data were recorded prospectively. In-hospitalmortality, major adverse cardiac events (MACE), and other clinicaloutcomes were investigated retrospectively.

RESULTS: Thirty-four, 22, 10, and 18 among 84 patients with STEMIunderwent CABG within 6 hours (hrs), 7-24 hrs, 1-3 days, and 4-7 daysfrom onset of symptoms to surgery, respectively. Thirty-two among 84(38%) patients were admitted to surgery complicated by preoperativecardiogenic schock. Thus, preoperative and/or intraoperative intraaorticballoon counterpulsation was performed in 15 and 45 patients, whereaspreoperative extracorporeal membrane oxygenation was necessary in 2patients. Mean number of grafts per patient was 3.1�0.9. Aortic cross-clamp time, cardiopulmonary bypass time, and reperfusion time were67�21 min and 126�45 min, and 46�22 min, respectively. Ventilationtime, ICU and hospial stay were 54�53 hrs (mean�SD), 6.3�6.4 hrs and21�24 days, respectively. Overall in-hospital mortality was 13.1%. Onmultivariate logistic regression analysis, gender (Odds ratio [OR]: 8.7, 95%confidence interval [CI]: 1.2-62.5), the level extent of preoperative cardiactroponin I (OR: 1.2,CI: 1.1-1.4), and time from onset of symptoms tosurgery (OR: 1.1,CI: 1.1-2.8) were independent predictors of in-hospitaldeath.

CONCLUSION: Emergency CABG in STEMI patients unresponsiveto maximal non-surgical therapy can be performed with acceptable riskincorporating adequate management strategies.

CLINICAL IMPLICATIONS: The extent of acute myocardial dam-age and time period from symptoms to surgery are major variablespredicting mortality results and thus, may help the surgeon to decideabout the appropriate timing of surgical revascularization in patients withacute STEMI.


IMPACT OF MYOCARDIAL HYPERTROPHY AND PREOPERA-TIVE LEFT VENTRICULAR EJECTION FRACTION ON POSTOPERATIVE COMPLICATIONS AFTER AORTIC VALVE RE-PLACEMENT FOR AORTIC STENOSISJean-Louis Mariage MD* Pierre Bulpa MD Isabelle Michaux MDManuel Gonzalez MD Jacques Jamart MD Etienne Installe MD PatrickEvrard MD Mont-Godinne Hospital, Cliniques Universitaires de Mont-Godinne, Yvoir, Belgium

PURPOSE: Patients (pts) with aortic stenosis (AS) have a goodprognosis after aortic valve replacement (AVR). Morbidity and mortalityof AS pts with severe septal hypertrophy (SSH,�16mm) or supranormal(�70%) left ventricular ejection fraction (LVEF) have been poorlyinvestigated. We retrospectively analysed complications and outcome ofsuch pts after surgery.

METHODS: Between 10/98 and 03/03, 280 pts underwent AVR.Only pure AS pts were included; excluding aortic regurgitation,

ischaemic cardiomyopathy, associated coronary or thoracic aorticsurgery, or mitral disease. Eighty seven pts met the criteria. Analysiswas performed on 2 criteria: preoperative LVEF and septal thickness(ST). For LVEF analysis, pts were divided in 2 groups: GA: LVEF 50to 69% (n�29) and GB: LVEF �70% (n�44); and in 3 for the STcriteria: G1: ST�13mm (n�18); G2: 13�ST�16mm (n�31); and G3:ST�16mm (n�11). We analysed length of ICU and hospital stay;duration of ventilation; use of vasoactive drugs, calcium channel’sblockers or b-blockers; arrhythmia events, occurrence of renal failureor need for haemodialysis, and mortality. Usually pts after AVR stay atleast 2 nights in our ICU.

RESULTS: In LVEF analysis, 17% of pts in GB were ventilated �24hours in comparison with 0% in GA [p�0.036]. In ST analysis, 27.8% ofpts in G1, 35.5% in G2, and 54.5% in G3 stayed �2 nights in the ICU(NS). Two pts from G3 required haemodialysis [p�0.032]. There were nodifference in the length of ICU and hospital stay, use of vasoactive orvasodilator drugs, and occurrence of arrhythmia in group GA vs. GB, or ingroup G1 vs. G2 vs. G3. No patient died during hospital stay.

CONCLUSION: Using selective criteria, pure AS pts have an excellentprognosis after AVR; however pts with LVEF �70% have a higher risk ofprolonged ventilation, and SSH pts have a higher incidence of haemodi-alysis.

CLINICAL IMPLICATIONS: Diastolic dysfunction consecutive toSSH or supranormal LVEF pts could be improved by pharmacologicalintervention. Further studies are necessary to confirm this hypothesis.

DISCLOSURE: Jean-Louis Mariage, None.

SURGICAL OUTCOMES FOR THE MANAGEMENT OFCHRONIC PULMONARY THROMBOEMBOLIC DISEASEGonzalo V. Gonzalez-Stawinski MD* Arash Salemi MD Albert S. ChangMD Delos M. Cosgrove MD Bruce W. Lytle MD Nicholas G. SmediraMD The Cleveland Clinic Foundation, Cleveland, OH

PURPOSE: Chronic pulmonary thromboembolic disease (cPE) resultsin significant morbidity and mortality. Surgical therapy is aimed atalleviating the effects of the thrombus on oxygen saturation, pulmonaryhypertension, and improving outcomes. This study was conducted todetermine our experience with pulmonary thromboembolectomy as atherapy for cPE.

METHODS: A retrospective chart review identified patients undergo-ing pulmonary endarterectomy for chronic pulmonary thromboembolism.We obtained demographics, symptoms prior to surgical therapy, operativeprocedures, and outcomes.

RESULTS: Between December 1994 and December 2003 a total of 30patients were surgically treated for chronic pulmonary embolism. Therewere 13 males and 17 females. Average age was 49.2 yrs (range 21- 76 yrs).The most common presenting symptom was SOB in 26 (96.7%) patients.Half the patients (50%) had a past medical history of venous thrombo-embolic disease, 20% had a documented hypercoagulable state, but 93.3%of the patients had a vena cava filter placed preoperatively. Meanpreoperative systolic pulmonary artery presssures (PAP) was 77.9 mmHg(range 53 –107 mmHg). Surgical approaches included bilateral thrombo-embolectomies in 25 (83.3%) patients. Circulatory arrest was used in 29(97%. Mean arrest time of 33.2 minutes (range 6 –60 minutes). Postop-eratively there was a decrease in mean systolic PAP to 41.4 mmHg (range26-73 mmHg, p � 0.001). While mean saturations (SAT) increasedfollowing surgical intervention (pre op SAT 94.2% vs. post op SAT 96.1%,p � 0.014) this did not result in a decrease in supplemental oxygen use.The 30 day survival was 93.3 % with an overall survival of 80.3% (meanfollow-up of 3.5 yrs, range 7d - 10.3 years).

CONCLUSION: Pulmonary thromboembolectomy under circulatoryarrest is a safe and effective intervention which significantly improvespulmonary artery pressures, oxygen saturation and is associated with goodmid-term outcomes.

CLINICAL IMPLICATIONS: Pulmonary thromboembolectomy isan effective means of therapy for patients suffering of disabiling pulmo-nary symptoms as a result of chronic pulmonary thromboembolic disease.

DISCLOSURE: Gonzalo Gonzalez-Stawinski, None.




SHORT TERM OUTCOMES FOR THE ST. JUDE AORTIC CON-NECTORS: A REVIEW OF 348 IMPLANTSDouglas C. Miller MD* Timothy H. Trotter MD Mary Lane PhDUniversity of Oklahoma, Section of Thoracic and Cardiovascular Surgery,Oklahoma City, OK

PURPOSE: The use of aortic connectors for the performance of proximalanastomosis in beating heart surgery was initially embraced as a result of theease of performance and the ability to avoid the placement of clamps on theaorta. Concerns regarding the failure rates of these devices have promptedmost surgeons to abandon their use. We review the early clinical course of the348 proximal anastamoses performed with the St. Jude Symmetry AorticConector (SJAC) device in our beating heart CABG program.

METHODS: A review of the medical records of all patients whounderwent placement of SJAC was undertaken to evaluate for thepresence of recurrent angina, myocardial infarction, other cardiac event,or intervention in the cardiac catheterization lab.

RESULTS: Proximal anastamotic failure occurred in 13/124 (10.48%)patients with 22/348 (6.3%) of the grafts requiring intervention in thecatheterization lab at a mean interval of 9.2 months (range 0.5-18months).Overall mortality for the group of patients was 3/124 (2.42%) patients and theoperative mortality was 2/124 (1.6%). There were no deaths directly attrib-utable to SJAC failure. There were no strokes in any of the SJAC patients.

CONCLUSION: There is a risk of early graft failure with the use of theSJAC. These failures can frequently be managed in the cardiac catheter-ization lab with standard catheter-based interventions. The late failurerate of these devices remains poorly defined and further study of thosepatients with implanted SJAC should occur.

CLINICAL IMPLICATIONS: The introduction of SJAC allowed for per-formance of beating heart CABG with a lower incidence of stroke; however, thisbenefit appears to have been achieved at the cost of an increased early proximalanastamotic failure rate. The fate of spahenous vein grafts that have undergoneintervention is known to be less satisfactory than unintervened grafts and it isanticipated that the higher than expected early graft failure rate will translate topoorer long term saphenous vein graft patencies.

DISCLOSURE: Douglas Miller, None.

FACTORS INFLUENCING THE OUTCOME OF RESUSCITA-TION AFTER POSTOPERATIVE ARREST IN CARDIAC SUR-GERY PATIENTSPrashant C. Shah MD* Mikhail Vaynblat MD Murali Pagala PhD DineshBhaskaran MD Joseph N. Cunningham, Jr MD Maimonides MedicalCenter, Brooklyn, NY

PURPOSE: Cardiopulmonary arrest is an unexpected event in cardiacsurgery patients in the postoperative period. Most studies have alwaysadvocated an expeditious conversion from closed-chest to open-chestCPR for cardiac arrest after cardiac surgery. The present study wasdesigned to characterize the outcome of closed-chest compared withopen-chest CPR, to define potential factors associated with unresponsive-ness to closed-chest CPR, and to evaluate the need for open-chest CPRfor this subgroup of patients.

METHODS: A retrospective review was conducted for all cardiac surgicalpatients who underwent CPR for postoperative arrest between March 1995and April 2002. Extensive data pertaining to preoperative, intraoperativecharacteristics, postoperative complications, and periarrest factors were col-lected. All data were analyzed using various statistical models.

RESULTS: Of the 6,094 patients, 45 (0.74%) patients had a cardiacarrest within seven postoperative days and required CPR. Twenty-four(53%) patients underwent only closed-chest CPR, whereas 21 (47%)patients underwent a conversion from closed-chest to open-chest CPR.Within the closed-chest CPR group, 17 (71%) were successfully resusci-tated, while 7 (29%) died. Within the open-chest CPR group, only 3 (14%)were successfully resuscitated, while 18 (86%) died. A chi-squared testshowed that the difference in the proportion of successful outcomebetween closed and open CPR was significant (p�0.001). The 17 patientswho were successfully revived with closed-chest CPR were comparedagainst the other 28 patients as a whole who did not respond toclosed-chest CPR. Univariate predictors of failed closed-chest CPRincluded the presence of preoperative hypertension (p�0.001), thepresence of severe angina (p�0.06), and urgent/emergent nature ofsurgery (p�0.005). Univariate predictors of successful closed-chest CPRincluded elective nature of surgery (p�0.05) and shorter aortic cross-clamp times (p�0.05).

CONCLUSION: The above results confirm that open-chest CPR hasa poor overall outcome and may not be worthwhile for all casesunresponsive to closed-chest CPR.

CLINICAL IMPLICATIONS: Using the above outcome-associatedfactors may help the clinician determine which group of patients forwhom it may be futile or worthwhile to convert to open-chest CPR.

DISCLOSURE: Prashant Shah, None.

RIGHT VENTRICULAR BLEEDING ASSOCIATED WITH ME-DIASTINITIS: A NEW RISK FACTORXavier M. Mueller MD* David Greentree MD Dominique Dorion MDMarcel Martin MD Raymond Duperval MD Dominique Berard MDMichel Nguyen MD Serge Lepage MD CHUS, Sherbrooke, PQ, Canada

PURPOSE: Mediastinitis-related right ventricular (RV) rupture is apotentially life-threatening complication of cardiac surgery. Our experi-ence with this complication is analyzed.

METHODS: All the cases of mediastinitis recorded since the intro-duction of a prospective database for our cardiac surgery program werereviewed. All the patients with bleeding from the anterior surface of theheart during this interval were analyzed.

RESULTS: Among the 953 consecutive patients who underwent heartsurgery between January 2003 and May 2005, mediastinitis occurred in 20cases (2.1%). All 20 patients had coronary artery surgery, three of themcombined with aortic valve replacement. Four patients developed RVbleeding while waiting for their secondary chest closure. In the four cases,bleeding occurred between 1 and 6 days after sternal debridement. Onepatient died immediately of exsanguination. The other three had limitedbleeding which could be repaired at bedside with direct sutures. All 3patients had subsequent successful closure with pectoral flaps, but oneeventually died of multiple cerebral emboli. Notably, the four bleedingsoccurred among the 12 patients (33%) who had their pericardium leftopen at the time of the initial cardiac operation, while no rupture occurredamong the 8 patients (0%) who had their pericardium closed.

CONCLUSION: In this series, RV bleeding developed exclusivelyamong patients who had their pericardium left opened during their initialcardiac operation. The RV tear likely resulted from the distraction of thesternal edges which was transmitted directly to the fragile RV wall.

CLINICAL IMPLICATIONS: In order to prevent this severe compli-cation, we recommend systematic closure of the pericardium at the primaryoperation. When the pericardium has been left open, we recommend that theRV should be widely freed from the sternal edges during the debridementand that the chest should be closed as soon as possible.

DISCLOSURE: Xavier Mueller, None.

COMPARISON BETWEEN “SWAN-GANZ” DERIVED ANDECHOCARDIOGRAPHIC VARIABLES IN THE PREDICTIONOF HEMODYNAMIC COMPLICATIONS FOLLOWING CAR-DIAC SURGERYPierre-Marc Chagnon MD* Andre-Yves Denault MD Pierre Couture MDSylvie Levesque MS Jean-Claude Tardif MD Michel Carrier MD Mon-treal Heart Institute, Longueuil, PQ, Canada

PURPOSE: To compare hemodynamic and echocardiographic variables intheir ability to predict hemodynamic complications following cardiac surgery.

METHODS: We conducted a retrospective analysis of 243 consecutivepatients having undergone a cardiac surgical procedure in our center.Demographic, perioperative variables, “Swan-Ganz” derived hemodynamicprofile and a standard sequence of cardiac images to evaluate systolic anddiastolic function (using a multiplane TEE) were obtained after the inductionof anaesthesia but before sternotomy. The primary end point consisted of acomposite index of death, resuscitated cardiac arrest, the use of vasoactivesupport for more than 24 hours postoperatively, or the use of an intra-aorticballoon pump that was not present preoperatively.

RESULTS: 49 patients (20%) experienced hemodynamic complica-tions, defined by the composite index. These patients had higher Parson-net scores and body mass index, more complex surgeries and leftventricular dilatation, longer bypass and clamping time, more frequentdifficult separation from bypass (DSB), lower mean arterial pressure/mean pulmonary arterial pressure ratio (MAP/MPAP), lower fractionalarea change and higher regional wall motion score index (RWMSI). In theunivariate analysis, the only significant hemodynamic and echocardio-graphic variables were the MAP/MPAP ratio (3.38 � 1.51 vs. 3.76 � 1.17;OR 0.75, CI 0.56-1.00, p � 0.0524) and the RWMSI (OR 2.26, CI




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1.17-4.35, p � 0.0153). A multiple stepwise logistic regression showedthat the only 3 independent predictors of postoperative hemodynamiccomplications were the duration of cardiopulmonary bypass time (128 �57 vs. 90 � 42 min; OR 1.02, CI 1.01-1.02, p � 0.0001), aortic cross-clamptime (87 � 44 vs. 60 � 40 min, OR 1.02, CI 1.01-1.02, p � 0.0002) andDSB (82% vs. 45%, OR 5.47, CI 2.52-11.9, p � 0.0001).

CONCLUSION: No “Swan-Ganz” derived or echocardiographic vari-ables were found to be independent predictors of complications aftercardiac surgery. The duration of the procedure and DSB are the mostimportant independent predictors of hemodynamic complications follow-ing cardiac surgery.

CLINICAL IMPLICATIONS: Prevention of DSB could represent a po-tential strategy to reduce hemodynamic complications after cardiac surgery.

DISCLOSURE: Pierre-Marc Chagnon, None.

PERIOPERATIVE PHYSICAL THERAPY MANAGEMENT FOL-LOWING CARDIAC SURGERY: A SYSTEMATIC REVIEWTom J. Overend PhD* Cathy M. Anderson MS Jennifer Jackson-Lee BSc SDeborah Lucy PhD Monique Prendergast MS Susanne Sinclair BSc School ofPhysical Therapy, University of Western Ontario, London, ON, Canada

PURPOSE: Two local hospitals were amalgamating cardiac surgeryservices. There was a disparity in the perioperative physiotherapy careprovided following cardiac surgery at the two sites. Thus our purpose wasto carry out a systematic review of the evidence to determine the optimalperioperative physiotherapy management of cardiac surgery patientsfollowing CABG and/or cardiac valve surgery.

METHODS: Medline, CINAHL and EMBASE data bases were searchedfrom inception until April 2005, using key terms including physiotherapy,coronary artery bypass, cardiac surgery, valve surgery, postoperative complica-tions, atelectasis, breathing exercises, mobility, and education. A secondary searchof the reference lists of all identified articles was also carried out. A form wasdeveloped to standardize critical appraisal. Each study was reviewed indepen-dently by one of three pairs of reviewers. The pair then met to reach consensusbefore presenting the study to the entire research team for final agreement.Accepted papers were graded for strength of evidence and recommendationswere extracted for physiotherapy practice.

RESULTS: The search strategy yielded 138 articles. Seventy-fourstudies dealing with physiotherapy management of the CABG and/orcardiac valve surgery patient in the perioperative period were acceptedand critically appraised; 33 of these were rejected for methodologicalflaws. Evidence-based conclusions relating to physiotherapy practice wereextracted from 37 papers and combined into 13 recommendations:perioperative cardiorespiratory therapy (5), education (6), anxiety (1) andpain control (1). There was insufficient evidence to support recommen-dations for exercise, positioning, shoulder range of motion, and acuteeffects of cardiorespiratory treatment in the perioperative period.

CONCLUSION: Virtually all of the reviewed literature dealt withlow-risk patients. High-risk cardiac surgery patients thus require individ-ually determined, perioperative physiotherapy management. While peri-operative education and mobility remain important for routine patients,the evidence does not support other traditional postoperative cardiorespi-ratory physiotherapy treatment approaches.

CLINICAL IMPLICATIONS: The routine, low-risk cardiac surgerypatient requires little in the way of perioperative cardiorespiratoryphysiotherapy save for ensuring initial mobility assistance and provision ofeducation regarding breathing exercises and other self-treatments duringthe postoperative course.

DISCLOSURE: Tom Overend, None.

Cardiac Surgery: Congenital12:30 PM - 2:00 PM

SURGICAL TREATMENT IN NEONATES WITH AORTIC ARCHOBSTRUCTION OR INTERRUPTION WITH FUNCTIONAL SIN-GLE VENTRICLEMark Ruzmetov MD* Palasniswamy Vijay PhD Mark D. Rodefeld MDMark W. Turrentine MD John W. Brown MD Indiana University Schoolof Medicine, Indianapolis, IN

PURPOSE: The neonate with a functional single ventricle (FSV) andaortic arch obstruction or interruption other than hypoplastic left heart

syndrome (HLHS) poses a uniquely difficult challenge because of thestimulus for myocardial hypertrophy and failure from impedance tosystemic outflow and pulmonary vascular disease from pulmonary over-circulation.

METHODS: Among the patients with FSV and excessive pulmonaryblood flow, who underwent palliative surgery since 1990, 36 neonates hadaortic coarctation (n�32) or interruption (n�4). Patients with HLHSwere excluded. The median age at operation was 7.5 days (range 2 to 84days) and the median weight was 3.3 kg (range 2.7 to 5 kg). 28 childrenhave undergone a pulmonary artery banding (PAB) and aortic coarctationor interruption repair (78%), and 8 children (22%;8/36) underwent amodified Norwood procedure.

RESULTS: There were four early deaths and two late deaths after theinitial surgical palliation. The overall survival at 10 years was 78%.Follow-up has ranged from 6 months to 13 years (average 5.2 years). Ofthe 32 survivors, 19 have undergone a bidirectional cavopulmonaryanastomosis and 20 a Fontan procedure with no deaths. Twelve infantshave required Damus-Kaye-Stansel procedure (DKS) and three infantshave required bulboventricular foramen (BVF) enlargement for subaorticobstruction (two early deaths). In all survivors patients who underwentDKS or BVF enlargement (42%;15/36) regular sinus rhythm was main-tained postoperatively.

CONCLUSION: Our experience suggests that this high-risk subgroupof neonates with FSV and aortic arch obstruction or interruption is safelymanaged by initial palliation procedures (PAB with repair of aorticobstruction or modified Norwood procedure). This strategy, carefulsurveillance, and early relief of subaortic stenosis can maintain acceptableanatomy and hemodynamics for later bidirectional Glenn and Fontanprocedures.

CLINICAL IMPLICATIONS: Our experience suggests that thishigh-risk subgroup of neonates with FSV and aortic arch obstruction orinterruption is safely managed by initial palliation procedures (PAB withrepair of aortic obstruction or modified Norwood procedure).

DISCLOSURE: Mark Ruzmetov, None.

SURGICAL MANAGEMENT OF SUBAORTIC OBSTRUCTIONIN CHILDREN WITH SINGLE VENTRICLE PHYSIOLOGYMark Ruzmetov MD* Palaniswamy Vijay PhD Mark D. Rodefeld MDMark W. Turrentine MD John W. Brown MD Indiana University Schoolof Medicine, Indianapolis, IN

PURPOSE: Optimal prevention and treatment of subaortic stenosis(SAS) in the univentricular heart (UH) and high pulmonary blood flowremains controversial, especially when complicated by aortic arch obstruc-tion. Several surgical techniques have been used in infancy to palliate thisgroup of patients.

METHODS: From January 1980 to December 2004, 43 children withUH and systemic ventricular outflow obstruction underwent relief of SASsubsequent to pulmonary artery banding (PAB;n�34) and modifiedNorwood procedure (MNP;n�9). Median age at operation was 20 days(range; 2 to 298 days; 79% were less than 1 month) and the averagepreoperative pressure gradient across the ascending aorta and systemicventricle was 72�17 mmHg (range 31 to 135 mmHg). Three techniquesto relief SAS were performed: (1) the Damus-Kaye-Stansel (DKS)procedure (including MNP patients;n�32); (2) subaortic resection orventricular septal defect enlargement (n�7); and (3) apical aortic conduit(AAC;n�4).

RESULTS: Four patients (9%) died in the early postoperative period:three infants after DNP (33%), and one after PAB (3%;p�0.001). Theoverall survival at 1 and 10 years was 79% and 70%, respectively.Complete heart block requiring insertion of a pacemaker occurred in fivepatients (12%). Completion Fontan, hemi-Fontan and heart transplanta-tion have been performed in 25, 21 and 1 patient, respectively. Follow-upwas complete in all survivors at a mean time of 7.2�6.6 years (range; 3months to 23 years). Outcome was significantly worse in patients withassociated aortic arch obstruction (p�0.002), and with the presence ofAAC (p�0.006) or DNP (p�0.02).

CONCLUSION: Surgical relief of subaortic obstruction in patientswith UH and high pulmonary blood flow can be effectively palliated withPAB or DNP. DKS construction and ventricular septal defect enlarge-ment provide good long-term relief of SAS in select patients. SAS surgeryshould precede completion Fontan in most patients.

CLINICAL IMPLICATIONS: Surgical relief of subaortic obstructionin patients with UH and high pulmonary blood flow can be effectively




palliated with PAB or DNP. DKS construction and VSD enlargementprovide good long-term relief of SAS in select patients.

DISCLOSURE: Mark Ruzmetov, None.

DYNAMIC ATRIODIAPHRAGMOPLASTY WITH AUTOLOGI-CAL BIOLOGICAL VALVE: A NEW METHOD FOR FONTANREPAIRPavel Karakozov MD Iscander Baibekov PhD Valeri Chekanov MD*Milwaukee Heart Institute, Milwaukee, WI

PURPOSE: To ascertain whether atriomyoplasty, using the diaphrag-matic muscle flap as the front wall of the atrio-pulmonary tunnel, resultsin successful Fontan repair.

METHODS: Fontan operation, was performed on four adult mongreldogs. Autological biological valves were created in the superior andinferior vena cava openings. The tendinous-muscle flap of the diaphragm,along with the diaphragmatic nerve, was inserted as the front wall of theatrio-pulmonary tunnel. The flap was either directly inserted into thecirculatory system (2 cases) or applied externally onto the atrium wall (2cases) and was stimulated through the diaphragmatic nerve with 7 burstimpulses, at 6 volts each. Ventricular flap contraction was synchronizedwith contraction of the atrium.

RESULTS: Immediately after the operation, a sharp decrease wasregistered in cardiac output (2–2.5 L/min), arterial pressure (60–70mmHg), pulmonary pressure (12–15 mmHg) and capillary saturation(SO2 �60–65. Central vein pressure increased (13–15 mmHg). Signs ofright heart failure disappeared after beginning diaphragmatic flap stimu-lation. Before diaphragmatic flap stimulation began, pressure in thecreated neo chamber or right atrium was between 10/0–12/2 mmHg.Following initiation of flap stimulation, pressure in the neo chamber orright atrium was tracked for 3 hours and registered between 25/1–35/3mmHg. Central vein pressure ranged from 6–7.6 mmHg and arterialpressure from 100/50–120/70 mmHg. The created autological valvesfunctioned quite adequately with good locking function. Intraoperativeechocardiogram measured blood flow through the caval veins at 8-12mm/sec and the pulmonary artery at 70–80 mm/sec. The gradient in thecreated valves did not exceed 1–2 mmHg.

CONCLUSION: The stimulated, diaphragmatic flap plays the part ofthe actively contracting heart wall adequately without preliminary train-ing. Autobiological valves, created in caval vein openings, perform thelocking function properly, maintaining an adequate pressure level in theneo chamber or right atrium, comparable to the pressure in the rightventricle.

CLINICAL IMPLICATIONS: This new variant of the Fontan pro-cedure could be used in the repair of several complex congenital cardiacdefects.

DISCLOSURE: Valeri Chekanov, University grant monies TashkentCenter of Surgery Grant

MANAGEMENT OF ANOMALOUS LEFT CORONARY ARTERYARISING FROM THE PULMONARY ARTERY IN THE ADULT:CASE REPORT AND REVIEW OF THE LITERATUREFrank Manetta MD* Darren I. Rohan MD L M. Graver MD Long IslandJewish Medical Center, New Hyde Park, NY

PURPOSE: Anomalous origin of the left coronary artery (ALCAPA) isa rare congenital defect with an incidence of 1:300,000. These patientsoften present in infancy with anterior myocardial infarction, CHF ordeath. Adult type ALCAPA patients often present with symptomaticlesions, and therapy is aimed to restore a two coronary system. We presenta 52 year old female who presented with severe mitral insufficiency whounderwent preoperative cardiac catheterization and was found to have ananomalous left coronary artery arising from the main pulmonary artery.The patient underwent a mitral valve replacement along with re-estab-lishment of a dual coronary system with bypass grafting and ligation. Thepatient recovered without incident. A review of the literature wasundertaken to determine the optimum management of these asymptom-atic lesions in adults.

METHODS: We conducted a Medline review of the English literaturefrom 1966 through September of 2004. Fifteen articles containing 41patients �11 years old were identified. The patient data was tabulated andanalyzed.

RESULTS: The mean age at diagnosis was 34 (16-72). The male tofemale ratio was 1:2. 86% of the patients underwent surgical therapy. Of

these patients, 69% had a dual coronary system re-established either bydirect reimplantation of the left coronary artery or by grafting with eitherthe IMA or SVG. There were 2 perioperative deaths (5.7%). In the fivepatients reported with nonoperative therapy, there was a 40% incidence ofcardiac arrest in follow up.

CONCLUSION: Adult survival appears to be improved with surgicaltherapy for ALCAPA. Re-establishment of a dual coronary system withclosure of the fistula is the most common surgical therapy for adult typeALCAPA. Interestingly, the male to female ratio (1:2) in adults is reversedto that found in infants and children (2:1); suggesting men are moresusceptible to death as a result of this disorder if left untreated.

CLINICAL IMPLICATIONS: Asymptomatic adult patient with AL-CAPA are at increased risk for myocardial infarction and sudden death.

DISCLOSURE: Frank Manetta, None.

CARDIAC RELEASE OF B-TYPE NATRIURETIC PEPTIDE, CY-TOKINES, AND INFLAMMATORY MARKERS IN CONGENITALHEART DISEASE: PERIOPERATIVE SETTING UNDERGOINGCARDIAC SURGERY WITH CARDIOPULMONARY BYPASSPao-Hsien Chu MD* Yu-Sheng Chang MD Jaw-Ji Chu MD Chang GungMemorial Hospital and Chang Gung University, Taipei, Taiwan ROC

PURPOSE: BB-type Natriuretic Peptide (BNP) is a cardiac neurohor-mone specifically secreted by the cardiac ventricles in response to volumeexpansion, pressure overload, and resultant increased wall tension. Thisstudy was designed to explore whether it was possible to evaluate theperioperative setting of ventricular septum defect (VSD) and tetralogy ofFallot (TOF) by measuring BNP levels, cytokines and inflammatorymarkers.

METHODS: A prospective study conducted between June 2004 andFebruary 2005 included 16 consecutive patients who had been surgicallycorrected, including TOF (n�7; 44%), and VSD (n�9; 56%). Detailedclinical parameters were reviewed. The blood level of BNP, lactase,inflammatory marker (while blood cells, WBC; high-sensitive C-reactionprotein, hs-CRP), and cytokines (interleukine-6, IL-6; -8, IL-8; and tumornecrotizing factor-�;, TNF-�;) had been evaluated before and the dayafter operation.

RESULTS: The patient population was comprised of 4 (25%) womenand 12 (75%) men. The mean age of patients’ participants was 18 months,with an age range of 6 to 59 months. BNP levels showed lower in VSDcompared with TOF perioperation. In the TOF patients, BNP levels rosefrom 63 �/- 80 pg/ml before operation to 592 �/- 279 pg/ml 24 hours afteroperation (P�0.000); in VSD changed from 12.8 �/- 7 pg/ml to 140 �/-72 pg/ml perioperation (P�0.000). In VSD and TOF patients, BNP levelscorrelated significantly with Qp/Qs, and peak RVP/LVP. BNP levels werewell-correlated with the severity of the disease. The levels of lactase,hc-CRP, IL-6, IL-8 and TNF-;� were elevated significantly after postop-eration in VSD patients (P�0.000); but not WBC, IL-8 or TNF-�; inTOF.

CONCLUSION: We conclude that BNP is a useful diagnostic tool inthe identification of the condition and residual VSD for the patients withVSD and TOF. Levels of IL-6, and hs-CRP also increased significantlyafter surgery.

CLINICAL IMPLICATIONS: BNP is a useful diagnostic tool forperioperative evaluation.

DISCLOSURE: Pao-Hsien Chu, None.

OUTCOME OF PALLIATIVE SURGICAL CORRECTION FORSINGLE VENTRICLE PHYSIOLOGY WITH ECHOCARDIOGRA-PHY AS THE ONLY PREOPERATIVE ASSESSMENT TOOLAnnette Santiago MD* Enrique Carrion MD Cid Quintana MD Univer-sity of Puerto Rico, San Juan, Puerto Rico

PURPOSE: Single ventricle physiology occurs when one of the twoventricles is sufficiently small that a series circuit is incompatible withsurvival. Traditionally, all patients with single ventricle physiology undergocardiac catheterization before palliative surgical correction . Cardiaccatheterization carries small but appreciable risks, including arrhythmias,vascular damage, radiation exposure, patient discomfort, and parentalanxiety. Additionally, in the current atmosphere of cost containment, therole of preoperative cardiac catheterization versus echocardiographyassessment should be reevaluated. We postulate that by solely usingcommonly acquired echocardiographic information, patients with singleventricle physiology can undergo palliative surgical correction with bi-


Cardiac Surgery: Congenital, continued


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Glenn or Fontan procedure and safely avoid preoperative cardiac cathe-terization.

METHODS: We retrospectively reviewed the medical records of allthe patients who underwent biGlenn and Fontan procedure from April1995 through June 2003 at the Intensive Care Unit of the CentroCardiovascular de Puerto Rico y del Caribe. Inclusion criteria included allchildren with univentricular physiology who had a complete preoperativeechocardiogram performed within two weeks of surgery and who under-went palliative surgical corrections in the selected study period.

RESULTS: A total of 37 patients were identified to meet the criteria.The most common preoperative diagnosis was Tricuspid Atresia (n�15),followed by Single Ventricle (n�13) and Pulmonary Atresia (n�9). Therewas no discordance between echocardiography and surgical findings.Bi-Glenn was performed in thirty-two patients. One patient of thebiGlenn group died for an overall group survival of 96.8% . Twentypatients underwent Fontan procedure. Seventeen patients had undergoneprior Glenn shunt. The overall group survival was 100%.

CONCLUSION: Echocardiography is a valuable diagnostic tool ifperformed after a careful physical examination. It can provide theinformation needed for a complete and accurate diagnosis of congenitalheart diseases.

CLINICAL IMPLICATIONS: We conclude that morbidity andmortality after single ventricle palliative correction is not affected byechocardiography as the only preoperative assessment tool and thatroutine use of cardiac catheterism with its implicated complications andhigher costs may be avoided.

DISCLOSURE: Annette Santiago, None.

Cardiac Surgery: Interventions andPredictors12:30 PM - 2:00 PM

SAFETY AND EFFICACY OF IMMEDIATE POSTOPERATIVEASPIRIN IN OFF PUMP CORONARY ARTERY BYPASS GRAFT-ING PATIENTSYatin Mehta MD* Satish Kumar MD Altaf Bukhari MD Mayank Vats MDNaresh Trehan MD Escorts Heart Institute and Research Center, NewDelhi, India

PURPOSE: Preoperative aspirin administration, which is continuedduring the postoperative period in Coronary Artery Bypass Grafting(CABG) patients, has resulted in improvement in early as-well-as late graftpatency. However the precise complication rate as a result of immediate(i.e. within 24-hours) postoperative administration of aspirin has not beenfully evaluated especially in Off-Pump-CABG(OPCAB) patients and theexisting data has conflicting results.The aim of this study was to evaluatesafety and efficacy of immediate postoperative aspirin (i.e. �24 hours) inOPCABG.

METHODS: Out of 887 patients, who underwent OPCAB, only 750patients fulfilled the inclusion criteria and randomized into group-A(aspirin with-in first 24 hrs) and group-B (placebo till chest-tubes removal& then aspirin). Complete preoperative evaluation was done and surgical/anesthetic techniques were same in both group. Primary end-points ofstudy were:-Inhospital mortality, perioperative Myocardial Infarction(PMI), stroke, cerebral hemorrhage, reexploration and gastrointestinalischemia and hemorrhage. Seondary end-points were-amount of medias-tinal bleeding, blood/blood product transfusion and length of ICU/hospital stay.

RESULTS: Both groups were statistically similar regarding demo-graphic, comorbidities, preoperative anti platelet/anticoagulation andother cardiac-medications and total platelet-count. Outcome measures ingroup A & B respectively were:Mortality–1.6% v/s 0.5% p-0.286, PMI-2.7% v/s2.5% p-0.125,GI bleeding–1.1%v/s0.8% p-0.699, stroke 0.3%v/s0.3% p-1,Renal failure-3.5% v/s2.7%,p0.525, mediastinal drainage307.7�30.5ml v/s298.3� 29.3 ml p-001, reexploration3.5% v/s1.1% p-0.5,ICU stay 2.3�0.9v/s2.09 �.0.8days, p-0.001. Blood/blood products trans-fusion requirement in group A&B were: whole blood 0.76�1.23v/s0.60�0.90Units p0.04, platelet concentrate 1.2�0.8 v/s0.6�0.31Unitsp� 0.001, Fresh Frozen Plasma2.67� 0.21v/s1.33�0.14 Units P� 0.001,PRBC 3.8� 1.9 v/s1.7 � 1.2Units P� 0.001.

CONCLUSION: We conclude that early aspirin therapy i.e within 24hours after OPCAB may not be beneficial in prevention of postoperativeinflammatory injury rather it may increase the incidence of bleeding,blood/blood product requirement and re-exploration and other adverseoutcome.

CLINICAL IMPLICATIONS: Immediate postoperative administra-tion of aspirin in OPCAB patients should be avoided and the risk benefitratio of early aspirin therapy in OPCAB should be evaluated in double-blinded, Randomised-Controlled-Trials.

DISCLOSURE: Yatin Mehta, None.

CAN B-TYPE NATRIURETIC PEPTIDE LEVELS PREDICT THEOCCURRENCE OF ATRIAL FIBRILLATION IN THE POSTOP-ERATIVE PERIOD OF CARDIAC SURGERY?Alexandre R. Felipe MD* Renato V. Gomes MD Pedro M. Nogueira MDMarco Aurelio d. Fernandes MD Jorge Sabino MD Fernando G. AranhaMD Luiz Antonio d. Campos MD Hans Fernando d. Dohmann MDHospital Pro-Cardıaco, Rio De Janeiro, Brazil

PURPOSE: The usefulness of measuring B-type natriuretic peptide(BNP) levels in the postoperative (PO) period of cardiac surgery (CS) hasbeen frequently assessed.The objective this study is to correlate BNPlevels and occurrence of Atrial Fibrillation (AF) in the PO period of CS.

METHODS: Prospective study with a classic cohort of 77 patients (pts)undergoing CS and consecutively selected between August/2003 and January/2005. Their mean age was 66.9�9.89 years, 22 (28.5%) were females, and themean Euroscore was 4.26. The BNP level was measured in the preoperativeperiod (BNPPre), and in the first (BNP1) and sixth (BNP6) PO hours. TheBNP level was quantitatively measured by use of immunofluorescence(Biosite Triage BNP Test). The occurrence of AF in the PO period wascorrelated with the following variables: Euroscore; age; sex; preoperativecreatinine level and ventricular function; duration of ECC; SOFA on the firstPO day; and BNP (Pre, 1, and 6) levels. The statistical analysis comprised thefollowing tests: Student t; Chi-Square; Mann-Whitney followed by ROCcurve construction; and principal component analysis.

RESULTS: In the sample studied, 13 pts (16.8%) had AF in the POperiod. A significant correlation was observed between the BNP levels[BNPPre (0.01), BNP1 (0.011), and BNP6 (0.03)] and the occurrence of AF.None of the other variables tested correlated with the occurrence of AF. Afterthe principal component analysis, the 3 BNP levels maintained the correlationwith the occurrence of AF. BNPPre had a better AUC (ROC) (0.727), inwhich values greater than 100 pg/dL correlated with the occurrence of AF.

CONCLUSION: In the population studied, the occurrence of AF showeda correlation with the 3 BNP levels measured, and all of them wereindependently associated with the outcome. A BNPPre level greater than 100pg/dL correlated with the occurrence of AF in the PO period of CS.

CLINICAL IMPLICATIONS: The BNP showed to be a useful riskmarker for the occurence of FA.

DISCLOSURE: Alexandre Felipe, None.


Cardiac Surgery: Congenital, continued


EFFECTS OF CLOPIDOGREL IN OFF-PUMP BEATING HEARTSURGERYSimon Maltais MD* Karine Tetreault MS Quoc-Bao Do MD Notre DameHospital, Montreal, PQ, Canada

PURPOSE: Platelet-rich intracoronary thrombus is central to thepathogenesis of acute coronary syndrome, and patients scheduled forcoronary artery bypass graft (CABG) surgery today are receiving moreantiplatelet drugs. The use of such drugs, especially the Clopidogrel,before the surgery creates a major dilemma for cardiac surgeons. Ourprimary objective was to evaluate the role of Clopidogrel on operativebleeding and the timing of discontinuing the medication before surgery.Secondary objectives were to assess the incidence of blood and platelettransfusions following its use.

METHODS: We retrospectively analysed 453 patients undergoingoff-pump CABG surgery which received or not Clopidogrel in the last 3years, looking at the mean operative bleeding (per, post and total) anddetermining risks factors for blood or platelet transfusions using amultivariate analysis.

RESULTS: Clopidogrel in off-pump CABG surgery is associated withhigher operative and post-operative bleeding (702 vs 554 cc, p�0.03 and864 vs 603 cc, p�0.03). Stopping Clopidogrel 72 hours before surgerysignificantly reduces mean operative blood loss (554 vs 802 cc, p�0.0001).Patients off Clopidogrel for more than 72 hours don’t seem to bleed morethan the control group (p�NS). The use of Clopidogrel is associated withmore platelet transfusions (OR�11.79, [1.48; 93.86]), but blood transfu-sions seems similar in all group studied (p�NS).

CONCLUSION: Mean operative blood loss is higher in patients whoused Clopidogrel before surgery. Clopidogrel is associated with moreplatelet, but not blood transfusions after off-pump CABG surgery.Stopping Clopidogrel 72 hours before surgery shows similar meanoperative blood loss compared to control group.

CLINICAL IMPLICATIONS: Stopping Clopidogrel 72 hours beforesurgery shows similar mean operative blood loss compared to controlgroup.

DISCLOSURE: Simon Maltais, None.

USE OF A NEGATIVE PRESSURE CUIRASS TO IMPROVEHEMODYNAMICS FOLLOWING CARDIAC SURGERYRakesh K. Chaturvedi MD* McGill University, Montreal, PQ, Canada

PURPOSE: In most cases in patients with normal lungs, positivepressure ventilation (PPV) with positive end expiratory pressure (PEEP)reduces cardiac output by decreasing venous return. We hypothesizedthat in patients receiving PPV, continuous negative pressure (CNP)applied to the chest via a cuirass would counter the negative effects ofpositive pressure in the chest, yet result in lung expansion similar toPEEP.

METHODS: 20 patients with normal ejection fractions were studied 2hours post coronary artery bypass graft (CABG) surgery with the pericar-dium left open. The patients were ventilated on pressure supportventilation (PSV) and synchronized intermittent mandatory ventilation(SIMV) with PEEP. Parameters were studied during 4 modes: A (base-line-1)� SIMV, PSV and PEEP, B�SIMV & PSV without PEEP,C�SIMV & PSV without PEEP and with CNP applied to the thorax at -20cm H2O for 15 minutes, D (baseline-2)� SIMV, PSV and PEEP.Hemodynamic measurements were performed in the supine position aftera 15 minutes period of equilibration between each mode using a standardpulmonary artery catheter and arterial line. No patient was treated withadditional fluids or inotropes during the study. All comparisons were doneusing repeated ANOVA and the results of the 2 baselines were averaged,mean baseline (MB).

RESULTS: All patients were hemodynamically stable during the trial;HR, BP and gas exchange were not affected. The removal of PEEP (5 cmH2O) did not affect CVP, WP or CO significantly MB vs B and B vs C.However, CNP significantly lowered both wedge and CVP (p� .05)compared to before and after CNP MB vs C. The cardiac index (CI) andstroke volume index (SVI) also improved significantly with CNP com-pared to baselines MB vs C.

CONCLUSION: The use of CNP applied to the thorax in thepostoperative period appears to improve cardiovascular hemodynamicspossibly by increased venous return or by improving the contractility ofthe myocardium.

CLINICAL IMPLICATIONS: CNP may be beneficial as a noveltreatment modality for postoperative low output syndrome.

DISCLOSURE: Rakesh Chaturvedi, None.

LOW EXTUBATION TIMES IN CARDIAC SURGERY PATIENTSUSING THE RAPID SHALLOW BREATHING INDEXCharles E. Oribabor MD* Naim Mansuroglu MD Felix Khusid RRTAnthony Patten Mary Suleiman Jessica Primiano Leonard Lee MDAnthony Tortolani MD New York Methodist Hospital: Affiliate WeillCollege of Cornell University, Brooklyn, NY

PURPOSE: To utilize the Rapid Shallow Breathing Index (RSBI) tolower extubation times in open heart surgery patients.

METHODS: We studied 167 open heart surgery patients prospectivelybetween April 1st 2004 and March 30th 2005.This included 33 valvesurgery patients,122 coronary artery bypass graft (CABG),5 Stanford AAneurysm patients,1 aortic dissection,1 combined valve/aneurysm pa-tient,4 off pump CABG patients and 1 pericardial stripping. No patientswere excluded.EXTUBATION CRITERIA: Rapid shallow breathing in-dex�105. EXTUBATION HALTING CRITERIA:(1)Medisatinal Hem-orrhage� 200cc/hour(2)Ramsay Sedation scale�4(3)Metabolic or respi-ratory acidosis on continuous positive airway ventilation.(4)Postoperativecardiogenic shock EXTUBATION TIME : defined as time from arrival inthe intensive care unit to time extubated.REINTUBATION: was definedas any patient reintubated within 24 hours of extubation.Narcotic analge-sia with morphine was used for postoperative pain.The patients cardiacanesthesiologists were informed of the weaning criteria with the RSBI thatwas going to be used.Drager ventilators; model EVITA XL; whichcalculate and display the RSBI continuously were used.All patients wereplaced in a semi recumbent position once the immediate postoperativeblood samples had been taken.The head of the bed was raised to at least45 degrees. Patients with intra-aortic balloon pumps were paced in areversed trendelenburg position for weaning.Bedside physical therapywith incentive spirometers was commenced immediately post-extubation.

RESULTS: The overall mean extubation time was 2hours 40 minutes.The mean extubation time was unaffected by outliers who did not meetthe weaning criteria for extubation. This included a total of 6 patients whoremained intubated for� 18 hours. Zero reintubations. Overall meanextubation times were unaffected by the age,hemodynamic status,comor-bidity, or ejection fraction.

CONCLUSION: The utilization of the rapid shallow breathing indexas the sole criteria for weaning has lead to significantly low meanextubation times in cardiac surgery patients.No increased rates of reintu-bation were observed.Postoperative narcotic analgesia did not increasemean extubation times.

CLINICAL IMPLICATIONS: (1)Significant reductions in resourceutilization of the respiratory department and ventilatoryequipment.(2)Patient and family satisfaction at early extubation times.(3)Reduced length of stay in the intensive care unit.

DISCLOSURE: Charles Oribabor, None.

DIFFERENT HEART-LUNG MACHINE CONCEPTS INFLU-ENCE PLATELET AND MONOCYTE SURFACE-MARKER EX-PRESSION DURING CORONARY ARTERY SURGERYThomas Waldow MD* Gunter Schumann MD Volker Schmidt OliverTiebel MD Gabriele Siegert MD Michael Knaut MD Klaus MatschkeMD Herzzentrum Dresden, Dresden, Germany

PURPOSE: Function of various cellular blood components is alteredunder conditions of cardiopulmonary bypass (CPB) which can lead toactivation of pro- and anticoagulant systems. In the present study, theeffects of two different heart-lung-machine (HLM) concepts on theexpression of surface markers on monocytes and platelets are compared.

METHODS: In a prospective, randomized and single-blinded studysixty patients with elective coronary artery bypass surgery were recruitedinto three groups. A standard system (group 1) was compared with amodified HLM containing of a Deltastream pump, surface-modifiedtubing, and reduced priming volume (Optimized Mini-Circulation Car-diopulmonary Bypass System (OMCPB)) (group 2). In group 3 patientswere operated on without extracorporeal circulation (OPCAB). Blood wascollected at different time points before, during, and until 48 hours aftersurgical intervention. Platelets were incubated with either CD42b-FITC-/CD62P-PE- or Factor Va-FITC-/ Tissue Factor-PE-labeled antibodies.EDTA-anticoagulated blood was incubated with CD11b-FITC- / CD18-PE- labelled antibodies. Samples were analysed applying flow cytometry.


Cardiac Surgery: Interventions andPredictors, continued


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RESULTS: CD42b-expression decreased significantly at the end of theobservation period in group 1 disclosing significant differences to groups2 and 3. Platelet Factor Va-expression was significantly elevated in group1 during bypass compared to groups 2 and 3. Tissue Factor- andCD62P-expression showed no significant differences between groups.CD11b-expression on neutrophiles and monocytes increased significantlyunder bypass and until 30 minutes after bypass in groups 1 and 2compared to group 3 with higher values in group 1.

CONCLUSION: Activation of Factor X through monocyte CD11bexpression and Factor Va expression on platelet surfaces are synergisticconditions in thrombin generation under CPB. This procoagulant stimuluscould be significantly reduced using OMCPB.

CLINICAL IMPLICATIONS: Dysfunction of cellular blood compo-nents has a major influence on clinical outcome after use of CPB throughparameters like blood loss, systemic inflammation and micro-clot forma-tion. Use of an optimized HLM may influence some of these factors.

DISCLOSURE: Thomas Waldow, None.

CIRCADIAN RHYTHM HAS NO EFFECT ON MORTALITY INCORONARY ARTERY BYPASS SURGERYAjay K. Dhadwal MD* Mikhail Vaynblat MD Shyama BalasubramanyaMD Murali Pagala PhD Nancy Schulhoff RN Joshua H. Burack MDJoseph N. Cunningham Jr MD Maimonides Medical Center, New York,NY

PURPOSE: Circadian variation affects atherosclerosis at many levels,including a circadian outcome in the treatment of myocardial infarction byangioplasty and thrombolysis.This has not been studied in the surgicalpatient. The circadian variation in mortality dependant on the time ofsurgery was examined in patients undergoing coronary artery bypasssurgery (CABG).

METHODS: A 4 year retrospective review of all CABG patients(n�3140) from 1999 to 2002 at a single institution with an accreditatedtraining program was undertaken. The patients were divided into elective,urgent and emergency cases. The cases were subdivided according to thestart time of the operation as morning (7am-2pm �AM), afternoon(2pm-8pm�AF) and night (8pm-7am �NT) and as weekday (Monday toFriday �WD) or weekend (WE) cases. The outcome was mortality within30 days and compared for 4 different time frames: (1) AM vs. AF (2) AMvs. NT (3) AF vs. NT (4) WD vs. WE for each prioritized group. Riskfactors and number of anastamoses were compared for each group. SigmaStatistical package and z-test for 2 group comparison were used foranalysis. T-test was used to compare age and ejection fraction.

RESULTS: No statistically significant difference in mortality wasobserved for the elective and urgent groups for each of the time periodscompared (Table). The emergency cases had significantly increaseddeaths in the AM and NT compared to the AF (p�0.01 and p�0.05respectively). There was no statistically significant difference with respectto age, gender, number of anastamoses performed, ejection fraction andpreoperative risk factors between groups.

CONCLUSION: The mortality for non-emergent CABG is indepen-dent of the timing of surgery. Circadian variation does not influence theoutcome in cardiac surgical patients.

CLINICAL IMPLICATIONS: This study demonstrates that thebiological effect of circadian variation and environmental factors (eg.surgeon fatigue) has no effect on mortality in cardiac surgery. Thisreassures surgeons and patients alike that the outcome is independant ofthe time of the procedure.This should be noted prior to further work hourlegislation being introduced.

DISCLOSURE: Ajay Dhadwal, None.

RESCUE PERCUTANEOUS CORONARY INTERVENTION, RE-OPERATION, OR CONSERVATIVE TREATMENT IN ACUTEPERIOPERATIVE GRAFT FAILURE AFTER CORONARY AR-TERY BYPASS SURGERYMatthias Thielmann MD* Parwis Massoudy MD Guenter Marggraf MDBeate Jaeger MD Stefan Sack MD Raimund Erbel MD Heinz Jakob MDThoracic and Cardiovascular Surgery, West-German Heart Center Essen,University, Essen, Germany

PURPOSE: Perioperative graft failure after coronary artery bypass surgery(CABG) results in acute myocardial infarction (PMI), which necessitatesacute re-revascularization to salvage myocardium, thus preserving ventricularfunction and improving patient outcome. Whether rescue percutaneouscoronary intervention (PCI), emergency reoperation, or conservative inten-sive care treatment should be applied is currenly unknown.

METHODS: Perioperative graft failure after coronary artery bypasssurgery (CABG) results in acute myocardial ischemia/infarction (PMI), whichnecessitates acute re-revascularization to salvage myocardium, thus preserv-ing ventricular function and improving patient outcome. Whether rescuepercutaneous coronary intervention (PCI), emergency reoperation, or con-servative intensive care treatment should be applied is currenly unknown.

RESULTS: Repeat coronary angiography 4 (1-10) hrs (median andrange) after the onset of symptoms revealed acute perioperative bypassgraft failure in 73 patients and 98 out of 258 bypass grafts after CABG.The number and type of failing grafts were comparable between groups 1and 2, but significantly different to group3 (P�0.001). Acute PCI wasapplied in 27 patients, reoperation in 18 patients, and conservativeintensive care treatment in 28 patients. Maximum postoperative cTnIlevels were significantly different between groups 1 and 2 (92�16 versus205�42 ng/mL; P�0.001). Left ventricular ejection fraction was reducedduring the acute event compared to preoperative values (P�0.01) andsignificantly improved during follow-up within each group (P�0.02), butdid not differ between the groups. In-hospital and 1-year mortality were14.8% and 22.2% in group 1, 27.8% and 33.3% in group 2, and 14.3% and28.6% in group 3, respectively (P�NS).

CONCLUSION: Re-revascularization with rescue PCI was succesfullto relieve acute myocardial ischemia and decreased the extent of myocar-dial cellular damage. However, no statistically significant difference couldbe observed between different re-revascularization strategies in terms ofleft ventricular function and short- and mid-term outcome.

CLINICAL IMPLICATIONS: The cardiac cathlab should routinelybe available to identify the underlying mechanism of PMI after CABG andto reintervene immediately in case of acute graft failure.


SURGICAL INTERVENTION FOR ACUTE PULMONARY EM-BOLISMA. Salemi MD* G. Gonzalez-Stawinski MD B. W. Lytle MD D. M.Cosgrove MD G. Pettersson MD N. G. Smedira MD Cleveland ClinicFoundation, Cleveland, OH

PURPOSE: Acute massive pulmonary embolism (APE) resulting inhemodynamic instability is a fatal condition. Pulmonary embolectomyserves as definitive therapy for those in whom catheter embolectomy andthrombolysis are either contraindicated or unsuccessful.

METHODS: This study was performed to determine our experiencewith pulmonary embolectomy for APE. We performed a retrospectivechart review of patients undergoing pulmonary embolectomy for APEfrom October 1994 to August 2003. Charts provided demography,symptomatology, operative procedures, and short term outcomes.

RESULTS: A total of 13 patients underwent pulmonary embolectomybetween October 1994 and August 2003. Average age was 52 years (range 32to 65). Symptoms were present in all patients and 63% of patients hadhemodynamic instability at the time of operation. Diagnosis was establishedby either spiral computerized tomography or transesophageal echocardiogra-phy. Emergent surgery was undertaken in 70% of patients. Cardiopulmonarybypass was established in all patients with 30% requiring circulatory arrest.Overall survival was 63%. When comparing survivors to non-survivors, thelatter group was more likely to be operated on emergently. Of those whosurvived, all are well at a mean follow-up of 12.3 months.

CONCLUSION: Pulmonary embolectomy utilizing cardiopulmonarybypass and circulatory arrest is effective treatment in patients withmassive embolism and is associated with good short term outcomes.Operative mortality is increased when surgery is performed underemergent conditions.

Mortality(Deaths/Cases) AM AF NT WD WE

ElectiveCABG

16/6372.51%

2/2010.995%

0/100%

18/8352.16%

0/130%

UrgentCABG

48/15123.17%

23/6743.41%

0/310%

66/20603.20%

5/1523.29%

EmergencyCABG

6/2326.09%

1/372.70%

5/1827.78%

AM vs AF: p�0.01AF vs NT: p�0.05

10/6914.49%

2/922.22%




CLINICAL IMPLICATIONS: Pulmonary embolectomy for acutemassive pulmonary embolism serves as definitive therapy and should beutilized in patients refractory to other therapeutic modalities.

DISCLOSURE: A Salemi, None.

INFLUENCE OF THE USE OF VASOACTIVE AMINES ON B-TYPE NATRIURETIC PEPTIDE LEVELS MEASURED IN PA-TIENTS UNDERGOING CARDIAC SURGERYAlexandre R. Felipe MD* Renato V. Gomes MD Pedro M. Nogueira MDMarco Aurelio d. Fernandes MD Gustavo Rodrigues MD Fernando G.Aranha MD Luiz Antonio d. Campos MD Hans Fernando d. DohmannMD Hospital Pro-cardıaco, Rio De Janeiro, Brazil

PURPOSE: To establish the kinetics of BNP levels measured in the POperiod of CS, and to correlate the BNP levels with the use of vasoactiveamines (VA) in the first PO hour (PO1H).

METHODS: Prospective study with a cohort of 77 patients (pts) under-going CS, between August/2003 and January/2005. Mean age 66.9�9.89years, 22 (28.5%) females, mean Euroscore 4.26. The BNP level wasmeasured in the preoperative period (BNPPre), and in the first (BNP1) andsixth (BNP6) PO hours. Patients receiving VA [(dobutamine (DBT) and/ornoradrenaline (NAD)] at any dosage in the first PO hour were assessed andthe use of VA was correlated with the BNP1 and BNP6 levels. Statisticalanalysis: Wilcoxon Matched Pairs Test and Mann-Whitney test.

RESULTS: In the total of sample the mean BNP levels found were asfollows: BNPPre � 159.4 pg/mL � 217.9 (MED � 79.4); BNP1 �150.2 � 203.3 (MED � 77.1); and BNP6 � 243.0 � 237.0 (MED �168.5), between BNPPre and BNP6, the difference was statisticallysignificant (p � 0.0004). About the use of amines in our sample, 22 ptsreceived VA in the PO1H as follows: 7 pts, NAD � DBT; 12 pts, NAD;and 3 pts, DBT. A significant correlation was observed between the use ofDBT and the BNPPre (p � 0.004), BNP1 (0.024), and BNP6 (0.05) levels.The use of NAD did not correlate with the BNP levels. The DBT grouphad greater mean BNPPre, BNP1, and BNP6 levels than those in theNAD group (790x159, 1004x243, and 609x203pg/dL, respectively).

CONCLUSION: Was observed the difference between BNPPre andBNP6, this result cans establish a curve of the BNP kinetics in the PO ofCS. In the patients using DBT had greater BNP levels than thosereceiving only NAD, this may correlate with a worse degree of ventriculardysfunction among those pts.

CLINICAL IMPLICATIONS: This study showed the curve of theBNP kinetics in the PO period of CS.

DISCLOSURE: Alexandre Felipe, None.

IN-HOSPITAL EVOLUTION OF PATIENTS WITH AN CENTRALVENOUS OXYGEN SATURATION GREATER THAN OR EQUALTO 70% IN THE POSTOPERATIVE PERIOD OF CARDIACSURGERYPedro Miguel d. Nogueira MD* Alexandre R. Felipe MD Renato V.Gomes MD Marco Aurelio d. Fernandes MD Leonardo d. Pinto MD LuizAntonio d. Campos MD Jose Rodolfo Rocco PhD Hans Fernando d.Dohmann MD Hospital Pro-Cardıaco, Rio de Janeiro, Brazil

PURPOSE: Central venous oxygen saturation (ScVO2) has beenconsidered an important parameter for follow-up, prognostic estimate,and therapeutic target in the management of critically ill patients (pt-s).The objective this study is to assess the evolution of pts with anScVO2 � 70% in the postoperative (PO) period of cardiac surgery, and tocorrelate that finding with in-hospital mortality.

METHODS: A classic cohort of 128 consecutive pts was selected fromJanuary 2004 to August 2004. Blood samples were collected through acentral venous catheter properly positioned in the right atrium accordingto a previously validated method. The ScVO2 measurements were takenin the postoperative period as follows: immediately (SV0), after 6 hours(SV1), and after 24 hours (SV2). The pts were divided into 4 groups asfollows: GI (60 pts), none of the 3 measurements was � 70%; GII (33 pts),at least one of the 3 measurements was � 70%; GIII (22 pts), 2 of the 3measurements were � 70%; and GIV (13 pts), all measurements were �70%. The chi-square test was used for statistical analysis. In-hospitalmortality was defined as the occurrence of death during hospitalization.

RESULTS: In-hospital mortality in our sample was 8.6% and, in thegroups, it was as follows: GI, 16.7%; GII, 3.0%; and GIII and GIV, 0%, asshown in the annexed table. After applying the chi-square test, thedifferences in mortality rate were significant (P � 0.023).

CONCLUSION: In the population studied, at least one ScVO2 � 70%in the first 24 PO hours of cardiac surgery seems to have an impact onin-hospital mortality.

CLINICAL IMPLICATIONS: This study showed the importance ofa ScVO2 to idendificate the patients with greather risk of death.

DISCLOSURE: Pedro Miguel Nogueira, None.

MANAGING LIFE THREATENING VIRAL MYOCARDITISWITH DILATED CARDIOMYOPATHY BY DROTRECOGINALFA AND CIRCULATORY ASSISTED DEVICESTsung P. Tsai PhD* Shyh M. Tsao MD Yi L. Wu MD Jung M. Yu MDKuei C. Chan MD Kwo C. Ueng MD Chung Shan Medical UniversityHospital, Taichung, Taiwan ROC

PURPOSE: Acute fulminant myocarditis with dilated cardiomyopathycaused by Parvovirus B19 may present with cardiogenic shock refractoryto the maximum dose of inotropics and intra-aortic balloon pumping(IABP). The benefits of extracorporeal membrane oxygenation (ECMO)support for patients with life-threatening myocarditis has been estab-lished. Drotrecogin alfa, recombinant human activated protein C, hasantithrombotic, anti-inflammatory and profibrinolytic properties. Theeffectiveness from the circulatory support (ECOM or IABP) and activatedprotein C use in managing acute myocarditis with dilated cardiomyopathycaused by Parvovirus B19 has to be defined.

METHODS: Four patients( 2 male, 2 female, mean age 37.2 years)presented with congestive heart failure 3 to 4 days after flu-like symptoms(intermittent fever 38�39°C, dyspnea and chest tightness). Chest roent-genograms showed cardiomegaly and bilateral pulmonary infiltrates. EKGrevealed non-specific ST wave changes. 2-D echocardiograms demon-strated severe myocardial dysfunction with LVEF, measured between18.4 to 22% (mean, 19.5%). Coronary angiography was performed in eachpatient and excluded ischemic heart disease. Acute decompensation withmore than 2 organ failure (heart and lungs) and unresponsive to more than2 inotropics and acute respiratory therapy were indications for the use ofcirculatory support by IABP (3pts) and/or ECMO (3pts) as well asactivated protein C (3pts). Serological test and myocardial biopsy forParvovirus B19 was positive in 3 pts and one pt, respectively.

RESULTS: All three pts with ECMO and IABP support were weaned.Follow-up LVEF measured were 53%, 53%, 55% and 60%, respectively.However one pt died one month later because the deterioration of her SLEcondition and repeated infection. There were no neurologic sequelae in survivors.

CONCLUSION: Use of circulatory support and activated protein C isan effective alternative for treating life-threatening viral myocarditis withdilated cardiomyopathy, especially caused by Parvovirus B19 virus.

CLINICAL IMPLICATIONS: Parvovirus B19virus can cause severemyocarditis with dilated cardiomyopathy and circulatory collapse. Com-bined use of Drotrecogin alfa and ECMO and/or IABP is an effectivenovel therapy for this cohort of patients.

DISCLOSURE: Tsung Tsai, None.

Cardiology: Arrhythmias12:30 PM - 2:00 PM

COMPLAINCE TO ANTIPLATELET THERAPY AFTER SIROLI-MUS-ELUTING STENT IMPLANTATION IN VARIOUS SOCIO-ECONOMIC POPULATIONVimesh K. Mithani MD Padmaja Akkineni MD Anuj Agarwal MD*Mahesh Bikkina MD St Joseph’s Hospital and Medical Center, Paterson,NJ

PURPOSE: It has been shown that there are differences in outcomesin acute coronary syndromes due to income disparities. Antiplatelet

Groups Alive Death

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therapy (aspirin and clopidogrel) is essential for preventing adverseoutcomes after stent implantation. The cost of this treatment particularlyclopidogrel may pose hindrance to compliance in low-income and unin-sured population. It has been recommended that with the sirolimus-eluting stents the length of treatment with these antiplatelet agents islonger than conventional bare-metal stents. We looked at the compliancein different income populations who received sirolimus-eluting stents at asingle-center registry.

METHODS: The purpose of the study was to assess the non-compliance rate with the antiplatelet regimen in the insured populationcompared to uninsured low-income population and whether it wasassociated with recurrent hospitalizations, myocardial infarctions, ordeath. There are a total of 100 patients, who underwent sirolimus-elutingstent implantation, from April 2003 to October 2003 were followed atthree months. It comprised of 50 patients in each socioeconomic armsfrom the registry of a single medical center.

RESULTS: The non-complaince rate with the antiplatelet therapy ininsured versus uninsured low-income population is 2 patients (4%) versus12 patients (24%) respectively at three months. All these patients werenon-complaint to clopidogrel and one patient from the uninsured low-income population was non-complaint to aspirin as well. None of thepatients from of the insured population were hospitalized or had myocar-dial infarction or death. One patient (2%) from the uninsured populationhad ST elevation myocardial infarction with stent thrombosis at 8 days andunderwent successful revascularization. This patient was non-complaint toclopidogrel.

CONCLUSION: There is a significant incidence of non-complaincerate with antiplatelet regimen particularly clopidogrel among the lowsocioeconomic population due to cost issues.

CLINICAL IMPLICATIONS: Non-complaince to antiplatelet regi-men is an important factor to consider prior to coronary intervention sincestent thrombosis secondary to inadequate antiplatelet therapy has signif-icant morbidity and mortality.

DISCLOSURE: Anuj Agarwal, None.

REDUCED EJECTION FRACTION AFTER MYOCARDIAL IN-FARCTION: IS IT SUFFICIENT TO JUSTIFY IMPLANTATIONOF A DEFIBRILLATOR?Patrizio Pascale MD* Patrick Taffe PhD Claude Regamey MD LukasKappenberger MD Martin Fromer MD University Hospital, Division ofCardiology, Lausanne, Switzerland

PURPOSE: Improved survival after prophylactic implantation of adefibrillator in patients with reduced left ventricular ejection fraction(EF) after myocardial infarction (MI) has been demonstrated in patientswith remote MI experienced in the 1990’s. The absolute survival benefitconferred by this recommended strategy must be related to the currentrisk of arrhythmic death which is evolving. This study evaluates themortality rate in survivors of MI with impaired left ventricular functionand its relation to pre-discharge baseline characteristics.

METHODS: Clinical records of patients who had sustained acute MIfrom 1999 to 2000 and were discharged with an EF � 0�40 were included.Baseline characteristics, drug prescriptions and invasive procedures wererecorded. Bivariate and multivariate analyses were performed using aprimary endpoint of total mortality.

RESULTS: 165 patients were included. During a median follow-up of30 months (interquartile range 22-36) 18 patients died. One and two-yearmortality rates were 6�7% and 8�6%, respectively. Variables reflectingcoronary artery disease and its management (prior MI, acute reperfusion,complete revascularization) had a greater impact on mortality thanvariables reflecting mechanical dysfunction (EF, Killip class).

CONCLUSION: Mortality in survivors of MI with reduced EF issubstantially lower than reported in the 1990’s.

CLINICAL IMPLICATIONS: This decreased absolute mortalityimplies a proportional increase in the number of patients needed to treatwith a prophylactic defibrillator. The risk of event may even be sufficientlylow to limit the detectable benefit of defibrillators in patients with theprognostic features identified in our study. This argues for additional riskstratification prior to the prophylactic implantation of a defibrillator.

DISCLOSURE: Patrizio Pascale, None.

PERMANENT RIGHT PHRENIC NERVE PARALYSIS FOLLOW-ING CATHETER RADIOFREQUENCY (RF) ABLATION FORPAROXYSMAL ATRIAL FIBRILLATION (PAF)Long X. Le MD* Patricia J. Sime MD University of Rochester School ofMedicine, Rochester, NY

PURPOSE: Introduction: Transcatheter radiofrequency ablation hasemerged as an important treatment modality for PAF [1]. The risk ofthromboembolism, pulmonary vein stenosis, and cardiac perforation hasbeen documented. However, only one case of transient right phrenicnerve injury during pulmonary vein (PV) RF ablation has been reported[2]. We document a case of permanent right phrenic nerve paralysisfollowing PV-RF ablation.

METHODS: Case Report: A 61-year-old man with a 6-year historyof PAF was admitted for PV-RF. His physical examination wasunremarkable. An echocardiogram showed normal cardiac chambersize and function and four pulmonary veins. Electrophysiology studiesrevealed idiopathic AF with multiple pulmonary vein foci. PV-RFablation was performed as described by Haissaguerre [1,3]. A total of41 RF pulses for duration of 2080 seconds was required to ablate thearrhythmogenic foci. On post-procedure day one, he complained ofdyspnea and orthopnea. A ventilation/perfusion scan was negativefor pulmonary thromboembolism. A chest X-ray revealed elevation ofthe right hemidiaphragm (Figure I). Fluoroscopy confirmed paralysisof the right hemidiaphragm. Pulmonary function tests (PFT) revealedmoderate restrictive pulmonary physiology (Table I). On post-procedure day six, his symptoms improved but right hemidiaphragmelevation persisted. Five months later, he was asymptomatic.However, the chest X-ray, fluoroscopy, and PFT revealed per-sistent right hemidiaphragm paralysis and restrictive pulmonaryphysiology.

RESULTS: Discussion: Phrenic nerve paresis is an uncommon butpotentially disabling complication of PV-RF ablation. Three mechanismsof injury have been implicated: 1. heat from the catheter contact site tothe nerve [4]; 2. injury from the high intensity electromagnetic fieldgenerated at the catheter tip [5]; and 3. generation of a resonance currentaround the heart [6]. In this patient, the second mechanism seems mostlikely to induce direct nerve injury secondary to electroporation fromlocally generated electromagnetic field.

CONCLUSION: Conclusion: This case report demonstrated thatPV-RF ablation can induce significant nerve injury around theheart.

CLINICAL IMPLICATIONS: Implication: Careful preventiveprecautions during the PV-RF ablation procedure are recommended.

Multivariate analysis of the associations betweenselected variables and all-cause mortality

All-cause death Hazard ratio (95% CI) p Value

Age 1�067 (0�997-1�142) 0�059Male sex 2�076 (0�652-6�610) 0�216Left ventricular EF 1�020 (0�939-1�108) 0�634Previous MI 3�632 (1�356-9�728) 0�010Acute reperfusion 0�267 (0�072-0�992) 0�049Documented complete

revascularization(acute or not)

0�279 (0�074-1�050) 0�059


Cardiology: Arrhythmias, continued


DISCLOSURE: Long Le, None.

DOFETILIDE THERAPY: IN PATIENTS WITH ATRIAL FIBRIL-LATION AND PACEMAKERS/DEFIBRILLATORSPramod M. Deshmukh MD* Vera Hackett Sharad Chandrika MDElizabeth Miller Guthrie Healthcare System, Sayre, PA

PURPOSE: Dofetilide (Tikosyn) treatment for atrial arrhythmias re-quires initiation of the drug in the hospital, careful attention to multipleQTc intervals, and adherence to standard guidelines. Ventricular pacing,by widening the QRS interval, can prolong the QTc interval. As no dataexists regarding monitoring of the QTc interval in patients with ventricularpacing, our objective was to assess the effect of ventricular pacing on QTcintervals in patients receiving dofetilide.

METHODS: Over a two year period, 119 patients including 50 patientswith implanted device (ID), [permanent pacemaker (PPM), � internalcardioverter defibrillator (ICD)] and 69 patients without ID were admit-ted for initiation of dofetilide using institutional protocol. Baseline andserial QRS intervals and QTC intervals (with manual correction) wereutilized to guide drug therapy. In patients with ID (PPM � ICD), longerQTC intervals were accepted (in patients with PPM due to QRS widening;in the ICD group due to perceived safety) to achieve therapeutic drugeffect.

RESULTS: Fifty patients with ID (mean age 71.7 yrs), 68% with ahistory of antiarrhythmic therapy (AAR), were compared to 69 patientswithout ID (mean age 61.7 yrs), 50% of whom also had history of AAR.Their ECG parameters are shown in Table 1. Within the group with ID,QRS (duration) and QTc intervals were significantly longer than in PPMcategory. In each group, 96% of the patients were discharged to home insinus rhythm and 4% of the patients required dofetilide to be discontin-ued due to torsade de pointes. After mean follow-up of 65 � 30 weeks inthe ICD group, only one patient required discontinuation of dofetilidetreatment due to torsade de pointes. None of the patients experienced afatal outcome.

CONCLUSION: Ventricular pacing is associated with significant QRSwidening and, therefore, prolongation of QTc interval.

CLINICAL IMPLICATIONS: Maximum limit of 500 msc. for QTcinterval used for patients without ID may be safely extended by anadditional 30 msc. in patients with ID and dofetilide therapy.

DISCLOSURE: Pramod Deshmukh, None.

THE IMPACT OF STRESS ON HEART RATE VARIABILITY OFON-CALL PHYSICIANSStavros E. Mountantonakis MD* Dimitrios A. Moutzouris MD CraigMcPherson MD Yale University - Bridgeport Hospital, Bridgeport, CT

PURPOSE: The analysis of heart rate variability (HRV) has beenrecommended for the study of the impact of work-stress on the autonomiccardiac control. The literature related to the effect of work stress onphysicians on-call is extremely limited. Our study aimed to evaluate therole of stress on the HRV of on-call physicians.

METHODS: Twenty six healthy physicians (11 men,15 women) un-dertook a 24-hour Holter-ECG recording while being on-call, as well ason a normal work-day at least 3 days after the day on-call. The mean agewas 34�7,49 years (range: 25-51 years). All recordings started at 3 p.m.and lasted 24 hours.

RESULTS: The physicians presented decreased values of StandardDeviation of all filtered RR intervals over the length of the analy-sis(SDNN) during the day-on call in comparison with a normal workday(SDNN: 89.9 and 110.9 respectively, p�0.05). The rhythm disturbancesduring the day on-call were clearly more (p�0.05) and included sinustachycardia and bradycardia, sinus pauses, supraventricular tachycardia, aswell as premature atrial and ventricular systoles.

CONCLUSION: Psychological and physical stress at working environ-ment as well as sleep deprivation may result in adrenergic surge thatpredisposes to cardiac arrhythmias. In our study, the on-call physicianspresented decreased SDNN. Although it is already known that decreasedHRV correlates with increased morbidity and mortality, the studies aboutthe clinical use of this marker in healthy subjects are few.

CLINICAL IMPLICATIONS: Our findings demonstrated a negativeimpact of stress on the cardiac rhythm during an on-call day. It would beinteresting to further investigate the significance of occupational stress inarrhythmogenesis in healthy and non-healthy individuals as well as theprognostic value of decreased HRV seen in our study.

DISCLOSURE: Stavros Mountantonakis, None.

INCORPORATION OF MEDICAL ADVANCES IN CLINICALPRACTICE WITHIN GUTHRIE HEALTHCARE SYSTEMPramod M. Deshmukh MD* Sailatha Padmanabhan MD Sudhakar SatturMD Mary Romanyshyn Steven Alexander Guthrie Medical Center, Sayre,PA

PURPOSE: Despite a large body of scientific evidence, primaryprevention of sudden cardiac arrest remains a clinical challenge. Theextent of incorporation of medical advances in practice remains unknown.We sought to evaluate how MADIT II (the second Multi-center Auto-matic Defibrillator Implantation Trial) findings were utilized in retrospec-tive manner.

METHODS: Guthrie Healthcare System is a large multidisplinaryorganization serving 500,000 patients in a primary service area of sevencounties and comprises of 228 physicians. We evaluated all echocardio-grams performed between October 2003 (beginning of reimbursement byCMS for MADIT II criteria) to October 2004. Using ICD codes, patientswith cardiomyopathy, ischemic heart disease, and heart failure wereidentified. This group was further stratified for MADIT II criteria.Medical records were evaluated for presence/absence of heart failure,presentation with clinical arrhythmias, events leading to implantation ofdevices, QRS morphology and duration, screening by individual physi-cians (including holter monitors, event monitors), and clinical referrals toelectrophysiology services.

RESULTS: A total of 3538 echocardiograms were performed betweenOctober 2003 and October 2004. Of these, 591 patients were identified tohave cardiomyopathy and heart failure, 109 patients met MADIT IIcriteria. Thirty-one patients (28.4%) received ICD implant. Of these, 27patients received biventricular ICD and 4 patients received biventricularpacemaker. Twenty-nine patients had either spontaneous or inducibleventricular tachycardia. Solely based on MADIT II criteria, only 2 patients

PFT on three days and five months post-procedure,showing restrictive physiology.*

Three-days post-procedure Five-months post-procedure

Predicted Observed %Predicted Predicted Observed %Predicted

FVC 4.90L 2.53L 52% 4.59L 2.72L 59%

FEV1 3.41L 2.22L 65% 3.67L 2.27L 62%

FEV1/FVC 70 88 126% 79 83 105%

TLC 7.28L 4.48L 62% 6.88 4.53L 66%

*FVC, forced vital capacity; FEV1, forced expiratory volume-1 second; TLC, total lung




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were referred for procedure as an out-patient by their primary carephysician; 29 patients were identified during routine follow-up or hospi-talization.

CONCLUSION: Despite widely published findings and efforts toeducate primary care physicians, only a small percentage of patients whofulfill MADIT II criteria were referred for ICD implantation.

CLINICAL IMPLICATIONS: In the light of recently publishedguidelines by CMS for implantation of defibrillator without electrophys-iology studies, further education for primary care physicians is necessary.

DISCLOSURE: Pramod Deshmukh, None.

ANXIETY AND P-WAVE DISPERSION IN HEALTHY YOUNGPOPULATIONHuseyin Uyarel MD* Sennur Unal MD Hulya Kasikcioglu MD ZeynepTartan MD Bulent Uzunlar MD Hasan Samur MD Ahmet Karabulut MDErtan Okmen MD Nese Cam MD Siyami Ersek Cardiovascular andThoracic Surgery Center, Istanbul, Turkey

PURPOSE: P-wave dispersion (Pd), defined as the difference betweenthe maximum and the minimum P-wave duration (Pmin) and maximumP-wave duration (Pmax) are electrocardiographic (ECG) markers thathave been used to evaluate the discontinuous propagation of sinusimpulses and the prolongation of atrial conduction time, respectively. Pdin normal subjects has been reported to be influenced by the autonomictone, which induces changes in atrial size and the velocity of impulsepropagation. However, the association between Pd and anxiety has notbeen studied in normal subjects.

METHODS: Pmax, Pmin and Pd were measured in 726 physically andmentally young healthy male volunteers, aged 21.23 � 1.25 years (range20-26). The Spielberger State-Trait Anxiety Inventory (STAI) was scoredconcomitantly.

RESULTS: Blinded intra- and interobserver reproducibility of theP-wave duration and Pd measurement were evaluated, and comparisionrevealed a Pearson correlation coefficient of 0.87 and 0.89 for the P-waveduration, 0.93 and 0.90 for Pd, respectively (p�0.001). Pmax and Pd weresignificantly correlated with the STAI-1 subscale (State Anxiety Scale)(r � 0.662, p�0.001; r � 0.540, p�0.001, respectively) and STAI-2subscale (Trait Anxiety Scale) (r � 0.583, p�0.001; r � 0.479, p�0.001,respectively). Pmin didn’t show any significant correlation with anxiety.Across 3 variables included in a multiple linear regression analysis, STAI-1and STAI-2 were the significant independent determinants of Pmax andPd. Beta coefficients indicated that the contribution of STAI-1 was muchmore than STAI-2 on Pmax (66.3%, 33.7%, respectively) and Pd (65%,35%, respectively).

CONCLUSION: The State Anxiety Scale and The Trait Anxiety Scaleis associated with an increase in Pmax and Pd. Association of Pd resultedfrom augmentation of Pmax. This is the first study to show relationbetween Pmax, Pd and anxiety.

CLINICAL IMPLICATIONS: The stimulation of sympathetic ner-vous system during anxiety may be the underlying mechanism of pro-longed of Pmax and Pd. Extrapolating from these findings, our resultspoint to a cardiac autonomic imbalance in patients with anxiety.

DISCLOSURE: Huseyin Uyarel, None.

Cardiology: Diagnosis and Treatment ofCoronary Disease12:30 PM - 2:00 PM

NUCLEAR STRESS TESTS IN ISOLATED AND SIGNIFICANTLEFT MAIN CORONARY ARTERY DISEASE: THERE IS NOUNIQUE PATTERN OF PERFUSION DEFICIT AND ABSENCEOF PERFUSION DEFICITS DOES NOT RULE OUT THE DIAG-NOSISVijay Shetty MD* Nitin Mahajan MD Deepak Thekkoott MD Jacob ShaniMD Gerald Hollander MD Edgar Lichstein MD Alvin Greengart MDJoshua Kerstein MD Bilal Malik MD Maimonides Medical Center,Brooklyn, NY

PURPOSE: Left main coronary artery (LMCA) obstruction is the mostpotentially dangerous coronary disease. There is limited data on use of

nuclear stress test to identify patients with Isolated And Significant LeftMain Coronary Artery Disease (ILMCAD).

METHODS: We compared nuclear stress test results for patients withILMCAD (n�25; Group I) with stress results of patients with isolatedLAD disease (n�25; Group II). Group I was selected over a period of 10years. We compared electrocardiographic portion and perfusion deficits inthe study groups.

RESULTS: Electrocardiography portion of stress tests was non-reveal-ing. In group I, perfusion deficits were absent in 4 (16%) patients. Thedifferent patterns are compared in figure 1. Inferolateral and inferior wallischemia were commonly seen in group I as compared to significantlyhigher proportion (p�0.02) of anterior wall ischemia in Group II. Theperfusion deficits in group I were independent of site of LMCA stenosis,coronary artery dominance, electrocardiogram changes, and severity ofsymptoms.

CONCLUSION: This is the largest series of nuclear stress test resultsanalysis involving ILMCAD. There is no unique pattern of ischemiaassociated with ILMCAD. Nuclear stress test may vary from being normalto diffuse ischemia in 3 vessel distribution. Its role may be limited to beingan adjunct to clinical parameters including electrocardiography for diag-nosing ILMCAD.

CLINICAL IMPLICATIONS: Nuclear stress tests in diagnosingILMCAD may be limited to being an adjunct to clinical parametersincluding electrocardiography.

DISCLOSURE: Vijay Shetty, None.

TECHNICAL FEASIBILITY BASED ON LMCA STENOSIS CLAS-SIFICATION AND SHORT TERM CLINICAL OUTCOMES AF-TER UNPROTECTED LMCA PERCUTANEOUS INTERVEN-TIONS WITH DRUG ELUTING STENTS: A SINGLE CENTEREXPERIENCENarpinder Singh MD* Abdul Kani MD Augustin DeLago MD AlbanyMedical Center, Albany, NY

PURPOSE: We sought to evaluate procedural technical feasibility;MACE including cardiac mortality at hospital discharge and thirty dayfollow up after stenting unprotected LMCA stenosis with DES stents. Wealso sought to classify and define the various anatomical variations ofLMCA stenosis.

METHODS: Total of forty one consecutive patients with LMCAstenosis underwent stenting in our institution. To define the location andcomplexity of LMCA disease lesions, we devised the classification ofLMCA. DeLago’s LMCA stenosis classification includes 4 types and threeclasses (Figure 1). Different stenting techniques were used based onlocation of lesions. Patients were followed for the first three months. Arepeat coronary angiogram was requested routinely after six months.

RESULTS: Mean age was 67�14 with range of 28 to 90. Forty-fourpercent were males; 28% were smoker; 72% had HTN; 75 % had DM;and 68 hypercholestremia. Fifty- six percent presented as UA, 8% asrecent acute MI and 36 % had abnormal stress test. Initial proceduralsuccess rate was 100%. At 30 days follow-up was 0%. MI (Non Q wave)4.8%. At 30-day follow-up, CVA, TVR, CABG and death outcomes were0%. Mortality at three months was 2.4%.

CONCLUSION: Conclusion: Stenting of the unprotected LMCAstenosis provided excellent immediate result. Unprotected LMCA steno-sis can be treated safely and effectively with DES coated stent and may be




an effective strategy for treatment of LMCA disease in certain subsetpatient.

CLINICAL IMPLICATIONS: Our classification of LMCA stenosishelps to understand the complexity of the lesions and based on thatvarious stenting technique like direct stenting, stent into the branch withosteal lesion and dilation of the other branch if needed, kissing stents,Culottes stenting and V stent technique can be used. Certainly Type 1 andType 2 lesion are technically easy to stent and Type 3AC, Type 4 AC arevery challenging and technically complex to do.

DISCLOSURE: Narpinder Singh, None.

META-ANAYLSIS OF TRANSIENT LEFT VENTRICULAR API-CAL BALLOONING SYNDROME BASED ON GENDER ANDRACEDaniel Donohue MD* Mohammad-Reza Movahed MD University ofCalifornia, Irvine Medical Center, Orange, CA

PURPOSE: Transient Left Ventricular Apical Ballooning (LVAB) wasfirst described in Japan in the early 1990’s. Since then it has been reportedin many countries worldwide. It typically presents after physical oremotional stress with chest pain, ECG changes, positive cardiac markersand marked akinesia of mid to apical left ventricular wall with ballooningappearance despite normal coronaries. The goal of this study was toperform meta-analysis of the published cases in regards to race andgender.

METHODS: Using pubmed, we searched all published manuscriptsrelevant to left ventricular apical ballooning syndrome. We included caseseries and individual case reports in this study. We evaluated the effect ofgender and race on the presentation of LVAB using uni and multi-variateanalysis.

RESULTS: A total of 185 patient cases were identified that wereincluded in the analysis. Most cases were females, totaling 173 patients(93.5%). Asians and Caucasian were the majority of the reported races.Asians on average were older (70 �/- 9.5 yo vs 64 �/- 12.7 yo), less likelyto have; their syndrome precipitated by emotional stress (26.5% vs51.7%), positive cardiac markers (77.1% vs 97.6%), present with chestpain (55.4% vs 81.0%), or with T wave inversion (67.3% vs 95.8%), butwere more likely to have ST elevation on EKG (97.1% vs 83.3%). Therewere no differences in regards to complications or death.

CONCLUSION: LVAB is becoming more recognized in differentraces. While predominantly effecting females, the presentation is similarto men. However, there are significant differences in the presentation ofLVAB between Asians and Caucasians.

CLINICAL IMPLICATIONS: Clinical presentation of LVAB differsbetween Caucasians and Asian which needs to be considered in patientpresenting with LVAB.

DISCLOSURE: Daniel Donohue, None.

ACUTE MYOCARDIAL INFARCTION WITH NORMAL EPICAR-DIAL CORONARY ARTERIES ON ANGIOGRAM: HOW REAL ISIT?Muhammad U. Rehman MD* Vijay Rupanagudi MD Umang Patel MDRaju Ailiani MD Javeria Shakil MBBS S. Banuru MD S. Niranjan MD P.Krishnan MD Coney Island Hospital, Brooklyn, NY

PURPOSE: Acute myocardial infarction (MI) is invariably caused bynear total or total occlusion of epicardial coronary arteries by a thrombussuperimposed on an unstable atheromatous plaque. However, normalcoronary arteries on angiograms performed in patients with acute myo-cardial infarction have been described. The aim of our study was to see ifand how often myocardial infarction occurs in the setting of normalcoronary arteries visualized by angiography in patients seen in a commu-nity hospital.

METHODS: All coronary angiograms done in Coney Island hospitalfrom January 1995 to July 2002 were reviewed. 1699 patients with normalcoronary arteries were identified. These charts were reviewed for evi-dence of acute myocardial infarction based on EKG findings and presenceof elevated cardiac enzymes. Potential causative factors for myocardialinfarction and incidence of ST elevation MI (STEMI) versus non-STelevation MI (NSTEMI) were also studied.

RESULTS: We identified 17/1699 (1%) patients who presented withacute myocardial infarction with normal coronary arteries by angiography.Mean age - 52.75; Age range - 24 to 81; Male - 10, Female 7, M/F - 1.5:1.6/17 (35.3%) had STEMI. 5/6 (83.3%) had potential causative factors (3/5had cocaine abuse, 1/5 had hyperviscosity due to polycythemia, 1/5 hadhypercoaguable state due to lupus anticoagulant). 11/17 (64.7%) hadNSTEMI. Only one of these 11 patients (9.1%) had an identifiable cause(cocaine abuse).

CONCLUSION: Normal coronary arteries on angiography essentiallyexcludes acute myocardial infarction. In rare instances when it occurs,potential causative factors include cocaine abuse, hypercoaguable disor-ders and hyperviscosity states.

CLINICAL IMPLICATIONS: Patients with acute myocardial infarc-tion and normal coronary angiogram must be evaluated for potentialcausative factors, such as cocaine abuse, hypercoaguable disorders andhyperviscosity states, specially in patients with STEMI.

DISCLOSURE: Muhammad Rehman, None.

PREVALENCE OF MODERATE OR SEVERE LEFT VENTRIC-ULAR DIASTOLIC DYSFUNCTION IN PERSONS WITH SUS-PECTED MYOCARDIAL ISCHEMIA WITH AND WITHOUT ANABNORMAL ADENOSINE OR EXERCISE SESTAMIBI STRESSTEST OR PRIOR CORONARY REVASCULARIZATIONGautham Ravipati MD* Wilbert S. Aronow MD Albert J. De Luca MDTamana Walia MD John A. McClung MD Robert N. Belkin MD NewYork Medical College, Valhalla, NY

PURPOSE: To determine the prevalence of moderate or severe leftventricular diastolic dysfunction (LVDD) in patients with suspectedmyocardial ischemia with and without an abnormal adenosine or exercisesestamibi stress test (SST) or prior coronary revascularization.

METHODS: The patients included 171 men and 164 women, meanage 63 years, with suspected myocardial ischemia who underwent a SSTand Doppler and tissue Doppler interrogation of the mitral inflow andmitral annulus, respectively. Moderate LVDD was diagnosed if the peakearly diastolic transmitral flow velocity (E)/peak late diastolic transmitralflow velocity (A) was 0.75-1.50 and one or both of the following werepresent: the E/peak early diastolic myocardial velocity (Ea) was �10 orthe peak systolic pulmonary vein flow velocity (S)/ peak diastolic pulmo-nary vein flow velocity (D) was �1. Severe LVDD was diagnosed if theE/A was �1.5 and one or both of the following were present: the E/Ea was�10 or the S/D was �1. LVDD was evaluated blindly by a singleexperienced echocardiographer without knowledge of the clinical charac-teristics or whether the SST was normal or abnormal. A left ventricularejection fraction (LVEF) of �50% was considered abnormal.

RESULTS: Moderate or severe LVDD was present in 117 of 142patients (82%) with an abnormal SST or prior coronary revascularizationand in 11 of 193 patients (58%) with a normal SST and no prior coronaryrevascularization (p�0.001). Moderate or severe LVDD was present in 34of 38 patients (89%) with an abnormal SST or prior coronary revascular-ization and an abnormal LVEF and in 4 of 8 patients (50%) with a normalSST and no prior coronary revascularization and an abnormal LVEF(p�0.01).


Cardiology: Diagnosis and Treatment ofCoronary Disease, continued


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CONCLUSION: There is a very high prevalence of moderate or severeLVDD in patients with suspected myocardial ischemia, especially if thereis an abnormal SST or prior coronary revascularization.

CLINICAL IMPLICATIONS: There is a very high prevalence ofmoderate or severe LVDD in patients with ischemic heart disease,especially in those with an abnormal LVEF.

DISCLOSURE: Gautham Ravipati, None.

STRESS-INDUCED APICAL BALLOONING SYNDROME CANBE SUSPECTED BASED ON CLASSIC ECHOCARDIOGRAPHICFINDINGS AND CLINICAL PRESENTATIONDaniel Donohue MD* Chowdhury Ahsan MD Mohammad-Reza Mova-hed MD University of California, Irvine Medical Center, Orange, CA

PURPOSE: Stress induced apical ballooning has been described as areversible condition involving the apical left ventricular wall, sparing thebase, and causing a ballooning appearance of the left ventricular duringsystole despite normal coronaries. However, there are no data about earlydiagnosis of Apical ballooning syndrome using echocardiography.

METHODS: We are presenting four cases of apical ballooning seen atour institution with echocardiographic correlation. We compared angio-gram with echocardiographic finding prior to angiogram.

RESULTS: All Echocardiograms showed similar anatomical apicalballooning of the left ventricular apex. The diagnosis of apical ballooningsyndrome was suspected based on echocardiography in conjunction withclinical data before cardiac catheterization was performed. In one case, inaddition to classic left ventricular apical ballooning, marked right ventric-ular apical akinesia was present on the initial echocardiographic examina-tion Subsequent angiograms in all patients showed classic apical balloon-ing and normal coronaries.

CONCLUSION: Apical ballooning syndrome can be suspected basedon classic echocardiographic findings and clinical data prior to angiogra-phy.

CLINICAL IMPLICATIONS: Therefore, we suggest that echocardi-ography should be utilized more for the early diagnosis of this diseasebased on careful anatomical evaluation in conjunction with clinical data.Wall motion analysis should reveal apical ballooning appearance involvingmany coronary territories with discrepancy to electrocardiogram andcardiac enzyme elevation. Furthermore, the additional presence of rightventricular apical akinesia during echocardiographic examination makesthe diagnosis of this syndrome more likely.

DISCLOSURE: Daniel Donohue, None.

ISOLATED AND SIGNIFICANT LEFT MAIN CORONARY AR-TERY DISEASE: DEMOGRAPHICS, HEMODYNAMICS ANDANGIOGRAPHIC FEATURESNitin Mahajan MD* Deepak Thekkoott MD Gerald Hollander MD BilalMalik MD Sunil Abrol MD Jacob Shani MD Edgar Lichstein MDMaimonides Medical Center, Brooklyn, NY

PURPOSE: This paper describes the demographic, angiographic andhemodynamic characteristics of forty-six patients with isolated and signif-icant LMCA disease (ILMCAD)in an attempt to determine the etiology ofILMCAD.

METHODS: We identified 46 patients with ILMCAD from ourdatabase over 10 years (Group I) and compared them with 83 consecutivepatients that underwent catheterization in our lab (Group II). We alsocompared ostial vs. distal ILMCAD.

RESULTS: Group I represents 0.1% of catheterization patients.Unstable angina was the commonest presentation followed by non STelevation myocardial infarction, elective catheterization, syncope anddyspnea on exertion. The comparison of study groups is shown in table 1and figure 1.Mean left ventricular ejection fraction is similar in bothsub-groups (ostial disease-49%, distal disease-50%). About half the pa-tients with ILMCA (n�24/46:52%) disease had the classical “jet stream-ing” of contrast and was seen more commonly in patients with ostial andmid ILMCA disease. About one-fifths of ILMCA patients (9/46:20%)demonstrated retrograde filling from right coronary artery. Ventricular-ization was seen in only 4 patients. The majority of patients (23/44:52%)had normal segmental wall motion. An inverse relation was seen betweenthe severity of LMCA stenosis and left ventricular ejection fraction. Theleft ventricular end diastolic pressure had no correlation with leftventricular ejection fraction or severity of LMCA stenosis.

CONCLUSION: This is the largest study of patients with ILMCAD.Risk factors for atherosclerosis were commonly seen. Non-atheroscleroticcauses of ILMCAD were not seen. ILMCAD is more common in women.Diabetes is more commonly associated with distal lesion. There is a trendsuggesting ostial lesion is more common in smokers and women.

CLINICAL IMPLICATIONS: This study provides evidence in favourof atherosclerosis being the cause of ILMCAD. It is hoped that aggressivetreatment of atherosclerotic risk factors will reduce the prevalence ofILMCAD.

Table 1. Comparison of Demographic Profile ofPatients With ILMCA Disease (Group I) With General

Population Seen in Cardiac Catheterization Center(Group II).

Risk FactorsGroup I(n�46)

Group II(n�83)

Pvalue

Age (in years) 65�13 65�14 Nsd*SexMale 22 (48%) 57 (69%) 0.02Female 24 (52%) 26 (31%) 0.02RaceWhite 44 (96%) 75 (90%) NsdNon-White 2 (4%) 8 (10%) NsdHypertension 33(72%) 59 (71%) NsdHypercholesterolemia 30(65%) 58 (70%) NsdDiabetes Mellitus 20(43%) 24 (29%) NsdSmoking 12(26%) 18 (22%) NsdFamily history 18(39%) 36(43%) NsdIndication of CatheterizationAngina 20 (43%) 28 (34%) NsdMyocardial Infarction 9 (20%) 23 (28%) NsdElective 13 (28%) 22 (26%) NsdOthers (syncope, dyspnea on

exertion, and others)4 (9%) 8 (10%) Nsd

* Nsd- No statistically significant difference.




DISCLOSURE: Nitin Mahajan, None.

Cardiology: Diagnosis and Treatment ofHeart Failure12:30 PM - 2:00 PM

THE PROGNOSTIC VALUE OF HIGH SENSITIVITY C-REAC-TIVE PROTEIN LEVEL IN PATIENTS WITH CHRONIC HEARTFAILUREGhaith M. Mulki MD Pamela Cianci MSN Marc A. Silver MD* Univer-sity of Illinois at Chicago/Advocate Christ Medical Center, Oak Lawn, IL

PURPOSE: High sensitivity C-reactive protein (hsCRP) assay has beenfound to be a useful biomarker for cardiovascular risk stratification. Littleinformation exists regarding its prognostic impact in outpatients with heartfailure (HF) as well as its correlation to other biomarkers or outcomes.

METHODS: Serum levels of hsCRP were obtained in 89 patients withstage C HF. All patients were followed in a specialized HF managementcenter for 2-24 months (average 13.5�6.06). The primary end point wasmajor adverse cardiovascular events defined as cardiac hospitalization orcardiac death.

RESULTS: The average age of the subjects was 62.8�14.2 years(range19-88). The etiology of HF was ischemic in 36 patients (40.45%)and non-ischemic in 53 patients (59.55%). There were 46 men and 43women, 72 patients with systolic dysfunction and 17 patients with diastolicdysfunction defined as LVEF � 50%. The baseline hsCRP ranged from0.03 to 8.4 mg/dl and averaged 0.86�1.39 mg/dl. HsCRP levels were �0.1 mg/dl in 14 patients (15.8 %), 0.1-0.3 mg/dl in 25 patients (28%),and � 0.3 mg/dl in 50 patients (56.2%) (p�0.0001). Adverse cardiovas-cular events were significantly higher in patients with increased hsCRP(88.23% vs. 19%, p � 0.006, using hsCRP level of 0.2 mg/dl as a cutoff).Patients with systolic dysfunction had higher levels of hsCRP compared topatients with diastolic dysfunction (0.95 mg/dl vs. 0.46 mg/dl, respectively,p � 0.030). There was no significant difference in hsCRP levels inischemic HF compared to non- ischemic HF (0.92 mg/dl vs. 0.81 mg/dl,respectively, p � 0.72). There was no significant correlation betweenbaseline hsCRP levels and baseline BNP levels.

CONCLUSION: Our findings establish that hsCRP is elevated inpatients with stable Stage C HF independent of the etiology. IncreasedhsCRP levels were associated with significantly higher adverse cardiovas-cular events. The elevations in hsCRP and the cardiovascular outcomesare independent of other important biomarkers.

CLINICAL IMPLICATIONS: In conclusion, our data suggests thatelevated hsCRP is an independent prognostic marker for risk stratificationin patients with chronic HF.

DISCLOSURE: Marc Silver, None.

HYPERKALEMIA AND RENAL DYSFUNCTION IN CONGES-TIVE HEART FAILURE PATIENTS WITH CONCOMITANT USEOF SPIRONOLACTONE AND FUROSEMIDENobuyuki Anzai MD* Hiroko Anzai MD Rieko Mitobe MD Makiko AnzaiMD Sadako Furuya MD Anzai Furuya Clinic, Oyama, Japan

PURPOSE: This study aimed to identify predictors of hyperkalemiaand renal impairment in congestive heart failure (CHF) patients takingspironolactone and furosemide.

METHODS: Ninety (90) consecutive patients with CHF, 46M/44F,mean age 73.8 (range 56.4 -91.2 yrs) were studied. We started 26 patientswhile 20 patients were already taking spironolactone and furosemidewhen the study started. We measured blood electrolytes every twomonths. The study started from April 2003 and lasted two years. Meanobservation duration was 489 days for 124 patient years with a mean 19visits and a mean 25 days between visits.

RESULTS: Baseline characteristics: Mean(SD) left ventricular ejectionfraction (LVEF): 39.5%(15.1); mean(SD) creatinine concentration(mg/dl): 0.91(0.25); mean serum potassium(mEq/dl): 4.3(0.4); mean(SD)dosage (mg/day): spironolactone: 14.9(7.3), furosemide: 30.3(14.1); pa-tients needing angiotensin converting enzymes (ACE) inhibitors or angio-tensin receptor blockers (ARB): n�50(50%), � blockers: 48(53%); meanpeak creatinine concentration: 1.07(SD 0.34) mg/dl; mean peak potas-sium: 5.0(SD 0.5)mEq/dl. A total of 45(50%) had creatinine � 1.04mEq/dl, 16(18%) � 1.30, 9(10%) � 1.50. Relative to baseline, 24(27%)patients had creatine increase by 20%, 15(17%) by 30%, 8(9%) by 50%,2(2%) by 100%. A total of 39(43%) patients had potassium � 5.0 mEq/dl,9(10%) �5.5, 2(2%) � 6.0. Patients taking spironolactone and furosemidebefore study started did not differ significantly from patients we started interms of hyperkalemia (potassium �5.5)(11.5% vs. 15.2%, p�0.54) andazotemia (creatinine � 1.30)(15.3% vs. 14.1%, p�0.82). We logisticallyregressed (30% increase in serum creatinine concentrations) with age, sex,use of ACE inihibitors, ARBs, � blockers, and dosage of spironolactoneand furosemide. Age (odds ratio 1.24(95% confidence index interval1.01-2.54)for each ten years)) was an independent risk factor for azotemi-a.For hyperkalemia (potassium � 5.5), we added to the model baselinecreatinine concentrations and found that age (1.03(0.84-2.86)) was apredictive factor.

CONCLUSION: Age was a predictor of hyperkalemia and azotemiafor patients taking spironolactone and furosemide with moderately de-creased LVEF.

CLINICAL IMPLICATIONS: Caution should be taken while doseadjustment and continuous monitoring may be needed in elderly patients.

DISCLOSURE: Nobuyuki Anzai, None.

IMPACT OF LEFT VENTRICULAR ASSIST DEVICE DESTI-NATION THERAPY ON VENTRICULAR RE-SYNCHRONIZA-TIONSmitha G. Agadi MD* Helen Lonergan-Thomas RN Sharon Brennan RNPamela Cianci MSN Mark Slaughter MD Marc Silver MD AdvocateChrist Medical Center, Oak Lawn, IL

PURPOSE: Heart failure (HF) is a lethal disease process thatinvolves progressive ventricular remodeling and symptom worsening.Two strategies applied to HF populations include biventricular re-synchronization pacing (BiVP) and left ventricular assist as destinationtherapy (DT). While there may be some overlap in these populationsthe therapies are generally thought of separately. Among the benefitsof BiVP are ventricular resynchronization and improved oxygen con-sumption. Little information is known about the impact of DT oncardiac desynchronization and its impact on ventricular electrome-chanical recovery.

METHODS: We analyzed the ECG intervals of 16 patients whoreceived DT with a Heartmate XVE (Thoratec) secondary to end stageHF. Patients whose baseline ECG was paced (7) were excluded fromanalysis. The remaining 9 patients (8 men) were aged 50-79 (mean64.8) years. The patients were supported from 1-180 days at the timeof analysis.

RESULTS: The mean patients were supported from 1-180 days at thetime of analysis. Heart baseline and follow-up intervals are shown in thetable below.

CONCLUSION: While none of the intervals changed significantlyduring DT support, there was a trend towards improvement in QRSduration; of patients supported, the average improvement in QRSDwas 15.4 msec (10.5%) whereas for patients supported � 20 days theimprovement was 37.5 msec (21%). The only 2 patients to improveQTc were those supported 180 days. On the other hand PR did notimprove in any patient.

CLINICAL IMPLICATIONS: In summary, DT allows for long-termventricular support and recovery. Improvement in cardiac desynchronizationwithout BiVP may also occur after ventricular support. Longer observationneeds to be applied to this phenomenon and to consider the potential forLVAD support to restore normal ventricular resynchronization.




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DISCLOSURE: Smitha Agadi, None.

CHEST RADIOGRAPHIC CORRELATES OF SERUM BNPLEVELSShahnaz Begum MD Xiaoqian Zhang MD Louis Salciccioli MD ArashGohari MD Jason M. Lazar MD* SUNY Downstate Medical Center,Brooklyn, NY

PURPOSE: Beta natriuretic peptide (BNP)is a biomarker of intravscu-lar volume and serum levels correlate with left ventricular filling pres-sures. The relationship between BNP levels and radiographicic findingshas not been well studied. Accordingly, the purpose of this study was todetermine the relationships between chest radiographic findings andserum BNP levels.

METHODS: We studied 88 consecutive patients hospitalized withcardiac and/or pulmonary symptoms who had chest xrays and BNPlevels determined within 24 hours. Chest radiographs were evaluatedfor the following findings: left atrial enlargement (LAE), pleuraleffusions, pulmonary vascular congestion (PVC), cardiothoracic (CT)ratio, and the vascular pedicle width (WPW). Pulmonary vascularcongestion was noted to be absent, mild, or greater than mild. TheVPW was measure was measured according to previously publishedmethods (Ely).

RESULTS: The duration of time between BNP levels and chestxrays was 80�/-20minutes. There was a direct correlation betweenserum BNP levels and CT ratio (r�.29,p�0.03). There were norelationships between BNP levels and either VPW (r�-.12, p�.16) orage (r�.10,p�.50). BNP levels were unrelated to the presence of PVC(p�.17),but were higher in patients with LAE (p�.04)and pleuraleffusions (r�.04). On multivariate analysis analysis, CT ratio was theonly independent correlate of BNP levels (r2�.09, p�.02). Logtransformation of BNP levels improved the correlation with CT ratio(r�.40, p�.001), but did not alter other univariate or multivariatefindings.

CONCLUSION: In an unselected group of patients hospitalized withcardiac and/or pulmonary symptoms, serum BNP levels are chiefly relatedto the CT ratio but not to other radigraphic findings.

CLINICAL IMPLICATIONS: Although the majority of studies focuson the diagnostic and prognostic value of BNP levels,a direct comparisonto standard clinical evaluation is essential in understanding the clinicalutility of serum BNP levle determination.

DISCLOSURE: Jason Lazar, None.

DETERMINANTS OF EXERCISE CAPACITY AND PERCEIVEDEXERTION IN PATIENTS WITH PRESERVED LEFT VENTRIC-ULAR SYSTOLIC FUNCTIONTanya Menard Louis Salciccioli MD Luther Clark MD Jason M. LazarMD* SUNY Downstate Meidcal Center, Brooklyn, NY

PURPOSE: Exercise capacity is known to be an important prognos-tic factor in patients with cardiovascular disease and in healthysubjects. While structural heart disease is found in a relatively smallproportion, other factors are likely responsible for reduced exercisetolerance in these patients. Indices of left ventricular (LV) diastolicfilling variably correlated with exercise time in select patient popula-tions including hypertensives and the elderly. Moreover, no study hasspecifically addressed the contribution of LV systolic and diastolicfunctional abnormalities to both exercise duration and perceivedeffort. The objectives of the study were to determine echocardio-graphic correlates of exercise capacity and of perceived exertion inpatients without structural heart disease.

METHODS: We studied 111 consecutive patients, age 53�/-13 years, whowere referred for echocardiographic stress testing. Patients underwent symptomlimited treadmill exercise testing according to Bruce protocol in all cases.Standard blood pressures and 12 channel electrocardiograms were performed.Baseline 2 dimensional and Doppler echocardiographic images were recordedimmediately prior to exercise. The primary end points were maximal exercisetolerance defined by mets and peak RPE.

RESULTS: Age was directly correlated with mets (r�.38,p�.�.001) but not with RPE (r�.21,p�.51). On univariate analysis,mets also correlated with: hemoglobin (r�.39, p�.001), E/A (r�.33,p�.019) E/Vp (r�-.41, p�.004) and E/E’ (r�-.41, p�.004). Multipleregression analysis showed that independent predictors of mets were:age and gender (r2�.58,p�.001). There was a direct correlationbetween RPE and LA size (r�.35, p�.013) and a trend towards acorrelation between RPE and LV mass index (r�.24, p�.09). Onmultivariate analysis, LA size remained the sole independent predictorof RPE (r2�.17, p�.021).

CONCLUSION: This study showed reduced exercise capacity mea-sured by metabolic equivalents (mets) is related to advanced age andfemale gender whereas perceived exertion is related to left atrial size.

CLINICAL IMPLICATIONS: There are age and gender relateddifferences in functional capacity but not in preceived exertion. Thespecific mechanism by which LA size modulates perceived exertion isunknown but merits further study.


Cardiology: Diagnosis of CardiovascularDisease12:30 PM - 2:00 PM

POOR AEROBIC FITNESS PREDICTS COMPLICATIONS ASSO-CIATED WITH BARIATRIC SURGERYJustin E. Trivax MD* Michael J. Gallagher MD Daniel V. Alexander MDAdam T. deJong MA Gopi Kasturi MD Keisha R. Sandberg MPH Syed M.Jafri Kevin R. Krause MD David L. Chengelis MD Jason Moy MD BarryA. Franklin PhD Peter A. McCullough MD William Beaumont Hospital,Royal Oak, MI

PURPOSE: Bariatric surgery provides substantial and prolongedweight reductions. Complications associated with bariatric surgery havebeen well-defined; although, the risk of developing these complications isunclear. Maximal oxygen consumption (VO2max), determined by cardio-pulmonary exercise testing (CPX), is a measure of aerobic fitness. The aimof this study was to assess the association between VO2max and compli-cations encountered with bariatric surgery.

METHODS: CPX was performed on 109 consecutive patients withmorbid obesity undergoing laparoscopic Roux-en-Y gastric bypasssurgery. Chart review was performed by reviewers blinded to the CPXresults.

RESULTS: Mean age was 46.0�10.4 years and 82 (75.2%) werefemale. Mean body mass index (BMI) was 48.1�7.5 kg/m2 and50.4�6.0 kg/m2 for women and men, respectively p�0.17. VO2maxmeasurements ranged from 6.8 to 27.7 ml/kg/min. Patients werestratified by tertile of VO2max. Mean VO2max in the first tertile was13.7�2.1, second tertile was 17.1�0.8, and third tertile was 21.3�2.1.Patients in the first tertile experienced longer operative room times,p�0.04, and greater number of ICU days, p�0.05. Composite com-plication rate, defined as death, unstable angina, myocardial infarction,venous thromboembolism, infection, gastrointestinal bleeding, renalfailure or stroke, occurred in 2/72 (2.8%) and 6/37 (16.2%) above andbelow a peak oxygen consumption of 15.8 ml/kg/min (lowest tertile)respectively, p�0.02. No complications occurred in patients with bothVO2max � 15.8 ml/kg/min and BMI � 45 kg/m2. In comparison toother cardiorespiratory parameters, the area under the receiver oper-ating characteristic curve was highest for VO2max in predictingcomplications (AUC�0.72, p�0.0001.) Multivariate analysis found thefirst tertile of VO2max to have an odds ratio of 10.9 (95% CI1.01-73.80, p�0.04) for the prediction of postoperative complications.

CONCLUSION: Poor aerobic fitness, determined by a low VO2max,predicted complications associated with bariatric surgery.

CLINICAL IMPLICATIONS: VO2max should be determined priorto bariatric surgery to assess the risk of surgical complications. Cardiore-spiratory fitness is potentially modifiable and should be optimized prior toelective surgery with the goal of reducing surgical complications.

Interval Baseline Follow-Up

PR (msec) 173.8 185.2QRS (msec) 146.2 130.8QTc (msec) 460.6 463.7


Cardiology: Diagnosis and Treatment ofHeart Failure, continued


DISCLOSURE: Justin Trivax, None.

DOES THE AORTIC ATHEROSCLEROTIC PLAQUES SEVER-ITY CORELLATE WITH EMBOLIC EVENTS?Chandra K. Nair MD* Xuedong Shen MD Huagui Li MD DhanunjayLakkireddy MD Senthil Thambidorai MD David Cloutier BS Mark J.Holmberg MD Aryan N. Mooss MD Syed M. Mohiuddin MD TheCardiac Center of Creighton University, Omaha, NE

PURPOSE: The impact of aortic atherosclerotic plaques (ASP) dem-onstrated by transesophageal echocardiography (TEE) is controversial. Itis also unclear whether the severity of ASP correlate with embolic events.The purpose of this study was to investigate the incidence of embolicevents in different grades of ASP.

METHODS: We studied 277 consecutive patients (male/female�153/124, age 66.2�13.4 years) without left atrial thrombus by TEE. Thethoracic aortic plaque severity was classified as Grade I (normal orminimal intimal thickening) in 86; Grade II (extensive intimal thickening)in 105; Grade III (atheroma � 5mm) in 70; Grade IV (atheroma � 5mm)in 11; and Grade V (mobile lesion) in 5 patients. The incidence of embolicevents, mortality and clinical characteristics were evaluated in patientswith different grades of ASP.

RESULTS: The incidence of embolic events was increased with theseverity of ASP (Grade II, 12%, Grade III, 16%, Grade IV, 27% andGrade V, 60%). Grade � IV had the highest incidence of embolic events(6/16, 38%) compared to grade I (11/86, 13%) (p�0.038). There was nosignificant difference in age, left atrial diameter, spontaneous contrastecho in left atrium, left ventricular ejection fraction and the prevalence ofcoronary artery disease, old myocardial infarction, aortic stenosis, aorticvalve calcification, mitral annulus calcification and left ventricular hyper-trophy between the groups (p�0.05). There was no significant differencein the percentage of patients with therapuetic anticoagulation or antiplate-lets between the ASP groups. During the follow-up of 38.7�32 months,there was no significant difference in cardiac mortality between thegroups (p�0.05).

CONCLUSION: The incidence of the embolic events is related to theseverity of ASP. There was significant increase in the embolic events inpatients with grade �IV ASP.

CLINICAL IMPLICATIONS: ASP detected by TEE is associatedwith embolic events and there is significant increase in the embolic eventsin patients with grade � IV ASP.

DISCLOSURE: Chandra Nair, None.

DOES MITRAL REGURGITATION PROVIDE PROTECTIONAGAINST THE FORMATION OF LEFT ATRIAL THROMBUSAND EMBOLIC CEREBRAL VASCULAR ACCIDENT IN PA-TIENTS WITH ATRIAL FIBRILLATION?Xuedong Shen MD* Chandra K. Nair MD Huagui Li MD Tom Hee MDDhanunjay Lakkireddy MD Mark J. Holmberg MD David Cloutier BSKaren Rovang MD Aryan N. Mooss MD Syed M. Mohiuddin MD TheCardiac Center of Creighton University, Omaha, NE

PURPOSE: Previous studies suggest that patients with mitral regurgi-tation (MR) have a reduced incidence of embolic cerebral vascularaccident (CVA), assuming that the regurgitating jet “washes out” andprevents the formation of left atrial thrombus (LAT). However, theincidence of MR in patients with LAT is largely unknown. The purpose ofthe study was to evaluate the incidence of MR in atrial fibrillation (AF)patients with LAT and its impact on embolic events.

METHODS: 69 consecutive patients (male/female�36/33, age70.2�11.7 years) with AF and documented LAT on transesophagealechocardiogram (TEE) prior to contemplated cardioversion were evalu-ated for MR. The thrombus was located in the left atrial appendage in 67and the left atrial body in 2 patients. The severity of MR by color flowimaging was classified into four grades, trivial (1�), mild (2�), moderate(3�) and severe (4�).

RESULTS: All but 2 (67/69, 97%) patients demonstrated MR. MRseverity was 1� in 20 (29%), 2� in 27 (39%), 3� in 17 (26%), and 4� in3 (5%) patients. During the follow-up of 29.1�27.5 months after TEE, 3patients (4.3%) with LAT in left atrial appendage had embolic CVA. TheirINR at time of CVA was 2.9, 3.84 and 2.5. The CVA incidence had nosignificant difference between patients with MR � 3� (1/18, 5.6%)compared to �3� (2/51, 3.9%) (p�NS). However, the incidence ofspontaneous echo contrast in left atrium was higher in patients with MR �3� (47/51, 92.2%) than MR � 3� (14/18, 77.8%, p�0.034).

CONCLUSION: MR is very common in AF patients with LAT,suggesting that MR may not protect against the formation of left atrialclot. The occurrence of embolic CVA also was not decreased by thepresence or severity of MR although the incidence of spontaneous echocontrast in left atrium was lower in patients with � 3� MR.

CLINICAL IMPLICATIONS: The embolic events are not related tothe severity of MR. Further studies with larger number of patients andlonger follow-up seems indicated.

DISCLOSURE: Xuedong Shen, None.

RIGHT VENTRICULAR MECHANICAL DELAY AND GLOBALVENTRICULAR DYSFUNCTIONAngel Lopez-Candales MD* Kaoru Dohi MD Raveen Bazaz MD KathyEdelman University of Pittsburgh Medical Center, Pittsburgh, PA

PURPOSE: Several abnormalities in both right ventricular (RV) size andfunction tend to occur in patients with pulmonary hypertension (PAH). However,there is no data regarding the effect of PAH on RV free wall mechanicalactivation in these patients that can contribute to global dysfunction.

METHODS: We studied several well-established echocardiographic pa-rameters used to assess RV performance in a heterogeneous group of patientswith varying degrees of PAH as well as in a group of healthy volunteers andthen used tissue Doppler imaging (TDI) to investigate if abnormalities in RVfree wall mechanical activation occur with RV dysfunction.

RESULTS: Prospective data collected in 20 patients with varying degrees ofPAH (mean age 51 � 13 years, WHO class average 2.8 and mean pulmonarysystolic pressure 78 � 24 mmHg) were compared to similar data retrospectivelyobtained from 20 healthy volunteers (mean age 45 � 15 years). Patients withvarying degrees of PAH had worse RV performance parameters than healthyvolunteers (RV fractional area change 37 � 13% versus 52 � 5%, p �0.0001; RVmyocardial performance index 0.76 � 0.31 versus 0.29 � 0.11, p �0.0001; andEccentricity Index 1.41 � 0.57 versus 0.98 � 0.06, p�0.005). Similarly, in thesepatients with an abnormal RV performance, TDI showed a statistically significantlower peak longitudinal RV free wall strain (-21.5 � 9.0% versus -28.0 � 4.1%,p� 0.01) and a significantly delayed time-to-peak strain (459 � 76 msec versus388 � 29 msec, p�0.0005) values than healthy volunteers; a very strongcorrelation between RV mechanical delay and RV fractional area change (r �-0.89) was noted.

CONCLUSION: RV free wall mechanical delay, as documented byTDI, was identified in patients with varying degrees of PAH. Further-more, there is strong correlation between RV free wall mechanical delayand overall global RV performance in these patients.


Cardiology: Diagnosis of CardiovascularDisease, continued


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CLINICAL IMPLICATIONS: This novel echocardiographic tech-nique has the potential for identifying patients with subclinical RVdysfunction.

DISCLOSURE: Angel Lopez-Candales, None.

SCREENING FOR ATHEROSCLEROSIS: INITIATING SEC-ONDARY PREVENTION FOR HIGH-RISK YOUNG TO MID-DLE-AGED ADULTSAna M. Schaper PhD* Vicki L. McHugh MS Sharon I. Barnhart RNMichelle A. Mathiason MS Kwame O. Akosah MD Gundersen LutheranHealth Systems, La Crosse, WI

PURPOSE: The Framingham risk score is recommended for identify-ing individuals at high risk for a future event. However, the burden ofcardiovascular disease resides in patients stratified as low and intermedi-ate risk simply because of the large number of people receiving thisclassification. We propose the need to move beyond risk stratification forcardiovascular disease to identifying the presence of atherosclerosis inyoung to middle-aged adults who are truly at risk. The purpose of thisanalysis is to compare and contrast the role of Framingham risk stratifi-cation in the identification of atherosclerosis and risk for future events ina young to middle-aged population.

METHODS: Men (� 55 years) and women (�65 years) without priorcoronary heart disease scheduled for elective cardiac catheterization werestudied. Subjects underwent coronary angiogram, carotid ultrasound andfasting lipid testing on the same day. Framingham risk scores werecalculated. Endpoints included the presences of atherosclerosis (carotidor coronary disease) and one-year outcomes (hard events and futurerevascularization).

RESULTS: Men (n�110) and women (n�136) were studied. Athero-sclerosis was present in 170 subjects (carotid disease n�149, coronarydisease n�124). Per Framingham risk classification, 73%, 8%, 19% ofsubjects presented as low, intermediate and high risk, respectively.Median follow-up was 19 months. 25 subjects developed 35 events thatincluded death (n�2), stroke (n�5), MI (n�5), and revascularization(n�23). Neither lipid testing nor Framingham risk scores predicted thepresence of atherosclerosis or future events. Overall, 16% of subjects withatherosclerosis who were classified as low or intermediate risk had eventscompared to 14% of those at high risk. No future events occurred insubjects without documented atherosclerosis.

CONCLUSION: Many young to middle-aged adults classified as lowor intermediate-risk have atherosclerosis and develop cardiovascularevents. Framingham risk scores were not predictive of either.

CLINICAL IMPLICATIONS: By shifting to a focus on identifyingand aggressively treating atherosclerosis, screening can easily be accom-

plished using non-invasive strategies, such as carotid ultrasound to reducethe overall burden of disease.

DISCLOSURE: Ana Schaper, None.

THE EIGENVALUES OF THE ELECTROCARDIOGRAM: ANEW ELECTRICAL CARDIAC MARKER FOR ACUTE MYO-CARDIAL INFARCTIONDavid M. Schreck MD* Summit Medical Group, Summit, NJ

PURPOSE: To derive a 12-lead standard ECG from 3 measured leadsusing a universal patient coefficient matrix and to detect the presence ofacute MI from an EV index calculated for both the measured and derivedECGs.

METHODS: Twenty training ECGs of varying pathology were ac-quired and digitized resulting in a 300x12 voltage-time data array formathematical processing. The simplex optimization (SOP) technique wasused to derive a 12x3 universal patient coefficient matrix from the 20 caseECG training set. A different set of 55 test cases, including 37 normal and18 acute infarction ECGs, were similarly acquired and digitized, fromwhich leads I, aVF, and V2 were chosen as the measured 3 lead-vectorbasis factor space. The SOP coefficient 12x3 matrix was then multiplied bythe [I, aVF, V2} measured lead-vector 3x300 matrix yielding the derived12-lead ECG 300x12 matrix. The 55 measured and derived test caseECGs were graphically compared for diagnostic and morphologic corre-lation.

RESULTS: All 55 test case ECGs were predicted correctly. Nosignificant morphologic or diagnostic changes were noted in the derivedECGs. Significant differences between normal and acute MI weredetected at EV3% (p � 0.05) for both measured and derived ECGs andthe EV index predicted pathology in all cases correctly. The reduction ofthe measured 12-lead ECG data set to 3 leads allowed the display of avector plot of the movement of the electrical forces resulting in a3-dimensioanl spatial ECG curve.

CONCLUSION: A universal patient coefficient matrix has beenderived to allow 12-lead standard ECG derivations from 3 measured leadsacquired using the SOP technique. This study also demonstrated that anEV index may differentiate normal from acute MI pathology.

CLINICAL IMPLICATIONS: Using this new technology, it is nowpossible to perform instantaneous, real-time, point of service, cost-efficient 3-lead rhythm processing using bed-side cardiac monitoringsystems to produce a derived 12-lead ECG. Continuous monitoring of theEV index provides a dynamic electrical marker for acute MI.

DISCLOSURE: David Schreck, None.

TYPE II DIABETES MELLITUS IS INDEPENDENTLY ASSOCI-ATED WITH NON-RHEUMATIC AORTIC VALVE STENOSIS ORREGURGITATIONMohammad-Reza Movahed MD* Mehrtash Hashemzadeh BS M. MazenJamal MD Department of Medicine, Division of Cardiology, University ofCalifornia, Irvine, Orange, CA

PURPOSE: Diabetes mellitus (DM) is a major risk for cardiovasculardisease and mortality. There is a recent study that found DM wasassociated with aortic stenosis in univariate but not in multivariateanalysis. The goal of this study was to evaluate any association betweenDM and non-rheumatic aortic valve stenosis or regurgitation using ICD-9codes in a very large database.

METHODS: We used PTF documents containing discharge diagnosesusing ICD-9 codes of inpatient treatment from all Veterans HealthAdministration hospitals. The data were stratified using ICD-9 code forDM (n�293,124), and a control group with hypertension (HTN) but noDM (n�552,623), and the ICD-9 code for non-rheumatic aortic valvedisorder(424.1). We performed multivariate analysis adjusting for coro-nary artery disease, congestive heart failure, smoking and hyperlipidemia.Continuous and binary variables were analyzed using c2 and Fisher’sExact tests.

RESULTS: Non-rheumatic aortic valve disease diagnosis was presentin 7,322 (2.5%) of DM patients vs. 10906 (2.0%) in the control group.Using multivariate analysis, DM remained strongly associated with non-rheumatic aortic valve disease: (odds ratio (OR): 2.23, 95%; confidentialinterval (CI): 2.16 to 2.30 p�0. 000).

CONCLUSION: Type II diabetes mellitus is independently associatedwith non-rheumatic aortic valve disorders (regurgitation and stenosis)suggesting the direct negative effect of DM on aortic valve structure.




CLINICAL IMPLICATIONS: Patient with DM may need closefollow-up for the occurence of aortic valve stenosis or regurgitation.

DISCLOSURE: Mohammad-Reza Movahed, None.

ANATOMICAL BASIS OF CARDIOTHORACIC NEUROSTIMU-LATIONAnselmo De La Fuente MD* Maria Jose Saez MD Ana Insausti MDIgnacio Pascual MD Ricardo Insausti MD Hospital de Navarra, Pam-plona, Spain

PURPOSE: Our objectives are to determine in rodents, (a) the levelsat which sensory afferents to heart and lungs enter the spinal cord and (b)the termination of cardiothoracic afferent fibers in spinal gray matter.Such information is required to understand neurostimulation and toprogress development of rodent experimental models.

METHODS: Under general anaesthesia and mechanical ventilation, 50young Wistar rats were subjected to thoracotomy such that a neuroana-tomical retrograde tracer (horseradish peroxidase or Fast Blue) could beinjected with precision into either the pericardium, left atrium, root of theleft lung, or the left lung parenchyma.After appropriate survival timesanimals were sacrificed and perfused with the adequate fixatives. Spinalganglia and segments were identified, and those between C4 and Th12were removed individually and cryoprotected. Segments were sectioned at50�m and studied under the microscope to create a “map” of the columnand the distribution of tracer deposit within it.

RESULTS: Segments C8 through T4 contained retrogradely labeleddorsal root neurons projecting to the heart, while C8-T6 were labeledafter depositing tracer in the lung.Central branches of dorsal root ganglioncells entered laminae I and II.

CONCLUSION: Information from the heart is collected in the fourupper segments of the thoracic cord, but some information from the lungsalso arrives in these segments. Neurostimulation of spinal segments C8-T4will block afferents entering laminae I and II, including pain afferentsfrom the heart. The blocking of pain afferents from the heart may explainthe clinical improvement observed in angina patients under neurostimu-lation.

CLINICAL IMPLICATIONS: The description of the anatomicalbasis of cardiothoracic neurostimulation provides a long-awaited scientificexplanation of clinical findings. The experimental model developed anddescribed here provides a way to further investigate cardiac neurostimu-lation.

DISCLOSURE: Anselmo De La Fuente, None.

COAGULATION STUDIES IN PATIENTS WITH THROMBOSEDPROSTHETIC HEART VALVES AND INTRACARDIAC CLOTSLayla A. Mammo PhD Tanya M. Saou’r Atia W. Sheereen PhD M ShoukriPhD Jalal N. Saour MD* King Faisal Specialist Hospital, Riyadh, SaudiArabia

PURPOSE: To investigate the association of FVL, prothrombinG20210A and MTHFR C677T mutations in patients with thrombosedProsthetic Heart Valves and intracardiac clots.

METHODS: Blood from consenting healthy donors serving as theControl population (610 males and 111 females) and thirty one (31)pa-tients with thrombosed PHV, left ventricular clot and left Atrial clot wascollected. The DNA was extracted and stored at -70°C until needed .Testing for the mutations was done by the Polymerase Chain reactionusing restriction enzymes and by the Roche Light Cycler.

RESULTS: Nine subjects from the Control population tested positivefor FVL (1.25%); two for prothrombin G20210A (0.28%); and 180(25.4%) for MTHFR C677T. Thirty-one patients were tested.Twenty-fourwith thrombosed PHV, five with left ventricular clot and two with leftatrial clot. Two patients tested positive for FVL (6.4%), one for prothrom-bin G20210A (3.2%) and twelve for MTHFR C 677T (38.7%) mutations.

CONCLUSION: Our data suggest an association between FVL,prothrombin G20210A and MTHFR C677T mutations in patients withthrombosed PHV and intracardiac clots. However, upon comparing thepatient population to the normal population no significant difference wasfound for FVL(P Value� 0.11)and no significant difference for prothrom-bin G20210A (P value � 0.27) whereas for MTHFR C677T the differencewas significant(P value ��0.01). More data is needed to confirm thisobservation.

CLINICAL IMPLICATIONS: Valve thrombosis and systemic throm-boembolism continue to be the most serious complication in patients with

prosthetic heart valve (PHV) on long-term anticoagulation therapy. Whileunder treatment with oral anticoagulants is a recognized cause for thesecomplication, other factors possibly play a role as not all patientsunder-treated develop a coagulation problem.Factor V Leiden (FVL)prothrombin G20210A and the 5,10-methylenterahydrofolate-reductase(MTHFR)C677T mutations have been associated with venous & possiblyarterial thrombosis. No studies as to whether or not these factors areassociated with valve thrombosis or intracardiac clots in patients with PHVare available to date.

DISCLOSURE: Jalal Saour, None.

THE USE OF RADIOLOGICAL IMAGING IN THE INITIALWORKUP OF SYNCOPEM. Shubair MD N. Jallad MD H. Aziz MD M. Ismail MD* M.A. KhanMD St. Joseph’s Regional Medical Center, Paterson, NJ

PURPOSE: To evaluate the workup of patients admitted to thehospital with syncope and to evaluate that clinical practice guidelines forsyncope were followed.

METHODS: We retrospectively reviewed medical records of 104patients (50 males, 54 females, age range 23-93; mean age 63.8 yrs) withthe principal diagnosis of syncope over a period of 6 months and examinedtheir initial diagnostic workup including CT-head and carotid Dopplerultrasound.

RESULTS: Only one patient had focal neurological deficit on initialpresentation. Both his carotid ultrasound and CT-head were abnormal. 55(52.8%) patients had carotid doppler ultrasound and 62 (59.6%) patientshad CT-head despite normal physical examination; both tests werenormal.

CONCLUSION: These data suggest that the use of imaging studies inthe evaluation of syncope has a low diagnostic yield. Careful history, andphysical examination should help guide diagnostic testing.

CLINICAL IMPLICATIONS: The use of published clinical guide-lines for syncope is a good tool for the diagnostic workup. Patients with nofocal neurologic deficit on physical examination are unlikely to benefitfrom radiological imaging.

DISCLOSURE: M. Ismail, None.

CORRELATION OF CARDIOVASCULAR RISK SCORES WITHMYOCARDIAL HIGH-ENERGY PHOSPHATE METABOLISMRalf H. Zwick MD* Gert Klug MD Matthias Frick MD Michael SchockeMD Christian Wolf MD Werner Jaschke MD Otmar Pachinger MDBernhard Metzler MD Cardiology, Innsbruck University, Innsbruck,Austria

PURPOSE: Our preliminary data suggested a decrease of humanmyocardial, high-energy, phosphate metabolism in patients with hyper-cholesterolemia. Therefore we intended to prove its association withestablished cardiovascular risk scores.

METHODS: Our study included 99 healthy, asymptomatic malepatients (mean age 52.2 �/- 8.8) with normal ejection fraction. Allunderwent echocardiography and cycle ergometry to exclude a latentcoronary insufficiency. Blood was taken to evaluate cardiovascular riskscores: ESC cardiovascular (CV) risk, ESC coronary heart disease (CHD)risk, Procam and Framingham CHD score. Then Phosphorus-31, two-dimensional chemical shift imaging (31P 2D CSI) of the heart wasperformed in all subjects using a 1.5 Tesla whole-body magnetic reso-nance (MR) scanner. The ratios (R) between phosphocreatine (PCr) andbeta-adenosine-triphosphate (beta-ATP) were calculated for the leftventricular myocardium and divided into tertiles (R1-R3).

RESULTS: There was a significant effect regarding differences acrosstertiles (R1-R3) within the cardiovascular risk scores (Kruskal WallisANOVA for ESC CV, p�0.001; ESC CHD, p�0.001; Procam, p�0.003;Framingham CHD, p�0.001). Bivariat analysis revealed an associationbetween myocardial PCr-beta-ATP ratios and the ESC CV (p�0.001, r�-0.444), ESC CHD (p�0.001, r� -0.434), Procam (p � 0.027, r � -0.222),Framingham CHD (p�0.001, r � -0.380) score and patients with low Rhad a significant higher risk of cardiovascular events than those in thehigher tertiles.

CONCLUSION: We are the first to show a correlation between themyocardial high-energy, phosphate metabolism and cardiovascular riskscores.




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CLINICAL IMPLICATIONS: Myocardial high-energy, phosphate me-tabolism may be of relevance in primary prevention of cardiovascular disease.

DISCLOSURE: Ralf Zwick, None.

AN ABNORMAL RIGHT VENTRICULAR APICAL ANGLE ISINDICATIVE OF COMPROMISED RIGHT VENTRICULARFUNCTIONAngel Lopez-Candales MD* Kaoru Dohi MD Anca Iliescu MD Ross C.Peterson MD Kathy Edelman Raveen Bazaz MD University of PittsburghMedical Center, Pittsburgh, PA

PURPOSE: Presence of right ventricular (RV) dysfunction is anadverse prognostic indicator but current echocardiographic methods havesome limitations.

METHODS: RV apical angles in systole and diastole were correlatedwith known parameters of RV function in patients without pulmonaryhypertension (Group 1) and in patients with pulmonary hypertension(Group 2). RV apical angles were significantly smaller in both systole(22 � 7 degrees) and diastole (33 � 6 degrees) in Group 1 patients whencompared to Group 2 (54 � 18 degrees, p�0.0001 and 59 � 17 degrees,p�0.0001, respectively).

RESULTS: Group 2 patients had statistically larger RV systolic anddiastolic areas (19� 9 versus 8 � 3 and 27� 9 versus 17 � 3, p�0.0001;respectively) and smaller maximal TV annular excursion (2.5 � 0.44 versus1.5 � 0.66, p� 0.00001; respectively) than Group 1. Group 2 hadstatistically larger RV apical angles in both systole and diastole whencompared to Group 1 (54 � 18 and 59 � 17 versus 22 � 7 and 33 � 6,p� 0.00001, respectively). The peak pulmonary systolic pressures werenot only inversely correlated with RVFAC (R � -0.62; p�0.001) but alsowith maximal TV annular excursion (R � -0.69; p�0.001). A very stronglinear correlation was noted between the RVEDA and RV diastolic apicalangle (R � 0.81, p�0.0001) and between the RVESA and RV systolicapical angle (R � 0.89, p�0.0001). RV apical angle also had a statisticallysignificant inverse correlation with measures of RV function. A represen-tative end diastolic four chamber still frame image of a normal and apatient with an abnormal RV apical angle is shown.

CONCLUSION: Therefore, we conclude that this new measurementof RV apical angle is simple and useful to quantify RV apical structural andfunctional abnormalities that are well correlated with global RV impair-ment in patients with chronic pulmonary hypertension.

CLINICAL IMPLICATIONS: Ease of data acquisition, reproducibility, andlack of cumbersome geometric analyses allow for easy clinical application.

DISCLOSURE: Angel Lopez-Candales, None.

TEACHING CARDIAC AUSCULTATION VIA THE INTERNET:THEORY BECOMES REALITYMichael J. Barrett MD* Katherine A. Thomas MS Maryann Kuzma MDDrexel University College of Medicine, Blue Bell, PA

PURPOSE: The ability of medical students to recognize heart soundsis alarmingly low (�21%). We previously demonstrated students wholistened to intensive repetition of abnormal heart sounds in a classroomsetting achieved a proficiency score of 85%. This followup study investi-gated if similar results could be obtained using the Internet.

METHODS: 64 third year medical students were randomized to eitheran intervention (I) group (N�50) or control (C) group (N�14). Theintervention students were instructed to download a digital audio file(mp3) from a web page. This file contained auditory recognition exercisesof 4 basic cardiac murmurs (Aortic Stenosis, Aortic Regurgitation, MitalRegurgitation, Mitral Stenosis) and 2 extra heart sounds (S3, S4). Eachheart sound was repeated 400 times interspersed with clinically relevantcomments. The 14 control students downloaded a sham file with noauditory instruction. Two tests of auscultatory proficiency were adminis-tered: a pretest before the intervention and a posttest after the interven-tion. At both tests, all subjects listened to prerecorded heart sounds in arandomized sequence and wrote the name of the sound on blank answersheets.

RESULTS: For the intervention students, the pretest proficiency scorewas 29.6 � 15.7% (Mean �SD) and increased significantly to 82.0 �16.9% on the posttest (p�0.001). The average improvement was 52points. No significant improvement was seen in controls: pretest 38.8 �/-17.3% and posttest 44.6 �/- 17.6% p�0.15.

CONCLUSION: Third year medical students demonstrated dramaticimprovement in cardiac auscultation after listening to a digital audio filedownloaded via the internet. These improvements were equal to thatobtained with classroom instruction using a similar approach of intensiverepetition of abnormal sounds.

CLINICAL IMPLICATIONS: This study confirms to importance ofintensive repetition in learning cardiac auscultation and demonstrates thatthis type of learning can be effectively communicated via the internet.This method of instruction is associated with significant cost savings andexpanded geographic reach.

DISCLOSURE: Michael Barrett, Shareholder Michael Barrett, MDhas an ownership interest in MED-Ed Consulting, Inc.

INTERVENTRICULAR SEPTAL FLATTENING OBSERVED ONTHE MYOCARDIAL PERFUSION IMAGES STRONGLY CORRE-LATE WITH RIGHT VENTRICULAR OVERLOADMohammad-Reza Movahed MD* Absalam Hepner MD Paul Lazotte DONorah Milne MD University of California, Irvine Medical Center,Orange, CA

PURPOSE: Background: Flattening of the interventricular septum(D-shaped Septum) detected during echocardiographic examination iscorrelated with significant right ventricular (RV) overload. There are noreports of this finding with cardiac gated SPECT imaging. We report anobservational study correlating this finding with the presence of RVoverload.

METHODS: Method: Retrospectively we compared eight cases withflattening of the interventricular septum on cardiac gated SPECT imagingof which echocardiographic correlations and clinical data were availablefor the presence of RV overload.

RESULTS: Results: All patients but one had pulmonary hypertensionranging from 42 to 52 mmHg measured by echocardiographic dopplerstudies. Except one all patients had reasons for RV overload (chronicobstructive pulmonary disease in three, history of atrial septal defect inthree, pulmonary embolism in one and obstructive sleep apnea in one).Septal flattening present on gated SPECT images was seen in 50% of thecases by echocardiography. Other signs of RV overload (RV enlargement,RV hypertrophy) were observed by echocardiography in five patients andby the gated SPECT in seven patients.

CONCLUSION: Conclusion: The presence of interventricular septalflattening on gated SPECT studies correlates with right ventricularoverload and should be routinely assessed during interpretation of gatedSPECT studies.

CLINICAL IMPLICATIONS: We suggest that more attention shouldbe given to the shape of the interventricular septum during interpretationof gated SPECT studies and the term of septal flattening should be




routinely used and reported similar to echocardiographic descriptions ofthe septum in patients with suspected RV overload.


LISTENING TO THE AORTIC VALVE: NOVEL ACOUSTICANALYSIS PREDICTS AORTIC VALVE CALCIFICATION ANDCARDIOVASCULAR EVENTSKian Keong Poh MB, BCh* Mark Y. Chan MBBS Hong Yang MD LiengH. Ling MBBS National University Hospital, Singapore, Singapore

PURPOSE: Aortic valve calcification (AVC) measured by multislicecomputed tomography (MSCT) has previously been shown to be ofprognostic importance. We aimed to determine if a novel acoustic methodof evaluating heart sounds in pts with valvular aortic stenosis (AS) orsclerosis is a useful alternative.

METHODS: ECG-gated acoustic data recorded from the precordialaortic area using an electronic stethoscope were subjected to energy-based continuous wavelet transformation by a laptop software program,which extract the dominant systolic frequency (DF). These were com-pared to AVC quantified in Agatston units (AU) by MSCT and echocar-diographic indices of AS severity, determined independently. Patientswere prospectively followed up for occurrence of cardiac death andsymptom-driven aortic valve replacement.

RESULTS: Of 50 pts (age 68�11 yrs, 58% males), 35 had lone AS ofvarying severity and 15 with aortic valve sclerosis. Mean aortic valve areaindexed to body surface area (AVAI), AVC, DF and left ventricularejection fraction (EF) were 0.94�0.50 cm2/m2, 1037�1476 AU, 103�69Hz and 62�14% respectively. DF correlated significantly with AVC,maximal pressure gradient across the aortic valve (Pmax), AVAI and aorticvalve resistance (r�0.62, 0.61, -0.51 and 0.60 respectively, all P�0.001).In a multivariate linear regression model incorporating AVC, AVAI andPmax, the only independent predictor of DF was AVC (��0.37, P�0.03).Over 15�7 months, 7 pts reached the composite endpoint. Pts with eventshad higher DF (170�65 vs 93�64 Hz, P�0.005). For prediction of theendpoint, the areas under receiver characteristic curves for DF, AVC,AVAI, age and EF were 0.82(P�0.007), 0.79(P�0.013), 0.88(P�0.001),0.50(P�NS) and 0.65(P�NS) respectively. A threshold of 145 Hz for DFprovided optimal sensitivity of 86% and specificity of 81% of predicting anevent.

CONCLUSION: DF derived from novel acoustic analysis of aorticvalve stenosis or sclerosis correlates well with AVC by MSCT and offersprognostic information in these patients.

CLINICAL IMPLICATIONS: Acoustic analysis of heart sound mayprovide a simple and useful non-invasive adjunct in the management ofpatients with aortic valve calcification.

DISCLOSURE: Kian Keong Poh, Grant monies (from sources otherthan industry) National Healthcare Group (Singapore) and SingaporeHeart Foundation grants.

VASCULAR FUNCTION IS ABNORMAL IN PATIENTS WITHOBSTRUCTIVE SLEEP APNEAHossein Sharafkhaneh MD* Max Hirshkowitz PhD Biykem Bozkurt MDAmir Sharafkhaneh MD Baylor College of Medicine, Houston, TX

PURPOSE: Oxygen desaturations and sleep fragmentations are fre-quently seen during sleep in OSA. These events provoke heightenedsympathetic activity and may impair vascular function. We investigatedflow and nitroglycerin-mediated (FMD and NMD, respectively) vasculardilation in middle-aged (�65) and elderly (� 65) patients with moderateto severe OSA.

METHODS: We recorded polysomnograms from 18 male subjects(mean age � 55 �10.99]) with symptomatic OSA and measured FMDand NMD in brachial artery using high-resolution vascular ultrasoundwith a 10-MHz linear-array transducer. The right brachial artery diameter(BAD) was measured at baseline, and then a pneumatic tourniquet wasplaced around the forearm and inflated to a pressure of 200 mm Hg for5 minutes. BAD measurements were repeated at 15 seconds, then at everyminute for 5 minutes following cuff deflation and following administrationof 0.4 mg of sublingual NTG. The FMD was expressed as a percentagechange of diameter after reactive hyperemia relative to the baseline scan.Likewise, the NMD was expressed as a percentage change of diameterafter NTG administration relative to the baseline scan.

RESULTS: Mean [SD] ESS was 14 [7], mean [SD] AI and AHI were30[34] and 50 [33] respectively, and lowest and mean O2 saturations were75% [22%] and 93%[3%] respectively. Brachial artery diameter (mm) atbaseline, 1 minute post hyperemia, and 3 minutes post NTG were 0.45[0.09], 0.48 [0.06], and 0.49 [0.05] mm. Baseline and post NTG diameterswere significantly different (p � 0.01). The FMD and NMD were 1%[2%] and 11% [3%], respectively (p� 0.001). Our study did not haveenough power to detect any difference in FMD and NMD in elderlyversus middle-aged adults.

CONCLUSION: Endothelial dependent vascular function is impairedin subjects with moderate to severe OSA. Further studies will evaluate theeffect of therapeutic intervention to determine if this is a reversiblealteration in vascular function.

CLINICAL IMPLICATIONS: Restoration of endothelial dependentvascular function may be useful in evaluation obstructive sleep apneatreatment.

DISCLOSURE: Hossein Sharafkhaneh, None.

THE NEW PERICARDIAL STRUCTURE IN VIBROACOUSTICDISEASEJose I. Fragata PhD* Emanuel Monteiro MD Mariana Alves-Pereira MSNuno A. Castelo-Branco MD Pediatric Cardiac Surgical Unit, Santa-Marta Hospital, Lisbon, Portugal

PURPOSE: The anatomical study of the pericardium in vibroacousticdisease (VAD) patients was prompted by the echo-imaging resultsobtained initially in aircraft technicians. With informed consent of VADpatients, submitted to cardiac surgery for other reasons, pericardialfragments were removed for study in order to determine the nature of thisabnormal thickening.

METHODS: The parietal pericardium fragments were removed dur-ing surgery. None had a record of any kind of pericarditis, nor of any typeof diastolic problems, and there was no previous history of diabetes orrepeated streptococcal infections. Fragments were removed at the begin-ning of the surgery, during the opening of the pericardial sac. Eachfragment was divided in two and pinned in dentist wax in a Petry dish withthe serosal surface facing up. The specimens for light microscopy wereformalin-fixed, paraffin-embedded, hematoxylin, eosin and fuschsin-rhes-orcin stained.

RESULTS: Normal pericardium has three layers: serosa, fibrosa andepipericardium. Five layers of tissue were identified, instead of theclassical three: serosa, internal fibrosa, loose tissue layer, external fibrosa,and epipericardium. The external and internal fibrosa are composed oforganized, wavy collagen bundles. Images of apoptotic (programmed)death were seen in the mesothelial layer, and non-apoptotic (mechanical)cell death was observed in all other layers. A large amount of cellulardebris was present in all fields, however, not inflammatory process waspresent. Imaging frequently disclosed the presence of cell debris insidethe small lymphatic vessels.

CONCLUSION: Given the large amount of cellular debris, auto-immune situations are certain to arise. Drainage of cellular debris seemsto be a major function of the surrounding lymphatic vessels.




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CLINICAL IMPLICATIONS: Pericardial thickening with no adias-tole, and no inflammatory process is a VAD diagnosis, and can certainly bethe cause of auto-immune situations.

DISCLOSURE: Jose Fragata, None.

MECHANOTRANSDUCTION IN PERICARDIAL TISSUE OF VI-BROACOUSTIC DISEASE PATIENTSMariana Alves-Pereira MS* Jose I. Fragata PhD Emanuel Monteiro MDNuno A. Castelo-Branco MD Environmental Sciences & Engineering,New Univ Lisbon, Caparica, Portugal

PURPOSE: Mechanical signalling among cells and tissues has beenshown to be an important, albeit lesser known, form of transducingpathological stimuli. Cytoskeletal (CSK) structures are organized inaccordance with tensegrity architecture and, as such, can bear mechanicalloads. Vibroacoustic disease (VAD) is a systemic pathology characterizedby the abnormal proliferation of extra-cellular matrices (ECM) in theabsence of an inflammatory process. The goal of this report is toqualitatively analyse the images obtained from vibroacoustic disease(VAD) pericardial fragments within the context of tensegrity structures.

METHODS: Drawing upon the numerous scanning and transmissionelectron microscopy images of VAD patients’ parietal pericardium, whichis abnormally thickened and discloses mechanical cell death in all layers.The abnormal thickening is due to the splitting of the fibrosa layer intotwo halves and, in between, the neo-formation of a loose tissue layer. Theinternal fibrosa layer follows the systolic and diastolic movements veryclosely while the external layer does not. The implications of thesesituations for CSK and ECM mechanotransduction are qualitativelyanalysed.

RESULTS: The new pericardial structure, composed of five layersinstead of three (due to fibrosa splitting and neo-formation of loose tissuelayer) is reminiscent of a pneumatic structure. The wave length of thewavy collagen fibres found in the internal fibrosa seem to be more variablethan that found in the external fibrosa. The loose tissue layer containsadipose tissue that, due to its viscoelastic properties, can attenuateexternal mechanical forces. In the meseothelial layer, there is a reinforce-ment of cell-cell connections, through an increased amount of desmo-somes. No hemidesmosomes were identified, however the boundarybetween mesothelial layer and lower basal lamina exhibits unusualconnection, reminiscent of anti-sesmic structures.

CONCLUSION: Tensegrity architecture of cells and tissue can greatlycontribute to the understanding of the biological response to LFN-exposure.

CLINICAL IMPLICATIONS: It is probable that pharmacologicalsolutions for LFN-induced pathology targeting CSK and ECM tensionwould be most successful.

DISCLOSURE: Mariana Alves-Pereira, None.

Cardiology: Echocardiography12:30 PM - 2:00 PM

SMALL PULMONARY ARTERIOVENOUS MALFORMATIONSIDENTIFIED BY SALINE CONTRAST ECHOCARDIOGRAPHYARE ASSOCIATED WITH MIGRAINE HEADACHETimothy D. Woods MD* Suresh Ramamurthy MD Medical College ofWisconsin, Milwaukee, WI

PURPOSE: Patent foramen ovale (PFO) has been linked to migraineheadache (MH), probably resulting from an unidentified vasoactivesubstance bypassing pulmonary metabolism. The prevalence of pulmo-nary arteriovenous malformations (PAVM) in a population without respi-ratory symptoms or hereditary hemorrhagic telangiectasia (HHT), adisease associated with PAVM, has not been described and may also beassociated with MH.

METHODS: Sixteen patients ages 20-55 undergoing a transthoracicecho for reasons other than pulmonary disease or symptoms wereconsented to also undergo a saline contrast echocardiogram (SCE) withand without Valsalva. If � 1 clear bubble(s) appeared in the left heart �3 cardiac cycles of right heart opacification at rest or with Valsalva, it wasclassified a PFO. If � 1 bubble(s) were evident in the left heart at � 5

cardiac cycles of right heart opacification at rest AND with Valsalva, it waslabeled late left heart contrast (LLHC), compatible with presence of aPAVM. Patients then completed a questionnaire previously shown instudies to be accurate in diagnosis of MH.

RESULTS: Three of the 16 patients (19%) had LLHC (5-20 bubbles),compatible with small PAVM. All 3 patients had questionnaires diagnosticof MH.

CONCLUSION: Small amounts of LLHC during SCE is not uncom-mon in patients without respiratory symptoms or HHT, and is compatiblewith the presence of small PAVM. Small PAVM appear to be significantlyassociated with MH. The presence of right-to-left shunt appears associ-ated with MH independent of the shunt mechanism.

CLINICAL IMPLICATIONS: Small amounts of LLHC are compat-ible with small PAVM and are not uncommon in patients withoutrespiratory disease. They should not be ignored when interpreting a SCE,as it appears they have clinical significance. The mechanism linking smallPAVM and MH may involve a vasoactive substance escaping pulmonaryendothelial metabolism, and requires further investigation.

DISCLOSURE: Timothy Woods, None.

EVALUATION OF ASYMPTOMATIC PATIENTS WITH CRONICCHAGAS DISEASE TRHOUGH THE ANALISYS OF DYNAMICELECTROCARDIOGRAM, ECHOCARDIOGRAM AND B-TYPENATRIURETIC PEPTIDESDivina S. Oliveira-Marques PhD* Manoel F. Canesin PhD Claudio J.Fuganti MD Antonio C. Pereira-Barretto PhD Londrina State University,Londrina, Brazil

PURPOSE: To evaluate asymptomatic patients with chronic Chagas‘disease in relation to the prevalence of ventricular arrhythmia, leftventricular dysfunction, and B-type natriuretic peptide levels ( BNP).

METHODS: Clinical evaluation, electrocardiogram (EKG). cardiotho-racic index (CTI),dynamic electrocardiogram, echocardiogram and BNPdosing were used to evaluate 106 patients from the Chagas DiseaseOutpatient Clinic, distributed into three groups: GI (50- normal EKG).GIIA (31-EKG with alterations characteristic of Chagas disease, and GIIB( 25- EKG with other types of alterations).

RESULTS: The most prevalent electrocardiographic alterations were:GIIA group: right bundle branch block, anterior division of de left bundlebranch block and inactive areas (18% each); GIIB group: alterations in theinfero-lateral repolarization and left ventricular hypertrophy (26%). CTImean values were similar (p�0,383). The prevalence of ventriculararrhythmia was greater in the GIIA (77%) and GIIB (75%) groups than inthe GI group (46%) (p�0,002). Ventricular dysfunction was more fre-quent in the GIIA (52%) and GIIB (32%) groups than in the GI group(14%) (p� 0,001). Systolic dysfunction was more prevalent in the GIIAgroup (29%) than in the GIIB (20%) and GI (2%) (p� 0,001). Diastolicdysfunction was more frequent in the GII (42%) and GIIB (28%) groupsthan in the GI (12%) group (p�0,005). B-type natriuretic peptide levelswere 30 � 88 pg/ml for the GI group, 66 � 194 for the GIIA group and24 � 82 for the GIIB group (p�0,121), respectively.

CONCLUSION: Arrhythmia and left ventricular dysfunction weremore prevalent in the asymptomatic patients with chronic Chagas‘ diseaseand EKG alterations than in patients with normal EKGs. BNP levels weresimilar among the groups.

CLINICAL IMPLICATIONS: Patients with asymptomatic chronicform of the Chagas‘disease and electrocardiographic alterations will haveto be submitted to the inquiry in relation to the presence of arrhythmiasand ventricular dysfunction.

DISCLOSURE: Divina Oliveira-Marques, None.

SCE Result Migraine Present p Compared to Normal

Normal 9 1PFO 4 2 p�0.04 p�0.035PAVM 3 3 p�0.013TOTAL 16 6

p Values computed using Two-Tailed Fisher’s Exact Test




GENDER SPECIFIC ECHOCARDIOGRAPHIC PREVALENCEOF VALVULAR HEART DISEASE IN A DATABASE OF 24,265PATIENTSMohammad-Reza Movahed MD* Mastaneh Ahmadi-Kashani BS BabakKasravi MD Ali Ghorbani MD University of California, Irvine MedicalCenter, Orange, CA

PURPOSE: : Prevalence of different valvular pathologies has not beenreported in female and male patients in large population-based studies.The goal of this study was to report gender specific prevalence of variousvalvular pathologies.

METHODS: We retrospectively analyzed 24,265 echocardiogramsperformed at our institution between 1984 and 1998. The prevalence ofmitral valve prolapse (MVP), regurgitation (MR) and stenosis (MS), aorticvalve regurgitation (AR) and stenosis (AS), bicuspid aortic valve andtricuspid regurgitation (TR) were calculated in female and male patients.

RESULTS: Echocardiograms were performed in 12,926 (53%) femalepatients and 11,339 (47%) male patients. Gender specific echocardio-graphic prevalence of different valvular abnormalities is shown in Table 1.

CONCLUSION: Conclusion: In this study, we compared echocardio-graphic prevalence of different valvular disease in female and malepatients. MS and moderate to severe TR were more prevalent in femalepatients. MVP, bicuspid aortic valve and severe AR were more prevalentin male patients. The other valvular conditions studied had similarprevalence in both female and male patients.

CLINICAL IMPLICATIONS: There are significant difference in theoccurrence of Valvular abnormalities between men and women that needsfurther investigation.


DENTITION AND AORTIC ATHEROSCLEROSIS; A TRANS-ESOPAHAGEAL ECHOCARDIOGRAPHIC STUDYRicardo Castillo MD Louis Salciccioli MD Jason M. Lazar MD* SUNYDownstate Medical Center, Brooklyn, NY

PURPOSE: Prior studies have shown a relationship between periodon-tal disease, acute myocardial infarction, and atherosclerosis. Microbesindigenous to the oral cavity and DNA of periodontal pathogens havebeen found in atheromatous carotid plaques. Oral pathogens may promoteinflammation and thrombosis leading to atherogenesis Periodontal diseasehas been found associated with coronary artery, carotid, and peripheralvascular disease. The objective of this study was to determine a possibleassociation between dental loss and aortic atherosclerotic disease. Trans-esophageal echocardiography (TEE) is an excellent technique to assessaortic atherosclerotic plaque.

METHODS: In 115 patients (age 59 �15 years, 63% female) referredfor TEE, clinical data were recorded. Periodontal disease was determined

as the number of missing teeth. Maximal aortic plaque thickness wasmeasured by TEE. Analysis was performed to determine correlates ofnumber of missing teeth and aortic plaque thicknes.

RESULTS: Univariate correlates of tooth loss were age, hypertension,aortic plaque size, Ca-channel blocker use, and a trend toward B-blockeruse. There was an inverse correlation with smoking. Univariate predictorsof aortic plaque thickness were age(r�. 41, p�.001), dental loss (r�.27,p�.003), and Ca-channel blocker use(p�.006). There was an inverseassociation with smoking. Stepwise regression demonstrated age to be thestrongest predictor of aortic atherosclerosis, with dental loss and Ca-channel blocker use also found to be independent predictors.

CONCLUSION: In conclusion, aortic atherosclerosis as determinedby maximal plaque size is associated with periodontal disease.

CLINICAL IMPLICATIONS: Poor dentition may be a simple clini-cal indicator of atherosclerosis. The association between poor dentitionand aortic atherosclerosis may be related to common risk factors or tochronic inflammation.


PREVALENCE AND PROGNOSIS OF INTRAPULMONARYSHUNTS IN PATIENTS WITH HEPATIC CIRRHOSISManisha Das MD* Wilbert S. Aronow MD Michael Langiulli MD PierreSalomon MD John A. McClung MD Leona Kim-Schluger MD DavidWolf MD Robert N. Belkin MD New York Medical College, Valhalla, NY

PURPOSE: The purpose of this study was to investigate the prevalenceand prognosis of intrapulmonary shunts in patients with hepatic cirrhosis.

METHODS: We investigated the prevalence and prognosis of in-trapulmonary shunts in 82 patients (56 men and 26 women), mean age 54years, with hepatic cirrhosis referred for contrast echocardiography as partof an evaluation for liver transplantation. Mean follow-up was 41 monthsin patients with intrapulmonary shunts and 42 months in patients withoutintrapulmonary shunts (p not significant).

RESULTS: Intrapulmonary shunts were present in 49 of 82 patients(60%) with hepatic cirrhosis. Baseline characteristics including theMELD score were not significantly different between patients with andwithout intrapulmonary shunts. At 41-month mean follow-up, 8 of 49patients (16%) with intrapulmonary shunts and 4 of 33 patients (12%)without intrapulmonary shunts had died (p not significant).

CONCLUSION: Intrapulmonary shunts do not significantly increasemortality in patients with hepatic cirrhosis at long-term follow-up.

CLINICAL IMPLICATIONS: Patients with hepatic cirrhosis withand without intrapulmonary shunts have a similar mortality at long-termfollow-up.

DISCLOSURE: Manisha Das, None.

ECHO-IMAGING FEATURES IN CARDIOVASCULAR STRUC-TURES IN VAD PATIENTSAmilcar Araujo MD* Joaquim Carranca MD Elia Batista MD Nuno A.Castelo-Branco MD Cardiology Unit (UTIC), St. Maria University Hos-pital, Lisbon, Portugal

PURPOSE: Previous studies show that low frequency noise (LFN,�500 Hz, including infrasound) induces changes in the extra-cellularmatrices (ECM). The pathology induced by excessive exposure to LFN iscalled vibroacoustic disease (VAD). The diagnostic method of choice hasbeen echocardiography because proliferation of the ECM can be visual-ized in thickened cardiac structures, namely pericardium and valves.Recently echocardiograms revealed an anatomical feature that could be aconsequence of Echo reveale anatomical feature echo revelased anatom-ical consequence of theis extra-thoracic pressure: visible hyperplasia of theeustaquian valve in the inferior vena cava. Is being observed in all patientsin this currently ogoing project.

METHODS: Study population: 30 selected male flight attendants, ave.age 48 (range 30-61), and 30 female flight attendants, ave. age 43 (range27-57). Total exposure time of all individuals was � 8 yr. Echo-Dopplerstudies were recorded on coded videotapes. Using a 0 to 3 point scoringsystem, 3 morphological parameters were evaluated: thickening of thepericardium, mitral & aortic valves and vena cava’ eustachian valve.

RESULTS: Echocardiograms of flight attendants (males and females)disclose pericardial thickening that may appear concurrently with cardiacvalve thickening , but with no consequences for diastolic mechanics.Thickened eustachian valve of the inferior vena cava were clearly visibleall the study population.

Type ofValvularDisease

Prevalencein

Females (%)

Prevalencein

Males (%)

OverallPrevalence

(%)

MR, all 24.4 25.0 24.7MR, mild 16.5 16.5 16.5MR, moderate 6.1 6.3 6.2MR, severe 1.9 2.2 2.0MS, all** 1.6 0.4 1.0MVP* 0.4 0.7 0.6AR, all 5.5 14.9 15.2AR, mild** 11.5 10.1 10.9AR, moderate 2.6 2.5 2.6AR, severe** 0.4 1.0 0.7AS, all 2.1 2.3 2.2Bicuspid aortic valve** 0.3 0.9 0.6TR, all** 18.5 16.7 17.7TR, mild 11.9 11.6 11.7TR, moderate* 4.4 3.7 4.0TR, severe** 2.3 1.5 1.9

* p � 0.01


Cardiology: Echocardiography, continued


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CONCLUSION: At the cellular level, LFN-exposed humans andanimals disclose transitory generalized fluid retention, which is main-tained throughout the duration of LFN exposure (occupational or envi-ronmental). This is very discreet, decays with ceasing LFN exposure, andis not comparable to generalized common oedema, This can causeunsuspected interthoracic hypertension and can, in turn, lead to general-ized extra-thoracic stasis.

CLINICAL IMPLICATIONS: Echo observation of a thicken eusta-quian valve can alert for a possible VAD diagnosis.

DISCLOSURE: Amilcar Araujo, None.

IMPORTANCE OF EARLY FLUIDS RESUSCITATION IN MU-RINE SEPSIS: ECHOCARDIOGRAPHIC STUDYMassimiliano Guglielmi MD* Sergio Zanotti MD Walker Tracy MDMagali Zanotti BA Felicitas Ross BA Joseph E. Parrillo MD Steven M.Hollenberg MD Cooper University hospital/UMDNJ, Camden, NJ

PURPOSE: Fluid resuscitation and antibiotic administration are criti-cal components of the early treatment of sepsis. We evaluated the impactof three different early resuscitation regimens on cardiac performance ina murine model of sepsis.

METHODS: 3 groups of 8 C57Bl/6 mice were made septic by cecalligation and double perforation (CLP); 5 controls had sham ligation. AfterCLP animals received 1 of 3 fluid regimens: 35mL/kg normal saline bolusSQ after surgery only (None), 35mL/kg after surgery and then every 6hr,(Partial) and 100mL/kg after surgery and then every 6hr (Full). All 3groups received ceftriaxone, 30mg/kg and clindamycin, 25mg/kg at 6 and12hr. Animals were anesthetized briefly with isoflurane for echocardiog-raphy using a high-resolution ultrasound system (30Mhz scan-head).Stroke volume (SV, �L) was assessed by Doppler in the aortic outflowtract and fractional shortening (FS, %) by M-mode in the short axis view.Cardiac output (CO, mL/min) was calculated as SV*HR.

RESULTS: From 3 to 9hr after CLP, CO was reduced from 25�2 to13�2 (None), 24�4 to 15�5 (Partial) and 26�5 to 17�4mL/min (Full),largely due to a reduction in SV, from 56�6 to 23�2 (None), 51�6 to28�7 (Partial), and 58�7 to 32�5�L; (Full) (p�0.05 vs baseline andsham operated animals in all groups. Heart rate did not change signifi-cantly. Animals that received aggressive resuscitation (Full) reached anormodynamic state at 15hours, CO 23�7; SV 48�9; HR 475�74, p�NSvs baseline and sham operated animals. Unresuscitated and underresus-citated animals remained in a hypodynamic state, CO 14�6; SV 30�10;HR 470�50 (None) and CO 15�3; SV 40�9; 395�35 (Partial), p�0.05vs baseline, sham operated and aggressively resuscitated animals (Full).

CONCLUSION: Adequate fluid resuscitation is mandatory to restorea normodynamic state in sepsis. In this murine model, which replicatesclinical sepsis, early underresuscitation can lead to a sustained hypody-namic state. Early and aggressive resuscitation is necessary to reestablishnormal hemodynamics.

CLINICAL IMPLICATIONS: Even seemingly minor degrees ofunderresuscitation early could potentially impair hemodynamics in laterphases of sepsis in patients.

DISCLOSURE: Massimiliano Guglielmi, University grant monies.

Cardiology: Epidemiology of Heart Failure12:30 PM - 2:00 PM

SURVIVAL BENEFIT ASSOCIATED WITH DISEASE MANAGE-MENT IN RURAL INDIGENT SYSTOLIC HEART FAILUREPATIENTSKathy Hebert MD Ron Horswell PhD Lee Arcement MD* ChabertMedical Center, Houma, LA

PURPOSE: Heart failure (HF) produces significant morbidity andmortality. Although HF disease management (HFDM) programs havebeen shown to decrease this morbidity, there is a paucity of data of theireffect on mortality, especially in indigent settings. The objective was todetermine whether participation in a HFDM program would be associ-ated with reduced mortality in an indigent population from rural Louisi-ana.

METHODS: Proportional hazards modeling was used to determinewhether patients participating in the HFDM program had improvedsurvival compared with patients receiving traditional outpatient care at thesame institution. Inclusion criteria consisted of an index hospitalizationwith discharge occurring between July 1, 1997 and May 30, 2002, hospitaldischarge diagnosis of HF, left ventricular systolic dysfunction � 40%documented during hospitalization, and at least 1 subsequent outpatientvisit. Data from patients having participated in the HFDM program priorto their index hospitalization were excluded. Patients were allocated to thedifferent management strategies in a nonrandomized non-blinded fashionat the discretion of the discharging physician.

RESULTS: Compared with patients who were given traditional care(n � 100), HFDM patients (n � 156) were younger (56.7 vs 60 years;P � 0.031), more likely to be African American (48.7% vs 33.0%; P �.014), more likely to be uninsured (47.4% vs 27%; P � .001), and morelikely to have an ejection fraction of 25% (73.1% vs 36%; P �.001).Overall comorbidity did not differ significantly between the groups.After controlling for differences in demographics, ejection fraction,and comorbidities, participation in the HFDM program was associatedwith a significant reduction in mortality compared with traditional care(adjusted hazard ratio, 0.33; P �.001). Median annual income for bothgroups was $ 11,300.

CONCLUSION: In this indigent population, participation in a HFDMprogram was associated with decreased mortality compared with tradi-tional follow-up care.

CLINICAL IMPLICATIONS: Utilizing disease management in thisdeadly disease should be considered and ascertaining the impact of thisexact disease management model in other heart failure populations shouldbe undertaken.

DISCLOSURE: Lee Arcement, None.

EXERCISE INDUCED DIASTOLIC DYSFUNCTIONVimesh K. Mithani MD Fayez Shamoon MD Sanjeev M. Patel MD*Dulce De Guzman Phillip John Emlata Tarnate Irvin Goldfarb MD St.Michael’s Medical Center, Seton Hall University School of GraduateMedical E, Newark, NJ

PURPOSE: Diastolic function is not evaluated routinely duringstress echocardiography. Little information exits regarding the inci-dence of diastolic dysfunction induced by exercise. The aim of thisstudy was to assess change in diastolic function by exercise echocar-diography. We hypothesized that patients with dyspnea may havehigher incidence of exercise-induced diastolic dysfunction withoutevidence of ischemia.

METHODS: We evaluated a cohort of 32 patients referred for exerciseechocardiography for dyspnea. Transmitral inflow pattern and TissueDoppler of mitral valve annulus were analyzed at rest and stress, alongwith evidence of ischemia.

RESULTS: Echocardiographic evidence of diastolic dysfunction at base-line was found in 13 patients. Out of 19 patients who had normal diastolicfunction at rest, 9 patients (47%) developed exercise-induced diastolicdysfunction at stress without evidence of segmental wall motion abnormalitysuggestive of ischemia. These patients demonstrated evidence of a relaxationabnormality with transmitral inflow pattern and Tissue Doppler of mitralvalve annulus. Exercise-induced diastolic dysfunction was more prevalent infemale (67%), and hypertensive patients (78%), and it was associated withreduced exercise capacity (7 METs vs. 9 METs). It was not related to age,exercise-induced ischemia or higher left ventricular diastolic pressure evalu-ated by the ratio of early transmitral flow velocity with the early diastolicvelocity of the mitral valve annulus (E/e � 10).

CONCLUSION: Exercise-induced diastolic dysfunction in patientswith dyspnea is common in female and hypertensive patients. It is notrelated with exercise-induced ischemia.

CLINICAL IMPLICATIONS: Exercise-induced diastolic dysfunc-tion is common in patients who undergo stress echocardiography forsymptoms of dyspnea. It should be one of the parameter evaluated duringthe test for these patients.

DISCLOSURE: Sanjeev Patel, None.


Cardiology: Echocardiography, continued


THE IMPACT OF RENAL DYSFUNCTION IN OUTPATIENTSWITH SYSTOLIC HEART FAILUREJun R. Chiong MD* Binu Jacob MD Robert F. Percy MD Hector P.Sanchez MD Anabel C. Castro MD Alan B. Miller MD University ofFlorida, Jacksonville, FL

PURPOSE: Renal function is an underappreciated prognostic factor inheart failure (HF), and renal insufficiency is commonly viewed as arelative contraindication for some proven efficacious therapies. It isunclear whether ACE inhibitors, aldosterone antagonists and beta-block-ers exert similar benefits in patients with kidney disease as these patientsare infrequently enrolled in HF trials.

METHODS: We analyzed data from a prospective cohort of heartfailure patients followed in a specialty clinic. Renal insufficiency wasdefined as creatinine clearance �60 mL /min using the Cockcroft-Gaultequation. Our hypothesis was that renal insufficiency was an independentpredictor of outcome as measured by hospitalizations.

RESULTS: In our database of 167 outpatients, 71 (42%) had creatinineclearances calculated at � 60 mL/min (Group 1; mean creatinineclearance of 81.6 mL/min); 96 (58%) had creatinine clearances calcu-lated � 60 mL/min (Group 2; mean creatinine clearance of 39.7 mL/min).There was no difference in the presence of co-morbidities includinghypertension, diabetes, and hyperlipidemia. Group 2 patients were older(71�17 versus 60�9 years) and had more atrial fibrillation (32% vs. 18%;p�0.043). The log of pro-brain natriuretic peptide (pro-BNP) level washigher in Group 2 (7.6 � 1.5 vs. 6.7 � 1.5; p�0.0001). The two Groupswere similar regarding the etiology of heart failure (52% ischemic inGroup 1; 57% in Group 2; p�NS), and advanced heart failure NYHAIII/IV (61% in Group 1; 62% in Group 2; p�NS). Patients in both groupsreceived identical therapy, except statin therapy (61% in Group 1; 41% inGroup 2; p�0.011). All cause hospitalization rate for Group 2 was greatercompared to Group 1 patients (1.6 vs. 1.2 admissions per patient;p�0.05).

CONCLUSION: Despite similarities in therapies, co-morbidities,NYHA functional class and etiology of heart failure, patients with renaldysfunction with systolic heart failure had a greater all cause hospitaliza-tion rate than patients with preserved renal function.

CLINICAL IMPLICATIONS: Abnormal renal function is prevalentin patients with systolic heart failure and is an independent prognosticfactor for hospitalization.

DISCLOSURE: Jun Chiong, None.

LEFT VENTRICULAR SYSTOLIC AND DIASTOLIC FUNCTIONIN HIV INFECTED RWANDANS: A PILOT STUDYJason M. Lazar MD* Biana Trost MD Louis Salciccioli MD KathrynAnastos MD SUNY Downstate Medical Center, Brooklyn, NY

PURPOSE: Left ventricular (LV) dysfunction is known to be present inHIV infected subjects. The prevalences of other risk factors for cardio-myopathy including hypertension, diabetes, coronary disease, obesity, andalcohol use are also high in this patient population in the United States,but are quite low in HIV infected Africans. This study sought to determinethe prevalence of LV systolic and diastolic function in HIV infectedRwandans.

METHODS: In Rwanda, 41 unselected patients (age 36�/-9 years, 10%male) without known cardiac disease underwent echocardiography. Nopatient had been treated with anti-retroviral therapy. LV mass and ejectionfractions (EF) were calculated according to the American Society of Echo-cardiography standards. Diastolic dysfunction was studied with pulsed Dopp-ler echocardiography. For each echo variable, 3-5 cardiac cycles wereaveraged. Significant LV systolic function dysfunction was predefined as�50%. Diastolic dysfunction was defined as E/A ratio�1.0 or �1 with eithera prolonged deceleration time (�250msecs) or a prolonged isovolumicrelaxation time (�120msecs). Clinical data were recorded.

RESULTS: There were low prevalences of cardiovascular risk factorsincluding: hypertension 2.4%, diabetes 2.4%, smoking 0%. LV systolicdysfunction was present in 2.4% of patients and diastolic dysfunction waspresent in 14.6%. LV dysfunction was unrelated to age or duration ofinfection.

CONCLUSION: In conclusion, LV dysfunction is common in HIVinfected Rwandans, and is predominantly diastolic rather than systolic. LVdysfunction was less common than prior reports from the United Statespossibly because of a lower prevalence of cardiomyopathy risk factors.

CLINICAL IMPLICATIONS: Further study of additional patients iswarranted in order to substantiate these initial findings. There may be aninteraction between HIV and other risk factors for LV dysfunction.


CLINICAL CHARACTERISTICS OF OBESE AND NORMALWEIGHT HEART FAILURE PATIENTSJun R. Chiong MD* Robert F. Percy MD Binu Jacob MD Hector P.Sanchez MD Anabel C. Castro MD Alan B. Miller MD University ofFlorida, Jacksonville, FL

PURPOSE: Excess weight is associated with a significantly increasedrisk of coronary artery disease, heart failure, and death in the generalpopulation. In patients with established heart failure, studies suggest thata higher body mass index (BMI) results in better outcomes compared topatients with a “healthy BMI”. It is unclear if these findings are applicableto the population of outpatients with stable heart failure, as theseobservations are not the primary design or endpoints of these trials.

METHODS: Given the uncertain role of obesity in the clinicalmanagement of patients with heart failure, we examined the relationshipof weight and outcomes among our outpatients with stable disease.

RESULTS: We analyzed obese (BMI �30 kg/m2) compared to normalweight patients (BMI 18.5 – 25 kg/m2) in our clinical informationmanagement for heart failure database (CIM-HF); there were 121patients who fulfilled the criteria. Fifty-one patients had a normal BMIand seventy patients were classified as obese. There was no difference inage, gender or medical therapy for heart failure. More obese patients hada previous history of hypertension (90% vs. 71% p�0.008), diabetes (64%vs. 14% p��0.0001), advanced New York Heart Association (NYHA)functional class III and IV (66% vs. 53%, p�0.046) compared to normalBMI patients. Hospitalizations were higher for obese patients (1.5 � 1.7vs. 1.1 � 1), but this was not significant.

CONCLUSION: Symptoms are worse and co-morbidities are moreprevalent in obese patients with systolic dysfunction and stable heartfailure, compared to normal weight patients.

CLINICAL IMPLICATIONS: Obese patients with chronic stableheart failure and systolic dysfunction (ejection fraction �40%) have worseoutcomes than similar patients with normal body mass index.


Cardiology: Epidemiology of Heart Failure,continued


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DISCLOSURE: Jun Chiong, None.

HEALTH-RELATED QUALITY OF LIFE IN PATIENTS WITHPULMONARY ARTERIAL HYPERTENSIONDarren B. Taichman MD* Jennifer Shin MD Laryssa Hudd BA ChristineArcher-Chicko RN Sandra Kaplan RN Robert Gallop MS Jason ChristieMD John Hansen-Flaschen MD Harold Palevsky MD University ofPennsylvania, Philadelphia, PA

PURPOSE: Improved outcomes with expanding treatment options forpatients with pulmonary arterial hypertension present the opportunity toconsider additional end-points in approaching therapy, including factorsthat influence health-related quality of life. However, comparatively littleis known about quality of life and its determinants in patients withpulmonary arterial hypertension. The purpose of this study was to evaluatehealth-related quality of life in adults with pulmonary arterial hyperten-sion, and identify factors associated with better or worse status.

METHODS: Health-related quality of life was evaluated in 216outpatients with pulmonary arterial hypertension using generic andrespiratory-disease specific measurement tools. Most patients had eitherWorld Health Organization functional Class II or III symptoms. Demo-graphic, hemodynamic and treatment variables were assessed for associ-ation with quality of life scores.

RESULTS: Patients with pulmonary arterial hypertension sufferedsevere impairments in both physical and emotional domains of health-related quality of life. Patients with idiopathic (“primary”) pulmonaryarterial hypertension had the best, and those with systemic sclerosis theworst health-related quality of life. Greater six-minute walk distancecorrelated with improved quality of life scores, as did functional Class IIversus Class III symptoms. Hemodynamic measurements, however, didnot correlate with quality of life scores. No differences in health-relatedquality of life were found between patients treated with calcium channelantagonists, bosentan or continuously infused epoprostenol.

CONCLUSION: Health-related quality of life is severely impaired inpatients with pulmonary arterial hypertension and is associated withmeasures of functional status.

CLINICAL IMPLICATIONS: Specific determinants of impairedquality of life suggest areas for targeted intervention.

DISCLOSURE: Darren Taichman, Consultant fee, speaker bureau,advisory committee, etc. Advisory board or speaker bureau for Actelion,Pfizer and CoTherix.

PREVALENCE AND IMPACT OF ANEMIA ON SURVIVAL ININDIGENT SYSTOLIC HEART FAILURE PATIENTS RECEIV-ING STANDARD MEDICAL THERAPYLee M. Arcement MD* Ron Horswell PhD Richy Lee PharmD KathyHebert MD Chabert Medical Center, Houma, LA

PURPOSE: Previous studies have shown an association betweenanemia and mortality in patients with heart failure. One question notaddressed is the anemia-mortality relationship within a heart failurepopulation enrolled in a disease management program receiving standardmedical therapy including Ace inhibitors and beta blocker medications.Also, the independant effect of anemia on survival has not been welldescribed in a rural indigent population.

METHODS: The sample included 328 patients with EF � 40% whoenrolled in a heart failure disease management program from 1999 to2003 in rural South Louisiana. Our database was reviewed and aproportional hazards survival model was estimated. Anemia was defined asa hemoglobin of �12g/dl in females and �13 g/dl in males. Termsconsidered for inclusion into the model were gender, African-Americanrace, age, ejection fraction (� 25% vs. 25-40%), QRS duration, NYHAclass (III/IV vs I/II), use of beta blockers, and use of ACE inhibitors.

RESULTS: The prevalence of anemia in this group was 29%. The finalmodel included age (HR�1.04, p�.023), ejection fraction � 25%(HR�2.71, p�.002), African-American race (HR � 1.21, p�.576), andanemia (HR� 2.55, p�.002, 95% CI 1.40 - 4.67). The median annualincome was $ 11,300 for both cohorts.

CONCLUSION: Anemia is common in this cohort. Anemia is stronglyassociated with mortality in a younger rural indigent heart failure popu-lation, even when patients are enrolled in a disease management programreceiving both Ace inhibitors and beta blockers.

CLINICAL IMPLICATIONS: Identifying this high risk subgroup isimportant and treating anemia may be considered. Ascertaining theimpact of treating anemia in this subgroup must be undertaken in futureclinical trials.

DISCLOSURE: Lee Arcement, None.

DIABETES IS INDEPENDENTLY ASSOCIATED WITH DE-CREASE LEFT AND RIGHT VENTRICULAR FUNCTIONNorah Milne MD June Herman MD Daniel Stobbe MD Kenneth P.Lyons MD Mohammad-Reza Movahed MD* University of California,Irvine Medical Center, Orange, CA

PURPOSE: Diabetes mellitus(DM) has been found to be an impen-dent risk for decreasing congestive heart failure and decreasing leftventricular function. However, right ventricular dysfunction has not beenstudied in detail patients with DM. The goal of this study was to evaluatethe occurrence of left and right ventricular dysfunction in diabetespatients.

METHODS: Randomly selected case of 200 patients, who underwentleft ventricular ejection fraction (LVEF) determination using bloodpooled scintigraphy, underwent simultaneous measurement of right ven-tricular ejection fraction (RVEF). The presence of diabetes mellitus wasstudied in patients with depressed LVEF and RVEF using uni- andmulti-variate analysis.

RESULTS: A total of 152 patients had RVEF and 155 LVEFmeasurements. Four out of 26 DM patients had RVEF less than 30 %(15.4%) vs 4 of 126 control ( 3,2%), p�0.01. Eleven out of 27 (40.7%)patients with DM had LVEF less than 30% vs 9 out of 128 patients (7%)of control, p�0.0001 Using multivariate analysis adjusting for coronaryartery disease, hypertension and chronic obstructive pulmonary disease,DM remained independently associated with LVEF or RVEF less than30% (for RVEF � 30%: odds ratio: 5.7 CI: 1.3-25.4, p� 0.02), for LVEF,30%: odds ratio: 12.9 CI: 3.8-43.7).

CONCLUSION: Diabetes mellitus is independently associated withleft and right ventricular dysfunction. The involvement of both ventricles




in DM patients, suggest that diabetic causes global toxic effect onmyocardial cells.

CLINICAL IMPLICATIONS: The deleterious effect of diabetesmellitus on global right and left ventricles, in part, may explain highmortality rate in this population.


VALUE OF SERUM CREATININE LEVELS IN CARDIORENALPATIENTS REFERRED FOR CARDIAC TRANSPLANTATIONShun Kohsaka MD* Kimberly Albright MD Reynolds M. Delgado, IIIMD Biswajit Kar MD Frank W. Smart MD Texas Heart Institute, BaylorCollege of Medicine, Houston, TX

PURPOSE: pproximately one third to one half of patients with heartfailure have renal insufficiency, which is one of the strongest predictors ofmortality in these patients. However, there is little evidence with which toweigh the risks of cardiac transplantation in heart failure patients whohave mild renal dysfunction.

METHODS: We reviewed the clinical and laboratory data of 140consecutive, stable heart failure patients who had mild renal insufficiency(serum creatinine, 1.1-2.5) referred to our institution for evaluation forcardiac transplantation from May 2004 to April 2005. We then assessedthe association between renal dysfunction and 1-year outcomes (eitherdeath from any cause or admission for heart failure). The combinedendpoint was compared with various levels of baseline serum creatininevalues: mild (1.1-1.5), moderate (1.6-2.0), and severe (2.1-2.5). Of the 140patients, 98 had follow-up visits where laboratory values were obtained. Inthis subgroup, logistic regression analysis was performed to the modelhazard ratio (HR) to achieve the combined endpoint.

RESULTS: The cohort was predominantly Caucasian (45%) and male(68%). After 1-year, the combined endpoint was met in 43%, 57%, and42% of patients with mild, moderate, and severe elevations of serumcreatinine, respectively. There was no statistical difference between the 3groups (Kruskal-Wallis One-Way ANOVA p�0.36). However, in the 98patients who had follow-up laboratory testing during the study period, adynamic change in serum creatinine levels was strongly associated with acombined outcome (HR, 1.70; 95%CI, 1.22-24.6; P�0.02). This associa-tion remained significant even after adjustment for other clinical variables,including patient age and baseline serum creatinine levels (HR, 1.71;95%CI, 1.18-26.1; P�0.02).

CONCLUSION: A dynamic change in serum creatinine values duringfollow-up is a strong independent predictor of a worse prognosis for heartfailure patients.

CLINICAL IMPLICATIONS: These findings suggest that monitor-ing of serum creatinine values may offer a readily accessible tool toidentify which heart failure patients would or would not benefit fromcardiac transplantation. A prospective, randomized trial to test thishypothesis is warranted.

DISCLOSURE: Shun Kohsaka, None.

ASSOCIATION OF REDUCED CARBON MONOXIDE DIFFUS-ING CAPACITY WITH MODERATE OR SEVERE LEFT VEN-TRICULAR DIASTOLIC DYSFUNCTION IN OBESE PERSONSGautham Ravipati MD* Wilbert S. Aronow MD Jasdeep Sidana MDGeorge P. Maguire MD John A. McClung MD Robert N. Belkin MDStuart G. Lehrman MD New York Medical College, Valhalla, NY

PURPOSE: To determine the association of reduced carbon monoxidediffusing capacity (DLCO) with moderate or severe left ventriculardiastolic dysfunction (LVDD) in obese persons.

METHODS: We investigated in 105 obese persons, mean age 45 years,the association of DLCO with LVDD. An abnormal DLCO was �80%.LVDD was investigated by Doppler and by tissue Doppler echocardiog-raphy. The Doppler echocardiographic data were analyzed blindly withoutknowledge of the clinical characteristics or whether the DLCO wasnormal or abnormal.

RESULTS: An abnormal DLCO was present in 62 of 105 persons(59%). Moderate or severe LVDD was present in 35 of 105 persons33%).Moderate or severe LVDD was present in 25 of 62 persons (40%)with an abnormal DLCO and in 10 of 43 persons (23%) with a normalDLCO (p�0.05).

CONCLUSION: Obese persons with a decreased DLCO have anincreased prevalence of moderate or severe LVDD.

CLINICAL IMPLICATIONS: Obese persons with a decreasedDLCO have an increased prevalence of moderate or severe LVDD, whichpredisposes them to develop diastolic heart failure.

DISCLOSURE: Gautham Ravipati, None.

Cough12:30 PM - 2:00 PM

EVALUATION AND TREATMENT OF PATIENTS WITH LARYN-GEAL DYSFUNCTION IN A PULMONARY PRACTICEClifford G. Risk MD* Nadine Y. Smith MS Clifford Risk, MD, Marlbor-ough, MA

PURPOSE: Patients with laryngeal dysfunction may present initially toa pulmonary practice with complaints of hoarseness, hypophonic pressivespeech, aphonia, cough, or aspiration. The goals of this study were toidentify a primary diagnosis, establish a program of goal directed therapy,and assess clinical response.

METHODS: Patients were evaluated and treated by a pulmonologistand speech-language pathologist with outside consultations by ENTspecialists. Treatments included: (1) Recruitment and habituation of themuscles of articulation, phonation and respiration resulting in improvedclarity of articulation (Lee Silverman Voice Techniques); (2) Softening ofglottal attack (resonance training, lingual hyperextension, open glottalexercises); (3) Vocal elicitation (gravity resistance exercises, vegetative andglottal sound production).

RESULTS: Fourteen patients were evaluated and treated. Diagnoseswere: neuromuscular disease (Parkinson’s disease, von-Recklinghausen’sdisease, idiopathic vocal cord paralysis), vocal cord injury (radiationnecrosis, atresia, intubation injury, carcinoma with scar tissue formation),hypertonic vocal cord strain, functional vocal cord weaknesss (presbypho-nia, vocal cord misuse and overuse, phycogenic etiologies).Concurrentpulmonary diagnoses included COPD, severe kyphoscoliosis, sinusitis,allergies and asthma.Treatment outcomes of 50% to 100% improvementin intelligibility of spoken content occurred in 13 patients, but wasunsuccessful in one patient (von-Recklinghausen’s disease).

CONCLUSION: Goal directed therapy of the patient with laryngealdysfunction, often in the setting of a concurrent pulmonary disorder, issuccessful in improving vocal function.

CLINICAL IMPLICATIONS: Pulmonologists should be aware of thebenefit of an interdisciplinary program for the patient with laryngealdysfunction.


EPIDEMIOLOGY OF CHRONIC COUGH IN A SPECIALISTCOUGH CLINICLee L. Phoa MBBS Wee Yang Pek MBBS* Tan Tock Seng Hospital,Singapore, Singapore

PURPOSE: To study the epidemiology of chronic cough in patientswho have failed earlier treatment in a primary healthcare setting.

METHODS: A prospective study was conducted on patients withcough for 3 or more weeks referred to our specialist cough clinic over a 6month period in year 2004. A total of 112 patients with normal Chest Xraywere recruited. Patients’ cough severity was assessed using a coughsymptom score (score of 1 to 8 based on severity of daytime and nocturnalcough) before and after treatment. All patients were subjected to astandardized protocol for history taking, examination, investigations andtreatment. Investigations included rhinoscopy, spirometry or methacho-line challenge test, skin prick test, thoracic and sinus imaging whenappropriate. Patients were started on empiric gastroesophageal reflux(GERD) treatment when no other obvious causes of cough were found. Aprotocol for pH monitoring in the event of poor response to GERDtreatment was in place.

RESULTS: Median age of our patients was 48 years (range 14 to 86)and median cough duration was 12 weeks (range 3 to 416). The meancough score at 1st consultation was 3.9 � 1.2 and 59 patients (49%) hada cough score of 4 at the 1st consult. At the end of the treatment period,13.6% of the patients were diagnosed to have asthma, 46.6% hadpost-nasal drip and 47.7% had GERD. Eighty-six patients (90.5%)




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reported improvement to treatment. The median time taken for symptomimprovement or resolution (final cough score 0 or 1) was 28 days (range7 to 256).

CONCLUSION: GERD and post-nasal drip were the 2 most commoncauses of chronic cough in patients treated in our specialist cough clinic.Though common, they were not identified and treated promptly in theprimary healthcare setting.

CLINICAL IMPLICATIONS: A greater awareness of GERD andpost-nasal drip as conditions resulting in chronic cough should bepromoted in the primary healthcare setting. Although diagnosis of theseconditions were delayed, they responded well to appropriate treatment.

DISCLOSURE: Wee Yang Pek, None.

COUGH-INDUCED RIB FRACTURES: REVIEW OF 54 CASESViktor Hanak MD* Thomas Hartman MD Jay Ryu MD Mayo ClinicFoundation, Rochester, MN

PURPOSE: To define the demographic, clinical, and radiologic fea-tures of patients with cough-induced rib fractures.

METHODS: Retrospective single-center study. Fifty-four patientswith cough-induced rib fractures diagnosed over an 9-year period from1996 to 2004.

RESULTS: The mean (� SD) age at presentation was 55 (� 17) years,42 patients were female (78%). Patients presented with chest wall painfollowing the onset of cough. Cough had been present for � 3 weeks atthe time of the diagnosis in 85% of patients. Rib fractures wereradiologically documented by chest radiography, rib film, computedtomography or bone scan. Chest radiography had been performed in 52patients and revealed rib fracture in 30 patients (58%). There were 112fractured ribs in 54 patients. One-half of the patients had more than onefractured rib. Right-sided rib fractures alone were present in 17 patients(26 fractured ribs), left-sided in 23 patients (35 fractured ribs), andbilateral in 14 patients (51 fractured ribs). The most commonly fracturedrib on both sides was the 6th rib. The fractures were most common at thelateral aspect of the rib cage. Bone densitometry was done in 26 patientsand revealed osteopenia or osteoporosis in 17 (65%).

CONCLUSION: Cough-induced rib fractures occur mostly in womenin whom reduced bone density is likely a risk factor. However, cough-induced rib fractures can occur in the presence of normal bone density.Chest radiography has a relatively low sensitivity for the diagnosis ofcough-induced rib fractures.

CLINICAL IMPLICATIONS: Cough-induced rib fractures are asso-ciated with chronic cough as opposed to acute cough, prevalence is muchhigher in females compared to males, and fractures may also occur inpatients with normal bone density.

DISCLOSURE: Viktor Hanak, None.

SINUS CT FINDINGS IN THE EVALUATION OF 702 CONSEC-UTIVE PATIENTS WITH CHRONIC COUGHTimothy I. Morgenthaler MD Ashok Patel MD Kaiser G. Lim MD* MayoClinic, Rochester, MN

PURPOSE: Evaluation of chronic cough in pulmonary practice oftenrequires either empiric trials of therapy or testing. The prevalence ofchronic sinusitis and the role of CT sinus is debated, with some suggestingit has no role, and others suggesting that it may be a useful test late in analgorithmic approach. Previous recommendations have been based onrelatively small series of patients. We wished to evaluate the role of CTsinus in our tertiary referral chronic cough practice.

METHODS: Retrospective review of chronic cough registry data.RESULTS: CT sinus was obtained in 159 (22.6%) patients referred for

chronic cough. Obtaining a CT was far more common among those withabnormal ENT physical exam findings (31% of 702, p�0.0001). Whenchronic rhinosinusitis was suspected clinically, the CT sinus was abnormalin 123 (77.4%). An abnormal CT findings was not significantly associatedwith abnormal ENT exam (p�0.5782). Fluid levels indicating acutesinusitis was present in 51 (32%), and again, an abnormal ENT exam wasnot predictive of acute sinusitis (p�0.0833).

CONCLUSION: Nearly three-quarters of patients who underwent CTfor a clinical suspicion of rhinosinusitis had and abnormal CT and nearlyone third had acute sinusitis. Physical exam was not predictive of acute orchronic sinus findings. It follows that occult sinus disease likely plays asignificant role in many patients with chronic cough referred to a tertiarycough clinic.

CLINICAL IMPLICATIONS: . In the absence of other explanationsfor chronic cough on initial evaluation, sinus CT should be considered.

DISCLOSURE: Kaiser Lim, None.

A SURVEY OF PATIENT’S PERCEPTION OF DISEASE BURDENIN CHRONIC COUGHKaiser G. Lim MD* Ashok Patel MD Timothy I. Morgenthaler MD MayoClinic, Rochester, MN

PURPOSE: We hypothesized that the burden of disease associatedwith chronic cough may include health care factors and concern over the“meaning” of the cough. We sought to understand how chronic coughaffected patients socially, psychologically and physically.

METHODS: All consenting adult patients presenting to our Pul-monary Division with chronic cough between November and Februaryof 2003 were surveyed with a Cough-related Disease Burden Ques-tionnaire (CRDBQ) prior to their evaluation and again 6 monthsafterward.

RESULTS: 139 subjects were available for analysis. Sixty-fivereturned the second questionnaire. The top four complaints are shownin Table 1. Anxiety over underlying illness correlated with lifestyleinterference, frequent doctor visits, medical expense, prescriptionexpenses, frustration and spouse moving out of the bedroom. Sleepdisturbances correlated with exhaustion (p �0.001). A third of patientsunder 65 years old had a spouse or roommate move out of thebedroom. On followup 6 months later, 18% reported complete reso-lution of cough, 34% had more than 50% improvement, 20 % had lessthan 50% improvement, 28 % reported that cough was worse (1/56) orunchanged (26.7%). Improved cough outcome was associated with lessanxiety about an underlying serious illness at baseline (p�0.001).

CONCLUSION: Both psychological and physical sufferings or burdenof disease appear to be chief reasons for seeking medical evaluation. Asidefrom Anxiety, two important major sources of suffering for the patients area) frequent physician visits and testing, and b) sleep disturbances.

CLINICAL IMPLICATIONS: Frequent doctor’s visit and testing forcough as a disease burden is an important consideration since manychronic cough algorithms employ empirical therapy and multiple returnvisits. Anxiety, physician visits, medications, and sleep disturbances weighhighly in patients concerns about chronic cough.

DISCLOSURE: Kaiser Lim, None.

THE EFFECTS OF AGING ON THE HUMAN COUGH REFLEXD. A. Sams DO* Thomas Truncale DO Stuart M. Brooks MD Universityof South Florida, Tampa, FL

PURPOSE: This study was designed to examine if there is a differencein the cough reflex between younger and older persons. A differencemight explain the greater susceptibility of older persons to respiratorytract infections and pneumonia.

METHODS: The study was the first granted approval by the Food andDrug Administration under an Investigational New Drug (IND) protocolfor human capsaicin inhalation investigation. Two groups of normalsubjects were recruited. All had normal spirometry, were current non-smokers � 10 years, had no prior/current respiratory disease/complaints

Table 1—Top 4 Complaints of Patients with ChronicCough

ComplaintsF

(%)M

(%)

�65yrs(%)

65y/o(%)

Cough�18 mos

(%)

Cough18 mos

(%)

Frustrated/Irritable/Angry

78 78 79 76 74 81

Frequent MD visit &testing for cough

77 75 77 76 69 82

Sleep Disturbances 78 82 82 76 83 76Interferes w/ social

gatherings74 75 78 71 69 80


Cough, continued


and no history of allergy or asthma. Measurements of exhaled breath nitricoxide (ENO), impulse oscillometry (IOS), and spirometry were recorded.Capsaicin inhalation challenge testing was performed according to themethod of Dicpinigaitis et al (Chest 123:685-8, 2003).

RESULTS: There were 27 participants with 17 younger (median age,22; range, 18-27 yrs.) and 10 older persons (median age, 74; range, 67-77yrs.) recruited. ENO was higher for older vs. younger subjects (37.8 and22.2 ppb respectfully, p�0.006). There was a tendency for the capsaicindose for cough initiation and C2 to be higher for older subjects, but therewas no significant difference for C5. Mean values for log C2 and C5 wererecorded, p values equaled 0.58 and 0.41 respectively. Serial IOS andFEV1 remained unchanged and showed good consistency. No adversereactions were observed in any subject.

CONCLUSION: Capsaicin challenge using pharmaceutical grade cap-saicin is safe for normal subjects of all ages. Serial monitoring withrepeated IOS and spirometry showed good reproducibility. Elevated NOlevels in the older age group suggested possible baseline airway inflam-mation and confirms our earlier published data. While there is sometendency for capsaicin cough initiation and C2 to be higher in olderpersons, the values among the 2 groups were similar for C5.

CLINICAL IMPLICATIONS: Cough reflex sensitivity and underly-ing inflammation may be important factors in determining why olderpeople are more susceptible to respiratory tract infections and pneumo-nia.

DISCLOSURE: D. Sams, None.

Critical Care Management12:30 PM - 2:00 PM

UTILITY OF BRONCHOSCOPY IN MECHANICALLY VEN-TIALTED PATIENTS WHO DEVELOPED HEMOPTYSIS INTHE INTENSIVE CARE UNITMaya Juarez BS* Petey Laohaburanakit MD Ken Y. Yoneda MD U.C.Davis School of Medicine, Sacramento, CA

PURPOSE: The etiology of hemoptysis in mechanically ventilated ICUpatients includes a wide spectrum of disorders. We evaluate the utility offiberoptic bronchoscopy when used to identify and diagnose the bleedingsource and potentially achieve hemostasis in such patients.

METHODS: A retrospective review of medical records of ICUpatients who developed hemoptysis while on mechanical ventilation at atertiary-care, 700-bed teaching hospital. All bronchoscopies done fromApril 1998 to December 2003 were reviewed.

RESULTS: Seventy-one bedside fiberoptic bronchoscopies were per-formed in 56 ICU patients on mechanical ventilation. Mean age was 55years, 35 were male. The amount of hemoptysis ranged from persistentblood-streaked sputum to massive. The bleeding source was localizedduring 66.2% (n�47) of all bronchoscopies, although additional diagnos-tics (radiology, repeat bronchoscopy, etc) after bronchoscopy were re-quired in 23% (n�16) of cases. Bronchoscopic findings were consistentwith the final consensus etiology of hemoptysis in 77% of cases (n�55).Only in 42% (n�30) of cases was the clinical impression prior tobronchoscopy consistent with the final diagnosis of the cause for hemop-tysis. Etiologies of hemoptysis included: pneumonia, coagulopathy, suc-tion trauma, pulmonary edema, trauma, neoplasm, pulmonary embolism,and granulation tissue. Diagnostic samples taken during 23 bronchosco-pies yielded positive results in 17 cases.Patients underwent at least onetherapeutic intervention after 51% of bronchoscopies (anticoagulationdiscontinued, antibiotics changed, transfusion, etc). Bronchoscopic inter-ventions were performed in 8 cases (11%), including deployment offogarty balloon, application of neosynephrine, repositioning of endotra-cheal tube, and removal of blood clots. Minor complications were evidentin 3 (4%) cases within 24 hours after bronchoscopy: transient desaturationonce, transient hypotension twice. The transient hypotension resolvedspontaneously, while the desaturation required slight endotracheal tuberepositioning.

CONCLUSION: Localization of the source of hemoptysis and deter-mination or confirmation of the etiology of hemoptysis is frequentlyachieved bronchoscopically, although intraoperative treatment is seldomdone.

CLINICAL IMPLICATIONS: Bedside fiberoptic bronchoscopy is asafe diagnostic tool with adequate diagnostic yield when used for theevaluation of hemoptysis in mechanically ventilated patients in the ICU.

DISCLOSURE: Maya Juarez, None.

EMPIRIC USE OF NOCTURNAL CONTINUOUS POSITIVE AIR-WAY PRESSURE IN MORBIDLY OBESE PATIENTS POST EX-TUBATIONAli A. El Solh MD* Alan T. Aquilina MD Lilibeth Pineda MD EileenBerbary RN University at Buffalo, Buffalo, NY

PURPOSE: To assess whether empiric nocturnal nasal continuouspositive airway pressure (CPAP) in non surgical critically ill morbidlyobese patients reduces pulmonary complications post extubation.

METHODS: We conducted a nonconcurrent prospective study ofnormocapnic morbidly obese patients (BMI�40 kg/m2) requiring me-chanical ventilation for at least 48 hours. Analysis of pulmonary compli-cations post extubation of critically ill morbidly patients assigned to eitherempiric nocturnal nasal CPAP or to standard medical therapy wereperformed. Data collected included sociodemographic variables, comor-bidity index, presence of obstructive sleep apnea (OSA), APACHE IIscore, and hospital length of stay.

RESULTS: Out of the 123 non surgical morbidly obese patients whomet the inclusion criteria, 53 patients were assigned to nocturnal nasalCPAP and 70 to standard medical therapy. Forty six patients were knownto have OSA on admission and 53 were diagnosed after hospital discharge.Twenty seven complications were reported during the course of the study.Sixteen needed rescue noninvasive positive pressure ventilation, 9 re-quired reintubation, and 2 developed cardiopulmonary arrest. The rate ofcomplications was comparable between those assigned to empiric CPAPand those to standard medical therapy (10 and 17 events respectively,p�0.7). The presence and severity of sleep apnea did not correlate withthe development of cardiopulmonary complications.

CONCLUSION: Although treatment of morbidly obese patients withthe diagnosis of OSA should resume post extubation, the application ofempiric nocturnal nasal CPAP in normocapnic morbidly obese patientsmay not reduce pulmonary complications post extubation.

CLINICAL IMPLICATIONS: Pending a randomized controlledstudy, the empiric use of nocturnal CPAP in non surgical critically illmorbidly obese patients may not reduce cardiopulmonary complicationspost extubation.

DISCLOSURE: Ali El Solh, None.

PROSPECTIVE APPLICATION OF A CLINICAL GUIDELINETO DIAGNOSE AND TREAT VENTILATOR ASSOCIATEDPNEUMONIA IN TRAUMA PATIENTS IMPROVES OUTCOMESScott Newbrough MD* Nikki Freeman PharmD Brian J. Daley MD DanaTaylor MD Ed Varnadoe PharmD UTMCK, Knoxville, TN

PURPOSE: Determine if a clinical guideline increased the initialadministration of appropriate empiric anti-microbial treatment to traumapatients with ventilator associated pneumonia (VAP). Secondary objec-tives evaluated duration of mechanical ventilation, ICU and hospitallengths of stay (LOS), drug cost of VAP treatment, and development ofsuper-infection.

METHODS: A VAP guideline for diagnosis and treatment was devel-oped with the guidelines of the American College of Chest Physicians andthe institution’s antibiogram. Once VAP was diagnosed, cultures wereobtained and intravenous antibiotics were started within twelve hours -vancomycin 15 mg/kg (renal ajusted dosing), ciprofloxacin 400 mg everyeight hours, and piperacillin/tazobactam 4.5 grams every six hours. Onceculture and susceptibilities were received, treatment was modified, andlimited to seven days. Prospectively enrolled patients were compared to aretrospective cohort before the guideline. Super infection was defined asdeveloping an infection with Serratia, Pseudomonas, Acinetobacter,Citrobacter, Enterobacter, or MRSA.T-test and Chi squared analysis hadsignificance assigned at p� 0.05.

RESULTS: Forty-nine trauma patients comprise this study; 36 retro-spective (12/2002 through 7/2003) and 13 prospective (12/2003 through12/2004). Before the guideline only 1/36 (2.8%) received appropriateinitial antibiotics; after implementation 4/13 patients (30.8%) receivedappropriate initial antibiotics at maximal doses, a significant improvement.Prospective patients had shoter duration of ventilation and ICU LOS justmissing statitiscal validity and hospital lengths of stay were statistically


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lower in the prospective study group. The mean cost of VAP antibiotictreatment per patient for the retrospective group was significantly higherthan the prospective group. Super-infection developed in 29/36 patients(80.6%) in the retrospective group, 8/13 patients (61.5%) developed asuper-infection in the prospective group, a decrease which just missedstatistical significance.

CONCLUSION: The guideline diagnosed VAP more carefully de-creasing unnecessary antibiotics and ultimately cost of treatment. It alsoincreased appropriate intial treatment and decreased length of hospitalstay, time on mechanical ventilation and super infections.

CLINICAL IMPLICATIONS: Precisely defining diagnosis, evidencebased treatment plans and reduced therapeutic variation improved out-come in complex trauma ICU patients.

DISCLOSURE: Scott Newbrough, None.

CURRENT PRACTICE OF CHEST RADIOGRAPHY IN CRITI-CALLY ILL PATIENTS IN THE NETHERLANDS: A POSTALSURVEYMarleen E. Graat Peter E. Spronk PhD Marcus J. Schultz PhD*Academic Medical Center, Amsterdam, Netherlands

PURPOSE: Although the consensus opinion of the American Collegeof Radiology is that daily routine chest radiographs (routine CXRs) areindicated in all ventilated patients (http://www.acr.org), studies suggestthat routine CXRs can be safely abandoned (Krivopal, Chest 2004; Price,CCM 2000).

METHODS: To ascertain current practice of CXRs in Dutch ICU-patients, a questionnaire was sent to ICUs throughout the Netherlands.Questionnaires were sent to the lead clinicians of ICUs with � 5 beds.

RESULTS: From the number of units responding (n � 28, 43.1%), themajority (n � 17, 60.7%) practiced a routine CXR-strategy, as opposed toa CXR on indication-approach. In most ICUs it was deemed necessary tohave (routine) CXRs to ordeal on the presence or absence of ARDS,pneumonia or pneumothorax (n � 20; 71.4%, n � 19; 67.9% and n � 21;75.0%, respectively), as well as the position of invasive devices (n � 21;75.0%). In most hospitals a daily meeting with the radiologist was held todiscuss CXRs (n � 19; 67.9%), but in more than half of hospitals theICU-physician thought that radiologists were not experienced enough toadequately judge CXR of critically ill patients (n � 16; 57.1%). If a CXRwas judged to be indicated, the reasons were in the majority of ICUs:introduction of invasive devices, such as endotracheal tubes, intravenouslines and thoracic drains (n � 22; 78.6%, n � 21; 75.0% and n � 27;96.4%, respectively), and hemodynamic/ventilatory deterioration (n � 14;50.0%); surprisingly, CXRs were also performed after resuscitation (n �12; 42.9%) and (mini)-tracheotomy (n � 18; 64.3%). Finally, mostICU-physician thought that CXRs, either routine or on demand, influ-enced daily practice in not more than 20% of performed CXRs.

CONCLUSION: In the Netherlands, the majority of ICUs still useroutine CXRs, although this survey suggests that a large number ofintensivists is doubting its value.

CLINICAL IMPLICATIONS: There is important lack of concensuson usefulness of routine CXRs in the Netherlands.


A CLINICAL TRIAL TO COMPARE THROMBOPROPHYLAXISOPTIONS IN THE MEDICAL ICU: CHALLENGES TO TREAT-MENTTara Roque MD JulieAnne Thompson MD Tunay Kuru MD* George-town University, Washington, DC

PURPOSE: To compare the efficacy of low-dose unfractionatedheparin (LDUH) and enoxaparin for the prevention of deep venousthrombosis (DVT) in the medical ICU.

METHODS: This was a prospective, randomized double-blinded trialto compare LDUH 5000 BID with enoxaparin. Patients were screenedwith a bedside Doppler ultrasound of the lower extremities at 48-72 hoursof ICU admission and again at 7 days. All patients, older than 18 years ofage, admitted to the MICU at Georgetown University Hospital wereeligible. Exclusion criteria included pregnancy; contraindication to anti-coagulation (e.g. uncontrolled hypertension,hemorrhagic stroke in thepast 3 months, active gastrointestinal bleeding); ongoing anticoagulanttherapy; intolerance to heparin; platelet count �80,000/ml; internationalnormalized ratio (INR) � 2.0. Written informed consent was obtained

prior to randomization.The primary endpoint was the diagnosis of DVT byDopplers or death.

RESULTS: From March 2003 to March 2004, 308 patients werescreened. Thirty(9.75%) were enrolled. Two patients (6.7%), one in eachstudy arm, were diagnosed with DVT by 72 hours; and one(3.3%)in theenoxaparin arm by 7 days.Patients were excluded for the followingreasons: Active gastrointestinal bleeding: 59 (19%), intracranial hemor-rhage: 18 (6%), hemorrhage from other sites (e.g. retroperitoneal): 4 (1%),already anticoagulated: 53 (17%), thrombocytopenia: 15 (5%), othercoagulopathy: 27 (9%), acute renal failure and denied entry by treatingphysician: 19 (6%), Expected ICU stay �48 hours: 61 (20%), withdrawalof support within 48 hours of ICU admission: 4 (1%), patient or familydeclined enrollment: 14 (4.5%), miscellaneous (morbid obesity, aorticdissection, intolerance to heparin: 4 (1%).

CONCLUSION: Despite medical prophylaxis, 10% of MICU patientsdeveloped DVT. Almost half the patients (49%, excluding those withMICU length of stay �48 hours and those already on anticoagulation) hadcontraindications to medical thromboprophylaxis.

CLINICAL IMPLICATIONS: Incidence of DVT in the MICUremains high, despite medical prophylaxis. Therefore, for MICU patients,combined medical and mechanical thromboprophylaxis should be consid-ered. Furthermore, a significant proportion of MICU patients havecontraindications to medical thromboprophylaxis. For this patient popu-lation, routine screening Dopplers may be warranted.

DISCLOSURE: Tunay Kuru, None.

Critical Care Outcomes12:30 PM - 2:00 PM

LIVER TRANSPLANTATION IN PATIENTS OVER SEVENTYYEARS OF AGEBangarulingam Sujay MD* Javier F. Aduen MD Rolland C. Dickson, MDWolf H. Stapelfeldt MD Denise M. Harnois, DO Jeffery . L. Steers, MDDavid J. Kramer, MD Mayo Clinic, Jacksonville, FL

PURPOSE: To investigate whether age at Liver Transplant (LT), olderthan 70 years compared with that of patients younger than 60 years isassociated with patient survival, length of stay, readmissions, or compli-cations.

METHODS: We retrospectively identified all first LT recipients atMayo Clinic in Jacksonville, Florida, from February 1998 to May 2004aged �70 years and case-matched with recipients �60 years according tothe etiology of end-stage liver disease, model for end-stage liver disease(MELD) score, and gender. The following data were collected: demo-graphics, Operative Time (OT),Warm Ischemic Time(WIT),Cold Isch-emic Time(CIT), intraoperative fluid requirement, length of ICU andhospital stay, complications, rate of readmissions, and survival. Numericaldata was summarized with the sample median and range. A log-rank testwas used to compare survival according to age group at LT. Wilcoxon’srank sum test was used to compare length of hospital and ICU stay, andreadmissions per month between groups. Fisher’s exact test was used tocompare the occurrence of rejection and complications between groups.

RESULTS: Forty patients older than 70 years underwent LT duringthe study period. Table 1 depicts the demographics and operativecharacteristics which are similar in both groups except for fluids requiredintraoperatively which was higher in patients �70 years. Rejectionappears to occur more often in patients �60 years. Although it did notreach a statistically significant difference, there was a tendency for higherinfectious complications and bile leak in patients older than 70.However,there was no difference in survival at 1 month or 1 year. Length of ICUand hospital stay and need for ICU and hospital readmissions were alsosimilar between the two groups (Table 2).

CONCLUSION: The outcome of liver transplantation in the elderly issimilar to that of younger patients, when they are matched for acuity andetiology. Older patients have less rejection and similar rates of infectionand biliary complications.

CLINICAL IMPLICATIONS: Patients should not be denied LiverTransplantation based on age alone.


Critical Care Management, continued


DISCLOSURE: Bangarulingam Sujay, None.

ACUTE PHYSIOLOGY AND CHRONIC HEALTH EVALUATION(APACHE)IV ICU LENGTH OF STAY BENCHMARKS FOR TO-DAY’S CRITICALLY ILL PATIENTSJack E. Zimmerman MD* Andrew A. Kramer PhD Douglas S. McNairMD Fern M. Malila MS George Washington University, Washington, DC

PURPOSE: To describe the development and validation of APACHEIV benchmarks for ICU length of stay.

METHODS: The equations used to generate ICU length of staybenchmarks were developed using ICU day 1 data for 116,209admissions to 104 ICUs at 45 hospitals during 2002 and 2003. Of theseadmissions 69,692 were used for model development and 46,517 wereused to validate the model. A linear regression procedure was used toestimate exact ICU stay in days and fractions of days. Predictorvariables were similar to those used for APACHE III estimates, butnew variables (mechanical ventilation, thrombolysis, the impact ofsedation on Glasgow Coma Score (GCS), and a rescaled GCS andPaO2:FIO2) were added, and different statistical modeling (restrictedcubic splines) was used. We assessed the accuracy of APACHE IV ICUstay predictions by examining the degree of correspondence betweenmean observed and mean predicted ICU stay (paired Student’s t-test),and by calculating a correlation coefficient (R2).

RESULTS: Based on relative explanatory power, the most impor-tant predictor variables were the acute physiology score (50%), ICUadmission diagnosis (14%), ventilator status (11%) and the inability toassess a GCS due to sedation (11%). As the acute physiology score rosethere was a linear increase in ICU stay until the score exceeded 80, atwhich point ICU stay decreased. For the validation data set theaggregate mean observed ICU stay was 3.86 days and mean predictedwas 3.78 days (p�0.001). Among 116 ICU admission diagnoses therewere only two significant differences (p�0.01) between mean ob-served and mean predicted ICU stay. The model’s R2 was 0.215indicating that the model accounted for 21.5% of the variation in ICUstay.

CONCLUSION: APACHE IV predictions of ICU stay are wellcalibrated and should provide useful benchmarks for evaluating efficiencyin U.S. ICUs.

CLINICAL IMPLICATIONS: Clinicians can use these benchmarksto assess their unit’s throughput efficiency and monitor the impact ofprotocols aimed at reducing ICU stay for specific patient groups.

DISCLOSURE: Jack Zimmerman, Consultant fee, speaker bureau,advisory committee, etc. Medical and Research Consultant.

HIGH TROPONIN LEVELS IN CRITICALLY ILL PATIENTSWITH RENAL FAILURE AND NO ACUTE CORONARY SYN-DROME: INCIDENCE AND IMPACT ON MORTALITYVijo Poulose MBBS* Siau Chuin MBBS Alvin Ng MBBS Chong-HiokTan MB, ChB Changi General Hospital, Singapore, Singapore

PURPOSE: High cardiac troponin levels are commonly seen inmedical intensive care (MICU) patients with renal failure and no clinicalevidence of acute coronary syndrome (ACS). We looked at the incidence

of elevated troponin levels in this group of patients and the impact onmortality.

METHODS: We prospectively collected data on all MICU patientswho met the following criteria:a) Renal failure - defined as serumcreatinine � 140 �mol/L (upper limit of reference range) b) No evidenceof ACS (anginal pain, acute ST or T changes on ECG). All patients whofell into the study group had a troponin T level done within the first 24hours of ICU admission. Troponin T levels � 0.1 ng/mL were consideredas high. Our primary outcome was the 28-day all cause mortality. We alsolooked at the correlation between the troponin levels and creatinineclearance as calculated from the Cockroft-Gault equation.

RESULTS: Fifty one patients met the study criteria. Twenty twopatients (43%)had elevated troponin T levels. Six of these 22 patientsdied (mortality rate 27%). The mortality rate in the 29 patients withnormal troponin levels was 34%. The severity of illness was similar inboth groups(using the Logistic Organ Dysfunction Score). The tropo-nin levels poorly correlated with the levels of creatinine clear-ance(r2�0.005).

CONCLUSION: In the absence of ACS, elevated troponin T levels inMICU patients with renal insufficiency do not appear to confer anincreased mortality.

CLINICAL IMPLICATIONS: High troponin T levels in this group ofpatients may not be an important risk factor for death. Larger studies areneeded to validate this finding.

DISCLOSURE: Vijo Poulose, None.

GASTRIC IMPEDANCE SPECTROSCOPY AND HEMODY-NAMIC VARIABLES BEHAVIOR IN DIFFERENT OUTCOMESAFTER CARDIAC SURGERYNohra E. Beltran Vargas MS* Gustavo Sanchez-Miranda MD MontserratGodınez Ursina Dıaz Emilio Sacristan PhD Universidad AutonomaMetropolitana, Iztapalapa, Mexico City, Mexico

PURPOSE: When blood flow is arrested during cardiopulmonarybypass (CPB), the tissue suffers progressive alterations. Gastric imped-ance spectroscopy, a novel tool used to monitor and detect tissue ischemiais compared with hemodynamic variables as CI, MAP, MPAP, CVP,PCWP; and regional perfusion variables as PCO2 gap and gastricintramucosal pH, to find differences according to outcome for patientsundergoing elective cardiovascular surgery.

METHODS: Impedance spectrometry probe and nasogastric tube(ISP/NGT), and a tonometer were placed in the stomach of 56 patientsunder coronary artery bypass (CABG) and/or valvular surgery withCPB and aortic cross-clamp. Hemodynamic monitoring was performedvia pulmonary artery and radial artery catheters, inserted before theoperation. Impedance spectra of the gastric wall and hemodynamicvariables were recorded perioperatively and for up to 4 hours aftersurgery. Pre-surgical and post- surgical measurements comparison wasmade to assess which variable is better associated with mortality usingANOVA.

RESULTS: Eighteen (34.61%) patients developed complicationswithin a 72h period after surgery; seven (13.46%) died. Nine (17.3%)patients developed complications after ICU release. Table 1 shows thatimpedance spectroscopy variables (R316 and X316) and CI showedsignificant differences between survivors and non survivors. The otherhemodynamic and regional perfusion variables did not differ betweengroups. Only CI, CO2 gap and pHi showed statistical differences beforeand after surgery.

CONCLUSION: Our data suggest that gastric impedance spectra maybe a good predictor of outcome after cardiac surgery. Further analysis isongoing to extract and assess the diagnostic/prognostic value of thesemeasurements.

CLINICAL IMPLICATIONS: Gastric impedance spectroscopy maybe a useful tool to assess splanchnic perfusion and tissue viability in criticalcare patients.

Table 1—Demographics and Operative Characteristicsof the Liver Transplant Patients <60yrs vs >70 yrs.

Patients

Age yrs

(S.D)

MELD

(S.D)

BMI

Kg/m2

(S.D)

OT Hrs

(S.D)

WIT min

(S.D)

CIT hrs

(S.D)

Fluids ml

(S,D)

�60 yrs 49.8

(�/-1.18)

16.41

(�/-6.94)

28.53

(�/-5.37)

5.35

(�/-1.57)

35.08

(�/-2.45)

7.21

(�/-32)

3784

(�/-1068)

�70 yrs 71.5

(�/-0.34)

16.88

(�/-6.82)

26.77

(�/-4.32)

4.77

(�/-1.36)

33.88

(�/-1.55)

6.68

(�/-29)

5535

(�/-2716)

P Value 0.9 0.27 0.09 0.86 0.60 0.003*


Critical Care Outcomes, continued


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DISCLOSURE: Nohra Beltran Vargas, Grant monies (from industryrelated sources) This research was supported by a grant from Innova-medica S.A. de C.V. with concurrent support from CONACYT.; Product/procedure/technique that is considered research and is NOT yet approvedfor any purpose. Innovamedica is sole assignee of the patent related to thetechnology using in this work. The impedance spectrometer is notcommercial yet.

PRE–INTENSIVE CARE UNIT LENGTH OF STAY AND OUT-COME IN CRITICALLY ILL PATIENTSRaquel Nahra MD* Christa Schorr RN David R. Gerber DO CooperUniversity Hospital, Camden, NJ

PURPOSE: To evaluate the relationship between pre-intensive carelength of stay and outcomes of patients transferred to the Intensive CareUnit (ICU).

METHODS: Data was obtained from the Project Impact database.Patients without a previous ICU admission transferred to the Medical-Surgical ICU (MSICU) between October 2002 and November 2004were reviewed. Medical patients came from general care and telemetryfloors. Surgical patients came from these areas, the operating room(OR), and the post anesthesia care unit. Patients were classified assurgical if surgery was performed in the OR within 7 days prior to ICUadmission. Patients were grouped by hospital length of stay (HLOS)prior to ICU admission: medical patients HLOS �5 days (GroupM1) or HLOS �6 days (Group M2); surgical patients HLOS �5 but�1 day (Group S1) or HLOS �6 days (Group S2). Variables analyzedincluded age, SAPS II survival probability, ICU and hospital LOS, andmortality.

RESULTS: Groups were demographically similar. Group M2 wassicker than M1. Acuity was similar between S1 and S2. Mortality washigher among patients with pre-ICU LOS �6 days versus those withpre-ICU LOS �5 days. HLOS was longer in groups M2 vs. M1 and S2 vs.S1. ICU LOS did not differ based on pre-ICU LOS. Observed deathsexceeded predicted in group S2.

CONCLUSION: ICU admission from a general care floor after �6days is associated with poor outcome as compared to earlier admission.Previous studies have invoked suboptimal care prior to ICU admission asthe reason for poorer outcomes. This idea is supported by the higheracuity of patients in Group M2. Poor organization, insufficient knowledge,failure to appreciate clinical urgency, inadequate supervision and failureto seek advice have been previousely suggested as factors in this subop-timal care.

CLINICAL IMPLICATIONS: Improving outcomes in patients trans-ferred to the ICU may require institutional changes. Prompt recognitionof deteriorations in patient condition and earlier interventions, such as theinstitution of a rapid response team may result in securing betteroutcomes.

DISCLOSURE: Raquel Nahra, None.

STUDY OF BACTEREMIA IN ICU PATIENTSAvanti Vigg MBBS* Arul Vigg MBBS Ajit Vigg MD Royal PrestonHospital, Preston, United Kingdom

PURPOSE: To evaluate the incidence, microbiological pattern &clinical outcomes of blood stream infection among ICU patients.

METHODS: A Retrospective study from a medical ICU (12 beds) ina tertiary care urban teaching hospital.Data was collected retrospectivelyfor all patients admitted to medical ICU from 1st January to 31stDecember 2004. Number of blood cultures collected were noted isolatedorganisms were recorded.

RESULTS: A total of 3657 patients were admitted to MICU during the12 month study period. 2091 blood cultures were sent during the period.There were a total of 370 episodes of bacteremia. Seven patients had morethan two episodes of bacteremia.The organisms were as follows :-Kleb-seilla Pneumoniae � 10; Klebseilla species � 40; Klebseilla Ornitho-lytica�3; Pseudomonas aerogenosa �12; Pseudomonas species � 67;Staph.aureus � 72; Strep.Pneumoniae�21; E.coli�26; Candida albi-cans � 45; Citrobacter diversus�2; Citrobacter freundii�3; Enterobacterspecies�9; Acinetobacter species�3; Salmonella typhi � 3; Coagulasenegative Staphylococcus�23; Streptococcus group ‘b’�2 & group ‘d’ � 5.The mortality in patients with bacteremia was 177/370 (47.8%) while itwas 103/1721 (5.9%). The mortality in those patients with 2 or moreepisodes of bacterima was 4/7 (57.1%).

CONCLUSION: Bacteremia occurred in 10% of all ICU admissions.1.9% had multiple episodes of bacteremia. Gram negative pathogens werethe commonest organisms seen in our clinical practice. Pseudomonosaspecies were the commonest(n�79) followed by Staph.aureus (n�72) &

Table 1

Variable

Survivors Non Survivors p

Pre-surgery Post-surgery Pre-surgery Post-surgery

R316 74.2�3.5 75.2�3.5 96.4�9.3 79.3�9.3 0.0024*X316 -16.6�1.5 -19.4�1.5 -26.9�3.9 -27.1�3.9 0.0003*CI 2.4�0.1 3.3�0.1 2.3�0.3 2.3�0.3 0.0270*CO2gap 7.0�1.2 18.2�1.2 8.6�3.3 25.2�3.3 0.0841pHi 7.34�0.01 7.21�0.01 7.30�0.04 7.17�0.04 0.2384MAP 75.0�1.3 80.7�1.3 73.8�3.3 75.7�3.3 0.2181PCWP 17.2�0.9 11.4�0.9 12.6�2.4 14.8�2.4 0.7532CVP 10.4�0.6 10.3�0.6 9.2�1.6 13.9�1.6 0.3031MPAP 27.3�1.2 25.2�1.3 26.5�3.5 24.5�3.5 0.7743

Table 1

Medical Patients M 1 M 2p

Value

Number 181 49Mean ICU LOS

(SD)5.4 (7.1) 5.6 (6.3) 0.85

Mean Hosp LOS(SD)

20.3 (24.5) 34.4 (23.6) 0.0004

Survival Probability-SAPS II (SD)

0.70 (0.29) 0.57 (0.32) 0.0082

Expected Mortality-SAPS II

30.00% 43%

Actual Mortality 32% 53% 0.0115Surgical Patients S 1 S 2 p

ValueNumber 96 103Mean Hosp LOS

(SD)15.2 (8.9) 28.3 (23.6) 0.0001

Survival Probability-SAPS II (SD)

0.87 (0.180) 0.84 (0.21) 0.28

Expected Mortality-SAPS II

13.00% 16%

Actual Mortality 8.30% 24% 0.0037

Table 2—Differences Between Actual and PredictedSurvival (%)

Predicted Survival Actual survival p

M 1 70 68 0.55M 2 57 47 0.15S 1 87 91.7 0.17S 2 84 76 0.02




Klebseilla(n�53). Candida species were grown on blood cultures in 12.1%of our ICU population.

CLINICAL IMPLICATIONS: Those with proven bacteremia hadhigher mortality than those without bacteremia.Hence it is prudent torecognize early these crtically ill patients with bacteremia and initiateprompt therapy to improve clinical outcomes.

DISCLOSURE: Avanti Vigg, None.

IMPACT OF A SEDATION PROTOCOL ON TRAUMA PA-TIENT’S CRITICAL CARE LENGTH OF STAYDiane K. Schuetze PharmD Rajesh R. Gandhi MD* Hillcrest BaptistMedical Center, Waco, TX

PURPOSE: Sedation management is an integral part of managingventilated patients. A standardized sedation practice to reduce intensivecare unit (ICU) length of stay (LOS) through implementation of aprotocol was the intention of the study.

METHODS: Evidence-based sedation guidelines for ventilated traumapatients were developed with input from physicians, nursing and phar-macy. The staff was inserviced and the protocol implemented in Septem-ber 2003. The protocol promoted propofol for short-term sedation (lessthan 48 hours) and midazolam for long-term sedation (greater than 48hours). Medication titration to a Modified Ramsey Scale of 3, dailyawakenings and dose reductions were included in the protocol. Theresults were retrospectively examined with a prospective application of theprotocol. A historic control group was used from the months prior toimplementation of the protocol. Two six-month retrospective reviews ofmechanically ventilated patients, baseline (Jan-June 2003) and post-protocol (Jan-June 2004), were performed.

RESULTS: A total of 39 patients were evaluated (baseline n � 14,post-protocol n � 25). The patients were predominately male (80% and68%) and the average age (32.8 years vs. 37.4 years) and Injury SeverityScores (20.5 vs. 26.4) were not significantly different between groups. Theamount of time on propofol was lower in the protocol group (24.1 vs. 35.3hours). The mean ICU LOS in the protocol group was lower than thebaseline group (5.2 days vs. 7.1 days). Overall LOS was lower in theprotocol group than baseline (7.96 days vs. 11.14 days). Preliminary datais presented.

CONCLUSION: Utilization of a sedation protocol that includes properselection of pharmacologic agents, sedation goals, daily awakenings anddaily dose reductions resulted in a trend toward decreased ICU LOS andoverall LOS. More data is needed to show significance.

CLINICAL IMPLICATIONS: Implementation of a sedation protocolmay be an effective means to reduce the number of ventilator days andsubsequent ICU LOS.

DISCLOSURE: Rajesh Gandhi, None.

THROMBOCYTOPENIA IN A COMMUNITY HOSPITAL ICU INLEBANONAli H. Debek MD* Hani Lababidi MD Pierre K. Bou-Khalil MD OthmanItani MD Anas Mugharbil MD American University of Beirut-MC,Beirut, Lebanon

PURPOSE: To determine the incidence, risk factors and outcome ofpatients with thrombocytopenia admitted to Makassed General HospitalICU Community Hospital ICU in Lebanon.

METHODS: A retrospective study of 103 medical and surgical patientsadmitted to a 6-bed ICU in a 200-bed community hospital from January1 to June 30, 2000.

RESULTS: Thrombocytopenia (platelet count � 100,000/mm3) oc-curred in 21 patients (20.4%). In multivariate analysis, female gender,sepsis, shock, transfusion requirements, duration of stay, and APACHE IIscore of � 20 were found to be independent risk factors for thedevelopment of thrombocytopenia. Thrombocytopenic patients had asignificantly higher mortality rate when compared to nonthrombocytope-nic patients (52.4% vs. 25.6%, p � 0.018). Highest mortality (80%) wasobserved when thrombocytopenia and DIC coexisted. Interestingly, noneof the patients with corrected platelet count died.

CONCLUSION: Thrombocytopenia in ICU patients is associated withhigher mortality particularly in the setting of DIC. This probably reflectsthe severity of the overall clinical status and the underlying disease. Itscorrection seems to improve prognosis.

CLINICAL IMPLICATIONS: Thrombocytopenia is an alarming signfor the intensivists to be aware of, because such patients have a high

mortality. Aggressive attempts to correct thrombocytopenia may alter thepatient’s outcome.

DISCLOSURE: Ali Debek, None.

THE EFFECT OF THE SEVERITY OF INHALATION SEVERITYACCORDING TO BURN SIZE ON EARLY MORTALITY IN SE-VERELY BURNED PATIENTSCheol H. Kim MD* Jin K. Kim MD Heung J. Woo MD Young I. ParkMD In G. Hyun MD Jung W. Shim MD Young M. Ahn MD Departmentof Internal Medicine, Hallym University College of Medicine, Seoul,South Korea

PURPOSE: Inhalation injury is a major cause of morbidity andmortality in burned patients. We performed this study to know theseverity of lower airway injury due to inhalation and the influence of theseairway injury on early mortality in severely burned patients.

METHODS: From Jan, 2004 to Jul, 2004, major burn patients withinhalation injury were enrolled prospectively. Bronchoscopic biopsy wasdone either at carina or at right (or left) 2nd carina. The pathologic gradesof biopsy was classified as follows: 0 � normal or minimal epithelial injury;1 � loss of cilia or moderate epithelial injury; 2 � severe epithelial injuryor basement membrane alteration; 3 � extensive ulceration. We analyzedAPACHE II scores, P/F ratio, 30-day ICU mortality and their correlationwith pathologic grades.

RESULTS: 68 patients (M�49, F�19) were enrolled. In survivors (40cases) and non-survivors (28 cases), there were no statistically significantdifference was seen among the patient’s age, sex, initial COHb, APACHEII scores and PaO2/FiO2 ratio. But the percent of total body surface area(%TBSA) burn and APACHE II scores were higher in non-survivors thanin survivors (p�0.05, p�0.05). In total patients, there were no significantdifference between the %TBSA and the pathologic grades of airway(p�0.056) but significant increased in trends of pathologic grade asincreasing the %TBSA (p�0.008). There were not correlation betweenpathologic grade of airway and APACHE II scores, PaO2/FiO2 ratio insurvivors and non-survivors. In survivors, significant negative correlationwas seen between the %TBSA and the pathologic grade of airway(r�-0.442, p�0.004) but, not in non-survivors (r�-0.226, p�0.25). Also,there were no significant difference in 30-day ICU mortality according toeach pathologic grade (p�0.708).

CONCLUSION: Increasing burn size concomitant with inhalationshowed increase in trends of severity of airway injury, but further studymay be needed whether the extents of lower airway injury due toinhalation affect on early mortality in severely burned patients.

CLINICAL IMPLICATIONS: The extents of initial airway injury dueto inhalation may not be sustained.

DISCLOSURE: Cheol Kim, None.

MAGNESIUM LEVEL PATTERNS AMONG CRITICALLY ILLTRAUMATIC AND NON TRAUMATIC BRAIN INJURY PA-TIENTSOusama Dabbagh MD* Hussam Jabri MBBS Haifa M. Malaika MBBSSofia Junaid MBBS Yaseen Arabi MD Abdullah Al Shimemeri MD KingAbdulaziz Medical City, Riyadh, Saudi Arabia

PURPOSE: To study the pattern of magnesium levels among traumatic(TBI)and non traumatic brain injury (CVA) critically ill patients.

METHODS: Patients admitted to ICU from january 2004 to january2005 were included .Inclusion criteria were the presence of traumaticbrain injury (TBI), thrombotic or hemorrhagic non traumatic strokes(CVA).Data was abstracted from a prospectively collected ICU database.Magnesium levels were collected retrospectively for the first seven daysof admission .Patients were classified into three groups (Contusion ,Hemmorhage and Thrombosis) based on their radiographic findings .

RESULTS: 90 patients were included (46 TBI and 44 CVA). CVApatients were older (60.84�16.4 vs. 28.21�14.9 p�0.001) had higherAPACHE scores (23.8�7.1 vs. 20.16 �4.6 p�0.01)and higher Glascowcoma scores GCS (8.9�4 vs. 5.5�2.6 p�0.006) .On the other hand TBIpatients had lower magnesium on admission (0.75�0.13 vs. 0.89�0.2p�0.019) and for the most part of the first week (see figure).There was nodifference in ICU mortality between the two groups . 25% of patients inthe TBI group had hypomagnesemia on admission versus 16% of the CVAgroup .27.2% of CVA patients had hemorrhage versus 56.5% among TBIgroup (P�0.001).Serum magnesium levels were compared among severalgroups of brain injury (hemorrhage versus thrombosis versus contusion )




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based on the radiologic findings and were not statistically different.Therewas no correlation between admission serum magnesium and Glascowcoma score GCS (R�0.03 ,P�0.8).

CONCLUSION: Serum magnesium levels seems to be lower amongtraumatic brain injury than non traumatic brain injury patients .Radio-graphic findings such as hemorrhage or thrombosis do not appear toinfluence serum magnesium .

CLINICAL IMPLICATIONS: Magnesium levels on admission andduring ICU stay are not influenced by the radiographic findings of braininjury .TBI seems to be associated with lower magnesium levels thanCVA. Whether this is specific to TBI or attached to other reasons is notknown.Other factors such as comorbid conditions and possibly hormonalor metabolic disturbances may be potential reasons .Further larger studiesare necessary to clarfiy these findings.

DISCLOSURE: Ousama Dabbagh, None.

INCIDENCE AND RISK FACTORS FOR HYPERCALCEMIA ININTENSIVE CARE UNITNathalie Gagnon MD* Francois Lauzier MD Francois J. LeBlanc MDLaval University, Quebec, PQ, Canada

PURPOSE: Immobilisation may be associated with excessive boneresorption leading to hypercalcemia and its complications such as delir-ium, renal failure and bowel dysfunction. Incidence, risk factors as well asclinical consequences of immobilisation-associated hypercalcemia are notknown for patients with extended intensive care unit (ICU) stay. Thisretrospective cohort study was designed to evaluate the incidence as wellas the risk factors of hypercalcemia for adult patients with extended (morethan 28 days) ICU stay.

METHODS: All medical records of adult patients with an ICU stay ofmore than 28 days from 2002 to 2005 were reviewed. For each patient, thehighest ionized calcemia was noted as well as the following informations:age, gender, race, weight, admission diagnosis, date of highest ionizedcalcemia with its associated creatinine level, diagnosis of septic shock,diagnosis of acute respiratory distress syndrome (ARDS), continuousveno-venous hemofiltration (CVVH), mechanical ventilation, parenteralnutrition, and corticotherapy.

RESULTS: Seventy-nine patients stayed in ICU for more than 28 days.Mean age was 53 � 18 year-old. Twelve patients (15%) died. 59 patients(75%) had mechanical ventilation, 13 (16%) had CVVH, 29 (37%) hadARDS. Sixteen patients (20%) had hypercalcemia with a mean ionizedcalcemia of 1,44 � 0,13 mmol/L (normal 1,15-1,29 mmol/L). Twelve ofthese patients were under CVVH.

CONCLUSION: Hypercalcemia is frequent in patients with extendedICU stay. CVVH seems to be strongly associated with hypercalcemia. Forthose patients under CVVH, hypercalcemia may be explained by the highcalcium concentration in our reinjection solutions (1,75 mmol/L). Aprospective study is needed to determine the real incidence of immobil-isation-associated hypercalcemia in patients without CVVH.

CLINICAL IMPLICATIONS: Clinicians may considered looking ationized calcemia in patients with extended ICU stay.

DISCLOSURE: Nathalie Gagnon, None.

Critical Care Therapeutics12:30 PM - 2:00 PM

IS ULTRA-SLOW INTRAVENOUS VITAMIN K ADMINISTRA-TION SUPERIOR TO FRESH FROZEN PLASMA FOR ACUTEREVERSAL OF ELEVATED INR?Murtaza Y. Dawood MD* Zubair A. Hashmi MD Uday K. Dasika MDForum Health - WRCS/NEOUCOM, Youngstown, OH

PURPOSE: The purpose of this study is to demonstrate the safety andefficacy of Vitamin K when administered as an ultra-slow intravenous drip(IVPB) in comparison to standard acute INR reversal utilizing fresh frozenplasma (FFP).

METHODS: A chart review of 44 patients was performed. Patientswere treated with PO, SQ, IV Push (IVP), IVPB, and IM Vitamin K forreversal of elevated INR at the attending physician’s discretion. IVPB wasadministered at 1mg Vitamin K in 50-100cc of 0.9% NaCl solution over2-4 hours. Acute INR reversal is defined as correction within 24 hours.Several patients were also treated with FFP after given Vitamin K. InitialINR, reversed INR, time to reversal, method of reversal, and complica-tions were recorded. Our results were reviewed in conjunction withestablished clinical data utilizing IV vitamin K therapy.

RESULTS: There were 22 (50%) males and 22 (50%) females in ourstudy. Vitamin K was administered as an IVPB in 16 (36.4%) patients, IVPin 2 (4.5%), IM in 2 (4.5%), PO/SQ in 24 (54.5%). Eleven (25.0%) patientsalso received FFP. Of those, 1 had received an initial IVPB drip ofVitamin K, 10 had received either SQ, PO, or SQ/PO doses of Vitamin K.There were no complications from Vitamin K administration irrespectiveof the route. Preliminary findings show, IVPB administration reversed theINR within 14h43m (�12h22m), IVP 12h13m (�5h43m), IM 29h11m(�22h39m), PO/SQ 35h50m (�14h22m). Patients who received FFP hadINR reversal within 16h03m (�13h06m). Additionally, average costs forINR reversal with IM, IVP, IVPB, SQ/PO, and FFP were $8.00, $4.10,$5.23, $6.72, and $251.85, respectively.

CONCLUSION: IVPB Vitamin K administration is a safe, effectiveand economically sound method of acute INR reversal. IVPB is superiorto the standard agent of FFP for acute reversal of elevated INR.

CLINICAL IMPLICATIONS: Based upon our results, a furtherstudy should be developed to consider the initial treatment of choice foracute reversal of elevated INR.

DISCLOSURE: Murtaza Dawood, None.

CHEMOTHERAPY ADMINISTRATION IN THE ICU: A 5-YEARRETROSPECTIVE ANALYSISNina D. Raoof MD* Mark Knott Stephen M. Pastores MD Louis P. VoigtMD Neil A. Halpern MD Memorial Sloan Kettering Cancer Center, NewYork, NY

PURPOSE: To characterize patients who received chemotherapyduring their intensive care unit (ICU) admission in a cancer hospital overa 5-year period.

METHODS: All ICU admissions between October 1998 and Septem-ber 2003 were identified from the institutional database and those whoreceived chemotherapy while in the ICU were specifically targeted forfurther study. We compared demographic data between patients whoreceived chemotherapy and those who did not. Variables assessed in-cluded age, gender, ICU length of stay (LOS), ICU mortality, post-ICULOS to hospital discharge, and long-term mortality as of October 2004.We constructed a clinical model to distinguish four subsets of patientsreceiving chemotherapy: three classes of critically ill patients (illness dueto their cancer, illness not due to their cancer, and illness due to otherdisease in a patient with no cancer) and one group of non-critically illpatients receiving high-risk chemotherapy.

RESULTS: There were 2,756 ICU admissions during the study period.Of these, 111 (4%) received chemotherapy representing 4.2% of ICUadmissions annually. Though they had similar gender distribution, pa-




tients receiving chemotherapy were younger, had longer ICU LOS, higherICU mortality, longer post-ICU LOS to hospital discharge, and higherlong-term mortality than ICU patients who did not receive chemotherapy.(Table 1) Of the patients receiving chemotherapy, the majority (78.4%)were critically ill from their cancer. Less than 10% had critical illnessunrelated to their cancer or were critically ill without cancer and 11.7%were not critically ill, but required ICU admission for high-risk chemo-therapy. (Table 2).

CONCLUSION: ICU LOS and mortality, post-ICU LOS to hospitaldischarge and overall mortality were higher in cancer patients whoreceived chemotherapy in the ICU than ICU patients who did not.. Themajority of patients who received chemotherapy during their ICUadmission were critically ill from their cancer.

CLINICAL IMPLICATIONS: Further analyses may identify patientsfor whom chemotherapy administration in the ICU is beneficial. Untilthen, we recommend careful patient selection.

DISCLOSURE: Nina Raoof, None.

DIFFUSE OPTICAL SPECTROSCOPY MONITORING OF CYA-NIDE TOXICITY AND TREATMENT USING HYDROXOCOBAL-AMIN IN AN ANIMAL MODELK. Kreuter BA* J. Lee PhD D. Mukai BS S. Mahon PhD T. WaddingtonMD J. Armstrong BA A. Cerussi PhD B. Tromberg PhD M. Brenner MDUniversity of California Irvine, Irvine, CA

PURPOSE: Currently, no reliable non-invasive methods of monitoringthe severity of in vivo cyanide toxicity and resulting physiological re-sponses. We developed a Broadband Diffuse Optical Spectroscopy (DOS)prototype system that combines multi-frequency domain photon migra-tion with near infrared spectroscopy to measure bulk tissue absorption andscattering between 600 and 1000nm wavelengths. This system was used tooptically monitor CN toxicity and treatment using Hydroxocobalamin(OHCO) by simultaneously quantifying oxy- and deoxy- hemoglobins,tissue saturation (StO2), and redox states of cytochrome C oxidase.

METHODS: A cyanide toxicity and treatment model using NewZealand White (NZW) rabbits we developed was used. A DOS probe wasplaced on the shaved inner thigh over the muscle of the right hind leg. Asodium cyanide solution of 6mg in 60cc saline was infused over thirtyminutes at a rate of 1.4cc per minute (4.2 mg total). Resultant CN toxicitywas then reversed by infusing Hydroxocobalamin at a rate of 0.5cc per

minute (700 mg total). DOS measurements and concurrent physiologicalmeasurements including arterial and venous blood gases, CO, and oxygensaturation, were obtained throughout the experiment. The non-invasiveDOS methods were compared to traditional invasive methods.

RESULTS: Broadband DOS measurements were able to monitor theprogression of cyanide toxicity and subsequent treatment with OHCOnoninvasively. By monitoring the tissue oxygen profile (OxyHb andDeOxyHb concentrations and STO2) and the concentration changes ofcytochrome c oxidase redox states, we successfully monitored the severityof in vivo cyanide toxicity and therapeutic effects of OHCO.

CONCLUSION: DOS enables non-invasive detection of CN toxicityand reversal using OHCO. DOS provides an opportunity for quantitativenon-invasive monitoring for a range of clinical conditions where specificsolute concentration measurements may be important.

CLINICAL IMPLICATIONS: DOS can be a effective method for invivo non-invasive monitoring of diseases associated with hemoglobinsaturation, or cytochrome oxidase dysfunction such as cyanide toxicity, andcould be also be used to monitor a wide range of chromophores thatabsorb in the near infrared region.

DISCLOSURE: K Kreuter, Product/procedure/technique that is con-sidered research and is NOT yet approved for any purpose. Unapprovedprocedure-use of hydroxocobalamin for treatment of cyanide poisoning.

IMPROVED OUTCOMES AMONG PATIENTS WITH HIGHESTLIKELIHOOD OF HAVING SEVERE SEPSIS WHO ARETREATED EARLIER WITH DROTRECOGIN ALFA (ACTI-VATED)Frank R. Ernst PharmD* Shankar Viswanathan Ganesh Vedarajan JasonReynolds Bob Kohli Eli Lilly and Company, Indianapolis, IN

PURPOSE: Drotrecogin alfa (activated) (DrotAA) is indicated for patientswith severe sepsis (SS) at high risk of death. ICD-9-CM code 995.92 for SSbecame available in October 2002. We sought to characterize the likelihoodof having SS and determine whether patients most likely to have SSexperience different outcomes depending on timing of DrotAA treatment.

METHODS: We conducted a retrospective analysis of 2002-2003discharge data from �400 hospitals in the Premier Perspective(TM)Comparative Database (PCD). The PCD is a large U.S. clinical andeconomic database developed for quality and utilization benchmarking.We modeled patients’ likelihood of having SS, based on having code995.92. Our model included medication use, organ dysfunctions, patientdemographics and comorbidities, disease state indicators, DRGs, andmedical service use. We also stratified patients receiving DrotAA bytiming of initiation (Same-day, Next-day, or Later) relative to the first date

Table 1—Comparison of Chemotherapy and Non-Chemotherapy Receiving ICU Patients

Chemotherapypatients(n�111)

Non-Chemo-therapy

(n�2,756)

Age yr (M�SD) 51.5�16.4 61.3�15.5Gender (%F:%M) 43:57 41:59ICU LOS days

(M�SD)9.1�10.8 5.5�7.7

ICU mortality (%) 22.5 17.7Post-ICU LOS days

(M�SD)23.4�22.4 13.6�16.5

Mortality % (10/07/04)

81.4 65.6

Table 1—Chemotherapy Models

Chemo groups (4)n(111)

% oftotal n

Critically ill Due to their cancer 87 78.4Not due to their cancer 7 6.3Non-cancer disease 4 3.6

Non-critically ill; receiving high-riskchemotherapy for their cancer

13 11.7


Critical Care Therapeutics, continued


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of evident SS. Then we compared outcomes and resource use between thetiming-based subgroups.

RESULTS: Among patients receiving DrotAA who had the top 5% ofpropensity/likelihood scores, 1,265, 1,034, and 1,101 were Same-day, Next-day, and Later patients, respectively. Among these, Same-day and Next-dayDrotAA recipients experienced similar hospital survival rates (53.5% and52.9%), and higher rates than Later patients (41.8%; both p�.001). Averagecosts were lower for Same-day versus Next-day patients ($44,251 vs. $52,139;p�.0001), and both were lower than for Later patients ($87,227; bothp�.0001). Average LOS was also shorter for Same-day versus Next-daypatients (16 days vs. 19 days; p�.0002), and both of these were shorter thanfor Later patients (30 days; both p�.0001).

CONCLUSION: Patients with the highest likelihood of having SS whoreceive DrotAA earlier experience improved survival, costs, and LOS.However, most patients with the highest likelihood of having SS neverreceive DrotAA.

CLINICAL IMPLICATIONS: This may be the first study to examinevariation in timing of DrotAA treatment among patients most likely tohave SS, as determined by propensity scoring. For treated patients, earlierinitiation of treatment for SS is associated with improved outcomes.

DISCLOSURE: Frank Ernst, Employee Eli Lilly and Company

UTILITY OF INHALED NITRIC OXIDE IN ADULT POSTOPER-ATIVE CARDIAC PATIENTS WITH RIGHT VENTRICULARFAILURERammohan Marla MD* Douglas Oberly RRT Kevin P. Keating MDFrederick Knauft MD Hartford Hospital, Hartford, CT

PURPOSE: Inhaled nitric oxide (INO) acts as a pulmonary vasodilator andhas been FDA approved for hypoxic respiratory failure of the term and nearterm neonate. By lowering pulmonary vascular resistance, INO would be ofpotential benefit in patients with severe right ventricular dysfunction. Thisreport describes the largest series in the literature on the effects of INO inadult postoperative cardiac patients with right ventricular failure.

METHODS: Patients were considered eligible for inhaled nitric oxidetherapy if they were � 18 years of age, were post cardiac surgery, hadmoderate to severe right ventricular dysfunction by echocardiography, had aPAOP � 18 mmHg or RVEDV � 120 ml/m2, PVR � 200 dynes/sec andwere unresponsive or intolerant to maximal pharmacotherapy. Nitric oxidewas initiated at 5 ppm and increased until maximal benefit was observed(maximum dose 80 ppm). Outcomes measured included oxygenation andhemodynamic variables, dose and duration of therapy, and mortality.

RESULTS: Between March 1998 and October 2004, 97 patientsreceived INO therapy. 40 (41%) patients survived to discharge fromhospital. 57 (59%) died before discharge from hospital. Mean INO dosewas 48 ppm for the survivors and 53 ppm for non-survivors. Hemody-namic parameters in all groups are shown in the Table.

CONCLUSION: Our experience has shown that INO does decreasePVR and improve both CI and REF in patients with severe rightventricular dysfunction who have proven refractory to maximal pharma-cotherapy. Our experience shows improved right heart hemodynamics.Using Receiver Operating Characteristic Curve, a CI of 2.5 discriminatessurvivors and non-survivors, however with low sensitivity (62.5) andspecificity (66.7).

CLINICAL IMPLICATIONS: INO can be effectively used to im-prove right heart function in postoperative cardiac surgical patients whodid not respond to maximal pharmacotherapy. It is a useful adjunctivetherapy in lieu of right ventricular assist devices in such patients.

DISCLOSURE: Rammohan Marla, None.

THREE YEAR EXPERIENCE WITH A DROTRECOGIN-ALPHAPROTOCOL FOR SEVERE SEPSIS: ANALYSIS OF USE, COST,AND MORBIDITY IN A UNIVERSITY HOSPITALSonja D. Bartolome MD* Steven Q. Simpson MD Steve FlahertyPharmD Amy R. O’Brien-Ladner MD Timothy Dwyer MD TimothyWilliamson MD University of Kansas, Kansas City, KS

PURPOSE: The PROWESS trial delineated a role for the use ofdrotrecogin-� in severe sepsis. However, this drug is associated withsignificant cost, which was projected to be $1.5 million annually in ouruniversity hospital setting, based on charts coded for septicemia. There-fore, a protocol to allow its appropriate use but discourage misappropri-ation was needed. A group of pharmacists, critical care physicians andnurses developed a protocol using data from the trial.

METHODS: Physicians prescribing drotrecogin were required tocomplete a standardized order form which required that the infectedpatient display �2 signs of the systemic inflammatory response syndrome(SIRS), and a minimum of one organ dysfunction. Also, an intensivist wasrequired to approve the use. Exclusion criteria were left at the discretionof the intensivist. These forms were collected over a 40 month period anddemographics, associated costs, and adverse events were compiled.

RESULTS: 122 patients were prescribed drotrecogin between 12/01and 04/05. Of these patients, 53.3% were in the medical ICU, 30.3% weresurgical, and 16.4% were in the burn ICU. The average age was 49.1 years(range 18 - 91. 55.1% were male, 44.9% female. Mean APACHE II attime of infusion in 82 patients was 25.6 (range 12 - 45). The most frequentadverse events in this population were death during infusion (14.9% or 18patients) and bleeding (6% or 7 patients). Total hospital cost of the drugwas $806,669, or an average of $7333 per patient. Overall 28 day all causemortality was 33.6%.

CONCLUSION: Drotrecogin in our institution was used in patientswith a high severity of illness as assessed by APACHE II. Complicationswere comparable to previous studies. Drug costs were well belowanticipated numbers.

CLINICAL IMPLICATIONS: A prescribing protocol for the use ofdrotrecogin in severe sepsis which indicates inclusion criteria but notexclusion criteria, and is approved by a critical care specialist, can aid inguiding the use of this drug while promoting cost containment.

DISCLOSURE: Sonja Bartolome, Consultant fee, speaker bureau,advisory committee, etc. Simpson is a member of the Lilly Lecture Bureauand has received consulting fees from Eli Lilly.

RESIDENTS’ KNOWLEDGE AND LEARNING OF CRITICALCARE PHARMACOTHERAPY: EVALUATION OF A FORMAL-IZED WEB-BASED EDUCATIONAL MODELNicole Weimert PharmD Brian R. Zeno MD* Joseph Mazur PharmDAlice Boylan MD Medical University of South Carolina, Charleston, SC

PURPOSE: Little data have been published that define the knowledgebase of US housestaff regarding critical care pharmacotherapy or whetherthis knowledge base can be effectively improved through a web-basedself-study program. We therefore sought to determine housestaff knowl-edge of key critical care concepts, and to reassess this knowledge followingcompletion of a series of educational modules.

METHODS: This was a single center pilot study using housestaff(PGY1 through PGY3). Housestaff were given pretests consisting of 40questions in ABIM format from several different aspects of critical carepharmacotherapy. This was followed by didactic powerpoint modules oneach of the subjects designed by subspecialists in critical care. Followingcompletion of each of the modules, a posttest consisting of the samequestions was provided to evaluate objective improvement. The followingsubjects were included: antibiotics, antifungals, vasopressors and ino-tropes, status epilepticus, hypertensive emergencies, toxicology, sedation,neuromuscular blockade and nutrition.

RESULTS: Fifteen housestaff completed the pretest, modules, andposttest. The pretest showed a deficit in knowledge across all subjects withan average of 29% of the questions being answered correctly. Althoughthe posttest showed a modest 5% relative improvement following themodules, this did not reach statistical significance (p�.18).

CONCLUSION: Our housestaff come from a multitude of medicalschools across the country and have USMLE scores well above thenational average. Despite this, there was a uniform lack of educationand/or retention in this area despite formalized pharmacology educationduring medical school. It appears that this an area that needs either




increased emphasis or periodic reeducation and exists as a significantvulnerability to patient safety in its current state.

CLINICAL IMPLICATIONS: Housestaff need to be able to properlymanage critically ill patients. Didactic lectures may serve to improveknowledge of key concepts and facilitate appropriate patient management.Given the limited time and resources of busy academic critical careclinicicans and work hour restrictions of housestaff, this model allowsresidents an opportunity for structured didactic education without affect-ing patient care or lengthening rounds.

DISCLOSURE: Brian Zeno, None.

DEATH: A ONE-COMPARTMENT DRUG MODEL EQUATIONTerry Fagan MD* VA Medical Center, Wilkes-Barre, PA

PURPOSE: To find an easier way to estimate and use serum levels ofvancomycin and aminoglycosides.

METHODS: The one compartment model with volume of distribution(Vd) in liters, and drug clearance (CLd) in liters/day was examined withdrug clearance approximated by creatinine clearance (CCR). This modelgenerally gives a reasonable approximation for vancomycin and theaminoglycosides. The equation for serum level half-life (T1/2) � 0.693 *VD / CLd was used, along with peak serum level (P) and trough serumlevel (T), to give a useful one-compartment equation called DEATH.

RESULTS: Define D as mg of drug given per day. Define H asnumber of drug half-lives between doses of the drug. Define E as drugexcretion � CCR. Define the amplitude A as P-T. Define T � 2.Manipulation gives D � E*A*T/H. Example1: CCR � 40. You desirevancomycin P � 32 and T � 8. Then E � 40, A � 24, and the numberof half-lives from 32 down to 8 is 2 . D � 40*24*2/2 � 960. If vancomycinVd � 40 L, each dose would be 40*(32-8) � 960. Hence your dosingwould be 960 mg QD. Example2 CCR � 20 , tobramycin 200 mg QD,estimated tobramycin VD � 20 L. Then E � 20, A � 10 and D � 200.Then 200 � 20*10*2/H. Hence H � 2 half-lives. Thus the trough T mustbe 1/4 of the peak P, and since P-T � 10, then P � 13.3 and T � 3.3.Example3: Amikacin 500mg Q 12h gives trough � 10. Amikacin Vd � 25L. D � 1000, A � 20. The peak � T�20 � 30. Peak of 30 to trough 10requires 1.5 half-lives. Using the DEATH equation: 1000 � E*20*2/1.5gives E � CCR � 38 ml/min.

CONCLUSION: The DEATH equation D�E*A*T/H can be used toestimate dose, serum levels, and CCR.

CLINICAL IMPLICATIONS: The DEATH equation is useful forvancomycin and aminoglycosides.

DISCLOSURE: Terry Fagan, None.

DAILY MEASUREMENT OF NASAL NITRIC OXIDE (NO) INHEALTHY NON-SMOKERS AND TRACHEOTOMIZED ME-CHANICALLY VENTILATED PATIENTSJiYeon Choi MSN* Leslie A. Hoffman PhD Jigme M. Sethi MDUniversity of Pittsburgh School of Nursing, Pittsburgh, PA

PURPOSE: To describe the day-to-day variation in nasal NO (nNO)and ambient NO (aNO) and examine the relationship between nNO andaNO in healthy non-smokers and tracheotomized patients.

METHODS: Two groups were recruited: 1) ten healthy non-smokers(50% male), aged 33.9 � 7.8 years with a body mass index � 30, no coldor flu-like symptoms in 30 days, known allergies, prescribed medicationsin 7 days, or diagnosis of acute or chronic illness, and 2) three tracheot-omized patients (33% male), aged 77.0 � 5.2 years, on mechanicalventilation (MV) for 43.67 � 31.90 days and undergoing daily weaningtrial. Tracheotomy placement was 8.33 � 4.51 days after initiation of MV.nNO and aNO levels were measured using a chemiluminescence analyzer(Model LR2000; Logan Research, Rochester, UK) with a sampling flowrate of 250 ml/minute.

RESULTS: In normals (n�10), nNO was measured for 3 consecutivedays (30 measures). There was no significant day-to-day difference innNO (p�NS). In tracheotomized subjects (n�3), nNO was measured fortwo, 3 consecutive day periods with an intervening 10 days (18 measures).Twelve measures occurred while on MV and 6 measures occurred afterweaning from MV (mean � SD � 723.66 � 391.75 ppb, and 1083.31 �302.90 ppb respectively). aNO levels varied each day in both normal andtracheotomized patients (range 0.65 – 104.50 ppb, and 1.00 – 112.20 ppb,respectively). In both groups, there were no significant correlationsbetween nNO and aNO (p�NS).

CONCLUSION: nNO levels had little day-to-day variation in healthynon-smokers. Additionally, nNO levels were not different when tracheot-omized patients were breathing either on or off MV. There was nosignificant relationship between nNO and aNO either in healthy non-smokers or tracheotomized patients, whether on or off MV.

CLINICAL IMPLICATIONS: Measurement of exhaled NO has beenproposed as a non-invasive marker of airway inflammations. Further studyis necessary to determine influence of an artificial airway and aNO levelson nNO.

DISCLOSURE: JiYeon Choi, Product/procedure/technique that isconsidered research and is NOT yet approved for any purpose. Thechemiluminescence analyzer (Model LR2000; Logan Research, Roches-ter, UK) is only available for research purposes at this time.

Critical Care Treatment12:30 PM - 2:00 PM

USE OF AN INCLINOMETER-DATA LOGGER TOOL FOR CON-TINUOUS RECORDING OF HEAD OF BED POSITION INPATIENTS UNDERGOING MECHANICAL VENTILATIONBoaz A. Markewitz MD* Jeanmarie Mayer MD Dwayne WestenskowPhD Stephanie Richardson PhD University of Utah, Salt Lake City, UT

PURPOSE: Ventilator-associated pneumonia remains a common prob-lem with attributable morbidity and mortality. Several preventive strate-gies are recommended including semi-recumbent positioning (head ofbed angle at 30 degrees or above) in the absence of contraindications.Most studies that describe this practice, however, assess head of bed(HOB) position infrequently (i.e., often just once per day). As such, thedata provided may not be reflective of what is occurring over longer timeintervals. We sought to determine the angle of the HOB once per minutein patients receiving mechanical ventilation.

METHODS: The HOB angle was measured using an inclinometer(Rieker, Inc.; Folcroft, PA) and the information was stored in a data logger(Onset Computers; Bourne, MA) until it was downloaded. The inclinom-eter-logger system was housed in a box which attached to the undersur-face of the head of the bed. Calibration curves for each of six inclinom-eter-logger boxes was obtained between 0 to 60 degrees at 5 degreeintervals. Each morning during the week a box was placed under the headof the bed of an intubated patient if the clinical team expected the patientto remain intubated at least for that day. Data was collected until thepatient was extubated.

RESULTS: 30 intubated patients were evaluated over a two monthperiod. The median time of intubation was 47 hours (range 2-340 hours).The mean HOB angle for each of the 30 patients ranged from 0-27degrees (median 21 degrees). The median percentage of time spent at orabove a 30 degree angle was 3% (range 0-62%). The median percentageof time spent at or above a 45 degree angle was 0% (range 0-2%).

CONCLUSION: This study indicates that semi-recubancy is rarelyachieved in patients receiving mechanical ventilation. We have developeda tool which allows for continuous measurement of HOB angle. Thismethod of monitoring shows promise as an assessment tool to improvepatient care and provide feedback to the healthcare team.

CLINICAL IMPLICATIONS: There is much room for improvementin pneumonia prevention.

DISCLOSURE: Boaz Markewitz, None.

nNO and ANO levels in Healthy Non-smokers andTracheotomized Patients

Healthynon-smokers

Tracheostomy

On MV Off MV

Measures 30 12 6nNO 1020.28

�266.68723.66

�391.751083.31�302.90

ANO 36.17�20.68 8.93�10.25 50.4�46.23




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ROLE OF KINETIC BEDS IN THE PREVENTION OF ATELEC-TASIS IN MECHANICALLY VENTILATED PATIENTSRachna Sahityani MD* Lawrence DeLorenzo MD Safdar Khan MDWilbert Aronow MD Dipak Chandy MD New York Medical College,Valhalla, NY

PURPOSE: Kinetic beds are designed to prevent pulmonary compli-cations, including atelectasis. The objective of this study was to determinethe effect of kinetic beds on the incidence of atelectasis in mechanicallyventilated patients.

METHODS: 50 kinetic beds, 20 Rotation modules and 20 Percussionmodules were introduced to the Westchester Medical Center on July 26,2001. A retrospective chart review of all mechanically ventilated patientsat this tertiary-care medical center who underwent bronchoscopy foratelectasis was conducted for 2 separate periods. The first was for theperiod immediately preceding the arrival of these beds i.e. July 2000 toJune 2001. The second period was from July 2002 to June 2003 whichallowed a year to pass after the introduction of these beds in order forhealthcare personnel to become aware of their presence and potentialbenefits.

RESULTS: Of the 3399 ICU admissions between July 2000 and July2001, 71 patients developed atelectasis while being mechanically venti-lated. Of the 3065 ICU admissions between July 2002 and June 2003, 83patients developed atelectasis. There was no significant difference in thehospital and ICU length of stay, ventilator utilization by the hospital andthe Case-mix Index between these 2 periods.

CONCLUSION: There was no decrease in the incidence of atelectasisin mechanically ventilated patients at our institution after the introductionof these kinetic beds despite their widespread availability.

CLINICAL IMPLICATIONS: Most studies have shown kinetic bedsto be potentially beneficial. However, all these studies were performedunder a strict protocol to ensure appropriate usage. Our institution didhave a protocol but did not require a physician’s order, thereby ensuringthat usage was almost entirely dependent on nursing personnel. The factthat our study showed no reduction in the incidence of atelectasis after theintroduction of these beds is probably related to their underutilization andnot to their lack of efficacy. To obtain a benefit from such an expensiveinvestment, institutions should consider physician orders as a means ofensuring appropriate utilization of these beds.

DISCLOSURE: Rachna Sahityani, None.

ACCURACY OF CLINICAL EVALUATION OF HEAD OF BEDELEVATIONNasir Awan MD* Chanaka Seneviratne MD Zenia Ceniza RN Taek S.Yoon MD Yizhak Kupfer MD Sidney Tessler MD Maimonides MedicalCenter, Brooklyn, NY

PURPOSE: Maintaining head of bed elevation (HOBE) greater than30° has been shown to decrease the incidence of ventilator associatedpneumonia. We prospectively studied the accuracy of clinical estimationof HOBE.

METHODS: HOBE was set at two levels 30° and 45° with the use ofa protractor. Nurses and physicians were asked to determine the HOBEangle. The position of the observer, whether the estimation was per-formed at the foot or the side of the bed, was evaluated.

RESULTS: One hundred and fifty nurses and fifty physicians partici-pated in the study. Overall, when HOBE was 30°, the average clinicalestimation was 50° (P�0.001). When the HOBE was 45°, the averageclinical estimation was 70° (P�0.001). When the observer was at the footof the bed, only 32 (16%) correctly estimated the position versus 90 (45%)of the observers correctly estimated bed position from the side of the bed(P�0.001). There was no difference between physicians and nurses in theaccuracy of the clinical estimation of HOBE.

CONCLUSION: Clinical evaluation of the angle of HOBE tends tooverestimate the angle of elevation. Measurement of the HOBE from theside rather than the foot of the bed is more accurate.

CLINICAL IMPLICATIONS: Use of protractors rather than clinicalestimation should be encouraged to maintain HOBE greater than 30°.

DISCLOSURE: Nasir Awan, None.

EFFECT OF THE PERIOPERATIVE METHYLPREDNISOLONEADMINISTRATION IN THE PAO2/FIO2 RELATION AFTERESOPHAGEAL RESECTION FOR ESOPHAGUS CARCINOMAAntonio M. Raimondi MD* Jose L. Amaral MD Universidade Federal deSao Paulo/ Escola Paulista de Medicina, Sao Paulo, Brazil

PURPOSE: Preoperative glucocorticoid administration has been pro-posed to reducing postoperative morbidity. It isn�t widely used beforeesophageal resection due incomplete knowledge of its effectiveness.Ob-jective:To assess the effects of preoperative glucocorticoid administrationin adults underwent esophageal resection for esophageal carcinoma.

METHODS: SEARCH STRATEGY: Studies were identified bysearching the Cochrane Controlled Trials Register, MEDLINE, EM-BASE, CancerLit, SCIELO, Cochrane Library and handsearching fromrelevant articles. The date of the last search for clinical trials for thissystematic review was December 2004. SELECTION CRITERIA: Thisreview included randomized of patients with potentially resectable carci-nomas of the esophagus that compare glucocorticoid with placebo beforesurgeries. DATA COLLECTION & ANALYSIS: Data were extracted bythe same reviewers, and the trial quality was assessed using the Jadadscoring. Relative risk and weight mean difference with 95% confidencelimits were used to assess the significance of the difference between thetreatment arms.

RESULTS: There were four randomized trials involving 146 patients.There weren’t differences in postoperative mortality, sepsis, anastomoticleakage, hepatic and renal failure between glucocorticoid and placebogroups. There was a decrease in postoperative respiratory complications(p � 0.005), multiple postoperative complications (p � 0.004) andpostoperative plasma levels of interleukin-6 (p � 0.00001) with preoper-ative glucocorticoid administration. There was a increase in postoperativePaO2/FiO2 ratio (p � 0.0001) with preoperative glucocorticoid adminis-tration.

CONCLUSION: Prophylactic administration of glucocorticoids is as-sociated with a amelioration in postoperative PaO2/FiO2 relation.

CLINICAL IMPLICATIONS: Perioperative methylprednisolone ad-ministration represented a potentially important biologic modifier ofpostoperative inflammatory responses and organ dysfunction.

DISCLOSURE: Antonio Raimondi, None.

CURRENT PRACTICE OF TRACHEOTOMY IN EUROPE: APOSTAL SURVEY IN THE NETHERLANDSDenise P. Veelo MD Marleen E. Graat Peter E. Spronk PhD Marcus J.Schultz PhD* Academic Medical Center, Amsterdam, Netherlands

PURPOSE: Tracheotomy is increasingly performed in critically illpatients requiring prolonged respiratory support, weaning and frequentbroncho-pulmonary toilet.

METHODS: To ascertain current practice of tracheotomy in criticallyill patients a simple questionnaire was sent to intensive care units (ICUs)throughout the Netherlands. Questionnaires were sent to the lead clini-cians of ICUs with � 5 beds.

RESULTS: From the number of units responding (n � 28, 43.1%), themajority (n � 17, 60.7%) practiced percutaneous tracheotomy as opposedto open surgical tracheotomy. In the majority of hospitals tracheotomy wasperformed by the intensivist (n � 19, 67.9%), followed by the surgeon(n � 15; 53.6%), and the ENT-physician (n � 9, 32.1%). Tracheotomieswere mainly performed in the ICU (n � 20; 71.4%), than in the operationroom, and more tracheotomies were performed by a team (i.e., for eachtracheotomy procedure more than one physician was present, n � 22,78.6%) than by a single physician (n � 2, 7.1%). In the majority of ICUsno antimicrobial prophylaxis was given before tracheotomy (n � 23;82.1%). Reasons for tracheotomy were polyneuropathy (n � 13; 46.4%),prolonged mechanical ventilation (� 14 days) (n � 22; 78.6%), and lowGCS (n � 18; 64.3%). Although it was the policy to perform the


Critical Care Treatment, continued


procedure as soon as possible after it was clear that the patient fulfilledcriteria for tracheotomy, in more than half of the cases tracheotomy wasperformed not earlier than after one week. Reasons varied from nooperating room available (n � 5; 17.9%) to uncertainty about indication(n � 8; 28.6%).

CONCLUSION: In the Netherlands, the majority of tracheotomies areperformed by the intensivist in the ICU, by using the percutaneoustechnique, and without antimicrobial prophylaxis.

CLINICAL IMPLICATIONS: Our data suggest that guidelines mustbe developed for this frequently performed procedure.


PERCUTANEOUS TRACHEOSTOMY EXPERIENCE AT A SIN-GLE INSTITUTIONFrancis J. Podbielski MD* Peter H. Bagley MD Ann E. Connolly MSNPatrick H. Bagley UMass Memorial Healthcare, Worcester, MA

PURPOSE: To review a single institution’s experience in the treatmentof patients requiring long-term airway access.

METHODS: Medical and surgical patients requiring tracheostomywere evaluated by a single surgeon. A decision for bedside percutaneousversus open tracheostomy was based on hemodynamic stability, patientanatomy, and coagulation profile.

RESULTS: A total of 131 patients underwent a planned percutaneoustracheostomy between 11/05/2001 and 04/12/2005. There were 74 menand 57 women, with an average age of 66.1 � 16.5 yrs (median � 71). Theduration of mechanical ventilation prior to tracheostomy was 16.1 � 8.7 d(median � 15). The majority of patients received a size #8 tube (n � 117),and the remainder a size #7 tube. There was one death in post-operativeperiod (i.e., within 30 d of the procedure) secondary to bleeding into theairway after the tracheostomy was downsized. One procedure requiredconversion to an open procedure due to excessive bleeding. Complicationsincluded three bedside explorations for bleeding (tracheostomy com-pleted successfully), one case of bleeding on POD #2 with a respiratoryarrest who was resuscitated successfully and had no further intervention,one semi-open procedure at the bedside secondary to morbid obesity, andfour cases done percutaneously in the OR for patient issues. Of the 130procedures performed successfully, 50 were done in a post-operativesetting and the remainder (n � 80) done for medical conditions.

CONCLUSION: Percutaneous tracheostomy is a widely employedtechnique used by surgeons, pulmonologists, and critical care physiciansto provide long-term airway access for patients requiring protractedweaning from mechanical ventilation. It generally does not require use ofoperating room facilities, and in skilled hands is safe and reliable. Ourseries demonstrates common complications encountered during thisprocedure and should be kept in mind by those physicians who arelearning this procedure.

CLINICAL IMPLICATIONS: Physicians performing percutaneoustracheostomy should be prepared to manage issues of bleeding andemergent airway access in the event of complications when performingthis procedure.

DISCLOSURE: Francis Podbielski, None.

IS PERCUTANEOUS TRACHEOSTOMY MORE LIKELY TOCAUSE TRACHEAL STRICTURE THAN OPEN TRACHEOS-TOMY?John R. Roberts MD* Gary K. Lovelady MD The Surgical Clinic,Nashville, TN

PURPOSE: Tracheostomies are often done to facilitate weaning fromthe ventilator, or to prevent tracheal strictures from prolonged intubation.After the technique of open tracheostomy was developed, reports ofstrictures were found in the literature, and techniques to avoid thosestrictures were developed. Percutaneous tracheostomy allows bedsidetracheostomy in the ICU, and thus avoid transporting a sick patient. Afterfinding tracheal strictures in several patients who had undergone percu-taneous tracheostomy we evaluated our experience in tracheal resectionsafter tracheostomy.

METHODS: All patients who had undergone tracheal resection wereanlyzed. Their age, sex, race, length of stay, ICU stay, reason fortracheostomy, reason for intubation and pulmonary function tests wereevaluated. Data were analyzed with means and standard deviations.Student’s t test was used to compare means–0.05 was accepted assignificant.

RESULTS: Twelve patients underwent resection for tracheal stricturedue to tracheostomy. Their average age was 51.6 years (range 28-76) and33% (4 patients) were women. Ten of twelve had preoperative pulmonaryfunction testing–average FEV1% was 36%. No patient was reintubated,but three patients spent additional time in the ICU (average 0.38 days;standard deviation 0.81 days). No patients died, nor suffered signficantcomplications. Three patients had strictures from open tracheostomy(25%) and nine from percutaneous tracheostomy (75%).

CONCLUSION: We can not compare the incidence of stricturebetween the procedures because the denominators are unknown. How-ever, these patients were drawn from a large geographic region whereopen tracheostomy is still more common than percutaneous tracheostomy.These data suggest that patients with percutaneous tracheostomy are atsignficant risk of tracheal stricture, perhaps more than those undergoingopen tracheostomy.

CLINICAL IMPLICATIONS: Patients undergoing percutaneous tra-cheostomy are at risk for tracheal stricture.

DISCLOSURE: John Roberts, None.

IMPLEMENTATION OF AN INTENSIVE INSULIN THERAPYPROTOCOL IN MECHANICALLY VENTILATED TRAUMA PA-TIENTSJohn P. Kepros MD* Jim Chalk MD Emmett McGuire MD LisbethHarris MS David Bar Or MD Michael Craun MD Kate Wilmes RNMichigan State University Department of Surgery, Lansing, MI

PURPOSE: Intensive insulin therapy has been shown to reducemortality in adult patients receiving mechanical ventilation admitted tothe intensive care unit. The use of exogenous insulin to maintain the bloodglucose level at no higher than 110 mg/dL was found to reduce morbidityand mortality regardless of whether the patients had diabetes. We studiedthe safety and feasibility of widespread implementation of a standardizedintensive insulin therpay protocol targeted to this range as part of amechanical ventilation bundle on a trauma service.

METHODS: 50 patients admitted to the ICU on the trauma serviceand requiring mechanical ventilation were treated with insulin infusionsper a standardized protocol to keep the blood glucose between 80 and 110mg/dL. Compliance with the protocol, mortality, frequency of hypoglyce-mia, rate of infusion and duration of insulin required, and cause ofmortality were measured and recorded.

RESULTS: Physician compliance in ordering the protocol was 90%.Only 5 did not receive the protocol. Of the other 45 patients who hadintensive insulin therapy ordered, 42 actually required insulin administra-tion (93.3%). Three patients died (6.0%) during the ICU stay. Hypogly-cemia (glucose 40 mg/dL or less) only occured in 2 patients (4.0%)withoutadverse sequelae. The mean duration of intensive insulin therapy was 6.5days. The range of insulin required was from 0 to 15 units/h. The causesof death were MODS from sepsis, a fatal cervical spine injury, and severetraumatic brain injury.

CONCLUSION: Intensive insulin therapy with a continuous infusionof insulin according to a standardized protocol can easily be performed incritically ill trauma patients requiring mechanical ventilation. A deter-mined approach to glucose control can be taken with minimal fear ofhypoglycemia.

CLINICAL IMPLICATIONS: Intensive insulin therapy has beenrecommended for implementation as standard therapy as part of amechanical ventilation bundle. Unfamiliarity, lack of real world data, andfear of hypoglycemia have been barriers to implementation. This studyshows that intensive insulin therapy with tight glucose contol is feasible ina critically ill population.

DISCLOSURE: John Kepros, None.

THE EFFECTIVENESS OF THE MISTY-OX HIGH FRACTIONOF INSPIRED OXYGEN (FIO2)-HIGH FLOW NEBULIZER ANDTHE THERA MIST AIR ENTRAINMENT NEBULIZER IN DE-LIVERING HIGH OXYGEN CONCENTRATIONSDonna D. Gardner RRT* David L. Vines RRT Richard B. Wettstein RRTJuan Garcia MD Jay I. Peters MD University of Texas Health ScienceCenter at San Antonio, San Antonio, TX

PURPOSE: Misty-Ox (MO)® nebulizer was developed to overcomeshortcomings of conventional air-entrainment devices. The MISTY OX ®is designed to deliver FIO2s from 0.60 to 0.96 with total gas flows from 42to 80 L/min. The THERA MIST® nebulizer is designed to deliver FIO2s




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from 0.36-0.96 with total gas flows from 47 to 74 L/min. We sought todetermine the actual delivered FIO2 when using the MISTY OX® andthe THERA MIST® via aerosol mask in normal subjects.

METHODS: Following informed consent, 12 healthy volunteers, hada size 8 french nasal catheter (NC) inserted through one of the nares withthe tip positioned at the level of the uvula. Subjects were placed on theTHERA MIST® connected to large bore tubing and an aerosol mask.Oxygen therapy was then initiated at a set FIO2 of 0.60 at 15 L/min, then0.80 and 0.95 at flush for a period of five minutes. The subjects were alsoplaced on the Misty-Ox ® connected to large bore tubing and an aerosolmask. Oxygen therapy was then initiated at a set FIO2 of 0.65, 0.85 and0.96 at 40 L/min flow using a high-flow flowmeter for a period of fiveminutes. With the subject breathing normally the gas was analyzed atthree sites: the nebulizers’ outlet, the subjects’ lip and from the subjects’pharynx. A previously calibrated oxygen analyzer measured the FIO2 ofthese samples. Three samples were obtained from each site, at each FIO2setting and the mean and standard deviations were calculated.

RESULTS: Means, standard deviations and ranges for the analyzedoxygen concentrations are included in the Table.

CONCLUSION: Delivered FIO2 using the Thera Mist and the MistyOx nebulizers can vary significantly from the set value. The delivered O2can be 10 - 20 percent below the set value.

CLINICAL IMPLICATIONS: Care should be taken when interpret-ing patients’ clinical response to oxygen therapy when using these devices.Patient may be receiving a FIO2 much less than anticipated based on thenebulizer setting.

DISCLOSURE: Donna Gardner, None.

Critical Care: Intensive Glucose12:30 PM - 2:00 PM

EFFICACY OF INTENSIVE INSULIN PROTOCOL AMONGCRITICALLY ILL MEDICAL AND SURGICAL PATIENTSOusama Dabbagh MD* Yaseen Arabi MD Ziad Memish MD SamirHaddad MD Salim Baharoon MD Sofia Junaid MBBS Hema GiridharMBBS Craig Grant RN Riette Brits RN Monica Pillay RN Salim KahoulRN Abdullah Al Shimemeri MD King Abdulaziz Medical City, Riyadh,Saudi Arabia

PURPOSE: to evaluate the efficacy of intensive insulin protocol tocontrol blood sugar in target of 4.4-6.1 mmol/l.

METHODS: Data was abstracted from an ongoing randomized con-trolled trial in a 21–bedded medical surgical ICU at a tertiary center inSaudi Arabia. Patients were included if admission blood glucose was 6.1mmol/l or higher.Patients were randomized to receive intensive insulintherapy (target blood glucose 4.4-6.1 mmol/l) or standard insulin therapy(target 10-11.1 mmol/l) using prewritten protocols. This study examinesthe efficacy of intensive insulin protocol in controlling blood glucose. Weexamined the time to achieve the target defined as the time (hours)needed to reach the upper limit of the target (6.1 mmol/l) for at least onereading. The number of blood sugar episodes above the target were alsorecorded (excluding the day of enrollment) and adjusted to the number oftreatment days. We also recorded the number of hypoglycemic episodes(blood glucose below 2.2 mmol/l) and adjusted to the number oftreatment days.

RESULTS: 103 patients treated with intensive insulin therapy wereanalyzed. Patients were treated for a mean of 8.8 � 6.7 days (range 1-33days) and a total of 914 treatment days. The mean inclusion blood sugarwas 10.7 � 4.5 (range 6.1-27). The target blood glucose was reached in amean of 6.7�3.3 hours. Average daily blood glucose levels are shown inthe figure. There were a total of 7480 readings above the target averaging8 /100 treatment days. There were a total of 138 hypoglycemic episodesaveraging 15/100 treatment days.

CONCLUSION: Intensive insulin therapy protocol was effective inachieving the target level of 4.1-6.1 mmol/l in a relatively short time (6.7hours) and for most of the treatment duration. This therapy was associatedwith the occurrence of hypoglycemia at a rate of 15/100 treatment days.

CLINICAL IMPLICATIONS: Physicians using intensive insulin ther-apy need to be aware of the frequency of complications; the impact ofwhich can be minimized by at least hourly monitoring of blood glucose.

DISCLOSURE: Ousama Dabbagh, None.

INTENSIVIST DIRECTED PROTOCOL REDUCES ICU ADMIS-SIONS FOR PATIENTS IN DIABETIC KETOACIDOSISJay M. Nfonoyim MD* Joseph Ng MD Igor Berengolts MD FasikaWeldearegay MD Saint Vincents Catholic Medical Center, Staten Island,NY

PURPOSE: Over 90,000 U.S. hospital admissions have DKA as aprimary diagnosis. Despite published management guidelines, there aresignificant differences in treatment plan, rate of ICU admissions andlength of stay. The use of an early intensivist directed protocol reduces theduration of acidemia and ICU admissions.

METHODS: Patients admitted into the ED, with a primary diagnosisof DKA during a two month period in 2005 (Intervention) were treatedwith early intensivist driven protocol utilizing crystalloids and a constantinfusion of insulin with IV boluses. Patients were treated with the standard0.1 units/kg IV bolus and 0.1 unit/kg/hour IV infusion of insulin titrated tothe blood glucose. However, in this study, the treatment was compli-mented with IV boluses of insulin based on blood glucose measurements.Outcomes measured were duration of acidemia, admission to ICU, andlength of hospital stay. Controls were retrospectively obtained by review-ing an equal number of randomly selected charts of patients admitted forDKA during the same period in 2004.

RESULTS: Both groups were matched according to their APACHE IIscores. The duration of acidemia in the intervention group ranged from2-13 hours, (mean 5.9) compared to the control group which ranged from7-19.5 hours (mean 11) p�0.001. Of the intervention group, 10 percentwere admitted to the ICU, compared to 30 percent of the control group.The mean length of stay for the intervention group was 4.0 days,compared to 4.5 days for the control group.

CONCLUSION: In the management of DKA, early intervention by anintensivist directed protocol of crystalloids and insulin with intravenousboluses during and in addition to a constant infusion of insulin, reducesthe duration of acidemia, subsequent admissions to the ICU and a trendtowards a shorter length of stay.

CLINICAL IMPLICATIONS: Involving a critical care team in themanagement of DKA patients early in their admission to the ER reducesthe rate of admissions to the ICU thereby decreasing the total cost of thehospitalization.

DISCLOSURE: Jay Nfonoyim, None.

Analyzed FIO2 (SD) for High Oxygen Concentration Devices*

Device Thera Mist Misty Ox

Set FIO2 .060 0.80 0.95 0.65 0.85 0.96

Location of AnalysisNebulizer Outlet .53(.03) .74(.05) .86(.05) .64(.03) .80(.03) .86(.04)Subject’s Lip .56(.04) .72(.06) .84(.05) .63(.03) .79(.04) .84(.04)Oropharynx .47(.03) .65(.05) .75(.06) .56(.04) .70(.06) .73(.06)

* Mean (SD) of all subjects




VALIDATION OF AN INSULIN INFUSION PROTOCOL IN DI-ABETIC PATIENTS UNDERGOING CARDIAC SURGERYVinay K. Sharma MBBS* Salim Harianawala MBBS Olukunle AjagbeMBBS Sohail Khan MBBS Alan D. Haber MD Graduate Hospital,Philadelphia, PA

PURPOSE: An increasing body of literature suggests that poor glyce-mic control is associated with worse outcome in critically ill patients andthat achieving good glycemic control with aggressive insulin therapyreduces morbidity and mortality. In our institution, a fairly simple insulininfusion protocol has been in place for patients undergoing cardiacsurgery. The hourly insulin drip rate is calculated as: (patient glucose ingm/dl – 60) x factor. The initial factor is usually 0.03 and is adjustedsubsequently. However, the source and validity of this protocol were notelucidated despite a literature search. This retrospective study aims toascertain the validity of the protocol.

METHODS: Charts of patients undergoing coronary artery bypassgraft (CABG) surgery were reviewed and 20 diabetic patients identified;10 who received the insulin protocol and 10 that did not. Data abstractedincluded patient demographics, parameters needed to determine theAPACHE III score on the day of surgery, and all fingerstick glucosereadings on 3 consecutive days starting from the day of surgery.

RESULTS: Nineteen of the 20 patients were males. The mean age(65 � 15 vs. 65 � 10) and mean APACHE III scores (14.4 � 8 vs. 14.6 �12) were similar between the control and insulin protocol groups,respectively. The mean glucose levels on each of the three days were 162,151 and 179 mg/dl in the control group and 157, 148 and 141 in theprotocol group. Glucose level was £145mg/dl in 41% (76/184) of readingsin the control group and 65% (228/353) of readings in the protocol group(p�0.0001; Chi-square). Glucose levels �60mg/dl occurred in 2.7%(5/184) of control and 0.6% (2/353) of protocol group readings (p�0.05;Fisher Exact Test).

CONCLUSION: In our cohort, this insulin protocol resulted not onlyin significantly better glycemic control, but also a significant reduction inthe incidence of hypoglycemia.

CLINICAL IMPLICATIONS: This relatively simple insulin protocolappears to optimise glycemic control in CABG patients and may also haveutility in non-CABG, critically ill patents.

DISCLOSURE: Vinay Sharma, None.

COMPUTERIZED PROTOCOLS FOR INTENSIVE INSULINTHERAPY: VARIATIONS IN RECOMMENDATIONS BASED ONDIFFERENT METHODS OF GLUCOSE MEASUREMENTSrinivas B. Chakravarthy MBBS* James F. Orme MD Boaz A. MarkewitzMD Chris Lehman MD University of Utah, Salt Lake City, UT

PURPOSE: Insulin protocols are increasingly used in ICUs to achievedesired glucose ranges while minimizing practice variation and potentially,harm to patients. Glucose levels may vary, however, with different testingmethods, and these differences may be clinically significant. Point of caretesting with glucometers is now widely performed, however, the adequacyof this method in critically ill patients is largely unknown. The purpose ofthis study is to evaluate the variations in recommendations given by acomputerized insulin protocol to glucose levels obtained by differenttesting methods.

METHODS: Patients admitted to the ICU with shock (SBP � 90 mmHg despite adequate volume resuscitation or requiring vasopressor ther-apy) were evaluated. When indicated, an arterial blood sample wasobtained and glucose was measured using a glucometer (ACCU-CHEKComfort Curve, Roche), as well as in the clinical laboratory (“goldstandard”) using the colorimetric plasma glucose analyzer (VITRIOS). Asimulation was subsequently run using this patient abstracted data on ourcomputerized insulin protocol. The computerized protocol has beenimplemented in our ICU since January of 2003 and targets a glucose levelof 80 to 110 mg/dl. The protocol uses the current blood glucose level aswell as the rate of decline in glucose to determine the insulin infusion rate.

RESULTS: Simulations were run on glucose results from 21 patients(61 total samples). The protocol treatment recommendation obtained foreach glucose level determined by the glucometer was compared to therecommendation obtained for the corresponding glucose level deter-mined by the clinical lab. See table for the results. Two out of the 21patients in our simulation had a difference of greater than 1 unit/hour ofinsulin infusion rate, between the recommendations.

CONCLUSION: Blood glucose determinations made with a glucom-eter can result in patients receiving higher doses of insulin, per oursimulation.

CLINICAL IMPLICATIONS: While our study shows statisticalsignificance in variations in insulin dosage, if a glucometer is used, theclinical significance is uncertain.

DISCLOSURE: Srinivas Chakravarthy, Grant monies (from sourcesother than industry) This study was supported by an award from TheCHEST Foundation of the American College of Chest Physicians andOrtho Biotech Products, LP.; Grant monies (from industry relatedsources) The glucometer, chemistry strips and reagents were provided byRoche.

NON-SUCCESSFUL INTENSIVE INSULIN THERAPY IN ICUPATIENTS IS NOT ASSOCIATED WITH CHANGES IN QUALITYOF LIFEJose Hofhuis RN Jan Bakker PhD Marcus J. Schultz MD Johannes H.Rommes MD Peter E. Spronk MD* Gelre Hospitals (Lukas site),Apeldoorn, Netherlands

PURPOSE: Recent data showed that intensive insulin therapy (IIT)improved the mortality and morbidity in post-operative intensive carepatients. IIT, bears the risk of hypoglycaemia, which might be associatedwith a decreased health related quality of life (HRQOL). We hypothesizedthat changes in HRQOL may be related to IIT.

METHODS: All measured blood glucose values (BGs) in all patientsadmitted �48 hours to a 10-bed mixed IC from 2001 – 2003 wereretrospectively collected. Severe hypoglycemia (BG � 2.2 mmol/) andhypoglycemia (BG � 4.4 mmol/l) were defined. Patient data were dividedin two groups: successful IIT group: patients with �75% of BGs in normalrange, and no (severe) hypoglycemia at any time during IIT; unsuccessfulIIT group: patients that did not fulfil the former criteria. HRQOL wasassessed using the Short-Form (SF)-36. Patients or proxies completed thisquestionnaire in the first 48 hours of admission and 6 months thereafter.

RESULTS: Mean BG was 6,9 � 1,5 mmol/l in the succesful group(N�45) and 8,7 � 3,2 mmol/l in the unsuccesful group (N�286). In thesuccesful group, the percentage of patients with severe hypoglycemia andhypoglycemia was 3,3% and 31%, respectively. In the first group, scores inthe physical functioning and general health domains decreased in the 6month evaluation period (P � 0,003 and P�0,001, respectively). Nochanges were found in the role physical, vitality, pain, social functioning,role emotional; and mental health domains. In the unsuccessful IIT group,scores in the physical functioning, role physical and general healthdomains decreased in the same period (all P�0,001). No changes wereobserved in the vitality, pain, social functioning, role emotional, andmental health domains. No differences between the groups could bedemonstrated with respect to scores in the HRQOL domains 6 monthsafter ICU discharge.

CONCLUSION: HRQOL decreases after IC-treatment, particularlywith respect to physical functioning and general health. This decrease wasindependent of successfulness of IIT.

Table—Results

Protocolrecommendation

Difference PGlucometer-

basedClinical

lab-based

Totalinsulin(units)

Mean 15.16 12.69 2.47 0.0025

SD 12.84 11.76 3.19Range 0 to 42.18 0 to 41.22 -0.8 to 13.41

Insulin rate(units/hour)

Mean 2.09 1.74 0.31 0.0017

SD 1.52 1.43 0.44Range 0 to 4.82 0 to 4.71 -0.12 to 1.55


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CLINICAL IMPLICATIONS: The impact of ICU treatment onHRQOL is not influenced by IIT.

DISCLOSURE: Peter Spronk, None.

General Thoracic Surgery12:30 PM - 2:00 PM

SUPERIOR MANAGEMENT OF ESOPHAGEAL PERFORA-TIONS: AN EMPHASIS ON DIVERSION AND DRAINAGEThomas A. Brown MD* Geoffrey M. Graeber MD Michael F. SzwercMD Gordon F. Murray MD West Virginia University, Morgantown, WV

PURPOSE: Uncontained esophageal perforation is a devastating injurywith a mortality rate approaching 20%. Early surgical repair supported byesophageal exclusion, early nutrional support, gastric drainage, and thor-ough pleural drainage should yield superior results.

METHODS: The records of all patients treated esophageal perfora-tions at one university medical center from 1988-2003 were collected andanalyzed. Optimal treatment consisted of surgical repair, proximal esoph-ageal and gastric decompression, thorough pleural drainage, initiation ofnutritional support within 2 days, and IV antibiotics.

RESULTS: Forty patients were identified (37 adult and 3 pediatric).The age range was 0-87 years (mean 59.1). The male: female ratio was 1:1.Overall mortality rate primarily, had nasogastric suction, pleural and/ormediastinal drainage, and nutritional support. All had successful repairswith 0% mortality.Thirty-four patients had esophageal perforations in thedistal two-thirds. Seven received conservative therapy of drainage, IVantibiotics, nutritional support, but no primary repair. Two died ofcontinuing sepsis and five survived. Twenty-six patients were treated earlywith 11.5% mortality and 7 patients were treated late with 14.3%mortality. Twelve patients received suboptimal therapy with one or moreof the major components of treatment being omitted. Four of thesepatients died (mortality rate 33.3%). Fifteen received optimal treatmentwith all of the major components with 0% mortality. Number of pleuraland mediastinal drains placed was proportional to survival, with 4-6 drainsyielding 0% mortality.

CONCLUSION: Prompt surgical repair supported by proximal esoph-ageal exclusion without defunctionalization, gastric decompression, thor-ough pleural drainage, nutritional support within 2 days, and IV antibioticsyields excellent results in patients suffering from uncontained perforationsof the distal two-thirds esophagus.

CLINICAL IMPLICATIONS: Early drainage and appropriate nutri-tional support yield excellent results in complex esophageal perforations.

DISCLOSURE: Thomas Brown, None.

THE EFFECT OF IMMUNOSTAINING WITH ANTI-OCT4 AN-TIBODIES ON THE EXPRESSION OF OCT4 IN MEDIASTINALGERM CELL TUMORSPao-Hsien Chu MD* Shih-Ming Jung MD Chang Gung MemorialHospital and Chang Gung University, Taipei, Taiwan ROC

PURPOSE: The Primary germ cell tumor (GCT) is a relatively raretumor usually located in the anterior mediastinum. A previous study haspostulated that OCT4 is a nuclear transcription factor that is expressed inpluripotent embryonic germ cells. This study attempted to identify andcharacterize OCT4 expression in the GCTs originating in the mediasti-num.

METHODS: A retrospective study conducted between 1983 and 2005included 46 consecutive patients with GCTs in the mediastinum whosetumors had been surgically excised. We examined histological sectionsfrom 46 primary GCTs in the mediastinum, including teratoma (n�27;58.7%), seminoma (n�10; 21.7%), yolk sac tumor (n�6; 13%), embryonalcarcinoma (n�1; 2.1%), and mixed GCTs (n�2; 4%; one consisted ofteratoma and yolk sac tumor, and the other teratoma, yolk sac tumor andseminoma). Each tumor was examined with hematoxylin and eosinstaining and with anti-OCT4 antibodies. An overexpression of OCT4 wasstudied using immunohistochemistry.

RESULTS: The patient population was comprised of 16 (34.8%)women and 30 (65.2%) men. The mean age of patient participants was25.1 years, with an age range of 9 to 56 years. The presentations included:

asymptomatic tumor (28.5%), dyspnea (17.1%), coughing (22.8%), supe-rior vena syndrome (5.7%), chest pain (20%), and fever (5.7%). Thetherapies administered were surgical excision (75%), followed by chemo-therapy (48.6%) and/or radiotherapy (31.4%). Serum tumor markers weremeasured for twenty (47%) of the 46 patients whose, including 68%elevated alpha-fetoprotein, 30% elevated beta subunits of human chori-onic gonadotropin, and 17% elevated carcinoembryonic antigen. Therewas greater than 90% nuclear staining of the embryonal carcinoma andseminoma tumor cells with little to no background staining. The otherGCT components (yolk sac tumor and teratoma) showed no staining.

CONCLUSION: We conclude that immunostaining with anti-OCT4antibodies is a useful diagnostic tool in the identification of primaryembryonal carcinomas and seminomas in the GCT originating in themediastinum.

CLINICAL IMPLICATIONS: anti-OCT4 antibodies is a usefuldiagnostic tool in the identification of mediastinal primary embryonalcarcinomas and seminomas.

DISCLOSURE: Pao-Hsien Chu, None.

UTILITY OF OPEN LUNG BIOPSY IN CRITICALLY ILL PA-TIENTSKalpaj R. Parekh MD* Timothy L. Van Natta MD Joan Ricks-McGillinRN Kelley McLaughlin RN Mark D. Iannettoni MD University of IowaHospitals and Clinics, Iowa City, IA

PURPOSE: The role of open lung biopsy in critically ill adult patientsremains controversial. The aim of this study was to determine thediagnostic ability, mortality and therapeutic impact of open lung biopsycritical versus non-critically ill patients.

METHODS: We conducted a retrospective review of all open lungbiopsies performed at our institution for diagnostic indications in the last5 years.

RESULTS: From January 2000-December 2004, 68 patients wereidentified who underwent open lung biopsy. Of these, 18 were critically ill(defined as requiring mechanical ventilation patients or requiring FiO2�1.0 by face mask). Fifty patients were non-critically ill (defined asin-patient/out-patient referrals with FiO2 requirements �1.0). Therapeu-tic change, defined as addition of a new agent was made in 9/18 (50%) forcritically ill patients, and in 25/50 (50%) non-critical patients. Theoperative mortality was 8/18 (44%) for the critical patients while it was0/50 (0%) in the non-critical patients. Of the critical patients for whom atherapeutic change was initiated, 6/9 (67%) survived and were discharged.

CONCLUSION: Our results indicate that open lung biopsy in criticallyill patients remains a high risk procedure with a high operative mortality.It does however have a diagnostic yield similar to that in non-critically illpatients.

CLINICAL IMPLICATIONS: Open lung biopsies continue to be achallenging problem in this difficult subset of patients. However, despitethe significant inherent risks it may still be considered to direct atherapeutic change when other non-invasive modalities have been ex-hausted.

DISCLOSURE: Kalpaj Parekh, None.

VIDEO-ASSISTED THORACOSCOPIC LUNG BIOPSY FOR THEDIAGNOSIS OF DIFFUSE INTERSTITIAL LUNG DISEASENoriyasu Usami MD* Kohei Yokoi MD Division of General ThoracicSurgery, Nagoya University School of Medicine, Nagoya, Japan

PURPOSE: Video-assisted thoracoscopic lung biopsy (VTLB) is gettinga position of the diagnostic methods for diffuse interstitial lung disease(DILD). In this study, we review our experience with this technique interms of postoperative complications and diagnostic accuracy.

METHODS: From January 1995 to December 2004, 50 consecutivepatients were intended to undergo surgical lung biopsy for the diagnosisof DILD. Actually 46 patients (88%) underwent VTLB and 4 (12%) wereneeded to conversion to open lung biopsy (OLB) due to the adhesion orpulmonary injury. We retrospectively analyzed those patients.

RESULTS: The patients consisted of 25 men and 25 women with meanage of 58.2 years (20-77 years). The preoperative respiratory functionswere %VC: 76.6 � 21.2% (38.5-131%), %FEV1.0: 83.8 � 22.6% (37.8-139.3%), %DLco: 65.2 � 19.3% (30.6-101.7%), and the blood gasanalyses were PaCO2: 41.4 � 3.8 torr (33.3-52.1 torr) and PaO2: 74.9 �9.3 torr (53.0-97.4 torr). Mean operative time was 55 minutes for VTLBand 83 minutes for OLB. The overall mean duration of chest tube


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drainage was 1.3 days. There was no operative mortality. Postoperativecomplications were seen in 4 cases (8%). Two patients had pneumothorax,and the other two experienced the exacerbation of DILD, which weresuccessfully treated with steroid pulse therapy. Although only one biopsywas considered inconclusive (2%), the remaining 49 patients established afinal diagnosis. Histological diagnosis revealed non-specific interstitialpneumonia in 26 patients, usual interstitial pneumonia in 11, and othertype of idiopathic interstitial pneumonias in the remainder.

CONCLUSION: VTLB for the diagnosis of DILD is a safe methodeven in patients with impaired pulmonary function, although somepatients needed to conversion to OLB due to the pleural adhesion or lunginjury. This study also supports the notion that patients with idiopathicinterstitial pneumonias may be at risk of exacerbation of their underlyingdisease following VTLB.

CLINICAL IMPLICATIONS: VTLB will contribute to the safe andeffective pathologic diagnosis of DILD in most cases, even if thepulmonary function is considerably impaired.

DISCLOSURE: Noriyasu Usami, None.

DOES VARIATION ON SURGICAL TECHNIQUES ALTER OUT-COME OF LUNG BIOPSY FOR INTERSTITIAL LUNG DIS-EASE?Bhanumathi Lakshminarayanan MD* Antonio E. Martin-Ucar MD Mi-chael F. Maguire MD Lynda Beggs David Beggs MD John P. Duffy MDEllis Morgan MD Thoracic Surgery, Nottingham City Hospital, Notting-ham, United Kingdom

PURPOSE: The reported accuracy of surgical biopsy for interstitiallung disease (ILD) is highly variable. We have audited our results todetermine whether operative techniques do alter outcomes.

METHODS: 123 patients [68 men and 55 women with a median ageof 57 (range from 18 to 84) years] underwent lung biopsy for diffuseinterstitial lung disease in our unit from 1992 to 2004. Video assistedthoracoscopy (VATS) was used on 66 cases (54%) and the rest underwenttraditional open biopsy. Outcomes of the study were: rate of definitivespecific diagnosis, change of diagnosis and change of therapy, complica-tions, and to assess the weight of surgical variables (surgical procedure,side, number and size of samples) as predictors of outcomes.

RESULTS: There was one postoperative death (0.8%) and 13 patients(10%) had any complication. A definitive specific diagnosis was obtainedin 91 cases (74%). A different diagnosis from presumed pre-operative onewas encountered on 59 (48%) cases, and a definite change of therapy wasconfirmed on 27 (22%) of cases. The type of procedure (either VATS oropen), or number and size of specimens did not significantly affect thechance of a definitive diagnosis, complications, change of diagnosis, orchange in therapy. (Table 1, p� non significant in all cases).

CONCLUSION: Lung biopsy can be done safely with high rates ofspecific diagnosis and low incidence of complications. We have not proventhat surgical variables alter the outcomes in terms of definitive or changeof diagnosis, complications or change of therapy.

CLINICAL IMPLICATIONS: Different approaches and techniquesdo not contribute to increase usefulness of surgical biopsy for ILD.

DISCLOSURE: Bhanumathi Lakshminarayanan, None.

THREE DIMENSIONAL IMAGE GUIDING SYSTEM FOR THETHORACOSCOPIC SURGERYToshihiko Sato MD* Seiki Hasegawa PhD Teruhisa Takuwa MD Yoshi-tomo Okumura MD Hyogo College of Medecine, Nishinomiya, Japan

PURPOSE: Development of 3D-image guiding system for the thora-coscopic surgery.

METHODS: Pneumothorax with radiologically-detectable bulla wasselected as objective disease for this study. This is partly because thetarget lesions are located on the surface of the lungs, and partly becauseimages of the virtual thoracoscopy derived from half-collapsed lungs mostmimic the real thoracoscopic images.MPR images and virtual thoraco-scopic images were reconstructed by 3-Dworkstation. The workstationmonitor was set next to the thoracoscopic monitor to facilitate thecomparison of these two images. Real-time virtual thoracoscopy guidingwas performed by an assistant surgeon who reconstructs, moves, androtates the 3D images of the lung synchronizedly with the real thoraco-scopic images. Marks were given to each bulla in the virtual images so asthe surgeons easily detect on the real thoracoscopy.

RESULTS: Virtual images gave good simulation to the real thoraco-scopic images. Even small bulla was detected under assistance of markingon the virtual image.

CONCLUSION: We report real-time 3D-image guiding system for thethoracoscopic surgery. This system gives reliable detection of bulla andreduction of operation time. Furthermore, operator could reduce the riskof misidentification of anatomical structure through comparison of realand virtual images.

CLINICAL IMPLICATIONS: Endoscopic surgery is accompaniedwith limited view and lack of perspective. On site real-time computer-guided endoscopic surgery system may be the key to this problem, butintroduction of such technology to thoracic surgery has been outstrippedin comparison with craniomaxillofacial surgery, cerebral nerve surgery,and orthopedic surgery.

DISCLOSURE: Toshihiko Sato, None.

Specificdiagnosis

Change ofdiagnosis

Change oftherapy

Technique VATS (n�66) 50 (76%) 28 (42%) 14 (21%)Open (n�57) 41 (72%) 31 (54%) 13 (23%)

Side Right (n� 64) 47 (73%) 33 (51%) 13 (20%)Left (n� 59) 44 (75%) 26 (44%) 14 (24%)

Number 1 sample (n�105) 76 (72%) 51 (49%) 22 (21%)1 sample (n�18) 15 (83%) 8 (44%) 5 (28%)

Size �4cm (n� 69) 50 (72%) 30 (43%) 12 (17%)�4cm (n�54) 39 (72%) 27 (50%) 15 (28%)


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FUNCTIONAL ASSESSMENT OF A NEW STAPLE LINE REIN-FORCEMENT IN LUNG RESECTIONDouglas M. Downey MD* Michael Michel MD Joseph G. Harre DVMJerry W. Pratt MD Keesler Medical Center, Biloxi, MS

PURPOSE: Staple line reinforcement is routinely performed duringnonanatomic lung resection utilizing bovine pericardium (peri-strips) andexpanded polytetrafluorethylene (ePTFE). Both materials have beenpreviously shown to increase staple line durability and reduce the overallincidence of prolonged air leak, however neither material has been shownto be truly absorbable in in vivo studies. Porcine small intestinal submu-cosa (SIS) has had many applications as a bioabsorbable tissue reinforce-ment, but has not previously been studied in either a human or animalmodel as a reinforcement for nonanatomic pulmonary resection. Itshealing properties are well documented in human and animal studies. Ourstudy strictly assessed immediate staple line strength in healthy pig lungtissue at different intrabronchial pressures to demonstrate SIS as aneffective pulmonary staple line reinforcement.

METHODS: Eight pigs were subjected to bilateral apical lung resec-tions with a GIA stapling device; one side was reinforced with SIS, whilethe other was not reinforced. The lung reinforced was chosen at randomso that each animal may serve as its own control. The lungs were theninflated to sequentially increased intrabronchial pressures (5 – 75 cmH2O) for 60-second intervals while the chest was filled with saline underdirect visualization monitoring for air leak.

RESULTS: Staple lines reinforced with porcine small intestinal sub-mucosa had significantly better durability as determined by Kaplan-Meiersurvival calculations with respect to leak rate as a function of pressure.

CONCLUSION: Reinforcement of staple lines with small intestinalsubmucosa (SIS) allows pulmonary staple lines to tolerate significantlyhigher intrabronchial pressures without demonstrating air leak at thestaple line.

CLINICAL IMPLICATIONS: Staple line reinforcement with SIS iseffective in terms of improving the leak threshold of the GIA staple lines.Potentially, SIS may prove to be a more suitable material for pulmonarystaple line reinforcement in individuals requiring nonanatomic lungresection, due to its healing properties. Long-term in vivo studies areunderway to characterize the SIS tissue reaction in the chest, its tendencytoward generation of pleural adhesions, resorption and tissue encapsula-tion.

DISCLOSURE: Douglas Downey, Product/procedure/technique thatis considered research and is NOT yet approved for any purpose. Cook,Inc. for providing the (10) staple line reinforcements (at the time of theproject not yet available for human use)for our project at no cost to ourinstitution. Each valued at $150.

MINIMALLY INVASIVE CLOSURE TECHNIQUES FOR RECAL-CITRANT BRONCHOPLEURAL FISTULASLindsey Clemson BS* James Lynch RRT Eric Walser MD JosephZwischenberger MD Thomas Black MD University of Texas MedicalBranch, Galveston, TX

PURPOSE: The treatment most often recommended for persistentsymptomatic central bronchopleural fistulas (BPF) involves thoracotomywith suture closure and transposition of a vascularized muscle flap oromentum to the bronchial leak site unfortunately, this can be ineffectiveor medically contraindicated. We used minimally invasive closure tech-niques including bioadhesives (glues), stainless steel coils and prolenemesh in combination with different imaging techniques to treat recalci-trant central BPF to achieve successful closure in 3 of 5 patients.

METHODS: We initially (n�2) utilized cyanoacrylate glue injectedtransthoracically under fluoroscopic guidance into the BPF lumen form-ing a plug. Next, two patients failed muscle flap transposition and CTguided transthoracic injection of a single coil plus Albumin/Glutaralde-hyde glue into the fistula. We then used a transtracheal guidewirepositioned under fluoroscopy to identify the fistula and thoracoscopicplacement of a prolene mesh patch over the defect secured by fibrinsealant to prevent glue dislodgement. Most recently, stainless steel coilsand cyanoacrylate glue were transthoracically injected into and adjacent toa postpneumonectomy bronchial stump under thoracoscopic visualization.

RESULTS: Glue injection under fluoroscopic guidance was successfulonce while in another, the glue plug was dislodged by coughing. Placinga prolene mesh patch over the BPF secured with fibrin sealant wassuccessful in 1/2 patients. Our most recent effort was to traverse the fistula

with coils and inject glue transthoracically. The coils served as a scaffoldto stabilize the glue within the tissue and successfully occluded the BPF.

CONCLUSION: Utilizing these minimally invasive alternative closuretechniques, we present the evolution of successful management ofrecalcitrant central BPFs in 3 of 5 patients. Due to a high intrathoracic tobronchial pressure gradient, one must stabilize the fistula plug. The use ofprolene mesh to cover the stump or the injection of coils perpendicularlyto the fistula provides a site for inflammation and fibrosis to occlude thefistula.

CLINICAL IMPLICATIONS: These image-guided transthoracictechniques provide alternative management for recalcitrant central BPFsin medically compromised patients.

DISCLOSURE: Lindsey Clemson, None.

THE CHEST WINDOW IN THE TREATMENT OF COMPLEXINTRA-THORACIC INFECTIONSRobin Varghese MD* Richard I. Inculet MD Dalilah Fortin MD RichardA. Malthaner MD London Health Sciences Center, London, ON, Canada

PURPOSE: Patients with an primary empyema,lung abcess,or post-pneumonectomy empyema, who are critically ill , may only toleratesurgical drainage of the infection. A study was undertaken to examine theoutcome of patients who had a complex intra-thoracic infection managedby rib resection and the creation of an open chest window.

METHODS: A retrospective review was undertaken of all patientspresenting to a single institution with a complex intra-thoracic infectionand who were treated with a rib resection and creation of a chest window.

RESULTS: Between 1998 and 2005, a total of 35 patients (8 females,27 males, average age 59 years) were treated in this fashion. There wasinsufficient data available for 3 patients. Twelve patients (34%) presentedwith a primary intra-thoracic infection (PII). Twenty patients (57%),developed an intra-thoracic infection secondary to an obstructing lungcancer or following a recent thoracotomy and pulmonary resection(SII).Average post-operative length of stay was 13 days (median 7.5 days).There were 5 postoperative deaths (14.3%); 4(SII)patients(2 died fromsepsis,1 from hemorrhage,1 from other cause) and 1 (PII) patient diedfrom sepsis. Eight (SII) patients (23%) died after discharge from hospitalfrom non- septic causes. Primary closure of the window was successfullyperformed in 2 (SII) patients (average time to closure-15.5 months) and 5(PII) patients (13.2 months). Closure of the window by secondary healingoccurred in 5 (SII) and 3 (PII) patients. Windows presently remain openor were open until death in 9 (SII) patients and 3 (PII) patients.

CONCLUSION: The open chest window technique successfully man-aged the intra-thoracic infection in 84% of the patients. It is associatedwith acceptable post operative mortality and length of hospital stay.Closure of the window, either by surgery or by secondary healing, can beaccomplished in large percentage of patients.

CLINICAL IMPLICATIONS: The use of the open chest window tomanage the desparately ill patient, with a complex intra-thoracic infection,remains an effective treatment strategy.

DISCLOSURE: Robin Varghese, None.

ENDOSCOPIC AND THORACOSCOPIC TRAINING ON THIELHUMAN CADAVERS: A MODEL TO TEACH ADVANCED PRO-CEDURESPhilippe Morand MD* Isabelle Fresard MD Christian Chanson MDGunter Rager MD Lukas Krahenbuhl MD Hopital Cantonal Fribourg,Fribourg, Switzerland

PURPOSE: The endoscopic procedures became more and morecomplex over the past years. These procedures require a special trainingwhich can be effectively and safely performed outside the operatingtheatre. Several training programs have been developed for teaching basicsurgical skills to young residents but very few methods are available foradvanced endoscopy and surgery. The Thiel method has several advan-tages over other training systems. Training on cadavers, compared toanimal models offers an anatomy identical to that found in patientswithout needing anesthesia. Moreover, a same cadaver can be used forseveral different procedures belongings to surgery and pneumology.

METHODS: The conservation of human cadavers is realized by theThiel method (Ann Anat 1992, 174: 185-195). The technique allows afloppy preservation of human tissue similar to that found in livingcounterparts. Our center organizes courses for endoscopy, thoracicsurgery, bariatric, antireflux, abdominal wall, colon and rectum surgery.




Five video monitors with camera system are available with the possibilityof computerized image recording.

RESULTS: Different courses were performed and evaluated by theparticipants (6 was the best and one the lowest voting). Course evaluationwas performed on an anonymous questionnaire for the course organisa-tion, theoretical and practical aspects and the tutors. The results were forthoracic surgery 5.73 � 0.05, endoscopy 5.82 �0.07.

CONCLUSION: Training on cadaver specimens gives the opportunityto perform major operations in endoscopy and thoracic surgery respectingthe human ethics. Difficult endoscopical and surgical procedures can beteached step by step under real anatomic situations in small groups.Therefore, it is probably the best method for advanced surgeons toimprove their performance. A good preservation of the tissue depends ona special know-how necessitating a tight collaboration with an anatomicaldepartment. From this point of view this method is reserved to a smallquantity of recognized national or international centers.

CLINICAL IMPLICATIONS: Reduced learning curve of complexsurgical procedures and higher quality control.

DISCLOSURE: Philippe Morand, None.

EARLY AND LONG-TERM RESULTS OF LUNG VOLUME RE-DUCTION IN PATIENTS WITH EMPHYSEMAKoji Chihara MD* Daisuke Nakajima MD Akihiko Yamashina MDMasanao Nakai MD Hisashi Sahara MD Toru Tsuda MD Tomoya KonoMD Akihiro Osumi MD Akihiro Aoyama MD Fenshi Chen MD NoritakaIsowa MD Shotaro Iwakiri MD Shizuoka City Shizuoka Hospital, Shi-zuoka, Japan

PURPOSE: We hypothesized that dyspnea in patients with emphy-sema was related with hyperinflation by highly destructed part withexcessive trapped air and poor perfusion which could be expressed as“air-oma”. Accordingly we selected patients for LVRS with functionalimaging modalities (HRCT, perfusion scan, dynamic MRI etc.)as well asfunctional examinations. We report early and long-term results of LVRSfor consecutive 31 patients.

METHODS: Between October 1995 and June 2003 we selected 31patients who felt severe dyspnea during walk. Their characteristics andmean values in function testing were as follows; a mean age of 68 yr (range52 - 80), BMI of 18 Kg/m2 (15-23), %FEV1 of 27% (11- 46), %RV of 263% (178-385), and 6 MWD of 287m (75 – 450). We decided airoma in theupper lobes of 12 patients, in the lower lobes of 12 patients, in both lobesof 6 patients, and in the middle lobe of 1 patient, and resected these bybilateral procedure in 17 patients, and by unilateral procedure in others.All patients were followed ranging from 1.8 to 9.5 years (median 6.5 yrs).

RESULTS: There was no in-hospital mortality. Two patients under-went reexploration for air leak, and two patients needed mechanicalventilation for a few months one month after LVRS. All patients exceptone reported decrease in dyspnea, and were satisfied with surgery. Elevenpatients out of 22 patients who underwent LVRS by Dec 1999 survivedmore than 5 years. The Kaplan-Meier survival after LVRS were 96.8%,93.6%, 90.1%, 72.1%, 49.3% at 1,2,3,4,and 5 years, respectively. Therewere no difference between survival of patients with upper lobe airomaand those with lower lobe airoma.

CONCLUSION: Lung volume reduction surgery for patient withemphysema selected by functional imaging modalities produces symptom-atic improvement in early-term, and better survival at least 3 years.

CLINICAL IMPLICATIONS: Lung volume reduction surgery is agood and promising palliative treatment for patients with advancedemphysema wherever the target area , or airoma, is located.

DISCLOSURE: Koji Chihara, None.

EMERGENCY LUNG RESECTIONS FOR LIFE-THREATENINGMASSIVE HEMOPTYSISAlexandru M. Botianu MD* Petre A. Botianu RN University of Medicineand Pharmacy From Targu-Mures, Romania, Targu-Mures, Romania

PURPOSE: This study analyses the outcome of patients with massivehemoptysis without response to conservative treatment and requiringemergency thoracotomy for hemostasis.

METHODS: Between 1990 and 2005 we performed emergencythoracotomy with lung resection in 4 patients with life-threateninghemoptysis with no response to conservative treatment. Etiology wastuberculosis in all patients, one being with an anaerobic overinfection andone with atypical mycobacteria. The procedures performed were: lobec-

tomy - 2 cases (one with simultaneous artery-bronchus stapling in apatient with 2 intraoperative cardiac arrests), pneumonectomy - 1 caseand one non-anatomic resection with lateral suture of a pulmonary arterybranch.

RESULTS: In all cases we achieved good hemostasis with no postop-erative bleeding. We encountered a high rate of peri-operative complica-tions: one patient with 2 intraoperative cardiac arrests, 3 patients withpostoperatve pneumonia and one postoperative death in a patient withpneumonectomy performed after 2 cardiac arrests resuscitated in anotherunit. Only one patient had an uneventful postoperative course.

CONCLUSION: Emergency thoracotomy and resection for massivehemoptysis has a high morbidity and mortality, especially when othercomplications occur (such as tracheo-bronchial innundation, acute anemiaor cardio-respiratory arrest). It should be reserved as a life-savingprocedure when other conservative treatments are ineffective or unavail-able.

CLINICAL IMPLICATIONS: Treatment of massive hemoptysisshould be early and aggressive. If conservative treatment (hemostaticdrugs, bronchoscopic hemostasis, embolisation) fail, the thoracic surgeonshould be called immediately. Surgery gives good results if resection isperformed in patients with stable hemodinamic and respiratory status,before development of other severe complications.

DISCLOSURE: Alexandru Botianu, None.

General Thoracic Surgery Interventions12:30 PM - 2:00 PM

USE OF RECOMBINANT FACTOR VII ACTIVATED IN SUR-GERY FOR PLEURAL EMPYEMAPetre V. Botianu RN* Alexandru A. Botianu MD University of Medicineand Pharmacy from Targu-Mures, Romania, Targu Mures, Romania

PURPOSE: The aim of our study is to evaluate the advantages of usingrecombinant factor VII activated to improve hemostasis during surgery forempyema and to establish the optimal dose and moment of administra-tion.

METHODS: During 36 months (march 2002 - march 2005) we usedrecombinant factor VII activated in 34 patients who underwent majorsurgery for empyema: 26 patients with pleuro-pulmonary decortication (4for overinfected posttraumatic hemothorax, 16 non-specific empyemasand 6 tuberculous empyemas) and 8 thoracopleuroplasties. A number of10 decortications were performed in cirrhotic patients. Intraoperativefindings and clinical criteria were used to evaluate the quality of hemo-stasis.

RESULTS: In all cases we achieved good hemostasis. We had nore-operation for hemostasis. There was a significant reduction of peri-operative blood losses and of transfused blood. Most patients requiredonly small doses (1,2 - 2,4 mg/60 - 120 IU) administered at the beginningof the procedure. We encountered no side effects and only one postop-erative death through sepsis in a patient with pulmonary gangrene.

CONCLUSION: Recombinant factor VII activated appears as anexcellent hemostatic agent for diffuse bleeding during surgery for pleuralempyema; it also improves closure of small aerian leaks and facilitatesre-expansion of the lung.

CLINICAL IMPLICATIONS: Use of recombinant factor VII acti-vated may improve the outcome of patients undergoing major surgery forpleural empyema. For a complete and correct evaluation, further pro-spective randomised studies are required.

DISCLOSURE: Petre Botianu, None.

TISSUE SEALANTS: THE ROLE OF ALBUMIN/GLUTARALDE-HYDE IN THORACIC SURGERYThomas Black BS* James E. Lynch RRT Joseph Zwischenberger MDUniversity of Texas Medical Branch–Galveston, Galveston, TX

PURPOSE: Sealants have been developed to achieve hemostasis ortissue adhesion during surgery. We examined the use of an Albumin/Glutaraldehyde sealant in 16 thoracic surgery patients as an adjunct tocontrolling air leaks on the lung parenchyma following resection. Air leak




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following pulmonary resection has been associated with an increase inmorbidity as well as increased length of stay.

METHODS: Since April of 2002 we have used an Albumin/Glutaral-dehyde sealant selectively at this institution for the intraoperative treat-ment of recalcitrant air leaks following pulmonary resections. All patientshad pulmonary resection with persistent air leaks intraoperatively at theparenchymal staple line or at the fissure dissection site at 20 cmH2Opressure lung inflation. After obtaining local IRB approval, we retrospec-tively compared 16 patients in which an Albumin/Glutaraldehyde sealantwas used with a “plug and cap” technique to seal air leaks on the surfaceof the lung to 16 case matched controls in which no air leaks were notedintraoperatively. We examined these patient’s records for differences inlength of operation, ICU time, number of days with chest tube, numberof days with air leak, chest tube output, and total hospital length of stay.

RESULTS: We found no difference in length of operation, ICU time,days with chest tube, days with air leak, chest tube output, or length ofstay. Patients treated with an Albumin/Glutaraldehyde sealant exhibitedno adverse reactions or need for reoperation for closure of persistent airleak.

CONCLUSION: Despite attempts to match with historical controls,we had a selection bias towards more severe airleaks in the sealant group.In this unblinded, retrospective, matched controlled outcomes studyAlbumin/Glutaraldehyde sealant normalized patients with recalcitrantintraoperative parenchymal airleaks following resection to those withoutintraoperative airleaks.

CLINICAL IMPLICATIONS: Albumin/Glutaraldehyde sealants rep-resent a valuble tool in the management of intraoperative closure ofrecalcitrant airleaks following resection.

DISCLOSURE: Thomas Black, Grant monies (from industry relatedsources) This study was funded in part by Cryolife the manufacturer ofBioGlue® an Albumin/Glutaraldehyde sealant.

PROOF-OF-PRINCIPLE CLINICAL TRIAL OF BEXAROTENEFOR THE TREATMENT OF NON-SMALL CELL LUNG CANCERW J. Petty MD* Konstantin H. Dragnev MD Vincent A. Memoli MDJames R. Rigas MD David Johnstone MD Ethan Dmitrovsky MDDartmouth Medical School, Hanover, NH

PURPOSE: Certain non-classical retinoids including the rexinoidcompound, bexarotene, bypass clinical resistance to classical retinoids.Bexarotene-treatment is associated with an improvement in survival in asubset of patients. We sought to determine mechanisms of reponse orresistance to bexarotene.

METHODS: Bexarotene-treatment was studied using a derived, RA-resistant human bronchial epithelial cell line and several non-small celllung cancer cell lines. We then performed a proof-of-principle clinicaltrial in patients with resectable NSCLC. Patients underwent a pre-treatment biopsy followed by eight days of oral bexarotene and surgicalresection. Pharmacokinetics and biomarker changes were assessed.

RESULTS: Bexarotene-treatment repressed expression of cyclin D1,cyclin D3, EGFR, and phospho-EGFR in vitro. In the proof-of-principleclinical trial, ten patients were evaluable for pharmacokinetic and lipidmeasurements and four patients were evaluable for changes in biomark-ers. A strong correlation existed between hyperlipidemia and tumor tissuedrug levels. The cases with the highest tissue concentrations of the drugdemonstrated repression of cyclin D1, cyclin D3, or EGFR while caseswith lower tissue concentrations did not.

CONCLUSION: Bexarotene treatment represses cyclin D1 and cyclinD3 both in vitro and in clinical lung cancers. A tumor tissue pharmaco-kinetic and pharmacodynamic relationship exists for this drug.

CLINICAL IMPLICATIONS: A correlation between tumor tissuebexarotene concentrations and bexarotene-induced hyperlipidemia mayhelp to explain why this drug would prolong survival in patients whodevelop hyperlipidemia.

DISCLOSURE: W. Petty, None.

ADJUVANT CHEMOTHERAPY AFTER SURGICAL RESECTIONFOR SMALL-CELL CARCINOMA OF LUNGEuntaik Jeong MD* Hakryul Kim MD Wonkwang Univ. Hospital, IksanJeonbuk, South Korea

PURPOSE: Small-cell carcinoma of lung has a tendency of rapidgrowth and early wide metastasis. In spite of high response rate ofcombination chemotherapy alone or with radiotherapy, overall long term

survival rate is very disappointed. According to autopsy findings, thecommon cause of failure is local recurrence in primary cancer site. So,surgical resection with combined chemotherapy has been recently at-tempted for very early stage of small-cell carcinoma of lung.

METHODS: We treated 10 patients (TNM I: 5 cases, II: 5 cases)undergoing surgical resection for small-cell carcinoma of lung withadjuvant chemotherapy in an attempt to prolong survival. Of these, 9patients received chemotherapy, and retrospective study was undertakenfor survival (Kaplan-Meier analysis).

RESULTS: Median survival time was 26 months, 2-, 5-year survivalrate was 68.6%, 46.7%. If 1 patient without chemotherapy was excluded,2-, 5-year survival rate was 76.2%, 50.8%. No survival difference was seenbetween patients with TNM I, II stages.

CONCLUSION: Adjuvant chemotherapy after surgical resection re-sults in prolonged survival for patients with TNM stage I, II small-cellcarcinoma of lung.

CLINICAL IMPLICATIONS: We can apply this adjuvant chemo-therapy after surgical resection for the improvemnet of survival of patientswith early stage small-cell carcinoma of lung.

DISCLOSURE: Euntaik Jeong, None.

RADIOTHERAPY FOR NON-SMALL CELL LUNG CANCER INPATIENTS WITH COMPROMISED HEARTSFederico L. Ampil MD* Shawn Milligan MD Glenn M. Mills MD GloriaCaldito PhD Louisiana State University Health Sciences Center, Shreve-port, LA

PURPOSE: Objective: Therapeutic options for patients with non-smallcell lung cancer (NSCLC) and compromised hearts are limited. Suchindividuals are not often included in randomized trials. Therefore, optimaltherapy in this particular group of people is unclear. We present ourexperience using radiotherapy for NSCLC in eight patients with cardiaccompromise because few reports of patient outcomes exist.

METHODS: Methods: Between 1993 and 2003, eight individuals withcompromised hearts (necessitating pacemaker assistance, coronary arterybypass surgery, or cardiac valve replacement) were treated by radiationalone (7 patients) or with chemotherapy (1 patient) for lung cancer. Themean follow-up period was 12.5 months.

RESULTS: Results: At diagnosis, the average patient age was 62 years.In most patients, tumor histology was non-small cell cancer, the diseasestage was advanced (stage III, 5 patients or IV, 3 patients), and a longhistory of smoking was documented. The survival rates at 6 months, 1year, and 2 years were 50%, 25%, and 25% respectively. The mediansurvival was longer in patients with stage III compared to that of personswith stage IV disease (11 months and 3 months respectively, p�0.04).There were no adverse cardiac events during and after irradiation.

CONCLUSION: Conclusion: The presence of cardiac compromise inlung cancer patients should not be viewed as a general contraindication forradiotherapy. Management of these neoplasms by radiation deservesconsideration because this treatment could favorably influence survival inselect patients with advanced, non-disseminated malignancy.

CLINICAL IMPLICATIONS: Although most patients with advancedlung cancer and coexisting, significant cardiac disorders may not live longenough to develop delayed cardiovascular sequelae, radiotherapy shouldbe administered with great caution to these individuals.

DISCLOSURE: Federico Ampil, None.

PROGNOSTIC FACTORS AND SURVIVAL IN PRE- AND PER-OPERATIVE DETECTED AND RESECTED N2 NON-SMALLCELL LUNG CANCEREdwin Van Velzen MD* Meander Medical Centre, Amersfoort, Nether-lands

PURPOSE: Patients with stadium III (pN2) non-small cell lung cancerform a heterogeneous group with broad differences in survival. Someselected patients seem to benefit from surgery, but in most patients othertherapies are preffered. The present study was performed to select groupsof patients who will and will not benefit from surgery.

METHODS: A total of 242 patients with stadium III (pN2) who allunderwent mediastinoscopy and tumor resection between 1977 and 1995were retrospectively reviewed. Mean age was 64.2 years. Mediastinoscopyshowed malignancy in 56 patients (23.1%). Resection was complete in 198patients. Most patients (n�150) had one mediastinal lymph node stationinvolved and T2 was the most frequently found T-status. Hundred and


General Thoracic Surgery Interventions,continued


sixty-six patients received adjuvant therapy, mainly radiotherapy.Statisticalanalyses were performed, using the Kaplan-Meier method, the log ranktest and Cox’s proportional hazards model.

RESULTS: The cumulative post-operative survival at 5 years was20.3%. The number of mediastinal stations involved (� 2; p�0.03)(Fig.1.)and age (� 60 years; p�0.035) significantly influenced survival whereasT-status (T1/T2 versus T3/T4; p�0.056) approached significance. Nodifferences in survival between patients with a positive versus negativemediastinoscopy, or between patients with a complete versus incompleteresection were found. However, all patients with a positive mediastinos-copy and incomplete resection died within 3 years. Multivariate analysisshowed the number of mediastinal lymph node stations involved (RR of0.33, 95% CI of 0.163 to 0.663; p�0.002) and age (RR of 1.013, 95% CIof 1.0 to 1.027; p�0.048) to be prognostic for survival.

CONCLUSION: Stadium III (pN2) patients with � 2 mediastinalstations involved (even detected at mediastinoscopy) and those aged � 60years can benefit from surgery. Patients with ’bulky’or fixed multistationdisease and those with a T3 or T4 tumor should not be operated upon.

CLINICAL IMPLICATIONS: Accurate staging of pN2 patients mayprevent them from an advanced (incomplete) resection with high mor-bidity and even mortality, but on the other hand, can sort out the patientswho will benefit from surgery.

DISCLOSURE: Edwin Van Velzen, None.

PHARMACOKINETIC ANALYSIS OF ISOLATED LUNG PERFU-SION WITH MELPHALAN IN PATIENTS WITH RESECTABLEPULMONARY METASTASESMarco J. Grootenboers MD* Jeroen M. Hendriks PhD Wim J. van BovenMD Catherijne A. Knibbe PharmD Paul E. Van Schil PhD Franz M.Schramel PhD St. Antonius Hospital, Nieuwegein, Utrecht, Netherlands

PURPOSE: Prognosis of patients with pulmonary metastases remainspoor with a 5-year survival of approximately 20-40% after completesurigical resection. Isolated lung perfusion (ILuP) is a promising surgicaltechnique to deliver high-dose chemotherapy with minimal systemictoxicity, however exact pharmacokinetics of melphalan (MN) during ILuPremain unclear. An extension trial of a previous reported phase-I clinicaltrial of IluP with MN combined with pulmonary metastasectomy forresectable lung metastases was conducted to perform pharmacokineticanalysis.

METHODS: From May 2001 to December 2004, 23 patients under-went ILuP with MN in increasing doses of 15, 30, 45 and 60 mgmelphalan at 37°C and 42°C consecutively, followed by surgical resectionof lung metastases. The pharmacokinetics of MN during ILuP wereinvestigated using concentrations in tumour, lung tissue, perfusate andplasma with different perfusate drug concentrations and perfusion tem-peratures.

RESULTS: In total, 29 procedures of ILuP with complete metastasec-tomy were performed. High concentrations of MN were recorded in theperfusate in comparison to low systemic concentrations. Although therewas a trend to correlation between the averaged MN concentrations in theperfusate after initiation of the procedure and the dose of MN at the startof the procedure, no significant correlation between perfusate and lungtissue or tumour MN concentrations could be recorded due to largevariability in MN concentrations and the small number of patients perdose level.

CONCLUSION: ILuP with melphalan resulted in high-dose localchemotherapy with minimal systemic concentrations. In this study, nosignificant correlation between perfusate MN concentrations and tumouror lung tissue MN concentrations could be observed.

CLINICAL IMPLICATIONS: The absence of correlation betweenthe perfusate and tumour or lung tisssue concentrations justifies furtherinvestigation of the pharmacokinetics of drugs during IluP in order to beable to account for observed variability.

DISCLOSURE: Marco Grootenboers, None.

SLEEVE-PNEUMONECTOMY FOR LUNG CANCER: FORWHICH PATIENTS?Dragan R. Subotic PhD* Dragan V. Mandarich PhD Nikola D. Atanasia-dis MD Ljiljana V. Andrich MD Institute for Lung Diseases, Belgrade,Serbia

PURPOSE: To analyse operative mortality, morbidity and factorsinfluencing long term survival in patients who underwent sleeve pneumo-nectomy for primary NSCLC.

METHODS: Retrospective study including 42 patients who underwentsleeve pneumonectomy for primary NSCLC in the period 1995-2004.Survival, operative mortality and morbidity were analysed and comparedwith control group of extended resections in the same period. Particularanalysis of the influence of the N-factor to survival was done. Statistics:X-square test, survival analysis using the Kaplan-meier method.

RESULTS: In the analysed group, 39 pts. underwent right and 3one-stage left sleeve pneumonectomy (M:F ratio 6:1). Compared to theperiod 1995-2002 with 36 pts, after inclusion of additional 6 pts. till 2004,operative mortality decreased from 19.44% to 16.66%. Operative morbid-ity was 26.19%. Before inclusion of the last 6 pts, 3 and 5-year survival was27.7% and 11.1% respectively. Two of the new 6 pts. are still alive twoyears after the operation, whilst two of them died 7 and 7.5 months afterthe operation from cancer dissemination. Additional two survived morethan one year and are still alive. There were no long term survivors withN2 disease.

CONCLUSION: Sleeve pneumonectomy can be done with acceptablemortality that should be well below 15%. Nevertheless, we support theattitude that such an operation is justified only if associated with 5-yearsurvival of at least 20%.

CLINICAL IMPLICATIONS: detailed preoperative assessment inorder to assess N-component is mandatory to achieve optimal patientselection for this type of lung resection.

DISCLOSURE: Dragan Subotic, None.

PREDICTIVE VALUE OF POSITIVE CYTOLOGY IN VIDEO-ASSISTED THORACIC SURGERY (VATS) PERICARDIAL WIN-DOWSiyamek Neragi-Miandoab MD* Luis M. Argote-Greene MD William G.Richards PhD Lambros Zellos MD Raphael Bueno MD David J. Sugar-baker MD Michael T. Jaklitsch MD Boston Medical Center, BostonUniversity School of Medicine, Boston, MA

PURPOSE: Pericardial effusions represent a terminal stage in patientswith malignant disease. A VATS pericardial window (PW) can palliatesymptoms. Longevity of the procedure may depend on pericardial fluidcytology.

METHODS: Retrospective review of 66 VATS PW for malignantpericardial effusion (MPE); males/female ratio 36/30, mean age 54.8 �




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14.3 (ranging from 19 to 79). Kaplan-Meyer survival curve and Log-RankList were used to analyze the data.

RESULTS: Mean hospital stay was 8.7 � 5.5 days. Overall mediansurvival was 5.4 months: 43% at 1 yr, 17.6% at 3 yrs, 10% 5 yrs. There wasno difference in survival between patients younger than 65 compared toolder patients. There was no difference in survival between genders.Mean survival in cytology negative patients (n�32) was 12 � 0.9 months,compared to 4.7 � 0.09 months in cytology positive patients (n�34,Log-Rank, p�0.0416). The 5-year survival in cytology negative patientswas 19%. Positive cytology predicted death within 36 months. There wasno correlation between length of hospital stay and survival. The one yearsurvival in lung and esophageal cancer patients was 32.7% and for all othercancers 44.8%, and the 2 year survival was 19.8% and 28.9% respective-ly(p � NS).Seven patients (8.2%) required repeat PW . Recurrenceoccurred in 4 cases after anterior PW only, in 2 cases after posterior PWonly, and in 1 case after combined anterior and posterior PW.

CONCLUSION: Pericardiotomy is an effective palliative interventionthat avoids repeated invasive procedures in 90% of cases. Positive cytologyof the pericardial effusion is predictive of short survival. Survival in thisseries is better than literature benchmarks.

CLINICAL IMPLICATIONS: Both an anterior and posterior PWshould be placed to avoid recurrence. Fluid cytology should be obtainedduring PW for prognostic purposes.

DISCLOSURE: Siyamek Neragi-Miandoab, None.

COMPUTER ASSISTED STAPLE RESECTION: UTILIZATIONOF A NEW TECHNIQUE FOR MAJOR PULMONARY RESEC-TION DURING MINIMAL ACCESS THORACIC SURGERYWickii T. Vigneswaran MBBS* Loyola University Medical Center, May-wood, IL

PURPOSE: Computer assisted stapling of tissues (CAST) is a newtechnology in evolution. It provides the surgeon with more ability to carryout procedures when minimal access is used for major surgical proce-dures. Preservation of the chest wall mechanics is a major factor in patientrecovery following pulmonary resection (PR). The posterolateral muscledividing thoracotomy, the ‘standard ‘approach for major PR is associatedwith decreased pulmonary function and late muscle atrophy. The alter-

nate approach of VATS for PR has major limitation including it isrestricted to small tumors, inadequate mediastinal lymphadenectomy andtumor implantation at port sites. A totally muscle sparing lateral thoracot-omy (MATS) is another approach that does not have the above limitations.The purpose of this report is to give our experience with CAST to dividelung parenchyma and to secure the vascular and bronchial structuresduring PR employing MATS.

METHODS: One hundred consecutive patients undergoing major PRusing the CAST, forms the basis of this report. All patients underwentMATS, sparing both latissimus dorsi and serratus anterior muscles. Thedata were collected prospectively for analysis.

RESULTS: The procedures included 77 lobectomies, 5 pnuemonec-tomies and 18 major wedge or segmental resections. The median numbersof staples used were 5(range 1-13). Major malfunctions were encounteredin 4 instances. Dislodgement of the cartridge from the cable occurredafter successful deployment of the staples in two instances and in oneinstance an incomplete staple formation on a vessel requiring additionalsuture placement and one bronchial stapling failed requiring sutureclosure.

CONCLUSION: We conclude that CAST for PR is feasible. Theresection of lung is made simpler, particularly of the bronchial andvascular structures. The use of this new technology is advantageous whenMATS is performed for lung resections.

CLINICAL IMPLICATIONS: The technology is a significant ad-vancement in currently available techniques for pulmonary resection. Thiswill allow wider use of complete muscle sparing thoracotomy as a standardof practice for lung resection in the future.

DISCLOSURE: Wickii Vigneswaran, Consultant fee, speaker bureau,advisory committee, etc. Advisory committee, Power Medical Interven-tions.

EXTENDED THYMECTOMY BENEFITS PATIENTS WITH MY-ASTHENIA GRAVISJennifer Knight MD* Laurie Gutmann MD Michael Szwerc MDGeoffrey M. Graeber MD West Virginia University, Morgantown, WV

PURPOSE: Treatment of Myasthenia Gravis includes medical thera-pies; anticholinesterase agents, immunosuppressive drugs, plasmaphoresisand gammagloubulin, also surgical therapy of a thymectomy. Medicaltherapies produce a remission rate low as 15%, surgical therapies high as80%. We will show that early thymectomy relative to the onset ofsymptoms results in remission or improvement of symtoms of MyastheniaGravis.

METHODS: A 10-year retrospective review (1993-2002) of all thymec-tomies in myasthenic patients performed at one institution was under-taken.

RESULTS: 28 patients reviewed (13 male/15 female), ages rangedfrom 5 to 74 (mean age of 39). Follow-up was 3 months to 6 years (3patients lost to follow-up). 11 patients had their thymus removed within 5months of the onset of symptoms, 10 of 11 (91%) had complete remissionor improvement of symptoms. Those whose thymus was removed within1 year of the onset of symptoms 15 of 19 (79%) had remission orimprovement. Those whole thymus was removed within 6 years, 19 of 25had remission or improvement. The mortality rate was 0 and thecomplication rate was 35% with complications that included respiratoryand cardiac problems, infections, and DVTs. While all patients underwenta median sternotomy, 2 patients had their thymectomies with a CABG andone patient was a redo. 5 of the 28 (18%) had thymomas.Patient StatusTime 0-5 months 12 months 6 yearsNo symptoms 8 4 (12) 4 (16)Improve-ment 2 1 (3) 0 (3)Same 1 1 (2) 1 (3)Worse 0 2 (2) 1 (3)Total 11 7 (19) 6(25).

CONCLUSION: Promptness of surgery relative to the onset ofsymptoms clearly shows a favorable outcome of thymectomy in myasthe-nia gravis. 91% of patients had improvement or complete resolution ofsymptoms if their thymus was removed within 5 months of the onset ofsymptoms. The benefit of a thymectomy is seen even for longstandingmyasthenics. Performing a thymectomy early as possible will greatlyincrease the chances for complete remission of this disease.

CLINICAL IMPLICATIONS: Complete thymectomy means betterimprovement in symptoms.

DISCLOSURE: Jennifer Knight, None.

Pathology of Malignant Pericardial Effusion n�

NSCLC&SCLC 32Breast Cancer 8Esophageal Neoplasm 5Non-Hodgkin-Lymphoma 5Leukemia 3Other Tumors and Metastatic Disease* 13

*(Thymoma 1, malig melanoma 1, chodrosarcoma 1, angiosarcoma 1,osteosarcoma 1, spindle cell neoplasm 1, rhabdomyosarcoma 1,nerve sheath tumor 1, mesothelioma 1, colon ca 1, ovarien ca 1,testicular ca 1, UKO)




FOLLICULAR BRONCHIOLITIS: ANALYSIS OF 12 CASESMichelle R. Aerni DO* Robert Vassallo MD Jay H. Ryu MD Mayo Clinic,Rochester, MN

PURPOSE: Follicular bronchiolitis is a bronchiolar lesion character-ized by the presence of hyperplastic lymphoid follicles with reactivegerminal centers distributed along bronchovascular bundles. This disordercan be idiopathic or occur in association with systemic disorders such asconnective tissue diseases or immunodeficiency syndromes. Relativelylittle is known regarding prognostic implications and treatment of thisdisorder.

METHODS: We conducted a computer-assisted search of the MayoClinic database to identify cases of follicular bronchiolitis seen in adults(21 years of age or older) at our institution over a 9-year period, January1, 1996 through December 31, 2004. Twelve patients were identified;relevant medical records and imaging studies were reviewed.

RESULTS: The median range of these 12 patients was 54.5 years(range, 33-81 years) and included 4 men. Four patients had a smokinghistory and included 3 current smokers. Most patients presented withcough and/or exertional dyspnea. Six patients (50%) manifested cracklesbut no digital clubbing was observed. The histopathologic diagnosis offollicular bronchiolitis had been obtained by surgical lung biopsy in 11patients (92%) and by bronchoscopic biopsy in one. Associated his-topathologic findings included granulomas (2 cases), nonspecific intersti-tial pneumonia (1 case), usual interstitial pneumonia (1 case), patchydesquamative interstitial pneumonia (1 case), and carcinoid tumorlets (1case). CT findings were variable and included nodules, ground-glassopacities, consolidation, and linear opacities. Pulmonary function findingswere similarly variable. Underlying disorders included Sjogren’s syndrome(1 patient), common variable immunodeficiency syndrome (1 patient),and bronchiectasis (1 patient). Six other patients had an elevated antinu-clear antibody titer or rheumatoid factor. Most patients were treated withprednisone � azathioprine with generally favorable response.

CONCLUSION: Follicular bronchiolitis is an uncommon form ofbronchiolar lesions that can be idiopathic or occur in association withconnective-tissue disorders, immunodeficiency syndromes, or ill-definedhypersensitivity reactions. This disorder is associated with variable find-ings on pulmonary function testing and CT scan.

CLINICAL IMPLICATIONS: Corticosteroid therapy appears to bebeneficial in the management of follicular bronchiolitis for most patients.

DISCLOSURE: Michelle Aerni, None.

LUNG FUNCTION IMPROVEMENTS WITH TIOTROPIUMBROMIDE IN CONSTRICTIVE BRONCHIOLITISRonaldo A. Kairalla MD* Marcelo J. Rocha MD Carlos R. Carvalho MDPulmonary Division-Heart Institution (InCor), University of Sao Paulo,Medical, Sao Paulo, Brazil

PURPOSE: Constrictive bronchiolitis is characterized by a fibrosinginflammatory process that surrounds rather than fills airways lumen,resulting in hyperinsufflation. HRCT demonstrates mosaic areas ofdecreased attenuation and vascularity and evidence of air-trapping. Thedisease is poorly responsive to steroids and adrenergics bronchodilators.Tiotropium bromide is a synthetic quaternary anticholinergic agent that isfunctionally selective for specific muscarinic receptors that mediate airwaysmooth-muscle contraction, and has an extremely long duration of action.

METHODS: Six patients, 3 female, mean age 54.8y (�8.7)non-smonkers, with clinical, HRCT and functional diagnosis of constrictivebronchiolitis, with lung biopsy in 4, were submitted to a trial of once-dailyinhalation of tiotropium (18 mcg).

RESULTS: Spirometry was performed before and 21 days after themedicationThe initial spirometry showed a an obstructive pattern(mean�SD): FVC�1.3�0.3L and FEV1�0.74�0.3L. After 21 days oftiotropium, in all patients the FVC improve more than 10%. Mean FVC alsosignificatively improve (1.65�0.4, p�0.004), but not the FEV1 (0.91�0.4).

CONCLUSION: In spite of fibrosing predominance in constrictivebronchiolitis, we observed a significant improvement of pulmonary func-tion after 21 days of tiotropium.

CLINICAL IMPLICATIONS: The influence of this finding on theevolution of the disease needs further investigation.

DISCLOSURE: Ronaldo Kairalla, None.

INFLUENCE OF INHALED DEXAMETHASONE ON THEBLEOMYCIN-INDUCED LUNG FIBROSIS IN RATSLi Xia MD* Shanghai pulmonary hospital, Shanghai, Peoples Rep of China

PURPOSE: To compare the effect and mechanism of inhaled withsystemic dexamethasone on the bleomycin-induced lung fibrosis in rats.

METHODS: 60 Sprague-Dawley rats were divided randomly intothree groups including bleomycin-induced lung fibrosis group (GroupA,n�20), inhaled dexamethasone group (Group B, n�20) and dexameth-asone group (Group B, n�20). Each group was again divided into foursubgroups, which were sacrificed on 1, 7 ,14 or 28 day. Bronchoalveolarlavage fluid (BALF)was got and the cells counting aswell as differentiationwere figured out, HE stain was performed on the lung tissue sections toobserve the extent of alveolitis and fibrosis, the semi-quantity of apoptosiscells in lung tissue was assay by in situ TUNEL(terminal deoxynucleotidytransferase-mediateddUTP nick endlabeling).

RESULTS: (1)Compared group B and C with group A got lowerpercentage of neutrophils (P�0.05). (2)More severe fibrotic lesion wasshown in the histological examination of the lung tissue sections of groupA Compared with group B and C. (3)the apoptosis index (AI) ofinflammatory cells in each subgroups of group B and C was higher than ingroup A, and there were no significance compared group B with C.

CONCLUSION: Inhaled dexamethasone can induce apoptosis ofpulmonary inflammatory cells and ameliorate the formation of bleomycin-induced pulmonary fibrosis as well as systemic dexamethasone.

CLINICAL IMPLICATIONS: Inhaled steroid drugs maybe improveinterstial lung disease.

DISCLOSURE: Li Xia, None.

SACOIDOSIS IN CHINA: A REVIEW OF HOSPITAL BASEDCOHORTHaiqing Chu MD* Tao Gui Shengxiang Ren BA Jingpo Zhang Huiping LiMD Guojun He MD Shanghai Pulmonary Hospital, Shanghai, PeoplesRep of China

PURPOSE: To study how to avoid delaying the diagnosis and misdi-agnosis through the substantive cases analyzed retrospectively.

METHODS: Selected the sarcoidosis cases involved from 1980 to nowfrom the archive of our hospital, analyzed their clinical manifestations,radiographic presentations, lab examinations such as PPD test, SACE,pulmonary function test, urine calcium and sera-calcium, 67Ga lung scan,and the way to confirm diagnosis.

RESULTS: 1,There were 125 female patients (63.1%) and 73 malepatients(36.9%) with the average age of 35.1 years old. The average durationof the disease was 6.1 months and stage evaluation showed that there were 3,86, 91 and 18 cases from stage 0 to 3 respectively. 2,35.4% of the cases werefound by the physical examination, while other 64.6% by complaint of varioussymptoms such as cough, breathless, fever, chest pain. The main extrapul-monary manifestation was superficial lymph node enlargement, eyesightfaintness, and skin lesions. 3,The usual presentation of the chest X-ray and CTwas hilar and/or mediastinal lymph node enlargement accompanied withbilateral diffusion lesion or not. It was prone to make a wrong diagnosis andthe rate of misdiagnosis is as high as 39.9%. 4,Among the various biopsymeans, mediastinoscopy lymph node biopsy is the most valuable, and thesuperficial lymph nodes, skin nodus, bronchial mucous and transbronchiallung biopsy are worth recommending.

CONCLUSION: We should pay higher attention to sarcoidosis whenthe followings happen: middle-aged patients or young femalepatients;long duration of disease; mild respiratory tract symptoms accompaniedwith superficial lymph node enlargement or skin;eye involved; bilaterallung diffusion lesion in radiographic presentation accompanied with orwithout hilar, mediastinal lymphadenopathy. To avoid failing to diagnoseor mistaking diagnosis ,we should go all out to confirm the diagnosisthrough the tissue pathological examination .

CLINICAL IMPLICATIONS: The multifarious forms and presenta-tions of Sarcoidosis and the low morbidity can make the diagnosischallenging, and it is prone to misdiagnosis in China.Through analyzingthe cases respectively,we can learn more about this disease and enhancethe diagnosis accurate rate.

DISCLOSURE: Haiqing Chu, None.


Interstitial Lung Disease12:30 PM - 2:00 PM


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THE SIGNIFICANCE OF PARTICULATE MATTER DETECTEDIN SARCOID GRANULOMAS USING POLARIZING LIGHT MI-CROSCOPYNavasuma Havaligi MD* Adarsh Bhimraj MD Robert T. Ownbey MDHan C. Ryoo PhD Frank Patrick Herbert Patrick MD Drexel UniversityCollege of Medicine, Philadelphia, PA

PURPOSE: We previously noted particulate matter (PM) under polarizinglight microscopy within the granulomas of patients diagnosed with sarcoidosis(Chest 2002;122:148S-149S). However, our preliminary research lacked a controlgroup. Therefore, we designed this study to examine tissue samples for thepresence of PM from patients without granulomas.

METHODS: Tissues samples from patients diagnosed with sarcoidosiswere retreived using slides routinely prepared and stored in PathologyDepartments. Normal tissues were selected from among autopsy speci-mens at our University hospital. A single pathologist reviewed each tissuesample using: 1) light microscopy for the presence of granulomas, and 2)polarizing light microscopy for the presence of PM within the multinu-cleated giant cells of the granuloma. Results were expressed as atwo-by-two table. This research project was approved by our University’sInstitutional Review Board as an exempt protocol.

RESULTS: Eighty tissue samples from patients diagnosed with sar-coidosis and eighty normal tissue samples were studied by light micros-copy and polarizing light microsccopy. Age and gender differencesbetween the groups were not significant. The two-by-two Table belowdisplays the Results. The majority of tissues in both groups had PMdetected. The differences between the groups was not significant.

CONCLUSION: PM was noted in the majority of tissues from bothpatients diagnosed with sarcoidosis and from normals.

CLINICAL IMPLICATIONS: The ubiquitous nature of PM intissues may result in granulomatous inflammation in patients diagnosedwith sarcoidosis by PM contact, PM inhalation and/or PM ingestion.Granuloma formation appears to require the presence of host suscepti-bility causing a reaction to the PM. Future investigations of the etiology ofsarcoidosis should include polarizing light examination of tissue for PM,identification of the chemical composition and structural heterogeneity ofthe PM, and new tests designed to identify host susceptibility to the PM.

DISCLOSURE: Navasuma Havaligi, None.

RESPONDER ANALYSES IN PATIENTS RECEIVING INFLIX-IMAB FOR CHRONIC SARCOIDOSIS WITH PULMONARY IN-VOLVEMENTM. Drent MD* M. A. Judson MD U. Costabel MD R. M. duBois MD M.Kavuru MD K. H. Lo MD C. Andresen MD R. Schlenker-Herceg MD E.S. Barnathan MD R. P. Baughman MD University Hospital of Maastricht,Maastricht, Netherlands

PURPOSE: Response to drug therapy may not be uniform across aheterogeneous population. Responder analyses, which dichotomize theresponse at a specific level of interest, can be helpful in gauging the utilityof an intervention. The objective of this study was to evaluate the responseto infliximab therapy in a randomized trial of 138 patients with chronicpulmonary sarcoidosis using clinically meaningful dichotomous endpointsfor pulmonary function, symptoms, and physical function.

METHODS: Primary and major secondary endpoint data at 24 weeksfrom a placebo-controlled study of infliximab were explored. The analysesare presented as the number (%) of responders using varying definitionsfor improvements in forced vital capacity (FVC), St. George’s RespiratoryQuestionnaire (SGRQ) score, Borg’s CR10 dyspnea score post 6 minutewalk (6MW), and 6 MW distance (6MWD).

RESULTS: At week 24, there was a trend for more subjects havingimproved pulmonary function as measured by FVC with infliximab

treatment using all definitions.All three groups responded similarly inSGRQ. For the combined infliximab group, there were more respondersusing Borg’s CR score post 6MW (p�0.028) or 6MWD (p�0.011). For6MWD, the difference would translate into a number needed to treat(NNT) of 6.

CONCLUSION: Responder analyses can be helpful in identifyingclinically meaningful treatment effects, and can be useful to help gaugethe NNT to achieve the level of benefit of interest.

CLINICAL IMPLICATIONS: Infliximab appears to be associatedwith larger improvements in some endpoints in a subset of subjects,despite aggressive medical therapy. A larger trial of infliximab in such apopulation appears warranted.

DISCLOSURE: M Drent, Grant monies (from industry relatedsources) Research grants; Consultant fee, speaker bureau, advisory com-mittee, etc.; Employee.

TREATMENT OF IDIOPATHIC PULMONARY FIBROSISSOLELY WITH ANTI-ACID GASTRO-ESOPHAGEAL REFLUXTHERAPY: A CASE SERIES OF FOUR PATIENTS WITH LONG-TERM FOLLOW-UPGanesh Raghu MD Steve T. Yang MBBS* Carolyn Spada RN JenniferHayes RN Carlos Pelligrini MD Singapore General Hospital, Singapore,Singapore

PURPOSE: Idiopathic pulmonary fibrosis (IPF) is a relentless, pro-gressive and fatal disease with no known effective treatment. Increasedacid gastro-esophageal reflux (GER) has been associated with IPF. Wespeculate that acid gastroesophageal reflux (GER) is an important factorfor the development and/or progression of IPF.

METHODS: Patients with new onset IPF and presenting with symp-toms and documented gastro-esophageal reflux disease (GERD) orabnormal acid GER by 24-hour esophageal pH probe testing, who refusedconventional therapy (prednisone and azathioprine) or other concurrentmedical treatments implicated for IPF and chose to be treated solely withanti-acid GER therapy.

RESULTS: Adequate suppression of acid GER was ascertained by24-hour esophageal pH monitoring. Patients were followed regularly withpulmonary function tests (PFT) over 2-6 years. The PFTs (Forced vitalcapacity [FVC] and diffusion capacity for carbon monoxide [DLCO]) in all4 patients stabilised or improved while being maintained on adequatedaily treatment for acid GER, and were alive at last follow-up. None of thepatients manifested acute exacerbation of IPF nor needed additionaltreatment for respiratory problems or antibiotics during this period. Aftermaintaining 4 years of improved status in PFTs and exercise testing whileadhering to treatment for acid GER, one patient’s deterioration correlatedwith poor compliance to daily treatment during the 5th year, although thePFTs at last follow-up 6 years since diagnosis showed stabilisationcompared to baseline. Another patient stabilised upon adhering toanti-acid GER treatment after an initial period of deterioration that wasassociated with non-adherence.

CONCLUSION: This case series suggests that acid GER might be animportant risk factor for IPF progression and that adequate treatment forabnormal acid GER may in part improve the outcome of patients with IPF.We also hypothesize that pulmonary fibrosis occurs in individuals who aregenetically susceptible to develop fibrosis from recurrent chronic acid GER.

CLINICAL IMPLICATIONS: Future clinical studies are indicated todetermine the efficacy of treatment for acid GER in IPF either incombination with other agents or as a sole agent.

Polarizablematerial �

Polarizablematerial -

GranulomatousInflammation �,n � 80

62% 38%

GranulomatousInflammation -,n � 80

80% 20%


Interstitial Lung Disease, continued


DISCLOSURE: Steve Yang, None.

AEROSOLIZED INTERFERON GAMMA: A NOVEL APPROACHTO THERAPY IN IDIOPATHIC PULMONARY FIBROSIS?Hooman Mobassery MD* Rany Condos MD Gerald C. Smaldone MDSUNY at Stony Brook University Hospital, Stony Brook, NY

PURPOSE: In controlled studies, subcutaneous injection of interferongamma (IFN-�) has been shown to be ineffective in the treatment ofidiopathic pulmonary fibrosis (IPF). One explanation for the lack ofefficacy may be inadequate drug levels in the lung interstitium usingsubcutaneous dosing strategies. We have developed an aerosol of IFN-�designed to target the airways directly. We present the dose to the lung,local cytokine response, and clinical course in a 38 year old woman withbiopsy proven usual interstitial pneumonia, treated with aerosolizedIFN-�.

METHODS: The patient received 400 �g of aerosol IFN-� (two 200�g doses) three times per week. Pulmonary function test (PFT), exercisetesting, and the University of California, San Diego shortness of breathquestionnaire (SOBQ) were performed and completed prior to startingIFN-� therapy and at the end of three months. Subsequent PFTs wereperformed at the discretion of the patient’s private pulmonologist.Bronchoalveolar lavage was assayed for transforming growth factor-beta(TGF-�) prior to the start and at the end of three months. The pattern ofdeposition and dose to the lung parenchyma were measured by gammacamera.

RESULTS: Clinical responses included decreased dyspnea with im-provement in her SOBQ measurement, stabilization of pulmonary func-tion tests (improvement in DLCO/VA from 51% to 68% and stabilizationof FEV1 and TLC) and improvement in objective parameters duringexercise testing (increased maximal oxygen consumption). The dose to thelung parenchyma, as measured by gamma camera, was 54.4 �g pertreatment with a peripheral deposition pattern. With this regimen,bronchoalveolar lavage TGF-�, a key molecular mediator of matrixdeposition, levels decreased.

CONCLUSION: This is the first report of aerosol treatment withIFN-� and measurement of lung deposition in a patient with IPF. Thisstudy illustrates the potential use of aerosolized IFN-� for the treatmentof IPF by means of targeted therapy directly at the site of disease.

CLINICAL IMPLICATIONS: This is a novel approach in thetreatment of IPF.

DISCLOSURE: Hooman Mobassery, Product/procedure/techniquethat is considered research and is NOT yet approved for any purpose.Interferone gamma is FDA approved but the delivery of this drug byaerosol is considered experimental.

CYCLOSPORIN A TREATMENT FOR ACUTE EXACERBATIONOF IDIOPATHIC PULMONARY FIBROSISSusumu Sakamoto PhD* Sakae Homma PhD Hisashi Takaya PhD AtsushiMiyamoto PhD Masateru Kawabata PhD Kazuma Kishi PhD EiyasuTsuboi PhD Kunihiko Yoshimura PhD Toranomon Hospital, Tokyo,Japan

PURPOSE: Idiopathic pulmonary fibrosis (IPF) is a progressive dis-ease with a devastating prognosis. Acute excerebation (AE) is consideredto be the worst condition during the clinical course of IPF, as it isunresponsive to most of the conventional therapies such as corticosteroid(CS) and eventually leads to death. New therapeutic approaches need tobe explored.

METHODS: We conducted a retorospective study on autopsied IPFcases developing AE who were then treated with CS combined withCyclosporin A (CsA) during the period from 1994 to 2004 to evaluate theefficacy of CsA for AE of IPF. The subjects comprised of 11 maleindividuals with a mean age of 69.9 years. The clinical features of theCsA-treated group were compared to those of the control non-CsA-treated group of 11 patients (11 males with a mean age of 67.0 years).

RESULTS: For AE, CS pulse therapy followed by CS maintenancetreatment (0.5-1.0 mg/kg) were conducted in all cases. The patients in theCsA-treated group also received a low dose of CsA (100-150 mg/day).Although 7 out of 11 patients (63.6%) in the CsA-treated group died ofAE, 4 (36.4%) recovered from AE. Only two patients died of the first AE,and other nine responded to the initial treatments and survived. However,they experienced repetitive AE and 5 cases eventually died of AEafterwards. In comparison, 7 out of 11 patients (63.4%) in the non-CsA-treated group did at the initial AE, and died other 4 at the followingsecond AE. The mean survival period after the first onset of AE was 285days in the CsA-treated group and 60 days the in non-CsA-treated group,respectively.

CONCLUSION: The prognosis in the CsA-treated group was signifi-cantly better than that in the group without CsA treatment in AE of IPF.

CLINICAL IMPLICATIONS: Administration of CsA combined withCS may be an efficacious approach for AE of IPF.

DISCLOSURE: Susumu Sakamoto, None.

ACUTE EXACERBATION AS PRESENTING OR COMPLICAT-ING FEATURE OF IDIOPATHIC PULMONARY FIBROSISJoseph G. Parambil MD* Jeffrey L. Myers MD Jay H. Ryu MD MayoClinic, Rochester, MN

PURPOSE: To define the clinicopathologic features and outcome ofacute exacerbations that occur in patients with idiopathic pulmonaryfibrosis (IPF), a disorder that is generally characterized by slowly progres-sive course.

METHODS: Retrospective single-center study.RESULTS: The median age of these seven patients was 70 years

(range, 59 years to 74 years); two were women. Four patients had asmoking history and included two current smokers. All patients wereexperiencing an exacerbation of dyspnea for a median duration of 14 days(range, 7 days to 28 days) prior to presentation. In three of these patients,the acute deterioration was the presenting feature of IPF while in theremaining four patients the diagnosis of IPF had previously been estab-lished. Chest radiography demonstrated bilateral mixed alveolar-intersti-tial infiltrates in all of them. Computed tomography revealed ground-glassopacities and consolidation bilaterally in all patients with associatedperipheral honeycombing in six of them. Echocardiography was per-formed in six patients and demonstrated pulmonary hypertension in all.Bronchoalveolar lavage fluid was obtained in five patients and revealedneutrophilia in all. Surgical lung biopsy showed diffuse alveolar damage(DAD) in five patients with associated collagen fibrosis and honeycombchanges typical of usual interstitial pneumonia (UIP). One biopsy showeda combination of UIP and organizing pneumonia while one biopsy showedonly DAD. Despite treatment with lung-protective ventilation strategiesand high-dose systemic corticosteroids, six patients (86%) died duringtheir hospitalization.

CONCLUSION: Although IPF is typically associated with an insidious,slowly progressive clinical course, acute exacerbations occur and may bethe presenting manifestation in some patients. In either situation, currentmanagement strategies including high-dose corticosteroid therapy appearto be relatively ineffective and the mortality rate is high.

CLINICAL IMPLICATIONS: Acute exacerbations of IPF occur andmay be the presenting or complicating manifestation in patients with IPF.




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In either situation, current management strategies including high-dosecorticosteroid therapy appear to be relatively ineffective and the mortalityrate is high.

DISCLOSURE: Joseph Parambil, None.

NONSPECIFIC INTERSTITIAL PNEUMONIA: COMPARISONOF THE CLINICOPATHOLOGIC FEATURES AND PROGNOSISWITH USUAL INTERSTITIAL PNEUMONIALi Xia MD* Shanghai Pulmonary Hospital, Shanghai, Peoples Rep ofChina

PURPOSE: Although nonspecific interstitial Pneumonia(NSIP) hasrecently been proposed as a histologic subtype of idiopathic interstitialpneumonia(IIP), a broad spectrum of clinicopathologic findings and avariable prognosis are less well characterized. In particular, it is less clearhow NSIP relates to usual interstitial pneumonia (UIP). the aim of thisstudy was to investigate the clinicopathologic features and prognosis ofNSIP, and its differential diagnosis from UIP.

METHODS: We analyzed the clinical, pathological findings andfollow-up information of 21 NSIP patients and 18 UIP patients withbiopsy-proven by open or video-assisted thoracoscopic lung biopsy.

RESULTS: NSIP was more often appeared in female and the clinicalmanifestations were nonspecific. High-resolution computed tomography(HRCT) demonstrated ground-glass, net and patchy attenuation in lung.Semiquantitative HRCT showed that the median fibrosis score in NSIPwas found to be 3 (rang ,0 to 7) compared with 5 (rang ,2 to 7) in UIP(p�0.01). Pathological characteristic showed a heterogeneous appear-ance. According to pathological characteristic, NSIP was separated intocellar and fibrosing patterns. The cellar NSIP ,fibrosing NSIP and UIPhad a mean age of 41,50 and 59, respectively. The frequencies ofFibroblast foci, muscle sclerosis, honeycombing change and pulmonaryarchitectural destruction of NSIP and UIP were 26.2% and 100% (P�0.001), 35.6% and 81.2% (P� 0.05), 28.4% and 85.8% (P� 0.001), 42.9%and 100% (P�0.05), respectively. A response to glucocorticoid and aprognosis was significantly better in NSIP than in UIP.

CONCLUSION: NSIP was not easily differential from UIP in thegeneral clinical manifestations. HRCT was helpful for the differentialdiagnosis of cellar NSIP and UIP. The definite diagnosis of idiopathicinterstitial pneumonia was depended on open lung biopsy.

CLINICAL IMPLICATIONS: Open lung biopsy was very importantin diagnosis of interstitial lung disease.

DISCLOSURE: Li Xia, None.

Intervention and Therapy for PleuralEffusions12:30 PM - 2:00 PM

TISSUE PLASMINOGEN ACTIVATOR INCREASES THE VOL-UME OF PLEURAL FLUID BY INFLAMMATORY RESPONSESIN RABBITS WITH EMPYEMAMoon Jun Na MD* Huai Liao MD Charalampos Moschos MD OnerDikensoy MD Wonder Drake MD Kirk B. Lane PhD Richard W. LightMD Pulmonary Department of Saint Thomas Hospital, Vanderbilt Uni-versity, Nashville, TN

PURPOSE: Recently, alteplase, a recombinant tPA, has been used forloculated parapneumonic effusions in humans. In rabbits with empyema,the administration of alteplase leads to the production of large amounts ofpleural fluid with no effects on the empyema. To analyze the character-istics of the increased volumes of pleural fluid seen after tPA is adminis-tered to rabbits.

METHODS: A chest tube was inserted into the right pleural cavity andempyema was induced by administering Pasteurella multocida intrapleu-rally in 2 subgroups of rabbits, with each subgroup receiving 6 doses oftPA 1mg (n�2) or 4mg (n�4) for 3 days. The pleural fluid volume, pH,glucose, protein, LDH, WBC count of pleural fluid were measured. After10days, the rabbits were sacrificed and an empyema score and a pleuralthickening score were recorded.

RESULTS: The total amount of pleural fluid drained was significantlygreater in tPA 4mg group than tPA 1mg group (204.5 ml vs 104.3 ml

p�0.05). The protein, glucose, pH, LDH, and WBC counts did not differsignificantly between tPA 1mg and 4mg group (p�0.05). But in bothgroups, the WBC counts were markedly increased to approximately100,000/mm3, the pH was consistently below 7.10 and the LDH levelswere markedly increased to 20x the upper normal limit for serum. TheGram stains were positive only for 1day after induction of empyema.

CONCLUSION: The intrapleural administration of tPA in rabbits withempyema markedly increases the volume of pleural fluid. The pleuralfluid is highly inflammatory as evidenced by very high WBC and LDH andreduced pH.

CLINICAL IMPLICATIONS: The results of this study suggest thatthe increased drainage seen with fibrinolytics may be the result ofaugmentation of the pleural inflammatory response rather than facilitateddrainage.

DISCLOSURE: Moon Jun Na, Grant monies (from sources other thanindustry) supported by Saint Thomas Foundation.

EXPERIMENTAL PLEURODESIS: INTRAPLEURAL INJEC-TION OF AZYTHROMYCIN, CLARITHROMYCIN OR LEVO-FLOXACINRenam U. Bumlai Francisco S. Vargas MD Milena M. Acencio BS LeilaAntonangelo MD Gabriela G. Carnevale PharmD Evaldo Marchi MDLisete R. Teixeira MD* Pulmonary Division, Heart Institute (InCor), SaoPaulo Medical School, Sao Paulo, Brazil

PURPOSE: Pleurodesis is commonly used to treat recurrent pleuraleffusion or pneumothorax. The ideal agent for pleurodesis is still beingsought. Previous studies demonstrated that intrapleural instillation oferythromycin, a macrolide antibiotic, could be a potential pleural scleros-ing agent. There is no studies demonstrating the effect of quinolones aspleural sclerosing. The aim of this study was to evaluate the intrapleuralinjection of azythromycin, clarithromycin or levofloxacin as pleural scle-rosing agents.

METHODS: Thirty rabbits, divided in 3 groups received, through achest tube, intrapleural administration of azythromycin (15mg/kg), clar-ithromycin (15 mg/kg) or levofloxacin (10 mg/kg) in a total volume of 2ml.After 28 days the animals were sacrificed and the degree of pleuraladhesions were evaluated in a score from 0 (no adhesions ) to 4 (completeobliteration of pleural space). Pleurodesis are considered when score �3.We also evaluated the microscopic changes for inflammation and fibrosisin scores from 0 to 4 according to the intensity of process. Statisticalanalysis: Descriptive Analysis (mean � standard deviation) and KruskallWallis ANOVA .

RESULTS: After the intrapleural administration of azythromycin,clarithromycin or levofloxacin we observed a few macroscopic adhesions.The scores were 1.2 � 0.5, 1.2 � 1.0 and 1.0 � 0.5 respectively, and nostatistical difference were observed among the groups. The microscopicanalysis of pleura and parenchyma showed discrete changes for all drugs,with a greater scores of pleural fibrosis in the clarithromycin group.

CONCLUSION: The intrapleural injection of azythromycin, clarithro-mycin or levofloxacin was ineffective in creating pleurodesis in ourexperimental model.

CLINICAL IMPLICATIONS: Macrolides or quinolones should notbe recommended as a pleural sclerosing agent, when a pleurodesis isattempt.

DISCLOSURE: Lisete Teixeira, None.

INTRAPLEURAL HEPARIN OR HEPARIN COMBINED WITHHUMAN RECOMBINANT DNAASE IS NOT EFFECTIVE IN THETREATMENT OF EMPYEMA IN A RABBIT MODELOner Dikensoy MD Moon J. Na MD* Zhiwen Zhu MD Wonder DrakeMD Edwin O. Donnelly MD Richard W. Light MD St. Thomas Hospitaland Vanderbilt University, Nashville, TN

PURPOSE: To investigate the effectiveness of intrapleural heparin orheparin combined with human recombinant DNAase in the treatment ofempyema.

METHODS: Empyema was induced in rabbits using 109 Pasteurellamultocida organisms in infusion agar injected via a surgically placed chesttube. Once empyema was verified, a blinded investigator administereddrugs via the chest tube. Randomly selected 6 rabbits in each treatmentgroup received either 1000 IU Heparin or 1000 IU heparin plus 1mghuman recombinant DNAase via chest tube. Control group (n�6)received 3 ml saline only. The rabbits received treatment every 12 hours




for a total of 6 treatments. The animals were sacrificed at day 10 and theamount of empyema and pleural thickening was scored macroscopicallyon a scale of 0 to 6. All the animals received intramuscular 100,000 Uprocaine penicilline every 24 hours until sacrifice.

RESULTS: The volume of gross pleural effusion was markedly higherin the heparin group (25.8� 10.7 mL) compared to either saline (8�8.9)or heparin plus human recombinant DNAase (6.8�6.1) groups(p�0.003). Comparison of the mean empyema and pleural thickeningscores did not show any significant difference between the groups (p�0.8,p�0.5, respectively). A week correlation found between total volume ofaspirated pleural fluid and pleural parameters of white blood cell countsand lactate dehydrogenase levels (r�0.546 and p�0.02, r�0.631 andp�0.02, respectively). One rabbit in saline group died of right heartfailure and two rabbits in heparin group died of diarrhea.

CONCLUSION: The intrapleural administration of either heparin orcombination of heparin with human recombinant DNAase is not moreeffective than saline in the treatment of empyema in rabbits. Intrapleuralheparin significantly increased the drainage of pleural fluid compared tocombination and saline group.

CLINICAL IMPLICATIONS: The intrapleural administration ofheparin alone or in combination with human recombinant DNAase is noteffective in the treatment of empyema in rabbits.

DISCLOSURE: Moon Na, None.

A NEW, RELIABLE MODEL OF EXPERIMENTAL PLEURODE-SIS IN MICEEvaldo Marchi MD* Francisco S. Vargas MD Milena M. Acencio BSGabriela G. Carnevale BS Leila Antonangelo MD Eduardo H. GenofreMD Lisete R. Teixeira MD Pulmonary Division, InCor and University ofSao Paulo Medical School, Sao Paulo, Brazil

PURPOSE: The experimental model of pleurodesis in rabbits has beenuseful in understanding the pathophysiology of the pleural inflammatoryinjury induced by several sclerosing agents. However, restrictions for theuse of rabbits in laboratory investigation are making this model lessaccessible. The aim of this study is to present a new experimental modelof pleurodesis in mice using talc or silver nitrate.

METHODS: Two groups of ten C57BL/6 mice received 0.5mLintrapleurally of talc 4mg/gr or 0.05% silver nitrate. After 28 days theanimals were sacrificed and the pleural cavity was opened and evaluatedfor evidence of macroscopic pleural adhesions and hemothorax (scores 0to 4), atelectasis (scores 0-2) and microscopic pleural and alveolarinflammation and fibrosis (scores 0 to 4). Statistics: student t-test.

RESULTS: Although both agents produced an efficient pleurodesis,silver nitrate was more effective than talc, with significant higher scoresfor pleural adhesions, microscopic pleural inflammation and fibrosis.Hemothorax, atelectasis and microscopic alveolar inflammation and fibro-sis were negligible in both groups.

CONCLUSION: Either talc 4mg/gr or 0.05% silver nitrate producedan efficient pleurodesis in our experimental model in mice.

CLINICAL IMPLICATIONS: We describe a new model of pleu-rodesis that may overcome the restrictions to the use of large andmedium-sized animals in laboratory investigation.

DISCLOSURE: Evaldo Marchi, None.

PLEURODESIS WITH TETRACYCLINE OR WITH TALC-VARI-ABLES MEASURED IN TERMS OF EFFECTIVENESSSara Freitas MD* Jessica Cemlyn-Jones MD Carlos R. Cordeiro PhDLuis C. Oliveira PhD Manuel F. Baganha PhD Departamento de CienciasPneumologicas e Alergologicas dos HUC, Coimbra, Portugal

PURPOSE: establish the effectiveness of pleurodesis according totreatment option (tetracycline, talc slurry or thoracoscopic talc poudrage)correlating analytical parameters of pleural fluid.

METHODS: retrospective analysis over a five year period fromJanuary 2000 to December 2004 which included 71 procedures carriedout in a Pulmonology department.Fifteen cases were excluded from thestudy for not fulfilling the required criteria.

RESULTS: Fifty-six pleurodesis were performed on 54 patients; 34procedures the sclerosant agent used was tetracycline and in 22 talc. 47cases the underlying cause was malignant pleural effusion, four pleuraleffusions of unknown aetiology, one pleural effusion due to Waldenstrommacroglobulinemia with lung involvement, one recurrent pneumothoraxand 1 hydropneumothorax.Failure was indicated by evidence of recurrentpleural fluid. Pleurodesis with talc was successful in 29 of 34 (85%) andwith tetracycline in 17 of 22 (77%).Analytical parameters of pleural fluidwere thoroughly evaluated showing mean pH measurement of 7.56,totalprotein 4.24 mg/dl. glucose 95 mg/dl, LDH 922 U/L, ADA 16.2 mg/dl insuccessful pleurodesis with talc;mean pH measurement of 7.34,totalprotein 4.39 mg/dl. glucose 88.8mg/dl, LDH 734.7 U/L, ADA 15.8 mg/dlin successful pleurodesis with tatracycline; mean pH measurement of7.73,total protein 4.39 mg/dl, glucose 88.8 mg/dl, LDH 734.7 U/L, ADA15.8 mg/dl in successful pleurodesis with talc; mean ph 7.34, total protein4.04 mg/dl,glucose 54.5 mg/dl, LDH 3078 U/L, ADA 9.87 mg/dl inunsuccessful pleurodesis with tetracycline; mean pH measurement of7.52, total protein 4.9mg/dl, glucose 45.5, LDH 3078 U/L, ADA 9.87mg/dl in unsuccessful pleurodesis with talc.Total cell count of pleuralfluid, blood measurement of reactive C protein and LDH were alsoconsidered in this study.

CONCLUSION: pleurodesis with talc was more successful than withtetracycline. The comparative study of successful and unsuccessful caseswith both the pleural sclerosants shows there are significant variations ofpleural glucose, LDH and ADA in talc pleurodesis and pH, glucose andLDH in tetracycline pleurodesis.

CLINICAL IMPLICATIONS: Talc is the agent of choice whenutilizing pleurodesis and pleural analytival parameters may be usefulprognostic tools.

DISCLOSURE: Sara Freitas, None.

EFFICACY OF TALC PLEURODESIS DEPENDING ON THEAMOUNT OF PLEURAL FLUID DRAINAGE AND CHEST XRAYFINDINGS PRIOR TO THERAPYGeorge Thommi MD* Michelle Christensen Patrick Meyers MD ChrisShehan MD Mathew McLeay MD Creighton University/Methodist Hos-pital, Omaha, NE

PURPOSE: To document the success or failure of talc pleurodesisdepending on CXR findings and the amount of pleural fluid drainage intwenty four hours prior to pleurodesis.

METHODS: A retrospective analysis was performed over a period offive years on patients treated with talc pleurodesis through chest tubes orby surgery (VATS or thoracotomy). The amount of pleural fluid drainedwithin 24-hours and chest x-ray findings were evaluated prior to pleu-rodesis. Success was documented if no recurrences of these effusions werenoted for at least period of three months and no further intervention wasnecessary.

RESULTS: 94 patients fit our criteria. 16 patients were discarded as noCXR was performed after pleurodesis. With CXRs showing minimalresidual pleural effusions, talc pleurodesis was successful in 100% ofpatients if the pleural fluid drainage was less than 100mls in 24 hours(30/30 patients); 60% successful if pleural fluid drainage was between100mls and 200mls in 24 hours (9/15 patients); 38% successful if thepleural fluid drainage was between 200mls and 300mls in 24 hours (5/13patients); and 20% successful if pleural fluid drainage was over 300mls in24 hours (4/20 patients). Only one out of eleven patients with pleural fluiddrainage over 300mls in twenty hours had talc pleurodesis via VATS thatwas successful (9%).

CONCLUSION: Talc pleurodesis is very successful when the pleuralfluid drainage is less than 100mls in 24 hours regardless of the method ofadministration. Patients with pleural fluid drainage less than 250mls in 24


Intervention and Therapy for PleuralEffusions, continued


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hours may also be successful if the chest x-ray shows minimal residualeffusions. Talc pleurodesis should not be performed if the pleural fluiddrainage is over 300mls or if CXR shows moderate and loculated pleuraleffusions.

CLINICAL IMPLICATIONS: The success of talc pleurodesis de-pends on the amount of pleural fluid drained in 24 hours as well as theamount of pleural fluid noted on chest x-rays prior to therapy, regardlessif performed via chest tubes or by VATS.

DISCLOSURE: George Thommi, None.

THORACOSCOPIC TALC POUDRAGE INDUCES FEVER ANDSYSTEMIC INFLAMMATIONMarios E. Froudarakis MD* Maria Klimathianaki MD Mihalis Pougou-nias MD Medical School of Crete, Heraklion, Greece

PURPOSE: Recent studies have reported fever as a side effect of talcpoudrage during thoracoscopic pleurodesis. However, thoracoscopy itselfis likely to induce systemic inflammatory reaction, as it is an interventionalprocedure. The aim of the study was to investigate whether systemicinflammatory response is due to talc poudrage or to thoracoscopy.

METHODS: We prospectively studied two groups of patients: the firstgroup, of 18 patients, underwent thoracoscopic talc poudrage and thesecond, of 17 patients, underwent only diagnostic thoracoscopy. Wemeasured body temperature, as well as white blood cells (WBC) countand CRP before (baseline), at 24h and 48h after the procedure. Noanti-inflammatory medication was permitted before, during or after theprocedure. All patients have a 3-month follow-up.

RESULTS: Baseline patients’ characteristics were similar in bothgroups. Temperature increased significantly in the thoracoscopic talcpoudrage group (overall p�0.005) especially at 9, 12 and 24 hour after theprocedure. Overall WBC count (p�0.004), neutrophils (p�0.03) andCRP (p�0.0001) were significantly increased in the group of patients whounderwent thoracoscopic talc poudrage. In the contrary, lymphocyteswere significantly decreased (overall p�0.01) in the thoracoscopic talcagegroup during the same period. Mild side effects were noted such as painduring and after thoracoscopy and subcutaneous emphysema. No severecomplication, such as infection or acute respiratory failure, was noted inboth groups during the hospitalization or during the follow-up period.

CONCLUSION: According to our results, fever and systemic inflam-matory reaction is due to talc poudrage and not to thoracoscopy.

CLINICAL IMPLICATIONS: Fever, especially in patients with talcpoudrage, is only due to a short term inflammatory reaction. Thisobservation should decrease significantly the overall cost of thoracoscopy.

DISCLOSURE: Marios Froudarakis, None.

THORACOSCOPY TALC POUDRAGE INDUCES T-LYMPHOPE-NIA IN THE PERIPHERAL BLOODMarios E. Froudarakis MD* Maria Klimathianaki MD Mihalis Pougou-nias MD Helen A. Papadaki MD Department of Pneumonology, MedicalSchool of Crete, Heraklion, Greece

PURPOSE: We have demonstrated that thoracoscopic talc poudrage(TTP) induces peripheral blood granulocytosis and lymphopenia. The aimof this study is to investigate whether lymphopenia concerns T-, orB-lymphocytes.

METHODS: We measured lymphocytes of the peripheral blood inpatients who underwent TTP, before (baseline), at 24h and 48h after theprocedure. Absolute lymphocyte numbers were analysed by flow cytom-etry for the evaluation of the CD3�, CD4�, CD8� cells (total T-lymphocyte, helper T-lymphocytes, cytotoxic T-lymphocytes respectively),the CD19� cells (B-lymphocytes), and the CD16�, CD56� and CD57�cells (NK-cells). No anti-inflammatory medication was permitted before,during or after the procedure. To this day 11 patients have been analysed.We used ANOVA repeated measurements for statistical analysis.

RESULTS: The mean age of our patients was 65.5�15.8 years. Malepatients were 6 (54.5%). All patients but one had carcinomatous pleuraleffusion (91%). The overall lymphocytes count was significantly decreasedfrom baseline in peripheral blood (p�0.007). Also, the CD3�, CD4� andCD8� count were significantly decreased from baseline in the peripheralblood (p�0.005, 0.02 and 0.03 respectively). No significant difference wasfound in the absolute number of CD19�, CD16�, CD56�, and CD57�cells.

CONCLUSION: Patients undergoing TTP display peripheral bloodT-lymphopenia following the procedure, probably due to enhanced

extravasation in the pleura. The duration of the lymphopenia and thepossible effect on the inflammatory process of pleurodesis is underinvestigation.

CLINICAL IMPLICATIONS: To understand the systemic effects ofthoracoscopic talc pleurodesis.This study is in part supported by a grantfrom Pierre Fabre Farmaka.

DISCLOSURE: Marios Froudarakis, None.

INTRAPLEURAL ALTEPLASE FOR THE COMPLICATEDPARAPNEUMONIC EFFUSIONBeth Y. Besecker MD* Lindsay Pell PharmD Maria Lucarelli MD MaryBeth Shirk PharmD The Ohio State University, Columbus, OH

PURPOSE: To review the outcomes of patients who received in-trapleural alteplase for complicated parapneumonic effusion (PPE) at ourinstitution.

METHODS: We conducted a retrospective review of all patients whoreceived alteplase for complicated PPE from January 2002 throughOctober 2003 at our 1,000 bed university hospital. Complicated PPE wasdetermined by presence of pneumonia (diagnosed by chest xray orpresence of organisms by bronchoalveolar lavage) and presence of pleuralfluid with loculations or evidence of infection (pH�7.2; glucose � 60mg/dl; or organisms present). Efficacy was defined as radiographicresolution of complicated PPE without requiring surgery. Safety wasdefined as lack of blood transfusion within 72 hours after alteplase.

RESULTS: Nine patients were reviewed. Pleural fluid pH ranged from6.0-8.0 and glucose 4-63mg/dL. Four drained frank pus consistent withempyema. Pleural fluid cultures were positive in 5 patients. Duration ofsymptoms prior to chest tube placement ranged from hours to 4 weeks(median 7 days). Seven patients showed radiographic evidence of locula-tions. All patients received alteplase 16mg in 100ml 0.9%NaCl instilledand retained in the chest tube for 2-4 hours daily until adequate response.Number of alteplase doses per patient ranged from 1-7. Seven patientsshowed complete or almost complete radiographic resolution of the PPE;one expired due to ARDS and one required surgical decortication. Onepatient received a blood transfusion 2 days after the last alteplase dose; nocausality was established.

CONCLUSION: Alteplase had acceptable efficacy and safety whenused according to the described regimen. Alteplase led to radiographicimprovement more often than expected considering the prolonged symp-tom-to-treatment time in our patients.

CLINICAL IMPLICATIONS: Literature supports early surgical in-tervention for patients with complicated PPE. When surgery is not anoption, intrapleural fibrinolytics may be used. Studies have evaluatedurokinase and streptokinase for management of complicated PPE, butalteplase data in adults is limited to case series. With the intermittentavailability of urokinase and streptokinase and concern about streptoki-nase use in patients with streptococcal infections, alteplase is a viablealternative.

DISCLOSURE: Beth Besecker, None.

MEDICAL THORACOSCOPY USING A FLEXIRIGID THORA-COSCOPE IN THE DIAGNOSIS OF PLEURAL EFFUSION OFUNKNOWN CAUSEAtsuko Ishida MD* Teruomi Miyazawa MD Yuka Miyazu MD YasuoIwamoto MD Koji Kanoh MD Mika Zaima MD Takeo Inoue MD St.Marianna Univ. School of Medicine, Kawasaki, Japan

PURPOSE: To evaluate the efficacy of the flexirigid thoracoscope as atool for the diagnosis in pleural effusions of unknown etiology.

METHODS: Between May 2002 and October 2004, 19 patients withpleural effusion who had remained undiagnosed even after thoracentesiswere performed medical thoracoscopy under local anesthesia using aflexirigid thoracoscope, a rigid thoracoscope with a bidirectional flexibletip. Patients were examined using supplemental oxygen, either in theendoscopy suite, or at the bedside in a general ward after premedicatedwith an intramuscular injection of hydroxyzine and pentazocine.

RESULTS: The mean age was 69 years, with a male/female ratio of5:1. A definitive diagnosis was made in 17 of the 19 patients (89%), 6malignant pleural mesothelioma, 5 metastatic pleural carcinoma, 4 tuber-culous pleurisy, 1 empyema, and 1 uremic pleurisy. The mean examina-tion time was 22 minutes. Complications observed were; 1 case of CO2narcosis, 1 case of pneumothorax, and 5 cases of subcutaneous emphy-sema. There were no fatalities.




CONCLUSION: The flexirigid thoracoscopy under local anesthesiacan be considered to be a rapid, easy, less invasive, and moreover anaccurate diagnostic procedure.

CLINICAL IMPLICATIONS: It is expected to become a routineexamination for pleural effusion of unknown etiology.

DISCLOSURE: Atsuko Ishida, None.

A MODIFIED SIMPLE TECHNIQUE FOR CHRONIC IN-TRAPLEURAL CATHETER PLACEMENT IN THE MANAGE-MENT OF MALIGNANT PLEURAL EFFUSIONSMaria Cirino MD* Jennifer Greenheck Kevin L. Kovitz MD TulaneUniversity Health Sciences Center, New Orleans, LA

PURPOSE: Bronchogenic carcinoma contributes to approximately onethird of malignant pleural effusions, followed by breast cancer andlymphoma. Chronic tunneled intrapleural catheters are effective in themanagement of recurrent malignant effusions, significantly reducingsymptoms with minimal patient discomfort and decreased length ofhospital stay. The Pleurx® catheter is usually placed into the pleural spaceusing the Seldinger technique by inserting a dilator with a peel-awaysheath over a wire. This step is the most difficult. The catheter is fedthrough the sheath and the sheath is peeled away. We report a simpleroption.

METHODS: We describe our experience using a modified techniquefor placement of the 16 catheters in 13 patients (eight as a primaryprocedure, eight as part of a thoracoscopy, 3 repeats). All but 2 hadtrapped lung. All patients had symptomatic malignant pleural effusionsand the catheter was placed for palliation. Technique: Entry site isidentified; sterile preparation and local lidocaine are used. 2 cm skinincisions are made 5cm apart. The catheter is inserted directly into thepleural space using forceps after tunneling between incisions without theneed for a guide wire or dilator sheath. Suction of pleural contentsconfirms position. Anchoring and postoperative care are not changed.

RESULTS: All patients had immediate relief of symptoms and cathe-ters were placed where desired. There were no early or late complications.Catheters were removed when drainage ceased (1 removed by an ERpractitioner unfamiliar with its function). Repeat catheters were placedfor later occurring symptomatic effusions or in alternate large loculatedspaces.

CONCLUSION: This modified technique is simple, safe and webelieve more efficient when performed by physicians trained for chesttubes and minimally invasive procedures. It is easy to learn, eliminates theintroducer step, allows targeting of smaller, narrower, or oddly shapedspaces and does not increase the rate of complications.

CLINICAL IMPLICATIONS: This modified technique may improveefficiency and widen the range of practitioners who safely and comfortablyperform this important palliative procedure.

DISCLOSURE: Maria Cirino, None.

SINGLE CENTER EXPERIENCE WITH 250 TUNNELLEDPLEURAL CATHETER INSERTIONS FOR MALIGNANT PLEU-RAL EFFUSIONAlain Tremblay MD Gaetane C. Michaud MD* University of Calgary,Calgary, AB, Canada

PURPOSE: To describe the use of tunneled pleural catheter in themanagement of malignant pleural effusion in a large group of patients ina clinical setting.

METHODS: Retrospective analysis of 250 sequential tunneled pleuralcatheter insertions in patients with malignant pleural effusion in a singletertiary care center.

RESULTS: 250 tunneled pleural catheter procedures for malignantpleural effusion were performed in 223 patients (19 contralateral proce-dures and 8 repeat ipsilateral procedures) during a 3 year period.Symptom control was complete following 97 (38.8%) procedures, partialin 125 (50%), absent in 8 (3.2%) in addition to 11 (4.4%) failed insertionsand 9 (3.6%) without assessment of symptoms at the 2 week follow-upvisit. Spontaneous pleurodesis occurred following 103 (42.9%) of the 240successful tunneled pleural catheter procedures and was more frequentwhen 20% or less of the hemithorax had fluid at 2 week follow-up (57.2%vs. 25.3%, p�0.001). Catheters stayed in place for a median of 56 days.Following successful catheter placement, no further ipsilateral pleuralprocedures were required in 90.1% of cases. Overall median survival

following catheter insertion was 144 days. Complication rates were lowand compared favourably with those seen with other treatment options.

CONCLUSION: Tunneled pleural catheter placement is an effectivemethod of palliation for malignant pleural effusion which allows outpa-tient management and low complication rates. Tunneled pleural cathetersshould be considered as a first line treatment option in the managementof malignant pleural effusion.

CLINICAL IMPLICATIONS: The use of tunneled pleural cathetersfor malignant pleural effusion is safe, simple and effective and should beconsidered in the palliation of this patient group.

DISCLOSURE: Gaetane Michaud, Consultant fee, speaker bureau,advisory committee, etc. Dr. Michaud received an honorarium fromDenver Biomedical for speaking at the Societe des pneumonlogues de lalangue francaise about the use of the Pleurx catheter for malignant pleuraleffusions.

ROLE OF INDWELLING TUNNELED PLEURAL CATHETERIN TREATMENT OF HEPATIC HYDROTHORAXShaheen U. Islam MD* Carla Lamb MD Fredric Gordon MD JohnBeamis MD Richard Palladino MD Lahey Clinic Medical Center, Burl-ington, MA

PURPOSE: Hepatic hydrothorax (HH) occurs in 5% of cirrhoticpatients. Current treatment includes repeated thoracentesis, trans-jugularintrahepatic porto-systemic shunt (TIPS), pleurodesis, pleuroperitoneal orperitoneovenous shunt. Use of indwelling tunneled pleural catheter(ITPC) in symptomatic HH has not been reported. We present ourexperience on the effectiveness and utility of ITPC in patients with HHand poor functional status, either as palliation or as a bridge to transplant.

METHODS: This is a retrospective case series. Patients had symptom-atic HH from hepatic failure and were not candidates for immediate livertransplantation. Over a period of 9 months we placed ITPC (PleurX;Denver Biomedical) in 4 patients. Follow-up data was collected by clinicalassessment and chart review.

RESULTS: The baseline characteristics are presented in table 1. ITPCremained in place from 4 to 155 days. ITPC placed in one patient forpalliation to avoid repeated thoracentesis for respiratory distress died after11 days from hepatic failure. The second patient died at 4 days from sepsisunrelated to ITPC placement. A third patient with failed TIPS iscontinuing to drain his symptomatic HH at home. The ITPC was removedafter one month in a fourth patient as her HH improved.There were nobleeding complications. ITPC was placed in two patients while receivingmechanical ventilation. Pleural fluid cultures after two months with ITPCwere negative in one patient. Another patient developed a subcutaneousswelling at the catheter site from leakage of pleural fluid. The cuff of ITPCmigrated outside the skin in one patient after one month.

CONCLUSION: ITPC can relieve symptomatic HH, improve qualityof life and reduce the number of repeated thoracentesis without anincreased risk for encepahlopathy. No serious immediate or long-termcomplications were experienced. A randomized controlled trial wouldidentify benefits of ITPC in HH.

Table 1: Baseline Characteristics at the Time of ITPCPlacement

Median (range)

Age (years) 59 (49-78)Platelet count (k/dL) 98 (58-194)Hematocrit (percent) 29.9 (29-38.5)Serum creatinine (mg/dL) 0.9 (0.8-1.7)International normalized

ratio (INR)1.4 (1.2-2.0)

Total serum bilirubin (mg/dL) 3.6 (1.0-6.5)Model of End-stage Liver

Disease (MELD) score16 (8-23)

Etiology of hepatic failure Alcoholic cirrhosis &hepatitis C (n�3)

Cryptogenic cirrhosis (n�1)




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CLINICAL IMPLICATIONS: ITPC may be a safe, reversible andless invasive alternative treatment of HH, with a palliative intent interminal patients or as a transition in patients awaiting transplantation.

DISCLOSURE: Shaheen Islam, None.

A SENSITIVITY ANALYSIS OF TUBE THORACOSTOMY FAIL-URE IN PLEURAL EFFUSION APPLICATIONSKelvin K. Shiu DO* Mark J. Rosen MD Paul Mayo MD Beth IsraelMedical Center, New York, NY

PURPOSE: Tube thoracostomy is commonly used for the treatment ofcomplicated pleural effusions. A fibrinolytic agent is often administeredthrough the tube as an adjunctive treatment when drainage is deemed“inadequate”, but this decision is neither standardized nor consistent. Weexamined the variations in the definition of inadequate drainage and thepotential failure modalities associated with the procedure.

METHODS: This study applied probabilistic risk assessment (PRA) toperform a quantitative evaluation of different failure modalities. An eventtree analysis was performed to model the temporal event sequence ofidentification of effusion location, assessment of loculation, and thoracos-tomy tube insertion and maintenance. Fault tree analysis was performedfor each of these events taking into account multiple tube insertions, tubeclogging and dislocations. Numerical values used for the quantification oftube thoracostomy failure were obtained from reviews of recently pub-lished trials and studies. A sensitivity analysis was also performed toprioritize the different failure contributors.

RESULTS: The analyses showed that the presence of multiple locula-tions contributes significantly to the overall rate of tube thoracostomyfailure in about 50% of cases. There are other failure modalities that leadto inadequate tube drainage, many of which are operator dependent, andothers procedural and protocol dependent. Sensitivity analysis reveals thatimprovements in tube placement and in tube maintenance procedurescould result in up to fifty percent reduction in tube thoracostomy failure.They may include pleural ultrasonography, and operator training.

CONCLUSION: Many factors contribute to failure of adequate tubethoracostomy drainage, the most important being loculations of theeffusion. Failure rates may be reduced with improvements in proceduresand protocols related to tube placement and maintenance.

CLINICAL IMPLICATIONS: This study reveals the potential diffi-culties of comparing different tube thoracostomy studies when the studypopulations comprise different loculated effusion percentages. Differ-ences in tube insertion protocols and tube maintenance could alsosignificantly affect the success of tube drainage. Our study furthersuggests that improvement in operator training in tube insertion andplacement may reduce tube thoracostomy failure.

DISCLOSURE: Kelvin Shiu, None.

RESULTS OF A SIMPLE METHOD IN PREDICTING THETHERAPEUTIC DECISION FOR THE MANAGEMENT OFPARAPNEUMONIC PLEURAL EFFUSIONSEvaldo Marchi MD* Andre L. Casarim MS Arianne C. Pereira MSThoracic Surgery - Medical College of Jundiai, Jundiai, Sao Paulo, Brazil

PURPOSE: Parapneumonic pleural effusions (PPE) are a commoncomplication of pneumonias. Although several studies have suggestedparameters to guide the management of PPE, this subject remaincontroversial. In this study we describe the outcome of patients with PPEtreated based on a simple model of evaluation that guides the optimaltherapeutic decision.

METHODS: Seventy-five patients with PPE and negative bacteriolog-ical findings were evaluated according to their image (chest radiograms,ultrasound or CT scans) and pleural fluid (WBC counts, neutrophilpercent and LDH levels) parameters. Based on the results of eachparameter, models were created to test the sensitivity, specificity andpredictive positive and negative values of the clinical or surgical (thora-costomy) therapeutic decision in predicting the outcome of the treatedgroups.

RESULTS: PPE patients with bacteriological negative findings andwith small effusions, WBC � 1,000cels/mm3, %N � 75% and LDH �1,000IU/L were clinically treated with a successful outcome (SE � 92%;SP � 90%). PPE patients with moderate or large effusions, or WBC �1,000cels/mm3, %N � 75% or LDH � 1,000IU/L were treated with earlychest tube drainage and successful outcome (SE � 95% and SP � 92%).

CONCLUSION: Simple models including the image evaluation of thepleural effusions and the levels of pleural fluid WBC, neutrophil percentand LDH were able to predict the optimal therapeutic decisions to treatpatients with PPE with higher sensibility and specificity.

CLINICAL IMPLICATIONS: Simple models including few param-eters can be applied in the clinical practice to predict the optimaltreatment for patients with PPE.

DISCLOSURE: Evaldo Marchi, None.

Interventional Pulmonology and AirwayMalignancies12:30 PM - 2:00 PM

SYNCHRONOUS LESIONS IN THE AIRWAYS OF AFRICANAMERICAN MEN DIAGNOSED WITH LUNG CANCEREric L. Flenaugh MD* Sadia Habib MD Nneka Okafor MD Nitin PuriMD Morehouse School of Medicine, Atlanta, GA

PURPOSE: To determine the percentage of African American(AA)men with synchronous lesions present at the time lung cancer is diag-nosed.

METHODS: AA men with newly diagnosed lung cancer underwentautofluorescencebronchoscopy (AF) with the D-Light system (Storz,Tuttlingen, Germany). Synchronous lesions were detected, locationsrecorded, and biopsied. Findings were classified as metaplasia, dysplasia,carcinoma-in-situ(CIS), and carcinoma by independent pathologists.

RESULTS: Twenty-three AA men with newly diagnosed lung cancerwere enrolled.Thirty-five lesions were biopsied. Squamouscell carinomawas the histopathology of the primary lesion in 57% of patients, adeno-carcinoma and small cell carcinoma in 26% and 17%,respectively. Of thesynchronous lesions, 51% were metaplasia, 13% were dysplasia, 13% wereCIS, 10% were synchronous carcinoma, and 13% were metastatic carci-noma. Significant changes in pre-procedure staging occurred in 13% ofthe patients following AF.

CONCLUSION: 1. Cancerization was present in 87% of AA men atthe time of the initial diagnosis with primary lung cancer.2. AF helpedidentify patients with lesions that carry a high risk of developing intosecond primary lung cancers. 3. AF improved the accuracy of staging andidentified synchronous lesions in 13% of the patients studied. Thisresulted in a change of the tumor staging and treatment options.

CLINICAL IMPLICATIONS: In select patient populations, AFcould prove to be an essential tool for improving healthcare disparities.

DISCLOSURE: Eric Flenaugh, Grant monies (from sources otherthan industry) The Georgia Cancer Center of Excellence: NIH #5 P60MD 47-1.

INCIDENCE OF ENDOBRONCHIAL MESTASTASES IN A NA-TIONAL REFERRAL ONCOLOGY THORACIC SERVICEJavier Kelly-Garcıa MD* Favio Martinez-Flores MD Marco AntonioFernandez-Corzo MD Silvia Colmenero-Zubiate MD Eric Marco Garcia-Bazan MD David Zamora-Lemus MD Hospital de Oncologia, MexicoCity, Mexico

PURPOSE: To determine the incidence of endobronquial metastasesin a National Referral Thoracic Oncology Service.

METHODS: We reviewed 5 years of bronchoscopic procedures. Weonly included patients where endobronchial metastases were suspected.Information was registered with respect to the primary tumor, symptoms,X ray studies, and location of endobronquial lesion, technique forobtaining samples, diagnosis and decision for surgical intervention.

RESULTS: From May 1999 to December 2004, 1735 bronchoscopicstudies were practiced, of these 127 were done to determine lungmetastases from extrathoracic tumors. In 41 patients bronchoscopicfindings consisted of tumor in 21 cases, mucosal infiltration 16 cases andextrinsic compression 4 cases. The most frequent symptom was cough andthe radiologic abnormality was presence of a mass. The primary tumoraccording to frecuency was breast, kidney and larynx. The majority oflesions were in the right bronchial tree. Endobronchial biopsy was positivein 37.5%, cytology brushing 25% and bronchial washing in 10%. Combi-nation of the three techniques was diagnostic in 34.1%, increasing to 60%




when other methods were utilized. Five patients underwent resection ofthe lesion.

CONCLUSION: Endobronquial metastases are associated with ad-vanced metastatic disease and bronchoscopy is useful in establishing thediagnosis and determining treatment in selected cases.

CLINICAL IMPLICATIONS: Provide better quality of life in pa-tients with endobronquial metastatic disease by improving treatmentoptions.

DISCLOSURE: Javier Kelly-Garcıa, None.

THE CORRELATION BETWEEN BRONCHOSCOPIC AND RA-DIOGRAPHICAL CHANGES OF ENDOBRONCHIAL LESIONSTREATED BY ELECTROCAUTERYEmad H. Ibrahim MD* Ahmed Mehalal MD Alexandria Faculty ofMedicine, Alexandria, Egypt

PURPOSE: To determine the correlation between the changes ofbronchoscopic narrowing of the endobroncial lesions and radiographicalchanges and lung functions following therapy by fiberoptic application ofelectrocautery.

METHODS: Consecutive 22 patients with endobronchial lesions.Electrocautery was applied and data were measured before and after oneweek of treatment. The radiographic signs were collected before and afterelectrocautery from plain x-ray and computed tomograpgy including thepresence of masses, atelectases, metasis, and pleural effusion. Anyreduction in the size of the tumour or atelectasis were consideredradiographic improvement. The circumference area of the patent area ofthe bronchus affected measured using the recorded video tape before andafter one week of electrocautery. Correlation between the improvementof bronchoscopic view and radiographic data were measured. Also,pulmonary functions were compared before and after one week ofelectrocautery.

RESULTS: Twenty two consecutive patients with endobrnochial le-sions were included in the study. Age 54�12.39 and males were 77.3% ofpatients. Malignant lesions were found in 90.9% of patients; of thosepatients 40.9% had squamous cell carcinoma, 13.6% had small cellcarcinoma. The majority (54.5%) had radiological evidence of lungmasses, followed by atelectasis in 31.8% of patients. There was evidenceof bronchoscopic improvement in 86.4% of patients and radiographicimprovement in 54.5% of patients. There was a positive correlationbetween bronchoscopic and radiographic improvement (p � 0.001). Also,we found a significant improvement in lung functions and oxgen tensionafter electrocautery.Oxygen tension before and after (65.2�11.3 &79.1�10.4)(P�0.001). FEV1/FVC was 76.4�10.5 and 83.6�8.1 respec-tively(p� 0.001) FEF25-75 was 1.7�0.7 and 2.5�1.2 respectively(p�0.004). Six minute walking was 214.1�50.2 and 277.9�48.1 respec-tively (p�0.001). There was an increase in the patent affected bronchusnarrowed by the lesions (1.1�0.2 cm)and (1.9�1.3cm)respectively(P�0.001).

CONCLUSION: Endobronchial lesions treated by electrocautery areassociated with improvement in lung fuctions, radiographic features andbronchoscopic narrowing caused by the lesions.

CLINICAL IMPLICATIONS: Electrocautery is a cheap effectivemethod to treat endobroncial lesions.

DISCLOSURE: Emad Ibrahim, None.

ARGON PLASMA COAGULATION FOR THE MANAGEMENTOF ENDOBRONCHIAL LESIONS VIA FLEXIBLE BRONCHOS-COPYSu-Ying Low MB, BCh* Philip Eng MBBS Singapore General Hospital,Singapore, Singapore

PURPOSE: To evaluate the effectiveness and safety of argon plasmacoagulation (APC) via flexible bronchoscopy (FFB) for the managementof both benign and malignant airway lesions.

METHODS: Retrospective review of consecutive case records of allpatients treated at the Singapore General Hospital with APC via FFBfrom May 2002 to December 2004.

RESULTS: A total of 35 patients underwent 41 procedures, all ofwhich were performed via flexible bronchoscopy under conscious seda-tion. Mean age was 62.4�16.4years, of whom 25/35 (71.4%) were male.Of the 41 procedures, 25/41 (61%) were performed on an outpatient basis.2/41 (4.9%) of patients were in the intensive care unit requiring mechan-ical ventilation for respiratory failure. Majority of patients 27/35 (77.1%)

had malignant endobronchial lesions. The remaining 8/35 (22.9%) pa-tients had benign airway lesions due to granulation tissue or benignstrictures causing airway obstruction. The mean APC procedure time was32.7�20minutes. There was no procedure-related morbidity or mortality.All patients experienced immediate symptomatic improvement in theirdyspnoea. The 2 patients who required mechanical ventilation could beweaned off the ventilator immediately post procedure and eventuallydischarged home. Repeat APC procedures were required in 4 patients (2patients needed 2 procedures, 2 patients needed 3 procedures) tomaintain airway patency. The median time between each procedure was63days (range 23-288days). Five patients proceeded on to have rigidbronchoscopy (with or without NdYAG laser application and stentdeployment) for further management of their airway obstruction.

CONCLUSION: APC can be used to help restore airway patency forboth the palliation of airway obstruction in malignant diseases andtreatment of benign lesions. It is a safe, simple, and economic alternativeto the current available array of therapeutic bronchoscopic modalities.However, repeated procedures may be required to maintain airwaypatency.

CLINICAL IMPLICATIONS: APC is a useful adjunct for themanagement of both benign and malignant airway problems which can besafely and effectively performed via FFB under conscious sedation.

DISCLOSURE: Su-Ying Low, None.

A COMPARISON OF ENDOBRONCHIAL ULTRASOUNDGUIDED BIOPSY AND POSITRON EMISSION TOMOGRAPHYWITH INTEGRATEDCOMPUTED TOMOGRAPHY IN LUNGCANCER STAGINGMark Krasnik MD* Felix Herth MD Peter Vilmann MD Birgit G. SkovMD Søren S. Larsen MD Gentofte University Hospital, Copenhagen,Denmark

PURPOSE: Exact staging of patients with non-small-cell lung cancer(NSCLC) is important to improve selection of resectable and curablepatients for surgery. Positron emission tomography with integrated com-puted tomography (PET/CT) and endoscopic ultrasound guided fineneedle aspiration biopsy (EBUS-TBNA) are new and promising methods,but indications in lung cancer staging are controversial. No studies havecompared the 2 methods. The aim of this study was to assess and comparethe diagnostic values of PET/CT and EBUS-TBNA for diagnosingadvanced lung cancer in patients, who had both procedures performed.

METHODS: 25 patients considered to be potential candidates forresection of verified or suspected NSCLC underwent PET/CT andEBUS-TBNA. The PET/CT and EBUS-TBNA diagnoses were confirmedeither by open thoracotomy/scopy, mediastinoscopy or clinical follow-up.Mediastinal involment of lung cancer was defined as tumour-stage �IIIA(N2), corresponding to N2-N3. Diagnostic values of PET/CT andEBUS-TBNA, with regard to the diagnosis of mediastinal involment oflung cancer, were assessed and compared.

RESULTS: 10 patients had a pos PETCT for mediastinal involmentwhile mediastinal involment were found in 5 patients with EBUSTBNA.The sensitivity of PET/CT and EBUS-TBNA were respectively67%% versus 100% for N2-N3 disease . PET/CT had a specificity of 68%,positive predictive value (PPV) of 40% and a negative predictive value(NPV) of 87%. EBUS-TBNA had a specificity of 100%, PPV of 100%,NPV of 100% for mediastinal involment.

CONCLUSION: EBUS-TBNA had a sensitivity , NPV and PPV fordiagnosing advanced lung cancer, superior to PET/CT.

DISCLOSURE: Mark Krasnik, None.

WHICH AREA IN A METASTATIC LYMPH NODE OF LUNGCANCER SHOULD WE PUNCTURE BY ENDOBRONCHIAL UL-TRASONOGRAPHY GUIDED TRANSBRONCHIAL NEEDLE AS-PIRATION?Noriaki Kurimoto MD* Hiroaki Osada MD Teruomi Miyazawa MD YukaMiyazu MD Atsuko Ishida MD St. Marianna University, Kawasaki, Japan

PURPOSE: To assess the location of cancer cells in a metastatic lymphnode from lung cancer for endobronchial ultrasonography guided trans-bronchial needle aspiration (EBUS-TBNA).

METHODS: We checked 124 metastatic lymph nodes (LNs), whichwere resected at the operation, histopathologically. We classified 124metastatic LNs into 3 major stages and 3 sub-stages. Stage I: early stage:stage Ia (marginal stage: metastasis located in the marginal area, the width


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of the metastasis is less than 1/4 of the width of the LN), stage Ib (marginalinvasive stage: metastasis located in the marginal area, the width of themetastasis is less than 1/2 of the width of the LN), stage Ic (central stage:metastasis located in the central area, the width of the metastasis is less than1/2 of the width of the LN), Stage II: invasive stage (metastasis advancedbeyond the center of the LN, the width of the metastasis is greater than 1/2and less than 9/10 of the width of the LN), Stage III: advanced stage (thewidth of the metastasis is greater than 9/10 of the width of the LN).

RESULTS: In 124 LNs, Stage I had 37 LNs (29%), Stage II had 16LNs (13%), and Stage III had 75 LNs (58%). In 79 LNs which width wasgreater than 5 mm, Stage I had 16 LNs (20%). There was no LN of StageIc in 124 LNs. In 72 LNs of adenocarcinoma, Stage I, II, III had 32%, 6%,and 62%, respectively. In 44 LNs of squamous cell carcinoma, Stage I, II,III had 27%, 27%, and 46%, respectively. In 12 LNs of small cellcarcinoma, Stage I, II, III had 25%, 50%, and 25%, respectively.

CONCLUSION: Metastasis existed in marginal area, not beyond thecenter of the LN, in 20-29% (Stage Ia�Ib) LNs of total LNs. We shouldpuncture the marginal area of metastatic LNs by EBUS-TBNA.

CLINICAL IMPLICATIONS: It is necessary to study the yield ofTBNA with the puncture in the ceter area vs.marginal area.

DISCLOSURE: Noriaki Kurimoto, None.

ASSESSMENT OF POSITRON EMISSION TOMOGRAPHY POS-ITIVE LYMPH NODES: ULTRASOUND-GUIDED TRANSBRON-CHIAL NEEDLE ASPIRATION OR MEDIASTINOSCOPY?Philippe E. Pierard MD* Gavin Plat MD Jean Faber MD ThierryPrigogine MD Vincent Ninane PhD CHU Charleroi, Charleroi, Belgium

PURPOSE: Positron emission tomography with 18-fluorodeoxyglucose(FDG-PET) is more accurate than CT scan for staging of mediastinal andhilar lymph nodes. Nevertheless, histological sampling of positive lymphnodes is required to exclude false positives. The diagnostic/staging yield ofendobronchial ultrasound (EBUS) guided transbronchial needle aspira-tion (TBNA) was assessed in this particular clinical setting. The number ofavoided surgical procedures was evaluated.

METHODS: All consecutive patients referred for staging and/ordiagnosis of mediastinal FDG-PET positive lesions were included. Datawere prospectively collected. TBNA sampling of lymph nodes wasperformed after EBUS. In case of negative results, further surgicalsampling or follow-up allowed to reach the diagnosis.

RESULTS: From January 2003 to June 2004, 33 patients wereincluded. The average number of TBNA samples per patient was 4.2 �1.5. Sensitivity of EBUS-TBNA for sampling of positive FDG-PET lymphnodes was 93%, negative predictive value 71% and accuracy was 94%.

CONCLUSION: The present study shows that TBNA combined withEBUS is a very safe and effective method to assess patients withFDG-PET positive lymph nodes. In 25 (76%) of the 33 patients, surgicalstaging procedures were suppressed.

CLINICAL IMPLICATIONS: EBUS-TBNA should be considered as aprimary method of evaluation of FDG-PET positive lymph nodes and mayreplace the majority of surgical mediastinal staging/diagnostic procedures.

DISCLOSURE: Philippe Pierard, None.

STAGING PATIENTS FOR CARCINOMA OF ESOPHAGUSWITH FLEXIBLE BRONCHOSCOPYRogerio G. Xavier MD* Marcelo Gazzana MD Pierangelo Baglio MDRoger Rodrigues MD Fabio Svartman MD Sabrina Garcia MD RonaldoCosta MD Hugo Oliveira MD Hospital de Clınicas de Porto alegre, PortoAlegre, Brazil

PURPOSE: Cancer of esophagus is one of the more prevalent neo-plasms from the aerodigestive tract. Although capable to be cured by itsearly recognition, patients have poor prognosis due to advanced stagesseen at time of diagnosis. Because invasion of adjacent structures aremainly to the lower airways in cases of cancer located in the upper 2/3 ofesophagus, bronchoscopic evaluation of such patients is recommended.

METHODS: Study design of historic cohort in a series of 87 patientswith carcinoma of esophagus submitted to flexible bronchoscopy (FB)from January 2003 to April 2005. They were predominant male (83.9%),67.5 y.o. mean age (SD � 8.4). Related symptoms were cough (41.4%),weight loss (39.1%), anorexia (13.8%), dyspnea (11.5%), weakness(11.5%). Smoking (94.3%) and alcohol (63.2%) consumption were high.After careful description of the bronchoscopy findings, a statistical analysiswas made by chi-square and Fischer exact tests (p�0.05).

RESULTS: Patients were examined by FB after nasal insertion (73.6%),intravenous sedation using propofol (90.8%) and fentanil (79.3%). The mainfindings were extrinsic compression (33.3%), secretion (14.9%), blunt carina(10.3%), vocal cord paralysis or larynx lesion (8.4%), mucosal infiltration(9.2%), endobronchial tumor (8.0%) and normal (31.0%). Diagnostic sampleswere taken with bronchial biopsy (13.8%), bronchoalveolar lavage (6.9%),transbronchial punction (4.6%) and bronchial brushing (3.4%). Complica-tions registered persistent hypoxemia (2.3%), bleeding (2.3%) and broncho-spasm (1.1%). Association was confirmed between respiratory symptoms andabnormal findings at FB (p�0.05).

CONCLUSION: FB demonstrates significant alterations closely re-lated to neoplasm in the airways of patients with carcinoma of esophagus(69%), without major complications.

CLINICAL IMPLICATIONS: Bronchoscopic evaluation is an easyand safe method for staging patients with carcinoma of esophagus.

DISCLOSURE: Rogerio Xavier, None.

FIBER BUNDLE OPTICAL COHERENCE TOMOGRAPHY SYS-TEM FOR ENDOSCOPIC AIRWAY IMAGINGSari B. Mahon PhD* David S. Mukai BS Tuqiang Xie PhD Zhongping ChenPhD Matthew Brenner MD University of California, Irvine, Irvine, CA

PURPOSE: Optical coherence tomography (OCT) is a novel, non-invasive technology which can provide high and ultrahigh resolutionstructural and functional endoscopic/bronchoscopic imaging informationin biological tissues, in-vivo, in real time, at resolutions as fine as 1um.Movable components such as MEMS micro motors, mirrors and lenses,etc., needed to provide scanning for image generation in 2 or 3 dimensionshave limited the utility of OCT endoscopy. We describe a novel approachto development of 3-D OCT probes using fiber-bundles for airway andpleural endoscopy that overcomes the requirement for internal movingparts within the probe.

METHODS: Using high resolution coherent optical conduits, a fiberbundle comprised of �50,000 individual fiber cores was fabricated.Various lengths were tested, and performance was optimized with GRINlenses at the proximal and distal ends, angled end polishing to preventback reflections, and index matching between optical components. Thecoherence of the bundle preserves spatial identity from proximal to distalends. This approach enables all moving parts to be located externally,proximal to the probe. Planar images are then scanned and constructedwith our OCT system.

RESULTS: This novel system was used to image samples of excisedrabbit trachea (Figure 1). The OCT image can delineate the micromorphology of the normal rabbit trachea including mucosa, sub mucosa,glands and cartilage rings. When compared to the OCT image from ourbench top OCT system, the current fiber bundle image fidelity, includingsignal to noise ratio, image depth, and contrast, is good, but slightlydegraded.

CONCLUSION: We describe a novel OCT endoscopic imaging probeapproach based on a coherent fiber-optic bundle and demonstrate itsfeasibility in imaging tracheal tissue at transverse and axial resolution ofapproximately 12 and 10 um, respectively.

CLINICAL IMPLICATIONS: Optimization of this fiber bundle methodwill enable the production of compact and solid 3-D capable imaging probeswithout any moving parts, that may be used for high and ultra-high resolutionendoscopic diagnostics including airway and pleural applications.

DISCLOSURE: Sari Mahon, Grant monies (from sources other thanindustry) Department of Defense; Grant monies (from industry related




sources) Independent peer reviewed research grant to develop lungcancer diangnositics from Philip Morris (3 year research grant).

A THIN 4MM VIDEOBRONCHOSCOPE WITH A 2MM OPERAT-ING CHANNEL IS USEFUL IN BYPASSING CENTRAL AIRWAYSOBSTRUCTION AND IN PROVIDING DIAGNOSTIC ACCESSTO PERIPHERAL PULMONARY LESIONSRex C. Yung MD* Jack Hill BSc Loretta Colvin RN Michael DrummondMD Eric Schmidt MD Johns Hopkins University, Baltimore, MD

PURPOSE: Flexible fiberoptic and video bronchoscopes (FOB andVB) are used for central airways examination and though the workingchannels clinical samples are retrieved by a variety of methods and usinga number of FOB/VB instruments. Ultrathin bronchoscopes have beenbuilt to negotiate past central airways narrowing and to direct sampling ofperipheral parenchymal lesions. However the 2.2mm to 3.5mm instru-ments either have no working channels or a small calibered channel thatoften preclude retrieval of diagnostic specimen. This report details utilityof a new thin videobronchoscope with improved manueverability, goodimaging and a 2mm working channel through which diagnostic specimensare retrievable.

METHODS: Diagnostic bronchoscopy is performed sequentially withOlympus series 160 VB and when necessary with a prototype 4mmOlympus thin VB (XBF-4B140Y1)to bypass central airways (up to 3rdgeneration segmentations)obstruction or to direct sampling of peripherallesions. Number of airway generations reached by the respective “normal”caliber bronchoscope (5.2 - 5.8mm) are recorded by segment, correspond-ing number of airway segments reached by the thin instrument issubsequently recorded. Time spent on exam and diagnostic yield arenoted.

RESULTS: 18 cases involving 10 males, 8 females ranging from ages 38to 83 were performed. 16 cancers (11 NSCLC and 5 metastases), 1aspergilloma and 1 tracheobronchomalacia cases included. 3 have hadairway stents placed, 2 had central airways obstruction and 4 hadnarrowing of segmentalk airways leading to lesions. On average,the thinVB reaches 5.95 generations of airways per airway segment, versus 4.42with standard bronchoscope. The number of segments reached is greaterin the lower lobe segments (6.8 on right and 7.0 on left) than the upperand middel lobe segments (5.0 and 5.5). No thin-bronchoscope relatedcomplications noted.

CONCLUSION: A new 4mm videobronchoscope with a full sizedworking channel is a useful addition to the current range of diagnosticflexible bronchoscopes.

CLINICAL IMPLICATIONS: Availability and training in the use ofthin bronchoscopes may enable greater diagnostic accuracy in sampling ofmore frequently detected peripheral lesions.

DISCLOSURE: Rex Yung, Consultant fee, speaker bureau, advisorycommittee, etc. I am a consultant to Boston Scientific Corporation, whichmanufactures some of the bronchoscopy equipment used in my diagnosticprocedures and that may be mentioned in the course of my presentation.;Other Olympus USA, manufacturer of the thin bronchoscope described inthis abstract, has provided a prototype for our testing and use.

AWAKE TRACHEOBRONCHIAL DILATATION WITHOUT THEUSE OF RIGID BRONCHOSCOPYAndrew C. Chang MD* Allan Pickens MD Mark B. Orringer MDUniversity of Michigan Medical Center, Ann Arbor, MI

PURPOSE: Benign tracheal strictures have historically been treated byrepeated dilatations using rigid bronchoscopy and general anesthesia. Analternative approach utilizing conscious sedation, fluoroscopy, flexiblebronchoscopy and Savary-Gilliard esophageal dilators is reported.

METHODS: A retrospective review of our patients undergoing awaketracheobronchial dilatation was performed, after approval for IRB exemp-tion was obtained. The procedure, performed with the patient receivingintravenous conscious sedation, is accomplished with flexible bronchos-copy through the oropharynx, passage of a guidewire into the airway, andsequential Savary-Gilliard bougie dilatation using fluoroscopic confirma-tion of guidewire and dilator position.

RESULTS: Since 2002, of 14 consecutive patients requiring bronchos-copy and tracheobronchial dilatation without other associated procedures,8 patients have undergone awake dilatation (AD) without rigid bronchos-copy (RB). Primary diagnoses included Wegener’s granulomatosis, idio-pathic tracheal stenosis, and anastomotic stricture or tracheomalacia. The

maximal dilator size achieved was significantly greater for patients under-going AD rather than RB (median size, 33F v. 30F, p�0.001, Student’st-test). All patients undergoing AD had lesions that were due to inflam-matory disease or that were not amenable to tracheal resection. Nopneumothorax, tracheal laceration, procedural death or complicationsoccurred. Patients were typically discharged several hours after theprocedure. Improvement in symptoms of airway obstruction was achievedin 7 patients. With a median follow-up of 9 months (range, 2 weeks to 34months), 3 patients have required repeat dilatation.

CONCLUSION: Tracheobronchial stenoses can be dilated effectivelyand safely using the Savary-Gilliard guidewire dilatation system underfluoroscopic guidance.

CLINICAL IMPLICATIONS: Awake flexible bronchoscopy andSavary-Gilliard wire-guided tracheobronchial dilatation appears to be lesstraumatic than rigid bronchoscopy and can be accomplished on anoutpatient basis without the use of either rigid bronchoscopy or generalanesthesia.

DISCLOSURE: Andrew Chang, None.

Interventional Pulmonology: GeneralInterventional Pulmonology12:30 PM - 2:00 PM

CT-SCAN DETERMINATION OF ADVANCED, HETEROGE-NEOUS UPPER LOBE EMPHYSEMA AT SITES PARTICIPAT-ING IN A MULTICENTER TRIAL OF THE INTRABRONCHIALVALVE DO NOT REQUIRE A CENTRAL CORE LAB FOR CON-FIRMATIONDavid Ost MD* Justin P. Smith MD Xavier Gonzalez MD Steven C.Springmeyer MD Robert McKenna MD Northshore, Long Island Jewish,Manhasset, NY

PURPOSE: Results of the National Emphysema Treatment Trial(NETT) demonstrated that patients with advanced, predominant upperlobe emphysema benefit the most from lung volume reduction surgery.Subjective upper lobe predominance and classification of emphysema asheterogeneous or homogeneous was based on scoring done by thedesignated radiologist at each NETT site. A central core lab was used byNETT for quality control. The purpose of this study was to evaluate ifcenters participating in a multicenter trial to evaluate the Spirationintrabronchial valve (IBV™) system could correctly select patients withadvanced heterogeneous, predominant upper lobe emphysema withoutthe need of a central core lab. NETT radiological criteria and grading wasrecommended to the sites.

METHODS: CT-scans corresponding to patients enrolled in the studywere evaluated by an independent, Board Certified Radiologist. Theradiologist was blinded to patient and clinical site identification. Theradiologist provided an independent determination of emphysema sever-ity, predominance and heterogeneity based on a grading scale 0 (noemphysema)to 4 (severe emphysema) using NETT guidelines.

RESULTS: CT-scans corresponding to 27 patients enrolled andtreated with IBV valves between January and July 2004 at 5 clinical siteswere reviewed and evaluated. Average grading values of 3.11�0.75 and3.07�0.78 were assigned to the right and left upper zones by theindependent radiologist. Values of 1.33�0.55 and 1.33�0.48 were as-signed the right and left lower zones.

CONCLUSION: Radiologist and/or investigators at each clinical siteparticipating in the IBV multicenter trial, correctly selected and enrolledpatients with advanced, heterogeneous and upper lobe emphysema.Guidelines established by the NETT study allowed for adequate selectionwithout the need of using a central core lab.

CLINICAL IMPLICATIONS: CT-scan based selection of patientswith advanced heterogeneous emphysema can be effectively done usingappropriate radiological training and guidelines at new clinical sitesparticipating in the IBV trial.

DISCLOSURE: David Ost, Grant monies (from industry relatedsources) Spiration Inc. is sponsoring clinical trial at my institution;Product/procedure/technique that is considered research and is NOT yetapproved for any purpose. Intrabronchial Valve IBV being evaluated forthe treatment of advanced emphysema.




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USE OF ENDOBRONCHIAL VALVE FOR THE TREATMENT OFPOSTPNEUMONECTOMY BRONCHOPLEURAL FISTULACOMPLICATED BY EMPYEMARabih I. Bechara MD* Armin Ernst MD Simon Ashiku MD RobertGarland RRT David Feller-Kopman MD Beth Israel Deaconess MedicalCenter, Harvard Medical School, Boston, MA

PURPOSE: A novel, multidisciplinary, approach to the management ofrefractory bronchopleural fistula using a one-way endobronchial valve.

METHODS: Emergent approval was obtained from our Internal ReviewBoard for the use of an endobronchial valve to obstruct the segmentalbronchus leading to the site of a bronchopleural fistula. The patient had apersistent air leak and empyema despite aggressive therapy with antibiotics,thoracotomy with a muscle flap and tisseal closure. In the operating theater,rigid bronchoscopy was performed under general anesthesia, and the exactlocation of the bronchopleural fistula was identified. A guidewire was placedunder vision, and a small size endobronchial valve (Emphasys Medical Inc.,Redwood City, CA) was loaded, inserted and deployed into the involvedairway with excellent fit. The segmental bronchus was then identified bythoracic surgery and a latissimus dorsi muscle flap was again used to buttressthe fistula and fill the pleural cavity.

RESULTS: Our new approach resulted in complete healing of thebronchopleural fistula, resolution of the empyema, and complete successof the surgical repair.

CONCLUSION: We conclude that the placement of an endobronchialvalve can prevent persistent air leak in the setting of refractory broncho-pleural fistula.

CLINICAL IMPLICATIONS: A multi-disciplinary approach to thetreatment of refractory bronchopleural fistula is necessary. Furtherstudies are required to define the role of segmental bronchial occlusionfor patients with this disease.

DISCLOSURE: Rabih Bechara, Product/procedure/technique that isconsidered research and is NOT yet approved for any purpose. Endo-bronchial valves (Emphasys Medical Inc., Redwood City California) arecurrently approved for endoscopic lung volume reduction in Europe, andare currently being investigated in the United States. This abstractpresents a novel use, which was approved.

HEMODYNAMIC IMPACTS OF EXPIRATORY DYNAMIC COL-LAPSE OF THE TRACHEAFaisal Khan MD* Elamin M. Elamin MD Mansura Ghani MD SouthernIllinois University, Springfield, IL

PURPOSE: Expiratory Dynamic Collapse of Trachea (DCT) wasrecently recognized as a possible mechanism for congestive heart failure(CHF). We studied the short and long term hemodynamic impact oftracheal stenting on DCT-CHF.

METHODS: A 68 year-old male was evaluated for repeated episodesof CHF after prolonged coughing spells in spite of different treatments.Extensive cardiac and pulmonary diagnostic evaluation for CHF wasunrevealing. At bronchoscopy, there was �90% expiratory collapse of thelower 6 cm of the posterior tracheal wall, without cartilaginous involve-ment. The hemodynamic impact of DTC was assisted by impedancecardiography with stroke volume index (SVI) measured at rest, duringcoughing, then two and four minutes after cessation of cough (Figure 1).Similar hemodynamic measurements (HM) were obtained six and twelvemonths after placement of an uncovered ultraflex tracheal stent (Micro-vasive, Natick, MA) to support the collapsible portion of the trachea.

RESULTS: At six and twelve months post-stenting the patient had norecurrence of CHF with HM demonstrated a statistically significantstabilization of the SVI (p�0.01) (Figure 1).

CONCLUSION: This was the first documented report of DCT-CHFwith cough induced intrinsic-positive end expiratory pressure leading todecrease in SVI. The later was reversed by tracheal stenting with thebenefits persisted at six and twelve months follow up. A prospective studyis currently under way for further evaluation of that process.

CLINICAL IMPLICATIONS: Expiratory Dynamic Collapse of Tra-chea should be considered in the work up of congestive heart failure.

DISCLOSURE: Faisal Khan, None.

SILICONE AIRWAY STENTS IN THE TREATMENT OF PA-TIENTS WITH DIFFUSE TRACHEOBRONCHOMALACIAAdnan Majid MD* Rabih Bechara MD Yoshihiro Nakamura MD DavidFeller-Kopman MD Simon Ashiku MD Malcom DeCamp MD ArminErnst MD Tufts-New England Medical Center, Boston, MA

PURPOSE: To evaluate the effectiveness of airway stents in thetreatment of diffuse tracheobronchomalcia (TBM) and their complica-tions.

METHODS: Single center retrospective analysis of medical recordsfrom patients with diffuse TBM referred to a major academic center fromJanuary 2002 to June 2004 who underwent central airway stenting(tracheal, main bronchus or both). Patient charts were reviewed forimprovement of symptoms and complications.

RESULTS: Number of patients stented: 29; number of patients withimprovement of symptoms: 23(80%), without improvement of symptoms6(20%); how did symptoms improve: off mechanical ventilation 4 (17%),less cough 12(52%), less shortness of breath 17(74%), less medications4(17%); number of complications:24 (83%),time of complications: �3months 20 (83%), �3months 4(17%), median 26 days (3-865 days);procedure related: 3(13%), stent related:21(87%) (infection 6(29%),migration 6(29%), obstruction 12(57%), breakage 1(5%),hemoptysis1(5%),respiratory failure 2(10%), cough 2(10%)).

CONCLUSION: Silicone stents improve symptoms in carefully se-lected patients with moderate to severe TBM. Unfortunately, treatmentwith these stents is associated with a significant number of short andlong-term complications that limits their use.

CLINICAL IMPLICATIONS: Airway stents currently have a role inidentifying patients with diffuse TBM who will benefit from central airwaystabilization.

DISCLOSURE: Adnan Majid, None.

USE OF SILICONE STENTS IN THE MANAGEMENT OF TRA-CHEOBRONCHIAL STENOSIS DUE TO TUBERCULOSISYonju Ryu MD* Eun Hae Kang MD Won-Jung Koh MD Gee Young SuhMD Man Pyo Chung MD O. Jung Kwon MD Hojoong Kim MD Divisionof Pulmonary and Critical Care Medicine, Samsung Medical Center,Seoul, South Korea

PURPOSE: To assess the usefulness and safety of silicone stentsplacement and to compare those between widely used Dumon stents andnewly designed Natural silicone stents in the management of tracheo-bronchial stenosis due to tuberculosis.

METHODS: The medical records of 69 patients (31 Dumon and 38Natural) requiring the placement of 75 silicone stents (35 Dumon and 40Natural) for airway stenosis due to tracheobronchial tuberculosis werereviewed and analyzed.

RESULTS: Ballooning was the leading method of dilation beforestenting (90%). Immediate and lasting relief of dyspnea or improvementof FEV1 was no difference between the Dumon and the Natural group.In both treatment groups, an equal proportion of patients (58% of theDumon group and 61% of the Natural group) had successful stentremoval with median 18 months vs 13 months of stent in situ, orderly.During follow-up, the occurrence of stent-related complications such asmigration (39% vs 63%), granuloma formation (42% vs 58%), mucostasis(19% vs 18%) and restenosis (48% vs 37%) were not significant different


Interventional Pulmonology: GeneralInterventional Pulmonology, continued


between the Dumon and the Natural group, respectively. Natural stentsand Dumon stents were equally easily inserted and removed. Duringfollow up for median 32months, clinical outcome was stationary in allpatients.Conclusion: The silicone stents replacement should be consid-ered in treating tracheobronchial stenosis due to tuberculosis. Both ofDumon and Natural silicone stents seemed to be appropriate, since theefficacy and safety of Natural stent proved to be similar to those of Dumonstent in the management of airway stenosis due to tracheobronchialtuberculosis.

CONCLUSION: Both of Dumon and Natural silicone stents seemedto be appropriate, since the efficacy and safety of Natural stent proved tobe similar to those of Dumon stent in the management of airway stenosisdue to tracheobronchial tuberculosis.

CLINICAL IMPLICATIONS: The silicone stents replacementshould be considered in treating tracheobronchial stenosis due to tuber-culosis.

DISCLOSURE: Yonju Ryu, None.

VIRTUAL NAVIGATION OF CENTRAL AND PERIPHERAL AIR-WAYSHiroshi Natori MD* Hirotsugu Takabatake MD Masaki Mori MDHiroyuki Koba MD Kensaku Mori PhD Takayuki Kitasaka PhD YasuhitoSuenaga PhD Sapporo Medical University School of Medicine, Sapporo,Japan

PURPOSE: This study was performed to understand the structure ofboth central and peripheral airways including bronchiloles and thealveolar space by the virtual bronchoscopy method. Image data for virtualnavigation were obtained from three-dimensional data of multi-detectorCT (MDCT) and of micro-focused cone-beam CT (MCT).

METHODS: Three-dimensional data of the chest were obtained fromclinical MDCT scans. Data of peripheral lung structure were obtainedfrom MCT scanning of a resected lung specimen which was chemicallyfixed and inflated by Heitzman’s method. Virtual navigation of thebronchial space on personal computers was performed by the custom-made program that was created by one of the author K.M.

RESULTS: Observation of the internal structures of the lung waspossible on any three dimensional sectional planes by volume renderingdisplay mode. High speed navigation from the trachea to subsegmentalbronchi was performed on clinical chest MDCT data. Navigation to thebronchioles, respiratory bronchioles, alveolar ducts, and alveoli weremade successfully on MCT data. Precise structures of alveoli were clearlyobserved on MCT data.

CONCLUSION: Virtual navigation from trachea to alveoli was per-formed. This method was useful for non-destructive three dimensionalunderstanding of the airways. Repeated non-limited navigation waspossible.

CLINICAL IMPLICATIONS: This system was useful for under-standing of the airways in education, training, and pre-bronchoscopicinformed consent for the patient with bronchial lesions or peripheral lungdiseases that require trans-bronchial lung biopsy.

DISCLOSURE: Hiroshi Natori, None.

NAVIGATED BRONCHOSCOPY AND ENDOBRONCHIAL UL-TRASOUND FOR BRACHYTHERAPY OF INOPERABLE PE-RIPHERAL LUNG CANCER: A FEASIBILITY STUDYHeinrich D. Becker MD* Wolfgang Harms MD Thoraxklinik, Heidel-berg, Germany

PURPOSE: To prove the feasibility and the safety of endobronchialhigh dose radiation of inoperable peripheral tumors of the lung bycatheter placement based on electromagnetic navigation and endobron-chial ultrasound.

METHODS: After localization of the lesion by electromagnetic navi-gation, confirmation of the position by endobronchial ultrasound andassessment of histology a brachytherapy catheter is placed via an extendedworking channnel, fixed at the nose and left in place for one week. Thepatient is transferred to the radiotherapy department. A total dose of 15Gyis applied by introducing an Ir192 source three times a week based ongeometrical optimization to the target volume. Follow-up includes ultra-sound guided biopsies and chest CT.

RESULTS: Six patients have been treated so far. The treatment hasbeen tolerated without major side effects or complications. The longestobservation period is more than one year with only minor cytological

residuals. The ultrasonic image of the tumor changed significantly corre-sponding to the histological response.

CONCLUSION: Brachytherapy of inoperable peripheral lung tumorsis feasible and is a safe procedure.

CLINICAL IMPLICATIONS: Brachytherapy could become a prom-ising approach for potentially even curative treatment of inoperableperipheral tumors of the lung sparing major damage to radiosentitivesurrounding tissue.

DISCLOSURE: Heinrich Becker, Grant monies (from industry re-lated sources); Technical support by SuperDimension Co., Herzliya,Israel.

EBUS TBNA IN DIAGNOSING HILLAR AND MEDIASTINALLESIONSMark Krasnik MD* Peter Vilmann MD Birgit G. Skov MD Felix HerthMD Gentofte University Hospital, Copenhagen, Denmark

PURPOSE: The aim of the present study was to test the use ofEBUS-TBNA in the evaluation of mediastinal and hillar lesions in patientswith an undiagnosed solid lesion of unknown origin in the mediastinumand hillar regions or enlarged lymph nodes in the mediastinum outlinedby CT.

METHODS: EBUS TBNA was prospective performed in 110 patients.7 patients with a tumour in the mediastinum and 103 patients withenlarged lymph nodes in the mediastinum or the hillar regions. Bronchos-copy and TBNA have been performed in all patients without obtaining adiagnosis.

RESULTS: A total of 7 tumours and 230 lymph nodes were biosied.EBUS TBNA was positive for cancer in 144 lymph nodes and 6 tumours.In 7 lesions the specimen was without conclusive material.In 85 patientsa malignant diagnose was obtained. In 18 patients a specific non malignantdiagnose was obtained (sarcoidosis, thymus, ectopic thyroid, granoloma-teous infection and fungal infection).. All the diagnosis was confirmedeither by EUS, mediastinoscopy or Thoracotomy/scopy. The diagnosticyield was 98% In 8 patients the malignant diagnose was obtained bypuncture of N1 lymph nodes.

CONCLUSION: EBUS TBNA is an effective and non invasive methodto obtain a diagnose in patients with lesions of unknown origin in themediastinum and hillar regions.

DISCLOSURE: Mark Krasnik, None.

REAL-TIME VIRTUAL ASSISTANCE FOR TRANSBRONCHIALNEEDLE ASPIRATION: FEASIBILITY STUDYJae J. Choi PhD* Eric D. Anderson MD Kevin Cleary PhD Seong K. MunPhD Georgetown University, Washington, DC

PURPOSE: Transbronchial needle aspiration(TBNA) is a commonprocedure for diagnosis of mediastinal and hilar lymphadenopathy. Cur-rently, pulmonologists prepare for this procedure by examining CT imageslices; then, they estimate the location of the lymph node or tumor duringthe bronchoscopy. The success rate for this approach is near 70%. Ourstudy aims to increase this success rate. By utilizing electromagnetictracking and a registration technique, corresponding virtual images thatshow the lymph node or mass behind the airway may be displayedsimultaneously alongside the real bronchoscope images. This techniquemay increase the accuracy of TBNA.

METHODS: A custom phantom was CT-scanned with fiducials on thesurface. We also developed image guidance software that includes manualsegmentation, point-based registration, tracking, 3D visualization, andvirtual bronchoscopy components. Using this software, we manuallysegmented the mass and generated a centerline to the biopsy target.Before inserting the bronchoscope, we registered the CT space and thepatient space by providing corresponding points in two spaces based onthe fiducials. For bronochoscope tracking, we used the Aurora electro-magnetic tracking device. Using a flexible bronchoscope, we inserted anelectromagnetically tracked catheter into the phantom. Using the frame-grabber card, we could capture the video sequence from the broncho-scope.

RESULTS: The average root-mean-square (RMS) registration errorwas 2.5 mm. The phantom model showed good correlation between thevirtual and video bronchoscopic images. The software displayed lymphnodes, great vessels, and adjacent structures by making the airwaystransparent. By providing real-time virtual display during the actualbronchoscopy, we expect to improve the accuracy of TBNA.




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CONCLUSION: This study is the first step towards our final goal ofproviding real-time assistance for TBNA with virtual images. Next, we willdevelop a real-time registration algorithm to align virtual and videobronchoscope images. We will narrow the search space by using theelectromagnetic tracking device, and estimate the virtual location that bestmatches the virtual and video images.

CLINICAL IMPLICATIONS: Virtual bronchoscopy with electro-magnetic tracking may lead to an improved yield of TBNA.

DISCLOSURE: Jae Choi, None.

CT-GUIDED TRANSTHORACIC NEEDLE BIOPSY OF SAR-COIDOSISAlisa Johnson BA* Jeffrey S. Klein MD Santiago Miro MD University ofVermont College of Medicine, Burlington, VT

PURPOSE: To determine the utility, sensitivity and complication rateof CT-guided transthoracic needle aspiration and core biopsy for samplingenlarged hilar and mediastinal lymph nodes in patients with presumptivesarcoidosis.

METHODS: A retrospective review of all transthoracic needle biopsiesperformed at one institution from 1995-present for diagnosis of enlargedhilar or mediastinal lymph nodes thought to reflect sarcoidosis and either1) symptoms requiring definitive diagnosis for treatment or 2) a history ofmalignancy where metastatic disease was a differential diagnostic consid-eration.

RESULTS: 28 patients, age range 34-74, males � 13, females � 15,underwent CT-guided aspiration (n�28) and core (n�19) biopsy using anextrapleural approach when possible. 9 patients had a history of prior orconcurrent malignancy. Using a combination or cytologic and histologicmaterial, a diagnosis of sarcoidosis and exclusion of malignancy waspossible in all patients (sensitivity � 100%). 8/28 patients (28%) devel-oped a postbiopsy pneumothorax, with 2 (7%) requiring small borecatheter drainage and one patient with self-limited hemoptysis.

CONCLUSION: CT-guided transthoracic needle biopsy, using acombination of aspiration and core biopsy techniques, has a high yield andacceptable complication rate for the diagnosis of sarcoidosis presentingwith enlarged mediastinal and hilar lymph nodes.

CLINICAL IMPLICATIONS: This minimally-invasive technique canprovide definitive pathologic diagnosis of sarcoidosis in patients withenlarged mediastinal and hilar lymph nodes, confidently excluding malig-nancy and obviating the need for further invasive diagnostic procedures.

DISCLOSURE: Alisa Johnson, None.

THE EFFECTS OF THE AGE DURING FLEXIBLE BRONCHOS-COPY: PREDICTORS OF COMPLICATIONSMario Polverino MD* ASL Salerno 1, Cava De Tirreni, Italy

PURPOSE: Elderly patients generally show a good tolerance of flexiblebronchoscopy (FBS). Patients’ age has not emerged as a specific riskfactor for bronchoscopy complications; FBS is well tolerated in theelderly, so that major modifications of the procedure because of patients’age alone are generally unnecessary. (Clin Chest Med 2001;22.2:301). Incontrast, Davies et al. reported that 21% of patients over 60 yrs developedpotentially serious, albeit transient, cardiac ischaemic events/rhythmdisturbances (ERJ 1997;10:695). The aim of our study was to evaluatepredictors of complications in FBS related to the patients’ age.

METHODS: We retrospectively analyzed clinical and functional char-acteristics, as well as bronchoscopic procedures referring to 88 patients,divided into two groups: group A): 43 patients £ 65-yrs old and group B:45 patients 3 66-yrs old. Collapse or consolidation were the most commonindications for FBS in elderly patients (56%), whereas indications in groupA were more heterogeneous.

RESULTS: 2 out of 43 patients of group A (4.65%) and 9 out of 45patients of group B (20%) showed minor complications during or afterFBS. The greater prevalence of complications in the elderly was related tothe greater number of diagnostic procedures in these patients (48 vs. 30)and to the comorbidities which were present in 9 out of 45 patients ofgroup B: it is worth mentioning that no elderly patient suffered fromcomplications in absence of comorbidity.

CONCLUSION: Elderly age is not a risk factor for complications inflexible bronchoscopy. If any, they are due to the comorbidities and to thegreater number of diagnostic procedures, related to the different patternof clinical indications.

CLINICAL IMPLICATIONS: Our paper analyze the predictors ofcomplications during flexible bronchoscopy and the relationship withpatient age.

DISCLOSURE: Mario Polverino, None.

RISK OF CANDIDEMIA IN PATIENTS WITH CANDIDA IN THEBRONCHIOALVEOLAR LAVAGETheophilus T. Ogungbamigbe MB, ChB* Kennedy Eneh MD Marie F.Schmidt MD Sharon Ngan MD Sekar Natarajan MD Danilo EnriquezMD Joseph Quist MD Interfaith Medical Center, Brooklyn, NY

PURPOSE: Candida is a common flora found in the mouth, throat andgastrointestinal tract of healthy individuals; although the presence ofcandida in patients who are acutely or chronically ill may have differentclinical implications. This study was performed to define the relationshipbetween the presence of candida in the bronchioalveolar lavage (BAL)and the subsequent development of candida in the blood.

METHODS: We reviewed the records of 62 patients with BALpositive for candida. All patients with oral thrush and those on antifungalagents were excluded from the study. None of the patients had candi-demia prior to the isolation of candida in the BAL. Out of those 62patients, 37 were male and 25 were female. The mean age was 58.2 (21 to93). In terms of comorbidity 21 patients out of 62 (33%) were HIV/AIDS,14 (23%) had lung cancer, 18 (29%) were on mechanical ventilator formore than 7 days.

RESULTS: 5 out of 62 patients (8%) developed candidemia, 3 out ofthose 5 also had candida in the urine leaving only 2 out of 62 patients (3%)with candida both in BAL and blood. These 2 patients developedcandidemia within 1 to 6 weeks after confirming candida in the BAL.None of those 5 patients with candidemia had transbronchial biopsypositive for candida. All 5 patients expired.

CONCLUSION: Since only 2 out of 62 had candida in both BAL andblood, it could be inferred that the isolation of candida in the BAL doesnot appear to increase the risk of disseminated candida infection. Oncecandidemia develops the mortality becomes very high. However it is notclear whether death resulted from candidemia; or rather from theassociated comorbid conditions.

CLINICAL IMPLICATIONS: The isolation of Candida in the BALdoes not appear to be of great clinical significance. It does not seem toincrease the risk of candidemia. The small sample size might be alimitation in our study. A larger study is required to confirm this result.

DISCLOSURE: Theophilus Ogungbamigbe, None.

DO OXYGEN SUPPLEMENTATION REQUIRED DURING FI-BEROPTIC BRONCHOSCOPYMayank Vats MD* Rakesh C. Gupta MD Deepa V. Khandelwal MBBSNeeraj Gupta MD Maheep Saluja MD Mukesh Tailor MBBS J.L.N.Medical College, Ajmer, Rajasthan, India

PURPOSE: Most common indication of flexible bronchoscopy (FOB)in our setting is bronchogenic carcinoma, usually associated with Chronic-Obstructive-Pulmonary-Disease, concomitant infection, and hence hyp-oxia. The aim of study was to establish the value of O2 -supplementationduring FOB to avoid catastrophic consequences of hypoxemia.

METHODS: Forty patients of C.O.P.D. and 10 controls were studiedfor oxygen saturation (SpO2) by pulse-oximetry during FOB and classifiedinto: -Group-1 (n�10):Age-&-sex matched healthy controls. Group-2A(n�10):FOB without O2-supplementationGroup-2B (n�15):FOB withO2-supplementation {nasal-catheter (rate-3 liters/min)}.Group-2B(n�15):FOB with O2-supplementation {pharyngeal-catheter (rate-3 li-ters/min)}.

RESULTS: In control-group mean % fall from baseline-values inPFT after premedication and local anaesthesia (L.A.) and in study-group after premedication it was insignificant (p�0.05). In study-group mean % fall from baseline after L.A. was 16.4�4% in FVC,11.2�2.6% in FEV1 and 12.1�5.5% in PEFR in group-2A, 14.8�3.5%in FVC, 15.5�3.9% in FEV1 and 16�6% in PEFR in group-2B and15.9�5.4% in FVC, 16.3�5.5% in FEV1 and 13�1.1% in PEFR ingroup-2C patients (p�0.01, Highly Significant). In control-groupmean-SaO2 at baseline was 97.7�2%.( Mean decline was-1.1%)(p�0.05). In 2A-group mean-fall in SpO2 after L.A. was insignificantbut highly significant fall of 7.9% in the mean SpO2 during FOB(p�0.001) and significant rise of 3.5% just after BronchoAlveolarLavage( BAL) (p�0.001) were observed. In group-2B patients signif-




icant rise in SpO2 was observed during FOB (p�0.01) and after BAL(p�0.001) and mean SpO2 were higher than the baseline. In group-2C, significant rise in mean SpO2 were observed during, after BAL and20-min after FOB. Transient hypoxemia (SpO2 �85%) was observedin group-2A-40% cases , 2B-6.6% and 2C-1.2% cases. Minimum SpO2observed during FOB were group-2A-87�4% , group-2B-92�3% andgroup-2C- 94�4%.

CONCLUSION: During FOB, SaO2 levels were significantly better inpatients with O2 –supplementation and were almost similar with nasal andpharyngeal-catheters.

CLINICAL IMPLICATIONS: The need for pulse-oximetry andsignificance of O2-supplementation in patients with hypoxia is empha-sized.

DISCLOSURE: Mayank Vats, None.

FLEXIBLE BRONCHOSCOPY PROCEDURES AT HIGH ALTI-TUDE AND INDICATION FOR ADDITIONAL OXYGEN SUP-PORT: THE MORELIA MULTICENTER EXPERIENCEE. A. Maldonado-Ortiz MD* Hector Herrera MD Julia Ramirez Pulmo-nary and Respiratory Care Uniit, Hospital de la Mujer, Morelia, Mi-choacan, Mexico

PURPOSE: Clinical desaturation could be present during diagnosis/therapeutical procedures using flexible fiberbronchoscopy FBC. Theuse of additional oxygen is subjet to great variations both withing andbetween countries. The role of geographical altitude during FBC andthe indication of additional oxygen support has not been well de-fined.To evaluate at 1951 meters above sea level the incidence ofadditional oxygen support and the main indication during FBC at 5differents community hospitals.

METHODS: Consecutive patients who underwent FB were prospec-tively evaluated. Epidemiological data, indications and oxygen saturationwas monitored before, during and after procedure and recorded at 5different intervals: a) in supine position,b) through nasal/oral route untilepiglotis, c) during tracheal evaluation, d) diagnostic/therapeutical proce-dure, e) at any moment when desaturation was detected.

RESULTS: 83 patients were enrolled but 3 excluded because domi-ciliary oxygen support. FBC was performed transnasally (97%), 100% of ppresented an episode of desaturation �90% for a period �30 seg. 35/80p,received additional oxygen support during FBC: nasal catheter (5/14.3%),face mask (22/62.8%), ventury mask (2/5.7%) and non invasive mechanicalventilation (6/17.1%).

CONCLUSION: Despite high altitude, in The Morelia multicentricexperience, the use of additional oxygen support to all population is notmandatory during FBC.

CLINICAL IMPLICATIONS: The rational use of additional oxygensupport could be elegible to those population who really need it, withpotential economical impact.

DISCLOSURE: E Maldonado-Ortiz, None.

Lung Cancer Biologic Markers12:30 PM - 2:00 PM

EXPRESSION OF AQP1, AQP3 AND AQP5 IN THE HUMANLUNG CANCER TISSUEMakoto Sugita MD* Sumiko Maeda MD Motoyasu Sagawa MD MiyakoShimasaki MS Yoshimichi Ueda MD Tsutomu Sakuma MD KanazawaMedical University, Ishikawa, Japan

PURPOSE: The movement of water across cell membrane is essentialto life. Recent investigations have demonstrated that aquaporins (AQPs),a family of water channels, are essential for maintaining the transmem-brane water transport. Among at least 11 AQPs identified in mammaliantissues, AQP1, AQP3, AQP4, and AQP5 have been recognized in the lung,however, their expression and functions in the normal and diseasedhuman lungs are poorly understood. In this study, we aimed to investigatethe expression of AQPs in the human lung cancer tissue. We examined

expression of AQP1, AQP3, and AQP5 by immunohistochemical stainingand real-time PCR.

METHODS: A total 48 fresh frozen lung tissue samples including 45lung cancer samples (27 adenocarcinomas, 10 squamous cell carcinomas,4 large cell carcinomas, and 4 small cell carcinomas) and 3 normal lungtissue samples were studied. Expression of AQP1, AQP3, and AQP5 wereexamined by immunohistochemical staining with polyclonal antibodiesagainst AQP1, AQP3, and AQP5. Their mRNA was extracted followinglaser-captured microdissection, and real-time PCR was used for quanti-tative analyses of mRNA expression of AQP1, AQP3, and AQP5.

RESULTS: AQP3 was well expressed in non-mucinous bronchioloal-veolar carcinoma (BAC) and well-differentiated adenocarcinoma, how-ever, AQP3 was poorly expressed in mucionus BAC. In contrast, AQP5was poorly expressed in non-mucinous BACs, however, AQP5 was wellexpressed in mucious BAC. In mucinous BAC and well-differentiatedadenocarcinoma, AQP1 was well expressed in 50% of the cases. Thereal-time PCR study confirmed the results of immunohistochemicalstaining.

CONCLUSION: Our results indicate that AQP1, AQP3, and AQP5 aredifferentially expressed in the human lung cancer tissue. The results wereconfirmed by both immunohitochemical staining and real-time PCR.Furthermore, the expression patterns of AQPs are found to be associatedwith pathohistological characteristics.

CLINICAL IMPLICATIONS: We speculate that the distinct expres-sion patterns of AQPs are associated with cancer-related genes. Therefore,expression patterns of AQPs may be used not only for markers of the lungcancer, but also for the therapeutic targets.

DISCLOSURE: Makoto Sugita, None.

PROMOTER -202 A/C POLYMORPHISM OF INSULIN-LIKEGROWTH FACTOR BINDING PROTEIN-3 GENE AND NON-SMALL CELL LUNG CANCER RISKJin Wook Moon MD* Yoon Soo Chang MD Young Sam Kim MD ChangHoon Han MD Shin Myung Kang MD Moo Suk Park MD Sung Kyu KimMD Joon Chang MD Se Kyu Kim MD Chul Min Ahn MD Departmentof Internal Medicine, Yonsei University College of Medicine, Seoul,Korea

PURPOSE: Insulin-like growth factor binding protein-3 (IGFBP-3)inhibits the mitogenic and anti-apoptotic activity of insulin-like growthfactor (IGF) by blocking the binding of IGF to its receptor. However,under certain circumstances, IGFBP-3 can enhance the activity of IGF byprotecting IGF from degradation. More than half of the inter-individualvariations in IGFBP-3 levels are known to be genetically determined bythe polymorphism at -202 locus of IGFBP-3 gene. Therefore, weattempted to ascertain whether the A-202C polymorphic variation ofIGFBP-3 gene constitutes a risk factor for non-small cell lung cancer(NSCLC).

METHODS: Our study included 209 NSCLC patients and 209 age-,gender-, and smoking status-matched control subjects. After extractingthe genomic DNA, we amplified the 168-base-pair (bp) fragment encom-passing the A-202C polymorphic site in IGFBP-3 gene. Each PCRproduct was digested with FspI enzyme and electrophoresed. The allelewas designated either C or A depending on whether the FspI restrictionsite was present or not.

RESULTS: The frequencies of each polymorphic variation in thecontrol population were as followes: AA � 95 (45.5%), AC � 91 (43.5%),and CC � 23 (11.0%). In the NSCLC subjects, the genotypic frequencieswere as follows: AA � 131 (62.7%), AC � 73 (34.9%), and CC � 5 (2.4%).We detected statistically significant differences in the genotypic distribu-tion between the NSCLC and the control subjects (p �0.05, Pearson’s �2–test). The NSCLC risk correlated significantly with AA genotype. UsingCC genotype as a reference, the odds ratio (OR) for the subjects with ACgenotype was 2.45 (95% CI: 1.17 - 5.40) and the OR for the ones with AAgenotype was 4.58 (95% CI: 2.17 - 10.30).

CONCLUSION: Our results indicate that there are differences in thegenotypic distribution at the A-202C polymorphic site of IGFBP-3 genebetween NSCLC and general populations.

CLINICAL IMPLICATIONS: The dysregulation of IGF axis shouldnow be considered as another important risk factor for NSCLC, apotential target for novel antineoplastic therapies, and preventativestrategies in high-risk groups.

DISCLOSURE: Jin Wook Moon, None.




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CIGARETTE SMOKE EXTRACT INHIBITS ALVEOLAR MAC-ROPHAGE CYTOTOXICITY AGAINST TUMORAL CELLSLea-Isabelle Proulx MS* Annie Spahr BSc Elyse Y. Bissonnette PhDCentre de Recherche, Hopital Laval, Institut Universitaire de Cardiologieet de, Quebec, PQ, Canada

PURPOSE: Cigarette smoke is composed of more than 4000 com-pounds including 20 pulmonary carcinogens. It is well known thatcigarette smoke contributes to the development of lung cancer, but thereis limited information about its role in the formation and the proliferationof tumoral cells. Alveolar macrophages (AM) play a major role inpulmonary homeostasis via mediator production and cytotoxicity againsttumoral cells. Therefore, we hypothesized that cigarette smoke extract(CSE) inhibits AM functions contributing to the development and theproliferation of tumoral cells.

METHODS: NR8383, a rat AM cell line, was exposed or not to CSE3% for 20 h in presence of LPS (10 ng/ml) and tumor necrosis factor(TNF) production was assessed in cell-free supernatants. AM cytotoxicityagainst WEHI-164, a TNF-sensitive fibrosarcoma cell line, was alsomeasured using a chromium51 release assay.

RESULTS: CSE significantly inhibited both AM TNF production(41.53 � 3.8 %) and TNF-dependent cytotoxicity (42.81 � 1.08 % forcontrol cells compared to 36.41 � 1.40 % for exposed cells).

CONCLUSION: The inhibition of AM TNF production by CSE maycontribute to the inhibition of AM cytotoxicity against TNF-sensitive cells.

CLINICAL IMPLICATIONS: A reduce cytotoxic activity of AMagainst tumoral cells may explain the persistence and the proliferation ofthese cells in people exposed to cigarette smoke.

DISCLOSURE: Lea-Isabelle Proulx, None.

CD1 GENOTYPES IN LUNG CANCER PATIENTSMehrnoosh Doroudchi PhD* Hossein Golmoghaddam MS Seid Moham-mad A. Ghayoomi MD Abbas A. Ghaderi PhD Shiraz University ofMedical Sciences, Shiraz, Iran

PURPOSE: It has been suggested that CD1a and CD1d moleculesinduce tumor-specific immune responses by presentation of tumor cellglycolipids to specific T cells and NKT cells. A decrease in the CD1aexpressing dendritic cells in lung cancer as a mechanism of tumor escapefrom immune system has been reported. Therefore, this study wasconducted to compare the genotypic frequencies of CD1a and CD1dgenes in lung cancer patients and healthy controls.

METHODS: Polymorphisms in exon 2 of CD1A (C622T) and CD1D(A354T) genes, were studied in 64 Iranian lung cancer patients comparedto 95 age/sex/ethnicity matched and 311 non-matched healthy blooddonors by a Polymerase Chain Reaction Sequence Specific Primermethod.

RESULTS: The frequencies of CC, CT and TT genotypes of CD1Agene among patients were 75%, 18.8% and 6.2% compared to 78.9%,28.1% and 0% in the matched control group and 79.7%, 18.7%, and 1.6%in the non-matched control group, respectively. There was a significantdifference in the genotype frequencies of CD1A between lung cancerpatients and matched controls (P � 0.047). However, the differencebecame less significant by comparing CD1A genotypes between patientsand 311 non-matched blood donors (P � 0.085). No deviations fromHardy-Weinberg equilibrium in control groups were observed. The onlyobserved genotype of CD1D among patients and controls was AAhompzygote genotype.

CONCLUSION: Our results suggest that there is a correlation be-tween CD1A genotypes and lung cancer. Although the exact effect of thispolymorphism on the protein expression or function is not understood, theresulted substitution of Threonine with Isoleucine in the antigen bindinggroove of the CD1a protein might affect antigen presentation potential ofthe molecule.

CLINICAL IMPLICATIONS: This study will help us in betterunderstanding of genetic susceptibility to lung cancer and might provideopportunities for developing screening methods and/or lipid vaccines forcancer therapy in future.

DISCLOSURE: Mehrnoosh Doroudchi, None.

LIPID PEROXIDATION AND PROSTAGLANDINS IN HUMANLUNG CARCINOMAGeorge G. Chen PhD* Tak W. Lee MD Hu Xu PhD Johnson H. YipMPH Anthony P. Yim MD Department of Surgery, Prince of WalesHospital, The Chinese University of Hong, Shatin NT, Hong Kong PRC

PURPOSE: Lung cancer formation is a multifactorial process. Lipidperoxidation is one of oxidative conversion of polyunsaturated fatty acidsto products known as malondialdehyde (MDA) or lipid peroxides. How-ever, there is limited information available for a systemic examination oflipid peroxidation, prostaglandin production and Bcl-2 in human lungcancer.

METHODS: The present study was to measure the lipid peroxidationin human lung cancer and to analyze how lipid peroxidation was associatedthe prostaglandin production and Bcl-2 expression. Fifty-two non-smallcell lung carcinoma (NSCLC) tissue samples and their correspondingnon-cancer tissue samples were used in this study.

RESULTS: The level of MDA was significantly increased in thelung cancer tissues, compared with non-cancer lung tissues. Of twoprostaglandins measured, thromboxane B2 (TXB2) was much higher inthe cancer tissues than non-cancer tissues. Though prostaglandin E2(PGE2) showed no significant difference. The changes in both TXB2and PGE2 were not related to cigarette smoking in cases we studied.The expression of Bcl-2, which is also functioned as an antioxidantagent, was significantly elevated in the tumor tissues, compared to thenon-tumor tissues. There was a positive correlation between MDA andTXB2 in both cancer and non-cancer lung tissues. MDA level wascorrelated with Bcl-2 in lung cancer tissues of Stages I and II but wasnot with those of Stage III. The cancer at the advanced stage appearedto have a higher level of TXB2.

CONCLUSION: An increase in the lipid peroxidation may be re-garded as an oxidant insult and also a marker for high-turn over of TXB2.In conclusion, our study demonstrated that the production of TXB2 wasincreased in lung caner tissue and that such an increase can result in lipidperoxidation which may be met by an elevation in Bcl-2 expression.

CLINICAL IMPLICATIONS: Our study suggests that the level oflipid peroxidation, thromboxane and Bcl-2 may serve as a marker forassessing the stage of the tumor and also monitoring the potentialmetastasis.

DISCLOSURE: George Chen, None.

SOLUBLE HER-2/NEU OVEREXPRESSION IN PATIENTS WITHLUNG CANCERMohammad A. Ghayumi MD* Mehrnoosh Doroodchi MD KambizAghasadeghi MD Shiraz University of Medical Sciences, Shiraz, Iran

PURPOSE: The Her-2/neu oncogene encode a growth factor receptor,P185. Overexpression of this protein is thought to confer a growthadvantage to tumors and has been associated with an adverse outcome inNon Small Cell Lung Cancer.

METHODS: This study is a case-control, cross sectional study toevaluate the clinical usefulness of soluble Her-2/neu as a marker in thediagnosis of lung cancer. Level of soluble Her-2/neu in 43 lung cancerpatients and 42 age/sex matched controls, measured by an enzymeimmunoassay method.

RESULTS: More than 93% of patients aged more than 55 years and83% of lung cancer patients were smoker. Mean serum level of solubleHer-2/neu in cancer patients was 6.07�10.37 ngr/ml which was signifi-cantly higher than that of control (P � 0.05). Cigarette smoking has noeffect on the level of soluble Her-2/neu. A cut off level of 6.1 ngr/mlrevealed a high specificity (95%) for diagnosis of lung cancer, with verylow sensitivity (14%). Conclusion: The results of this study show thehigher level of soluble Her-2/neu in the sera of lung cancer patients withhigh specificity and low sensitivity for a cut off level of 6.1 ngr/ml.

CONCLUSION: The results of this study show the higher level ofsoluble Her-2/neu in the sera of lung cancer patients with high specificityand low sensitivity for a cut off level of 6.1 ngr/ml.

DISCLOSURE: Mohammad Ghayumi, None.


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HOXB4-INDUCED APOPTOSIS IN REH CELLS IS NOT MEDI-ATED VIA THE INTRINSIC CASPASE-9 PATHWAYKamal K. Mubarak MD* Robert J. Pauley PhD Yanni Zhuang Larry TaitPhD Amro Aboukameel Ramzi M. Mohammad PhD Wayne StateUniversity, Detroit, MI

PURPOSE: Pathogenesis of primary pulmonary mucosa-associatedlymphoid tumors (MALT) and lymphomas remains unknown, but isthought to involve antigen stimulation leading to immortalization, andthen subsequent transformation into a more aggressive phenotype.HOXB4 is a homeobox transcription factor that is known to clonallyexpand hematopoietic stem cells. We have previously shown that HOXB4is also an apoptotic agent in the pre-B acute lymphoblastic leukemia cellline REH via the extrinsic pathway that activates caspase-8 and caspase-3leading to DNA disintegration. We now demonstrate that despite the factthat HOXB4 is homologous to the Drosophila gene Deformed, HOXB4-induced apoptosis in REH cells is not mediated via the intrinsic pathwaycascade that involves the second mitochondria-derived activator ofcaspase (SMAC) and caspase-9.

METHODS: The HOXB4 cDNA was ligated into the mammalianexpression vector pLNCX2 and REH cells were transfected with theplasmid construct using lipofection. Constitutive expression was con-firmed by immunocytochemistry.

RESULTS: The REH cells transfected with control plasmid beganto grow exponentially 4 weeks after transfection. Cells transfected withpLNCX2-HoxB4 declined in number and died. Immunocytochemicalstaining with anti-SMAC antibody was negative at 2, 3, and 4 weeksafter transfection. Similarly, no caspase-9 activity was detected at 2, 3,or 4 weeks. Parallel experiments re-demonstrated that FLASH(FLICE-associated huge protein) expression was expressed faintly at 2weeks, and more strongly at subsequent time points. Caspase-8 andcaspase-3 were faintly expressed at 3 weeks and more stronglythereafter.

CONCLUSION: Despite the sequence homology between the humanprotein HOXB4 and the Drosophila protein Deformed, the pathway ofapoptosis induced by these proteins is different. Deformed activatesReaper, but HOXB4 does not activate SMAC (a homolog of Reaper).Apoptotic pathways have diverged during the course of evolution.

CLINICAL IMPLICATIONS: Our results provide further mechanis-tic insight into the apoptosis induced by HOXB4 in cell lines derived fromhematological malignancies. Since HOXB4 causes clonal proliferation ofhematopoietic stem cells and apoptosis of hematological malignant celllines, targeting this pathway may be of therapeutic benefit.

DISCLOSURE: Kamal Mubarak, None.

P53 CODON 72 POLYMORPHISM IN IRANIAN LUNG CANCERPATIENTSMehrnoosh Doroudchi PhD* Seid Mohammad A. Ghayoomi MD Abdul-mohammad Pezeshki MS Mohammad J. Fattahi MS Abbas A. GhaderiPhD Shiraz University of Medical Sciences, Shiraz, Iran

PURPOSE: To investigate G/C (Arg/Pro) polymorphism in exon 4 ofthe p53 tumor suppressor gene in Iranian lung cancer patients.

METHODS: In this study, the frequency of the respective p53 alleleswas investigated in 64 Iranian lung cancer patients and 205 ethnicity-matched healthy blood donors by an Allele-Specific Polymerase ChainReaction method.

RESULTS: The frequency of Arg allele was 59% in control groupcompared to 49% in the lung cancer patients. The frequencies of Proallele in control and patient groups were 41% and 51%, respectively.Accordingly, there was no significant difference in the allele and genotypefrequencies between the patients and controls, as a whole. However, ahighly significant increase in the Pro allele was observed in patients withsmall cell lung cancer compared to controls (71% vs. 41%, P � 0.009). Inaddition, a trend of increase in the Pro allele was observed in small celllung cancer compared to non-small cell carcinoma of lung (71% vs. 46%,P � 0.05). No significant difference was observed in the frequencies ofp53 alleles between smoker and non-smoker patients (P � 0.4).

CONCLUSION: Our data indicate that, as a whole, there is noassociation between p53 codon 72 polymorphism and lung cancer,however, there is an accumulation of Pro allele in the small cell lungcancer in our patients.

CLINICAL IMPLICATIONS: The presence of Pro allele of the p53tumor suppressor gene in Iranian small cell lung cancer increases

heritable susceptibility to the disease and might provide clues for lungcancer screening in our population.

DISCLOSURE: Mehrnoosh Doroudchi, None.

Lung Cancer Evaluation and Diagnosis12:30 PM - 2:00 PM

USEFULNESS OF DETECTION OF P16 PROMOTER METHYL-ATION OF TUMOR SUPPRESSOR GENES IN SERUM DNAFROM NON-SMALL CELL LUNG CANCER PATIENTS USINGREAL-TIME PCRYasuhiro Suga MD* Kuniharu Miyajima PhD Hidetoshi Honda MDJitsuo Usuda PhD Tatsuo Ohira PhD Masahiro Tsuboi PhD NorihikoIkeda PhD Takashi Hirano PhD Harubumi Kato PhD Tokyo MedicalUniversity, Tokyo, Japan

PURPOSE: The application of molecular markers specific for lungcancer offers new possibilities for early detection. Recent evidencesuggests that tumor cells may release DNA into the circulation, which isenriched in the serum and plasma. p16 tumor suppressor gene can beinactivated by promoter lesion methylation in many tumor types includinglung cancer, We examined whether aberrant p16 methylation might alsobe found in the serum of patients with non-small cell lung cancer usingreal-time PCR.

METHODS: Serum samples were obtained from 95 patients withnon-small cell lung cancer, 66 adenocarcinomas, 23 squamous cellcarcinomas, 6 large cell carcinomas and 32 normal controls. All patientwere diagnosed at our hospital. We tested 127 samples to determine thequantity of p16 promoter methylation using real-time PCR.

RESULTS: Aberrant p16 promoter methylation of the tumorsuppressor gene was detected in 25 of 95 NSCLC patients (mean:18.613�5.090), but only 2 of 32 normal control (mean: 1.258�0.871).There was a statistical difference between non small cell lung cancerpatients and normal control (t-test: p�0.003). We drew the cutoff lineat 3.0. Sensitivity was 26.3%, specificity was 93.8%, accuracy was43.3%, positive predictive value was 92.6%. However there were nosignificant differences between p16 promoter methylation in serumand gender, smoking history, histological type and stage. Interestingly,we found a statistical difference about aging between less than 62 yearsold and over 63 years old in relation to p16 promoter methylation inserum of patient with non small cell lung cancer patients and normalcontrol.(p�0.0088; Fisher’s exact test) Some cases were initiallypositive for methylated p16 DNA in serum before surgery, and alltuned negative after curative surgery.

CONCLUSION: There was a significant difference between non smallcell lung cancer patients and normal control about the p16 methylationlevel.

CLINICAL IMPLICATIONS: Detection of aberrant p16 promoterrmethylation in serum using real time PCR appears useful for lung cancerdiagnosis, early detection and clinical follow up.

DISCLOSURE: Yasuhiro Suga, None.

TISSUE LEVELS OF PLATELET-DERIVED ENDOTHELIALCELL GROWTH FACTOR/ THYMIDINE PHOSPHORYLASE,VASCULAR ENDOTHELIAL GROWTH FACTOR AND CATHEP-SIN-D IN LUNG CANCER PATIENTSAliae A. Mohamed MD* Nagla T. Elmelegy MD Assiut UniversityHospital, Assiut, Egypt

PURPOSE: The present study aimed to acquire more informationabout the role of platelet derived-endothelial cell growth factor/thymidinephosphorylase (PD-ECGF/TP), vascular endothelial growth factor(VEGF) and cathepsin-D (Cath-D) as angiogenic factors in the pathogen-esis and progression of lung cancer.

METHODS: Patients: The study included histopathologically con-firmed lung biopsies of 37 patients with bronchogenic carcinoma, 12patients with benign chest diseases and 12 non -inflammatory nonmalignant biopsies as control. Bronchogenic carcinoma cases were classi-fied into squamous cell carcinoma (14), adenocarcinoma (10), large cellcarcinoma (6) and small cell lung carcinoma (7).


Lung Cancer Biologic Markers, continued


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RESULTS: The present study showed a significant increase in thetissue levels of studied bioindices in patients with lung cancer incomparison to other groups, with significant higher levels in patients withinoperable cancer, advanced stages, bulky tumors and with lymph nodemetastasis. Also, Significant higher tissue levels of VEGF and Cath-Dwere also demonstrated in lung adenocarcinoma cases.

CONCLUSION: The present study indicates the importance of thestudied bioindices as angiogenic factors in pathogenesis and progression oflung cancer.

CLINICAL IMPLICATIONS: Therefore the development of newtherapeutic agents with an anti- angiogenic action may be of greatimportance in the management of patients with lung cancer.

DISCLOSURE: Aliae Mohamed, None.

CORRELATION BETWEEN SURVIVIN EXPRESSION ANDPROGNOSIS IN NON-SMALL CELL LUNG CANCERSukran Atikcan MD* Ebru Unsal MD Funda Demirag MD Deniz KoksalMD Aydin Yilmaz MD Ataturk Chest Diseases and Chest SurgeryEducation Hospital, Ankara, Turkey

PURPOSE: Survivin is a recently identified protein as an inhibitor ofapoptosis, which supresses programmed cell death and regulates celldivision. In this study, we investigated the prognostic significance of bothnuclear and cytoplasmic survivin expression in non small cell lung cancer(NSCLC) and examined the association with clinicopathological parame-ters.

METHODS: The study comprised 58 male patients diagnosed NSCLCwith a mean age of 57.29�8.82 years; range 40-76 years. Patientsunderwent lobectomy (36%) or pneumonectomy (64%) with hilar andmediastinal lymph node sampling. Paraffin embedded tumor sectionswere retrieved for evaluation of nuclear and cytoplasmic staining ofsurvivin. Clinicopathological data, stage and survival of patients were alldetermined.

RESULTS: Cytoplasmic staining was found significantly increased insquamous cell carcinoma (p�0.003), whereas there was no associationbetween nuclear staining and histopathological type (p�0.837). Also, bothnuclear and cytoplasmic staining did not show any association with tumorstage (p�0.05). In univariate analysis there was significant correlationbetween nuclear survivin and short survival (p�0.0002). In multivariatesurvival analysis using Cox regression, only nuclear staining of survivin wasdetermined as an independent prognostic factor (p�0.001).

CONCLUSION: Localisation of survivin expression might have animportant regulatory mechanism in carcinogenesis and tumor progression.Nuclear survivin expression in tumor tissues might predict the prognosisin NSCLC, whereas cytoplasmic survivin has no prognostic significance.

CLINICAL IMPLICATIONS: Survivin expression in tumor tissuescan be used as a prognostic factor in lung cancer and can be helpful in theevaluation of disease.

DISCLOSURE: Sukran Atikcan, None.

MANAGEMENT OF PATIENTS AT RISK OF LUNG CANCERUSING CYTOMETRIC ASSAYSBojana Turic MD* Roger A. Kemp PhD Perceptronix Medical Inc.,Vancouver, BC, Canada

PURPOSE: We believe that Automated Cytometry of Quantitatively(AQC) stained cells from sputum and buccal mucosa provide informationthat can be used to guide the management of patients at risk for lungcancer. We have studied whether it is possible to construct a managementregime for patients at risk of developing lung cancer based on sequentialapplication of simple assays.

METHODS: Induced sputum specimens and buccal scrapings werecollected from 120 patients with confirmed lung cancer and 810 high risknegative patients. The specimens were prepared to slide and stained usingthe Feulgen-thionin process, which highlights DNA distribution in cellnuclei. They were scanned using a fully automated image cytometer whichproduces a single score for each specimen, indicating the likelihood ofpresence of malignancy. The buccal and sputum cytometry scores werecompared to see if the assay results provide essentially the same informa-tion or if they complement each other. The answer to this questionsuggests how the two tests can be used for patient management.

RESULTS: The correlation of the tests’ outcomes was significant(correlation�0.37) and suggests the assays could be used in a sequentialapproach for managing patients. The buccal assay eliminated 262 nega-tives (32%) at the cost of 9 false negatives (7.5%). See the figure below.After the addition of the sputum assay results, 87 lung cancer cases weredeemed “suspicious” (72.5%) at the cost of 125 (15.4%) false positives.

CONCLUSION: A simple buccal test can eliminate one third ofpatients from more comprehensive testing. The further application of thesputum assay provides high sensitivity and specificity for detecting lungcancer. The AQC testing approach has undergone a validation trialinvolving 1183 patients from clinical sites in six countries. Patients wereaccrued from March 2003 until October 2004. Results of the trial will beunblinded in June 2005 and presented at the conference.

CLINICAL IMPLICATIONS: Cytometry based assays may prove tobe an important tool for management of high risk patients.

DISCLOSURE: Bojana Turic, Employee Perceptronix Medical Inc.

Table 1: Clinical Characteristics of the StudiedPatients and Controls.

Variable

Controls

(n�12)

Patients with

benign chest

disease

(n�12)

Lung cancer

patients

(n�37)

Number 12 12 37

Gender (m/f) 8/4 5/7 27/10

Age (mean� SD)

Range

45.6�11.6

22-70

45.0�12.7

20-62

61.2�7.52

42-72

Smoking Non smokers

Ex-smokers Smokers

8 (80%)

2 (20%)

0 (0%)

7 (58.3%)

2 (16.7%)

3 (25%)

8 (21.6%)

11(29.7%)

18 (48.7%)

Final diagnosis Free COPD IPF

Bronchiectasis Old pulmonary TB

12 (100%) ---- -5 (41.8%)

3 (25.0%)

2 (16.6%)

2 (16.6%)

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Lung Cancer Evaluation and Diagnosis,continued


LUNG ADENOCARCINOMAS WITH MIXED SUBTYPES: A DIS-TINCT BIOLOGIC ENTITY?Joon H. Yim MD* Lee C. Zhu MD Andre Moreira MD New YorkUniversity Medical Center, New York, NY

PURPOSE: To present a new category of lung carcinoma termed“minimally invasive” adenocarcinoma, give criteria for its definition, and topresent data validating such a designation.

METHODS: 164 cases of primary lung adenocarcinomas resectedbetween 1992-2004 were reviewed and divided into 4 groups. Group I:BAC only (49); Group II: Mixed subtype with ��26�5 mm invasivecomponent (16); Group III: Mixed subtype with �5 mm invasivecomponent (63); Group IV: Invasive carcinoma only (36). Tumor size andlymph nodes metastasis were compared. P53 and Ki-67 staining wereanalyzed in 72 cases (14 from Group I; 9 from Group II; 13 from GroupIII; 36 from Group IV). The Ki-67 labeling index (LI) was determined bycounting 500-1000 tumor cells in three high-power fields (400X) of themost highly labeled areas. P53 overexpression was defined as the presenceof nuclear staining in �20% of tumor cells.

RESULTS: Progressively greater lymph node involvement was seenfrom Group I to Group IV (0%, 0%, 14.8%, 75%). The mean Ki-67 LI(6.2%, 7.5%, 22%, 44.6%) and frequency of p53 overexpression (8%,11%, 33.1%, 56.3%) also showed an increasing tendency from group Ito IV.

CONCLUSION: Data shows that adenocarcinomas with mixed sub-types (groups II, III) have characteristics between BAC (group I) andpurely invasive carcinoma (group IV), supporting the idea that this entityis an intermediate lesion between BAC and invasive cancer. A subgroupof this entity (group II) has characteristics and behavior more similar toBAC, suggesting that this subgroup could be defined as a form of earlyinvasive cancer, and may be clinically managed as such.

CLINICAL IMPLICATIONS: An increasing number of lung adeno-carcinomas resected fall into this category of mixed subtype adenocarci-noma. Many of them are being treated similarly to purely invasiveadenocarcinoma. This data suggests that such treatment is not necessary;more conservative therapy may be mandated.

DISCLOSURE: Joon Yim, None.

PLEURAL PLAQUES AND RISK OF LUNG CANCER: A PRO-SPECTIVE FOLLOW-UP STUDYGunnar N. Hillerdal MD* Karolinska Hospital, Stockholm, Sweden

PURPOSE: Whether asbestos exposure per se can increase the riskof lung cancer or if asbestosis is a necessary prerequisite for thisdisease has been and is still hotly debated in the literature (1-2).Pleural plaques is a fairly common radiological finding among men inthe general population and (provided that the plaques are properlydefined radiologically) is a good indicator of former usually occupa-tional exposure. In 1997, it was shown that in a material of more than1500 persons with pleural plaques but without radiological or func-tional signs of asbestosis, mortality in lung cancer was significantlyincreased (3). This cohort has now been followed further to seewhether the lung cancer risk remains high.

METHODS: The identity of all patients with lung cancer from 1992 to2003 from the Swedish Cancer Registry was matched with the plaquecohort. The study was approved by the Ethical Committe.

RESULTS: Between 1970 and 1985, 1596 men were include in thematerial, the vast majority from findings of a health survey. They wereborn between 1887 and 1948. At the end of 1991, 1126 were still alive.From 1992 to 2003, 10 lung cancers occurred in this small cohort. This ismore than expected.

CONCLUSION: The risk of lung cancer in the Plaque cohort ismoderately increased, strengthening the hypothesis that asbestos and notasbestosis is a contributing cause of lung cancer.

CLINICAL IMPLICATIONS: Pleural plaques should alert the clini-cian that the person in question has been exposed to asbestos andtherefore has a moderately increased risk for bronchial carcinoma.Refer-ences: 1 Hillerdal G, Henderson DW. Scand J Work Environ Health1997;23:93-103.2. Weiss W. Chest 1999;115:536-49.3. Hillerdal G. Chest1994; 105:144-50.

DISCLOSURE: Gunnar Hillerdal, None.

ENDOSCOPIC ULTRASOUND WITH FINE NEEDLE ASPIRA-TION FOR THE DIAGNOSIS AND STAGING OF ADVANCEDLUNG CANCERRosemary F. Kelly MD* Vita V. Sullivan MD Robert A. Kratzke MD AmyM. Holmstrom RN Frank A. Lederle MSN Douglas B. Nelson MDMandeep S. Sawhney MBBS VA Medical Center, Minneapolis, MN

PURPOSE: More than 70% of patients with lung cancer are notcandidates for a curative resection. Though many of these patients aresymptomatic and may benefit from palliative therapy, available modal-ities fail to obtain a tissue diagnosis in up to 30% of patients.Endoscopic ultrasound (EUS) guided biopsy is a technique, notroutinely used in lung cancer, that would allow sampling of lungmasses and metastasis involving the mediastinum, liver and adrenals.The accuracy and feasibility of EUS was reviewed to define its role inlung cancer diagnosis and staging.

METHODS: From March 2003 to January 2005, all patients at theMinneapolis Veterans Affairs Medical Center with suspected lung cancerand not candidates for curative surgery, were identified. Computedtomography (CT) and positron emission tomography scans were reviewed.Patients with lesions approachable by EUS were enrolled in the study.Outcomes were analyzed by final tissue diagnosis or serial imaging.

RESULTS: 68 patients met inclusion criteria. Three patients re-fused further studies. The remaining 65 patients constituted the studypopulation. EUS made a correct diagnosis in 57/65 patients (45 withmalignant and 12 with benign pathology). 29% of these patients hadundergone a failed prior attempt at tissue diagnosis. Over all, thesensitivity of EUS was 85%, specificity 100% and accuracy 88%. In the8/65 patients were EUS failed to obtain a tissue diagnosis, EUS wastechnically infeasible in 3. Malignancy was confirmed in these 8patients using video-assisted thoracoscopy (n�1), mediastinoscopy(n�3), CT guided biopsy (n�2) and bronchoscopy (n�1). Twocomplications of chest pain and hemoptysis were self-limited andresolved without intervention.

CONCLUSION: EUS provides an alternative method of tissue diag-nosis for advanvced lung cancer that is highly safe and accurate.

CLINICAL IMPLICATIONS: EUS complements bronchoscopy andCT by reaching central areas that are traditionally difficult to access. Ifavailable, it should be consider along with bronchoscopy and transthoracicneedle aspiration as a “first line” diagnostic procedure.

DISCLOSURE: Rosemary Kelly, None.




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EARLY RESULTS FROM LUNG CANCER SCREENING USINGSPIRAL CT OF HIGH-RISK INDIVIDUALSLynn Huffman MD* Prakash Pandalai MD Michael F. Reed MD JefferyNeu MSN Elsira Pina DO Kevin Redmond MD Abdul-Rahman JaziehMD Christopher Meyer MD Ralph Shipley MD John Howington MDUniversity of Cincinnati College of Medicine, Cincinnati, OH

PURPOSE: Lung cancer is the number one cancer killer. Chestcomputed tomography (CT) for early lung cancer detection is anapproach that relies on a presymptomatic phase for identification andintervention. Our objective was to determine if screening with chestCT can identify early-stage lung cancer in high-risk individuals in theOhio River Valley.

METHODS: Study subjects were recruited by local advertisement,letters to community and university physicians, and information providedon multiple university web sites. Inclusion criteria were: volunteers able tounderstand informed consent; age over 50 years; and a minimum of atwenty pack-year smoking history. Exclusion criteria were: symptomaticlung cancer at the time of screening; or a history of cancer in the past fiveyears. Subjects completed a questionnaire conducted by research person-nel and then underwent a screening thoracic spiral CT. Management ofnodules was based on a defined algorithm including the following criteria:annual follow-up CT for �5mm or no nodules; 6-month follow-up CT for5-7mm; review by committee for 8-12mm; and biopsy for �12mm.

RESULTS: From August 2001 through April 2005 131 subjects wereevaluated. Sex distribution was nearly equal. The average age was 64. Theaverage subject started smoking at 17. The average age of those who quitwas 56. The average pack-per-day smoked was 1.6. The average pack-yearsmoking history was 62. Fifty-six percent had at least one non-calcifiednodule. Five subjects had nodules greater than 12mm and four underwentbiopsy. Three patients had stage IA non-small cell lung cancer (NSCLC)and one had stage IIIA NSCLC. All patients diagnosed with lung cancerunderwent complete resections: two VATS lobectomies, one open lobec-tomy, and one open bilobectomy. There was no operative mortality. Todate no volunteer has undergone biopsy for a benign nodule.

CONCLUSION: Screening chest CT can identify early-stage lungcancer in high-risk individuals.

CLINICAL IMPLICATIONS: Early diagnosis allows surgical resec-tion that is often curative. A larger study will identify the specificparameters that define high-risk patients among whom screening willincrease survival.

DISCLOSURE: Lynn Huffman, None.

EFFECT OF SMOKING CESSATION AFTER DIAGNOSIS OFLUNG CANCER ON PERFORMANCE STATUS AND SURVIVALSevin Baser MD* Georgie A. Eapen MD Carlos A. Jimenez MD Amir Onn MDVickie R. Shannon MD Leendert Keus Rodolfo C. Morice MD E. Lin TheUniversity of Texas MD Anderson Cancer Center, Houston, TX

PURPOSE: To evaluate the impact of smoking history and smokingcessation after diagnosis on performance status and survival in patientswith lung cancer.

METHODS: Retrospective analysis of patients with NSCLC seen at ourpulmonary function laboratuary between Jan’01 and Nov‘01. Clinical charac-teristics, smoking history, comorbidities, survival, performance status, andpulmonary function tests were reviewed. We estimated the associationbetween smoking status after diagnosis and survival and performance changefrom baseline to 6 months and 12 months.

RESULTS: We studied 206 patients: 93 (45%) were smokers, 15 (7%)were nonsmokers, and 98 (48%) were former smokers (�1year). Therewas no significant association between smoking history at diagnosis andchange in performance status (ZUBROD) and survival. Of the 93smokers, 46 quit and 47 continued smoking after diagnosis. Stage, age,gender, and comorbidities were similar between these two groups. Therewas no significant association between smoking status after diagnosis andpatients’ survival. However, those who quit smoking maintained a betterperformance status at 6 and 12 months (p�0.006 and p�0.008) than thosewho continued smoking.

CONCLUSION: Smoking history before and after diagnosis of lungcancer did not affect survival, but patients who quit smoking maintaineda better performance status than those who continued smoking.

CLINICAL IMPLICATIONS: Smoking cessation after diagnosis oflung cancer has a beneficial effect on performance status but not onsurvival.

DISCLOSURE: Sevin Baser, None.

CORRELATION BETWEEN LUNG MASS SIZE IN NON-SMALLCELL LUNG CANCER (NSCLC) AND BRAIN METASTASESH. Aziz MD A. Blamoun MD M. Shubair MD M.M. Ismail MD* M.A.Khan MD St. Joseph’s Regional Medical Center, Paterson, NJ

PURPOSE: The aim of our study was to determine whether the size ofa primary NSCLC predicts the presence of brain metastases.

METHODS: We retrospectively reviewed the size of lung mass by CTscan of the chest in 35 patients (16 males, 19 females, age range 41-95 yrs;mean age 67.4yrs) who were diagnosed with NSCLC during the past twoyears whose CT scans of the brain were negative for brain metastases. Wethen compared it with the size of the lung mass in CT scan of the chestin 35 patients (16 males, 19 females, age range 41-91 yrs; mean age 65.7Yrs) who were also diagnosed with NSCLC but had CT scans of the brainthat showed brain metastases.

RESULTS: The size of lung mass in patients without brain metastaseswas smaller (mean 3.311�1.668cm; 95%CI� 2.738-3.884) than in thosewith brain metastases (mean 4.866�2.612cm; 95%CI�3.969-5.763). At acut-off of 3.9cm (determined by ROC curve analysis), the odds ratio ofbrain metastases was 13.96 (P�0.0001).

CONCLUSION: There is direct correlation between the size of thelung mass and brain metastases in NSCLC.

CLINICAL IMPLICATIONS: Lung mass size � 3.9cm in NSCLCpredicts the presence of brain metastases.

DISCLOSURE: M.M. Ismail, None.

IMPACT OF PULMONARY DYSFUNCTION AS A CAUSE OFINOPERABILITY FOR PATIENTS WITH NON-SMALL CELLLUNG CANCERSevin Baser MD* Vickie R. Shannon MD Georgie A. Eapen MD CarlosA. Jimenez MD Amir Onn MD Leendert Keus Rodolfo C. Morice MD ELin University of Texas, MD Anderson Cancer Center, Houston, TX

PURPOSE: To determine the role of pulmonary dysfunction as areason for inoperability for patients with NSCLC who were considered forsurgical treatment at the time of diagnosis.

METHODS: We studied all patients with NSCLC referred for preop-erative evaluation to our pulmonary function laboratory between January2001 and November 2001. Clinical characteristics, staging, smokinghistory, comorbidities, and clinical notes were reviewed. Pulmonaryfunction testing consisted of spirometry, lung volumes, DLCO, 133Xenonquantitative V/Q studies, and exercise testing when indicated.

RESULTS: We evaluated 206 patients (M�120;F�86) with NSCLC.Mean age was 64.7�10.1 yrs. Average predicted FEV1�70.3%�19.6%(range 25%-123%). One hundred and thirty- two (64%) patients had at

Lung Mass Size (cm) Metastases No Metastases

�3.9 26 6�3.9 9 29




least one comorbidity: DM 15 (7%), HTN 66 (32%), CAD 47(23%),COPD 18(9%), and asthma 5(2%). In addition, 59(29%) had history ofother malignancies. One hundred and ninety-one (93%) were smokers orformer smokers. After completion of their evaluation, tumor staging was:IA:28 (14%), IB:27(13%), IIA:8(4%), IIB:31(15%), IIIA:48(23%), IIIB:39(19%) and IV:25(13%). The histologic types were: adenocarcinoma87(42%), squamous 72(35%), large cell 43(21%), and BAC 4(2%). Onehundred had surgery. The remaining 106 did not have surgery because ofthe following reasons:.

CONCLUSION: Pulmonary dysfunction alone is the cause for inop-erability for nearly one-fifth of patients initially considered for surgicaltreatment for NSCLC.

CLINICAL IMPLICATIONS: Clear understanding of the frequencyof pulmonary dysfunction amongst lung cancer patients is cornerstone fordevelopment of treatment strategies alternative to surgery ( ie conformalXRT) or methods of improving lung function preoperatively (ie lungvolume reduction or pulmonary rehabilitation).


THE PULMONARY FUNCTION LOSS TO SMOKING PACK-YEAR IS AN INDEPENDENT PROGNOSTIC FACTOR IN NON-SMALL CELL LUNG CANCER PATIENTS HAVING SMOKINGHISTORYJeong-Seon Ryu MD* Hun-Jae Lee MD Jae-Hwa Cho MD Seung-MinKwak MD Hong-Lyeol Lee MD Tai-Hoon Moon MD Jae-Kap Lee MDInha University Hospital, Incheon, South Korea

PURPOSE: Smoking is a major risk factor causing lung cancer andchronic obstructive pulmonary disease. Smoking status has been known tobe an independent prognostic factor of lung cancer patients. We con-ducted this study to know if individual susceptibility to smoking is relatedto the survival in locally advanced or advanced non-small cell lung cancer(NSCLC) patients.

METHODS: From our prospective cohort of the lung cancer, afterexcluding non-smokers, we included locally advanced or advancedNSCLC patients who were completed with treatment(n�186) or treatedonly conservatively(n�151) in this study. All patients were performedpulmonary function testing at the time of diagnosis. We estimatedindividual susceptibility to smoking using a formula of (100-%predictedFEV1)/pack-year and categorized it by quartile based on the distributionamong study subjectsThe statistical analysis of the survival data wasperformed using SAS program (version 8.1). The duration of mediansurvival were defined as the time from diagnosis to death attributed tolung cancer and that were estimated by Kaplan-Meier method. Thedifference of survival curve among subgroups were evaluated by log-ranktest. To evaluate the effect of susceptibility to smoking on survival wasprognosis, Cox proportional hazard regression analysis was performed.

RESULTS: Clinical stage of the patients was IIIA in 65(19.3%), IIIB in120(35.6%) and IV in 152(45.1%). The median survival time was13.2months(95% CI: 11.9-15.0 months) for treatment group and4.9months(95% CI: 3.8-6.5 months) for conservative care group(P�0.001). In log-rank test survival time were significantly differentaccording to age, sex, body weight loss (�5%), %predicted FEV1, clinicalstage and individual susceptibility to smoking(P�0.005, 0.036, �0.001,0.006, �0.001 and �0.001, respectively). The hazard ratio adjustingcovariates among patients of highest quartile of susceptibility to smokingwas 1.90(95% CI: 1.49-2.38).

CONCLUSION: Therefore we suggest that individual susceptibility tosmoking is an independent prognostic factor of stage III and IV NSCLCpatients.

CLINICAL IMPLICATIONS: This study may be first of showingindividual susceptibility to smoking is an independent prognostic factor oflocally advanced or advanced NSCLC patients.

DISCLOSURE: Jeong-Seon Ryu, None.

EFFECT OF PULMONARY DYSFUNCTION ON SURVIVAL ANDPERFORMANCE IN PATIENTS WITH NON-SMALL CELLLUNG CANCERSevin Baser MD* Amir Onn MD Carlos A. Jimenez MD Georgie A.Eapen MD Vickie R. Shannon MD Leendert Keus Rodolfo C. MoriceMD E Lin University of Texas, MD Anderson Cancer Center, Houston,TX

PURPOSE: To evaluate the effect of FEV1 (% of predicted) at thetime of diagnosis on survival and performance status for patients withNSCLC.

METHODS: Retrospective analysis of patients with NSCLC referredto our pulmonary function test laboratory between January 2001 andNovember 2001. Clinical characteristics, smoking history, comorbidities,survival, pulmonary function tests, and performance status (ZUBROD) atbaseline, 6 months and 1 year were reviewed.

RESULTS: We studied 206 patients (M�120;F�86) with NSCLC.Mean age was 64.7�10.1 yrs. Fourty-five percent were smokers, 48%were former smokers, and 7% were nonsmokers. Average predictedpercent FEV1�70.3%�19.6% (range 25%-123%). Smokers and formersmokers averaged 52.4�30 pack-yr. Sixty-three percent of patients had atleast one type of comorbidity; DM 15 (7%), HTN 66 (32%), CAD47(23%). Also 59 (29%) patients had other type of malignancies. Thehistologic types were; Adenocarcinoma 87(42%), squamous 72(35%),large cell 43(21%), and BAC 4(2%). The stages of patients were IA:28(14%), IB:27(13%), IIA:8(4%), IIB:31(15%), IIIA:48(23%), IIIB:39(19%)and IV:25(13%). When corrected for tumor stage, comorbidities, and agethere was no significant association between initial FEV1% and patients’survival and change of their performance status.

CONCLUSION: Pulmonary dysfunction measured by FEV1 % ofpredicted at the time of diagnosis did not independently affect survival orchange in performance status for patients with NSCLC.

CLINICAL IMPLICATIONS: Degree of pulmonary dysfunctionmeasured by FEV1 is important for selection and outcome of surgicallytreated patients, but is not a determinant factor of performance andsurvival for patients with NSCLC overall.


IMPACT OF PRE-TREATMENT SYMPTOM BURDEN, RE-SPONSE TO TREATMENT, AND LABORATORY PARAMETERSON SURVIVAL IN SMALL CELL LUNG CANCERAnant Mohan MD* Abha Goyal Preet P. Singh Siddharth Singh R. M.Pandey MD Ashutosh K. Pathak PhD Manisha Bhutani MD RandeepGuleria MD All India Institute of Medical Sciences, New Delhi, India

PURPOSE: Predictors of survival and response to treatment in patientswith small cell lung cancer (SCLC) are ill-defined and unclear. In anattempt to assess the impact of simple characteristics like presentingsymptoms and laboratory values on survival, we undertook this retrospec-tive review of patients with SCLC.

METHODS: All newly diagnosed SCLC cases from December 2001through December 2004 were identified and clinical data on presentingsymptoms and laboratory findings from their hospital records noted. Theinfluence of various pretreatment factors on survival was investigatedusing Kaplan-Meier plots and Cox multivariate regression model.

RESULTS: 76 subjects were included (84% males, 91% smokers). 57%patients had five or more symptoms at presentation. The median survivalduration in patients with limited and extensive disease was 15.3 and 9.8months respectively. Overall survival was significantly associated withcumulative symptom burden (p�0.02), and strongly with symptomaticresponse to treatment (p�0.001). Survival was also significantly associatedwith Karnofsky Performance Status (KPS)(p�0.04) and disease extent(p�0.03). Patients with higher hemoglobin, serum sodium and serumglobulin had significantly better survival (p�0.02, 0.04, and 0.02 respec-tively). By multivariate regression analysis, hemoglobin, KPS and brainmetastases were found to be significant predictors of survival (p�0.01,p�0.02, and p�0.01 respectively). Multimodal therapy with both chemo-therapy (CT) and radiotherapy (RT) resulted in significantly greater

Reason for Inoperability N�206 (%)

Pulmonary dysfunction 38 (19%)Unresectable local-regional disease 34 (17%)Distant metastasis 22 (11%)Cardiac dysfunction 2 (1%)Cardiac risk�pulmonary dysfunction 2 (1%)Recurrence of disease 2 (1%)Patient refusal 1 (0.5%)Lost F/U 5 (2%)




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survival benefit than unimodal (either CT or RT), or no therapy (p �0.001 and p � 0.001 respectively).

CONCLUSION: Cumulative symptom burden, KPS, disease extent,and symptomatic improvement after treatment are useful predictors ofsurvival in SCLC.

CLINICAL IMPLICATIONS: Assessment of symptomatology andother clinical variables may be used as simple tools for risk-stratifyingpatients into those most likely to achieve survival benefit after therapy.This may also prove more cost-beneficial in developing countries forevaluating response to treatment compared to costly imaging procedures.

DISCLOSURE: Anant Mohan, None.

UTILITY OF SYMPTOMS AND RESPIRATORY STATUS IN THEASSESSMENT OF QUALITY OF LIFE IN PATIENTS WITHLUNG CANCERAnant Mohan MD* Preet P. Singh MBBS Siddharth Singh MBBS AbhaGoyal MBBS Manisha Bhutani MD Ashutosh K. Pathak PhD RandeepGuleria MD All India Institute of Medical Sciences, New Delhi, India

PURPOSE: A significant proportion of lung cancer patients depend onpalliative care, hence it is imperative to evaluate and maintain a satisfac-tory quality of life (QoL) in them. However, data with regard to Indiapatients is sparce. Quality of life was assessed in newly diagnosed patientswith lung cancer and its relationship with pre-treatment clinical parame-ters and respiratory status was studied.

METHODS: A 30-item, self-administered European Organization forResearch and Treatment of Cancer (EORTC) QLQ-C30 (version 3)questionnaire in Hindi was used. Clinical symptoms, Karnofsky perfor-mance status (KPS), and measures of respiratory status (including spirom-etry) were recorded.

RESULTS: The study included 93 patients (76 males, 80% smokers)with a mean (SD) age of 57.2 (11.0) years. 90% had non- small cell lungcancer. Median KPS was 70 (range, 50-90). Median number of symptomswas 4 (range, 1-7). Lowest scores were seen in the global health status andphysical function scales (Table). Fatigue, appetite loss and pain scoredhighest among symptom scales. Higher KPS significantly correlated withbetter global health status (p�0.001) and healthy level of functioning(p�0.001). The number of symptoms was significantly associated withglobal QoL (p�0.04) and physical, role, emotional and cognitive functionscales (p�0.05); however individual respiratory symptoms showed nocorrelation with QoL. Forced vital capacity, forced expiratory volume in 1second and peak expiratory flow rate showed positive correlation with allfunctional scales (p�0.05) except social scale. Age, gender, smokingstatus, pack years, histological type and symptom duration had noinfluence on QoL.

CONCLUSION: Patients with lung cancer have unsatisfactory qualityof life, with the global health status and physical functions being mostaffected. Number of symptoms, performance status, and pulmonaryfunctions has a significant bearing on quality of life.

CLINICAL IMPLICATIONS: Appropriate attempts to improvesymptoms and augment respiratory capacity may improve quality of life inlung cancer.

DISCLOSURE: Anant Mohan, None.

PATTERN AND DETERMINANTS OF SURVIVAL AMONGLUNG CANCER PATIENTS IN WESTERN PART OF INDIARamakant Dixit MD Sidharth Sharma MBBS* J.L.N. Medical College,Ajmer, India

PURPOSE: As a global problem, India is also witnessing the increasingtrends of lung cancer in both sexes. Despite many sporadic reports on the

clinical, radiological and pathological features of lung cancer from differ-ent part of country, Indian literature is scanty on the survival aspect oflung cancer patients. The present study is first one on pattern anddeterminants of survival among various histological types of lung cancerpatients from Western India.

METHODS: cases of histologically proven lung cancer patients wereevaluated in the light of clinical, radiological & pathological features.According to the histological diagnosis stage of the disease and perfor-mance status, patients received various treatment modalities. Thosecoming in follow up constituted the study population.

RESULTS: Lifespan could be assessed in 122 patients (110 males and12 females). 75.3% patients died within 6 moths of diagnosis and only6.5% survived more than a year. About 50% patients having performanceIndia 3 or 4 died within 3 months of their diagnosis. 42.8% cases ofsquamous cell carcinoma, 45.4% of adenocarcinoma and 50% of small cellcarcinoma survived no longer than 6 months. Average life span in SCLCwas 4.9% months and 4.1 months in NSCLC 55% of SCLC patients withED died within 3 months of diagnosis while similar proportion of stage IIIb and 83% of stage IV NSCLC patients died within 6 months In bothSCLC and NSCLC, Survival was better in those with performance indexzero or one and those receiving the chemotherapy. Generalized debilitydue to relapse, progression of disease or treatment related advance effectswas the commonest terminal event (67.2%) followed by pulmonaryembolism (31.1%), renal failure (14.7%) & others.

CONCLUSION: In our study the survival of patients with advanceddisease was poor and survival decreased further with poor performancestatus.

CLINICAL IMPLICATIONS: : Survival in lung cancer patients ispoor in this vary part of India and is significantly influenced by stage of thedisease, histological type, performance index and treatment modalitiesetc.

DISCLOSURE: Dr.Sidharth Sharma, None.

IMPLEMENTATION OF GUIDELINES: PREOPERATIVE AS-SESSMENT OF PATIENTS UNDERGOING LUNG RESECTIONSURGERY FOR LUNG CARCINOMA; A CASE STUDYNaim Y. Aoun MD* Eduardo Velez MD Katherine P. Hendra MD St.Elizabeth Medical Center, Boston, MA

PURPOSE: The pre-operative evaluation of patients with lung carci-noma being considered for resection has been outlined in a number ofpublished guidelines, including those from the American College of ChestPhysicians (ACCP) (Chest Supplement 2003). The current investigationwas designed to assess the utilization of these recommendations bythoracic surgeons.

METHODS: A web-based survey of 13 questions utilizing the ACCPstep-wise physiologic approach to these patients was e-mailed to all USmembers of the “Society of Thoracic Surgeons”.

RESULTS: The response rate was 10% (n�243). The geographicallocation and practice type were evenly distributed. The majority ofsurgeons (99%) routinely requested pre-operative pulmonary functiontesting (PFT). Most (82.6%) proceed with resection if the PFT is normal(FEV1 �60%), while 17.4% required more investigations. If theFEV1�60%, five physicians (2.1%)declined surgery, while the remainderproceed with further secondary evaluation including split function V/Qscan (60.3%), stair climbing (18%), cardio-pulmonary exercise testing(CPET) (14.2%) or walk test (5.4%). Abnormal results prompted furthertesting in 85.2% of respondents, while 14.8% declined surgery. Whenresponses were stratified based on the surgeons’ primary hospital affilia-tion, community (n�94) vs. teaching community and university (n�146),those without an academic affiliation withhold surgical resection based onabnormal secondary testing (29.5% v/s 15.1%, p�0.05). Similar resultswere found in practitioners performing fewer than 50 resections a year(n�157) as compared to those performing � 50 (n�86)(27.7% v/s 8.5%;p�0.05).

CONCLUSION: The results of this survey demonstrate that themajority of thoracic surgeons are following the ACCP guidelines forpre-operative evaluation of patients with lung carcinoma. However,surgeons in the community, and those performing fewer resections morefrequently decline surgery before completing the recommended physio-logic assessment.

CLINICAL IMPLICATIONS: For some patients with lung carci-noma surgical resection remains the best option for cure. Given thisfactor, a complete pre-operative physiologic evaluation should be com-pleted before patients are declined for resection. Broader implementation

Table 1. Mean (SD) EORTC- QLQ C30 Scores

Domain Mean Score (SD)

Global Health Status 39.0(20.9)Physical Function 48.7(27.2)Role Function 56.5(33.5)Emotional Function 57.3(28.6)Cognitive Function 69.8(28.7)Social Function 66.1(30.8)




of guidelines outlining this assessment, especially at the community level,may allow more patients to proceed with surgical therapy.

DISCLOSURE: Naim Aoun, None.

Lung Cancer Surgery12:30 PM - 2:00 PM

EFFECT OF LUNG RESECTION ON EXERCISE CAPACITYAND ON CO DIFFUSING CAPACITY DURING EXERCISEJeng-Shing Wang MD* E-Da Hospital & I-Shou University, Kaohsiung,Taiwan ROC

PURPOSE: To evaluate the effect of lung resection on lung functionand exercise capacity values including DLCO during exercise, and todetermine whether postoperative lung function including exercise capac-ity and DLCO during exercise could be predicted from the preoperativelung function and the number of functional segments resected.

METHODS: Design: Prospective study.Setting: Clinical pulmonaryfunction laboratory in a university teaching hospital.Patients: Twenty-eight patients undergoing lung resection at Vancouver General Hospitalfrom October 1998 to May 1999, were studied preoperatively and oneyear postoperatively. Interventions: We determined FEV1 and FVC, andmaximal oxygen uptake (VO2max/kg) and maximal workload (Wmax)achieved during incremental exercise testing. We used the 3-equationmodification of the single breath DLCO technique, method, to determineDLCO at rest and during steady state exercise at 70% of Wmax, and theincrease in DLCO from rest to exercise (70%-R)DLCO. We calculatedthe predicted postoperative (ppo) values for all the above parametersusing the preoperative test data and the extent of functioning broncho-pulmonary segments resected, and compared results with the actual oneyear postoperative results.

RESULTS: Following lung resection, there was a significant reductionin FEV1, FVC, and DLCO with decreases of 12%, 13%, and 22% ofpredicted respectively. There were also significant decreases inVO2max/kg of 2.1 ml/min/kg ( 8% of predicted VO2max) and in Wmax of12watts (7% of predicted Wmax). However, (70%-R)DLCO, did notsignificantly decrease after lobectomy but decreased after pneumonec-tomy. The calculated ppo values significantly underestimated postopera-tive values in pneumonectomy, but were acceptable for lobectomy.

CONCLUSION: Predicted postoperative results calculated by estimat-ing the functional contribution of the resected segments, are comparablewith those obtained using ventilation perfusion lung scanning, and

significantly underestimate postoperative lung function after pneumonec-tomy, but are acceptable for lobectomy.

CLINICAL IMPLICATIONS: Exercise tests may be better indicatorsof functional capacity after lung resection than measurements of FEV1and FVC or DLCO at rest.

DISCLOSURE: Jeng-Shing Wang, None.

IMPORTANCE OF EXERCISE TESTING IN DETERMININGEARLY RETURN TO WORK AFTER THE LUNG RESECTIONYoshinori Nagamatsu MD* National Hospital Organization Omuta Na-tional Hospital, Omuta Fukuoka, Japan

PURPOSE: Issue of earlier return to work after the lung resection isvery important for patients. Yet, there must be a determination of patient’sphysical ability to go back to work. Therefore, the institute has conductedthis study after lung resection.

METHODS: Between 1998 and 2005, the institute operated total of 97cases. 88 cases were lobectomy and 7 cases were bilobectomy, and 2 casespneumonectomy. 55 out of 97 patients were male and 42 patients werefemale. The average age is 68 years old. The exercise testing andspirometric lung function testing were done before and after the surgery.The exercise testing measured the maximum oxygen uptake per minuteper the body surface area (VO2max/m2) to determine patient’s physicalability, and spirometric lung function testing used two measurements suchas the vital capacity per the body surface area (VC/ m2) and forcedexpiratory volume in 1.0 sec per the body surface area (FEV1.0/ m2). Theinstitute decided 100 as its baseline before the surgery.

RESULTS: The average results of two weeks after the surgery were thefollowing: VO2max/m2 was 82%, VC/m2 was 68.7%, and FEV1.0/m2 was72.4% compared to results from before the surgery. 4 weeks later:VO2max/m2 result was up to 88.1%, VC/m2 increased to 74.8%, andFEV1.0/m2 went up to 77.7%. In this study, predetermined physicalability level was 80% as acceptable level to return to work. 60 cases out of96(62.5%) exceeded this level two weeks after the surgery; 71 cases out of94 cases (75.5%) met this level 4 weeks after.

CONCLUSION: The research shows the patient’s physical abilityrecoveries are quick after the lung resection; 62.5% patients have enoughphysical ability to return to work after two weeks, and 75.5% patients cango back to work 4 weeks after the surgery.

CLINICAL IMPLICATIONS: It is possible to use these exercise teststo determine when a patient is able to go back to work and to encouragethem to do so after the lung resection.

DISCLOSURE: Yoshinori Nagamatsu, None.

DOES PREOPERATIVE INTERVENTION PROGRAM IMPROVEPOSTOPERATIVE OUTCOME IN HIGH-RISK PATIENTS UN-DERGOING THORACIC SURGERY?Wai Ming M. Yung MBBS* Y.W. T. Mok MBBS S.O. Ling MBBS Y.N.Poon MBBS K.C. Wong MBBS C.W. Yim MBBS Kowloon Hospital,Hong Kong, Hong Kong PRC

PURPOSE: To assess the effectiveness of preoperative interventionprogram in reducing the incidence of postoperative pulmonary complica-tions (PPCs) and 30-day mortality rate after thoracic surgery in high-riskpatients.

METHODS: A 3-week preoperative intervention program, consistingof chest physiotherapy, exercise training, smoking cessation and psycho-logical counseling, was offered to high-risk patients with preoperativeFEV1�80% predicted or current smokers in a tertiary respiratory medicalcentre before undergoing thoracic surgery. The 30-day mortality rate andincidence of PPCs, which are defined as pneumonia, atelectasis, PaCO2greater than 50mmHg lasting for more than 48 hours after surgery, andrespiratory failure requiring mechanical ventilation, was compared tothose of a group of patients who did not participate in the program(control group).

RESULTS: Between April 1, 2000 and March 31, 2002, 42 patients inthe intervention group and 27 controls were studied. The baselinecharacteristics between the 2 groups were comparable except age and thepercentage of malignancy. 62% of patients in the intervention groupcompleted the 3-week training. In the intervention group, the mean6-minute walk distance improved by 38.6 metre (p�0.05) after training.There was no difference in the rates of PPCs and postoperative ICUadmission & the hospital stay between the intervention and control




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groups. The 30-day mortality rate, however, was lower in the interventiongroup and the difference approached statistical significance.

CONCLUSION: Preoperative intervention program improves themean 6-minute walk distance with statistical significance. It also reducesthe 30-day mortality rate. Randomized controlled trial is warranted forbetter assessment of its efficacy.

CLINICAL IMPLICATIONS: Pulmonary complications are commoncontributors to mortality and morbidity after thoracic surgery. The risk isincreased in smokers and those with preexisting lung diseases. Preopera-tive intervention program may help to improve the postoperative outcomein this group of patients.

DISCLOSURE: Wai Ming Yung, None.

ANEMIA AFFECTS OUTCOME AFTER SURGICAL RESECTIONFOR EARLY STAGE LUNG CANCERCliff P. Connery MD* Louis Harrision MD Karen McGinnis MDMaureen Reyes Andy Nabong BS Robert C. Ashton MD St. Luke’sRoosevelt Hospital, New York, NY

PURPOSE: Anemia has been implicated as a significant factor in thefailure of response for solid tumors in patients undergoing radiationtherapy and chemotherapy. The purpose of our study was to analyze thecorrelation of preoperative hemoglobin levels and survival after surgicalresection for early stage lung cancer.

METHODS: All patients undergoing resection for Stage I and IInon-small lung cancer from January 2002 through December 2003comprised the cohort. Patients were followed up to December 2004 ordeath. Demographics and risk factors, including age, prior thoracicsurgery, coronary artery disease, congestive heart failure, hypertension,diabetes, renal failure, peripheral vascular disease, steroid use, ASAclassification, Zubrod score, and neoadjuvent therapy, were analyzedalong with preoperative hemoglobin levels. Data was collected prospec-tively, based on Society of Thoracic Surgeons database model.

RESULTS: Preoperative hemoglobin was found to be an independentpredictor of intermediate survival for patients undergoing surgical resec-tion for early stage lung cancer. Hemoglobin levels greater than 14resulted in 100 percent survival as compared to levels less than 12 whichresulted in a 73.7 percent survival during the follow-up period. Using thePearson Correlation, hemoglobin was a significant factor in survival (p �0.007). The mean time to death was shortest in Group I, 5.41 (0.1-13.8).One death occurred in perioperative period in the cohort, Group I. Therewas one transfusion in the cohort, group III.

CONCLUSION: For patients with non-small cell lung cancer under-going surgical resection, hemoglobin was found to be a predictor ofsurvival. The exact mechanism or cause/effect relationship is theoretical atthis time. The effects of tissue hypoxemia and free radical generation needto be studied to assess the effects they have on tumor cell survival.

CLINICAL IMPLICATIONS: Further investigation is warranted todetermine if hemoglobin is a marker of overall risk or if it is a determinantof survival. Additionally, the question of optimization of preoperativehemoglobin prior to surgical therapy and its effect on survival should alsobe investigated.

DISCLOSURE: Cliff Connery, None.

EFFICACY OF CYBERKNIFER STEREOTACTIC RADIOSUR-GERY WITH SYNCHRONYTM MOTION TRACKING MODULEFOR TREATMENT OF MALIGNANCIES IN THE THORAXAmit V. Patel MD* Brian Collins MD Shakun Malik MD CarlosJamis-Dow MD David Earl-Graef MD Gregory Gagnon MD Eric D.Anderson MD Georgetown University Medical Center, Washington, DC

PURPOSE: To discern the effectiveness of CyberKnifeR stereotacticradiosurgery with SynchronyTM motion tracking on both central andperipheral thoracic tumors measured by both CT and PET imaging atthree-month and six-month intervals.

METHODS: All patients who underwent CyberKnife with Synchronyfor treatment of thoracic malignancies were enrolled. Patients weredivided into two groups according to the location of their tumors withinthe thorax. Peripheral nodules received a total of 45–60 Gy applied in 3fractions over a 7-10 day period while those with central tumors receiveddoses of 18-30 Gy over 3-5 treatments. CT of the chest and PET scanswere obtained at three-month and six-month intervals post treatment.

RESULTS: A total of 24 patients were enrolled since July 2004.Etiology of the ten peripheral malignancies consisted of primary NSCLC(7) and metastatic diseases including esophageal (1), muscle (1), and skin(1). Etiology of the 14 central lesions consisted of primary NSCLC (11),and metastatic diseases including colon (1), breast (1) and kidney (1).Tumor size ranged from 7mm to 8cm. The major side effect consisted offatigue. At three months, partial response was noted in first 7 patientstreated for peripheral nodules. A complete response was noted at 6months in the first patient with a peripheral nodule. Two patients withcentral tumors showed stable disease at three months. One central tumorpatient showed initial improvement, followed by progression of disease atthree months.

CONCLUSION: All patients tolerated the treatment well. Patientswith peripheral lung nodules who received Cyberknife with Synchronyhad a significant response to treatment.

CLINICAL IMPLICATIONS: Cyberknife stereotactic radiosurgerywith Synchrony motion tracking is a safe and effective modality fortreating tumors in the thorax. This treatment may be suitable fornon-surgical candidates and patients who refuse surgery. Cyberknife mayalso be an option in patients who have received prior irradiation.

DISCLOSURE: Amit Patel, None.

WEDGE VERSUS LOBECTOMY: COMPARING SURVIVAL INSTAGE I NON-SMALL CELL LUNG CANCERDennis J. Rassias MD* Alexander Kraev BA John Vetto MD MikhailTorosoff MD Adebambo Kadri MD Pasala Ravichandran MD ChristinaClement BS Riivo Ilves MD Albany Medical Center, Albany, NY

PURPOSE: The selection of lobectomy or wedge resection in stage Ilung cancer remains controversial. We investigated the impact of eachprocedure on long term survival in a multi-center analysis.

METHODS: The records of 293 patients were reviewed for age, sex,type of resection, tumor size, number of lymph nodes dissected, andpathology. Data was obtained through the Federal Social Security DeathIndex and Cancer Registries. Kaplan-Meier, Wilcox, Logistic Regression,

Groups

Hemoglobin(G/DL)

Frequency PercentRange Mean

I 9.7-12.0 11.1 Alive 14 70Dead 6 30

II 12.1-13.0 12.5 Alive 18 86Dead 3 14

III 13.1-13.9 13.48 Alive 16 89Dead 2 11

IV 14.0-16.1 14.85 Alive 20 100Dead 0 0


Lung Cancer Surgery, continued


and t-test analyses were used to examine survival, predictors of mortality,and correlations.

RESULTS: 217 patients underwent lobectomy and 76 had wedgeresection for Stage I lung cancer. The groups were similar with respect toage, tumor size and other co-morbidities. Overall, there was a trendtowards improved survival in patients who had lobectomy (mean survival5.8�0.3 vs. 4.1�0.3 years, respectively; p�0.112, see Graph 1). This trendgained statistical significance in smaller cancers, where lobectomies fortumors less than 30mm had better survival when compared to patientsthat had wedge resection (p�0.029, see Graph 2).

CONCLUSION: Although the overall difference in survival betweenlobectomy and wedge resection is insignificant, patients with tumorssmaller than 30mm showed a statistically significant survival benefit afterlobectomy.

CLINICAL IMPLICATIONS: Tumor size, therefore, is an importantfactor to be considered in pre-operative planning. Randomized trials arenecessary to confirm these findings.

DISCLOSURE: Dennis Rassias, None.

PROGNOSIS AND SURVIVAL FOLLOWING SURGICAL RESEC-TION FOR LUNG CANCER WITH N2 INVOLVEMENT OF THEMEDIASTINUMAdebambo M. Kadri MD* Dennis Rassias MD Riivo Ilves MD AlbanyMedical College, Albany, NY

PURPOSE: Surgical resection remains the primary modality for thepotentially curative treatment of anatomically resectable non small celllung cancer. The presence of mediastinal lymph node metastasis (N2disease) is known for its association with a poor prognosis. The value anddesirability of surgical resection for N2 disease remains controversial. Thepurpose of the study is to estimate the actuarial survival following surgicalresection for N2 disease and determine the prognostic factors whichinfluence survival.

METHODS: Between 1994 and 2003, 51 patients underwent lungresection for pathologically proven N2 disease. The records of thesepatients were retrieved from the Cancer Registry Database of the AlbanyMedical College and retrospectively analysed. Survival analysis was per-formed using the Kaplan-Meir method. The influence of several prognos-tic factors on survival was evaluated using the logrank test.

RESULTS: There were 51 patients, (30 men), mean age 64 years(range 37 to 85 years). Operative mortality was 2.2 years. The distributionof age, sex, and cell type was similar between the patients with N2 diseasand 241 other patients without N2 involvement, who underwent lungresection in the same time period. Advanced overall stage and advancedT stage were significantly more common in the presence of N2 diseease(P�0.001), and pneumonectomy was more commonly employed in thepresence of N2 disease (P�0.001). Overall 5 year survival was 20.3%.Survival was not influenced by stage, T stage, cell type, type of lungresection or the application of multimodality treatment.

CONCLUSION: The study confirms the poor prognosis associatedwith lung cancer with N2 involvement of the mediastinum. The lack ofprognostic importance of cell type, disease stage and type of lungresection suggests that in advanced lung cancer the important factor inprognosis is the presence of extrapulmonary disease.

CLINICAL IMPLICATIONS: The low operative mortality and the20.3% 5 year survival justifies surgical resection for those patients who arefound at intraoperative pathological staging to have N2 disease.

DISCLOSURE: Adebambo Kadri, None.

PRIMARY LUNG CANCERS DISCOVERED AS SOLITARY PUL-MONARY NODULE: REVIEW OF 209 CASESPier Luigi Filosso MD* Davide Turello MD Giovanni Donati MD FaustoPernazza MD Ottavio Rena MD Caterina Casadio MD Enrico RuffiniMD Alberto Oliaro MD University of Torino, Department of ThoracicSurgery, Torino, Italy

PURPOSE: to assess the prognostic factors and outcome of primarylung cancers (PLCs) discovered as solitary pulmonary nodules (SPNs).

METHODS: between 1999 and 2003 314 patients (223 male-71%-,mean age 64 years-range 21-81 years-) underwent surgical resection of aSPN. Of these 209 (66%) were PLCs, 56 (17%) lung metastases and 49benign lesions.

RESULTS: One hundred and ten (75%) out of 209 PLCs wereadenocarcinomas, 58 (18.7%) squamous cell carcinomas, 12 bronchi-oloalveolar carcinomas, 8 large cell carcinomas and 12 bronchialcarcinoids. Nine patients had mixed tumors. Twenty-six (12.6%) wereless than 1 cm. in size; 100 (47.5%) between 1.1 and 2 cm, and 83(39.9%) between 2.1 and 3 cm. One hundred thirty-seven (65.7%)were N0; 25(11.9%) were N1 and N2, respectively; in 22 (10.5%)lymphadenectomy was not performed. Three and five year overallsurvival rates were 70% and 52%, respectively. The following prognos-tic variables resulted statistically significant at multivariate analysis: thetumor histology (p�0.0005), the tumor size (p�0.007), the presence oflymphnodal metastases (p�0.00001), the visceral pleura invasion(p�0.0002) and the extent of resection (anatomic vs. limited resection)(p�0.004).

CONCLUSION: this is a surgical series with a high PLCs percentage(66%), the majority of which were at early stage. An early diagnosis andsurgical treatment represent the treatment of choice, especially in highrisk patients, providing a good survival.

CLINICAL IMPLICATIONS: in high risk patients PLC should beconsidered in occasionally discovered SPN. Early diagnosis and possiblesurgical treatment are mandatory.

DISCLOSURE: Pier Luigi Filosso, None.

DEATH HAZARDS FOLLOWING SURGICAL RESECTION FORNON SMALL CELL PRIMARY BRONCHIAL CANCER: A STUDYON THE POSSIBLE CURABILITY OF THE DISEASEAdebambo M. Kadri MD* Riivo Ilves MD Albany Medical Center,Albany, NY

PURPOSE: The favourable survival benefits of surgical resection forearly stage non small cell primary bronchial cancer is well recognized. Thevalue of lung resection for advanced lung cancer with locoregional spread




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or extrapulmonary disease is less clear. The aim of the study is todetermine the influence of disease stage on survival after resection forlung cancer, compare the annual death hazards for different stages of thedisease and determine if the prognostic significance of disease stagechanges with time.

METHODS: The study cosisted of a retrospective interrogation of theprospectively collected information in the Albany Medical College CancerRegistry Database on 292 patients who underwent pulmonary resectionfor lung cancer over a 10 year period. Survival analysis was performedusing the Kaplan-Meir method. Hazard Function calculations wereperformed to determine the annual risk of dying in the different stagegroups.

RESULTS: Operative mortality was 2.4%. Overall survival was 42.8%.Survival was significantly different for the different stages of the disease(P�0.001). Estimation of the instantaneous risk of dying revealed annualdeath hazards to be highest during the 5 year period for stage 3 disease.Death hazards subsequently declined for all stages. By the 5th year offollowup, the difference in death hazards between the stages had nearlydissapeared.

CONCLUSION: The study suggests that the prognostic significance ofdisease stage on early survival is diminished in later follow up.

CLINICAL IMPLICATIONS: The chance of potential cure increases withlonger follow up for patients with lung cancer with no evidence of systemicspread, who have undergone locoregional control by surgical resection.

DISCLOSURE: Adebambo Kadri, None.

Lung Transplantation12:30 PM - 2:00 PM

ASSESSING REGIONAL LUNG FUNCTION IN SINGLE LUNGTRANSPLANT (SLT) RECIPIENTS USING A NEW VIBRATIONRESPONSE IMAGING (VRI*) TECHNOLOGYMordechai R. Kramer MD* Yael Raviv MD Ruth Hardoff MD Merav GatMA Igal Kushnir MD Rabin Medical Center, Petach Tikva, Israel

PURPOSE: Background: In a well functioning graft following SLTmost of the ventilation (V) and perfusion (Q) shifts to the transplanted(Tx) side. A routing V/Q scan is performed periodically to asses the graftfunction. Chest auscultation usually discloses a difference between the Txand non-Tx lungs, however no quantitative nor regional assessment can bedone by the physical examination.VRI is a new system that records thevibrations produced by airflow and converts the signals to a dynamicimage of the lung. The vibration energy throughout the breathing cyclecan be quantified for any lung region, by integrating the energy over 40acoustic sensors .Objective: To evaluate the correlation between regionalvibration (VRI) energy and regional lung function as assessed by radio-nuclide V/Q scan.

METHODS: We examined 28 stable patients (12 F/16 M; age58.6�9.8 yrs: FEV1 58.3�15%) who underwent SLT (18 Left lung, 10Right lung). Patients underwent V/Q scans and VRI testing. For eachmode, the chest was divided into 6 areas, 3 at each side, and thecorresponding regional signals (fraction of the total radioactivity vs.fraction of the VRI energy units) were integrated and compared.

RESULTS: The regional VRI evaluations were found to be highlycorrelated with the V/Q results (R�0.92, p�0.001) (see figure). Theimages of all subjects shared similar features with hyperdynamic vibrationof the transplanted lung as compared to the native side with excellentcorrelation to the V/Q.

CONCLUSION: VRI has excellent corellation to lung V/Q scan instable patients following SLT.

CLINICAL IMPLICATIONS: These preliminary findings suggestthat VRI may provide a simple, radiation-free novel tool to assessqualitatively and quantitatively lung function in lung transplanted patientsand to monitor the patient during the post-operative period for acute orchronic rejection.* www.deepbreeze.com.

DISCLOSURE: Mordechai Kramer, None.

ROLE OF LUNG TRANSPLANTATION IN THE MANAGEMENTOF PATIENTS WITH LAM: BASELINE DATA FROM THE NIHLAM REGISTRYJanet R. Maurer MD* Jar-Chi Lee MS Gerald Beck PhD Kevin K. BrownMD Joel Moss MD Jay H. Ryu MD CIGNA HealthCare, Avon, CT

PURPOSE: Data on candidate selection and post-transplant follow-upin LAM patients is limited. An NIH-funded a Registry collected data onLAM patients including outcomes of patients undergoing or anticipatinglung transplantation. Baseline pulmonary function (PFT) and quality oflife data from that population is summarized.

METHODS: Patients enrolled between 8/98 and 10/01. Six centersregistered 243 patients. Initially, patients completed questionnaires de-tailing medical history, symptoms, laboratory values, treatment, andquality of life. PFTs were done. Follow-ups were at six months and/oryearly.

RESULTS: Of the 243, 13 (5.3%) were transplanted before enrollment(Group A); 21 (8.6%) were transplanted during the Registry period(Group B); 48 (19.8%) were waitlisted or evaluated for transplant duringthe Registry period (Group C); 161 (66.3%) were not listed or consideredfor transplant (Group D). Baseline PFTs of Group D and Group Apatients were not significantly different; however, baseline PFTs of GroupB patients were significantly worse than PFTs of Group A or Group Dpatients (p�0.015 and �0.001, resp.). Group A patients scored betterthan Group B patients in the SF-36 physical domain (p�0.003) and in theoverall St. George Questionnaire (p�0.006) and it’s activity domain(p�0.001). Group D and Group A scores were similar.

CONCLUSION: More than one-third of LAM Registry enrolleeseither had undergone transplant or were considered for transplant.

CLINICAL IMPLICATIONS: Pulmonary transplantation appears tobe associated with both better pulmonary function and quality of lifecompared to patients with physiologically advanced disease prior totransplant (Group B). Funded by NIH (NHLBI) Grant No 1 U01HL58440.

DISCLOSURE: Janet Maurer, None.

READMISSION TO AN INTENSIVE CARE UNIT AFTER LUNGTRANSPLANTATION: EXPERIENCE OF A SINGLE CENTERDeborah J. Levine MD* Luis Angel MD Sako Edward MD StephanieLevine MD University of Texas Health Science Center San Antonio, SanAntonio, TX

PURPOSE: Short-term survival after lung transplantation has im-proved such that over 90% of recipients are discharged post-operatively.Long term survival, however, can be complicated by the need forreadmission to an ICU in many patients. Respiratory failure is the mostcommon cause for re-admission, however,we found that a significantnumber of admissions are required for non-pulmonary issues. Thepurpose of this study is to evaluate the nature and frequency of icureadmissions post transplant.

.

N N*% Pred.FEV1 Mean (S.D.)

Group A 13 2 70.5(27.6)Group B 21 20 46.0(20.0)Group C 48 47 56.7(19.0)Group D 161 151 77.7(22.2)

N* � number of patients with FEV1 values




METHODS: We performed a single center review of 83 consecutivelung transplant recipients who were successfully discharged post trans-plant between 1/1999 and 4/2004. Evaluation included patient demo-graphics, pretransplant diagnoses, and time and diagnoses of admission toUniversity Hospital’s ICU up until 7/2004. Patient charts and ICD-9 codeswere used to document distribution of the primary diagnoses. Demo-graphics were compared to patients who did not require readmissionduring the study period.

RESULTS: A total of 83 single (21%)and bilateral (79%)lung trans-plants were performed at our institution from 1/99 to 5/2004. 28patients(34%) required re-admission to University Hospital’s ICU 49times until 7/2004. Demographics including age, type of transplant, sex,and pre-transplant diagnosis were not significantly different from thosenot requiring re-admission. Distribution of primary readmission diagnosesare outlined in Table 1. Pulmonary dysfunction was the major complica-tion leading to ICU admission (59%). 41% of admissions were distributedbetween non-pulmonary complications. Time to readmission ranged from27 days to 540 days with a mean of 200 days.

CONCLUSION: Respiratory failure was the most common reason forreadmission to our ICU post lung transplantation. However, there was adistinct subset of characteristic non-pulmonary issues that occurred withenough frequency (41%), that they warrant further evaluation.

CLINICAL IMPLICATIONS: Further study is needed to identifywhich clinical factors (pre-transplant co-morbidities,immunosuppressio-n,etc), either pre- or post transplantation, may predict a return to the ICUafter initial discharge following transplantation.

DISCLOSURE: Deborah Levine, None.

BRONCHODILATOR RESPONSE AS A PREDICTOR OF BRON-CHIOLITIS OBLITERANS SYNDROME IN SINGLE AND DOU-BLE LUNG TRANSPLANTSForest H. Mealey DO* Kevin McCarthy RRT Jeffrey Chapman MDCleveland Clinic Foundation, Cleveland, OH

PURPOSE: Brochodilator (BD) response is frequently requested inlung transplant patients. In earlier studies, bronchial hyperreactivity, asdetermined by BD response and methacholine challenge, has been shownto correlate with the development of Bronchiolitis Obliterans (BO) andBO Syndrome (BOS), however, these studies were limited by smallsample size, small numbers of single lung transplants (SLT) and theevolution of transplant medicine since completion. We reviewed data todetermine if BD response predicts BOS in single and double lungtransplants.

METHODS: Data from 432 patients, transplanted from 1991-2005,were reviewed. Exclusion criteria included expiration within one year oftransplant, follow up less than one year and anastomotic stenosis. Allpatients had serial spirometry per protocol pre and post albuterol MDI.BD response was determined by current ATS guidelines. BOS wasdetermined by decline in FEV1 as per current ISHLT criteria. Data wereanalyzed using the chi-squared test.

RESULTS: 221 patients met criteria. SLT was performed in 141(63.8%) patients. 31/221(14%) patients had a significant BD response.12/31 (38.7%) patients in the BD responder group developed BOS vs.45/145 (31%) of non-responders. The difference was not significant(p�0.484). In SLT, 8/24 (33%) with BD response developed BOS vs.29/119 (24.4%) non-responders (p�0.84). There were no significant

associations between BD response and single vs. double lung transplan-tation (p�0.394). COPD was the pre-transplant diagnosis in 12/24 SLTpatients with BD response vs. 21/90 SLT patients without BD response(p�0.084).

CONCLUSION: In this study BD response was not associated withthe development of BOS in DLT or SLT transplant patients. COPD wasmore commonly associated with BD response in SLT patients, though thisdifference was not significant.

CLINICAL IMPLICATIONS: BD response appears to have limitedclinical utility in predicting BOS.

DISCLOSURE: Forest Mealey, None.

MYCOBACTERIA ABSCESSUS IN LUNG ALLOGRAFT RECIPI-ENTSLeonardo Seoane MD* Denise Fuchs RN Gisele A. Lombard RNStephanie G. Laplace RN David E. Taylor MD Vincent G. Valentine MDOchsner Clinic Foundation, New Orleans, LA

PURPOSE: Most rapidly growing nontuberculous mycobacterial infec-tions are due to Mycobacterium abscessus. Isolated reports of M.abscessus infection after lung transplantation (LT) suggest this speciesposes a significant threat to lung allograft recipients(LARs). We report ourexperiences and clinical outcomes of M. abscessus infection following LT.

METHODS: We performed a retrospective chart review of 197 LARsperformed at our institution between 1991 and 2005. Infection wasdefined as symptoms in the prescence of chest radiograph changes andpositive cultures from a bronchoalveolar lavage (BAL).

RESULTS: Eight (4%) LARs were diagnosed with M. abscessuspulmonary infection. The transplant diagnosis included cystic fibrosis (3),emphysema (3), idiopathic pulmonary fibrosis (IPF)(1), and sarcoid (1).One LAR had M. abscessus prior to transplant and died because ofdisseminated infection peri-operatively. All underwent bilateral lungtransplants except the LAR with IPF. The most common symptoms weredyspnea, cough, and fever. Two deaths may be directly attributable to M.abscessus, since both patients died of respiratory failure with granuloma-tous pnuemonia on autopsy. Five patients responded to therapy asdemonstrated by improved symptoms and culture negativity on repeatBAL.

CONCLUSION: The prevalence of M. abscessus is relatively low postLT. Although it may be a potentially fatal pathogen in LARs, the majorityof infected LARs respond to therapy. A multi-institutional study mayfurther our understanding of M. abscessus infections among LARs.

CLINICAL IMPLICATIONS: M. absessus poses a significant threatto LARs. However, successful treatment of M. abscessus is possible postLT.

DISCLOSURE: Leonardo Seoane, None.

LONG-TERM OUTCOME FOLLOWING LUNG TRANSPLANTA-TION FOR PATIENTS WITH SARCOIDOSISAmit Gaggar MD* Keith Wille MD Kevin Leon MD Katherine Hart BSSusan Kerkhof RN David McGiffin MD K. R. Young MD University ofAlabama at Birmingham, Birmingham, AL

PURPOSE: End-stage sarcoidosis is characterized by severe pulmo-nary fibrosis and often poorly responsive to medical therapy. Lungtransplantation, therefore, may be the only treatment option. Currently,there are few studies evaluating long-term outcomes following transplan-tation for these patients. The aim of this investigation is to evaluate thepost-transplant morbidity and mortality of patients with sarcoid, comparedto recipients transplanted for idiopathic pulmonary fibrosis (IPF).

METHODS: This study is a retrospective review of all lung transplantrecipients at a tertiary care center over a 10-year time period (1994-2004).Data collected include patient demographics, bronchoscopy results, spi-rometry, development of bronchiolitis obliterans syndrome (BOS), andmedian survival post-transplantation.

RESULTS: Over the study period, 300 patients underwent lungtransplantation. Fourteen (4.7%) had sarcoidosis and 48 (16.0%) had IPF.Recipients in the sarcoid group were younger (mean age 41.3 versus 55.8years*) and predominantly female (93% versus 38%*), compared torecipients in the IPF group at the time of transplant (* p � 0.01,Mann-Whitney). Five of 14 (36%) sarcoid patients developed BOS versus15 of 48 (31%) IPF patients (p�ns). There was no significant differencein the time to BOS onset. Median survival was 1,365 days for the sarcoid

Table 1: Primary Diagnoses for Lung TransplantRecipients Readmitted to the ICU

Cause Percent

Pulmonary 59% (pneumonia, rejection, pleuraleffusion, pulmonary embolus)

Cardiac 10%Hematologic/Oncologic 8%Neurologic 8%Infectious Disease (not

including pneumonia)6%

Renal 6%Endocrine 2%


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group and 1,593 days for the IPF group (Hazard Ratio 1.28 by Kaplan-Meier analysis; [95% CI] 0.55-3.14; p � 0.54).

CONCLUSION: We observe similar long term outcomes for sarcoidand IPF recipients following lung transplantation.

CLINICAL IMPLICATIONS: Lung transplantation remains an op-tion for the treatment of end-stage sarcoidosis, as BOS and mortality ratespost-transplant are comparable to IPF.

DISCLOSURE: Amit Gaggar, None.

EFFECT OF OBESITY IN THE OUTCOMES OF LUNG TRANS-PLANT RECIPIENTSCesar A. Keller MD Debra Boswell RN* Javier Aduen MD HeidyDavid-Robinson RN Jefreey Shalev BS Francisco Alvarez MD MayoClinic, Jacksonville, FL

PURPOSE: Previous studies have reported increased mortality amongobese lung transplant (LT) recipients. This retrospective study evaluatedthe short and long term outcomes of obese (Body Mass Index or BMIequal or �30) lung transplant recipients, compared to non-obese(BMI�30) patients.

METHODS: Retrospective collection of data from the Mayo ClinicLung Transplant Database among 63 patients receiving lung transplantsfrom June 2001 to June 2004 at the Mayo Clinic. Demographic data,height and weight at time of transplant, BMI, clinical outcomes andsurvival rates were collected and compared among the 2 groups.

RESULTS: Out of 63 LT recipients, 48 (76%) were Non-Obese(weight� 67 �-15 kg and BMI� 24�-4), and 15 (14%) were Obese(weight� 92.4�-9 and BMI 31.4�-1). Clinical outcomes during lungtransplant were as follows: For Non-Obese recipients, the ICU stay was9�-11 days. The Lenght of stay (LOS) was 24�-19 days. Obese patientsrequired an ICU stay of 8�-9 days. The LOS was 24�-18 days (Notstatistically significant) The survival at 1 month, 6 months and 12 monthswere as follows. Non-Obese: 98%, 84% and 76% (mean survival 20�-12months). Obese recipients: 100%, 100% and 100% (mean survival 24�-10months up to the current date).

CONCLUSION: In our experience, 15 patients who were obese at thetime of transplant (BMI ranging from 30 to 35.6) had as good or betterimmediate post-op course after lung transplantation compared to Non-Obese patients (BMI ranging from 18 to 29.7). Survival rates for obeselung transplant recipients up to one year after transplant were as good orbetter than non-obese patients.

CLINICAL IMPLICATIONS: The assumption that a BMI � 30represents likelihood of increased morbidity or mortality among lungtransplant recipients may not be necessarily true. Larger studies withlonger follow up may find expanded criteria for potential lung transplantrecipients with BMI as high as 35 if these preliminary results areconfirmed by larger clinical trials.

DISCLOSURE: Debra Boswell, None.

VORICONAZOLE VERSUS ITRACONAZOLE FOR FUNGALPROPHYLAXIS AFTER LUNG TRANSPLANTATIONJohn H. Sherner MD* Scott Barnett PhD Shahzad Ahmad MD NelsonBurton MD Mary Schmidt MD Steven Nathan MD Walter Reed ArmyMedical Center, Washington, DC

PURPOSE: Aspergillus and other fungal infections are common causesof morbidity and mortality in lung transplant recipients. Most patientsreceive prophylaxis against fungal infections, but the optimal regimen hasnot been defined. The purpose of this study was to assess the efficacy ofvoriconazole as fungal prophylaxis.

METHODS: We retrospectively reviewed data from 56 lung transplantrecipients. Group A (n � 23) consisted of patients who underwenttransplantation after the introduction of voriconazole prophylaxis. GroupB (n�23) consisted of patients transplanted immediately prior to theintroduction of voriconazole, in whom itraconazole was used as prophy-laxis. Both groups received inhaled amphotericin B during their initialhospitalization adn continued oral antifungal prophylaxis until one yearpost-transplantation. The primary endpoint was positive BAL fungalcultures during the first year. We also assessed clnical events related toaspergillus and overall mortality.

RESULTS: The incidence of patients with positive bronchial culturesfor aspergillus at 1 year was 5/28 (18%) in the group A and 10/28 (36%)in group B (p � 0.134, ns). At the time of recovery of aspergillus, 4/5(80%) patients in group A were actually receiving voriconazole, versus

90% (9/10) in group B receiving itraconazole. The incidence of patientswith positive bronchial cultures for candida was 0 in group A versus 50%(14/28) in group B (p � � 0.0001). At one year, there was one clinicalaspergillus event in each group, non-fatal in group A and fatal in group B.There was an additional fatal aspergillus event in group B at month 25, aswell as an episode of scedosporium sepsis at month 13.

CONCLUSION: In our lung transplant population, the use of vori-conazole results in decreased airway colonization with aspergillus andcandida.

CLINICAL IMPLICATIONS: These findings suggest that voricon-azole is effective antifungal prophylaxis for lung transplant recipients. Theoverall low rate of clinically significant fungal events do not allow anyfurther conclusions to be drawn.

DISCLOSURE: John Sherner, None.

DIFFERENCES IN QUALITY OF LIFE AMONG PATIENTSLISTED FOR LUNG TRANSPLANTATIONLeonardo Seoane MD* Valerie Schacter Connie E. Thonpson RNLaPlace G. Stephanie RN David E. Taylor MD Vincent G. Valentine MDOchsner Clinic Foundation, New Orleans, LA

PURPOSE: There have been few studies on the quality of life amongpatients awaiting lung transplantation (LT). Patients with end stage lungdisease can be divided into those with either airflow obstruction (emphy-sema and cystic fibrosis) or restrictive physiology (idiopathic pulmonaryfibrosis). We assessed the quality of life of LT candidates with respect toobstuctive physiology (O) versus restrictive physiology (R).

METHODS: Of 108 patients listed for LT between January of 2000and August of 2004, 64 consented and completed the Medical OutcomesStudy Short Form 36 (SF-36). Demographics and other clinical charac-teristics obtained during evaluation for LT were analyzed and comparedwith the results of SF-36.

RESULTS: There were 18 patients in group R and 46 in Group O.Group O included an equal number of cystic fibrosis and emphysemapatients. Group O was significantly younger. Younger patients reportedless dyspnea with exercise and longer six minute walk distances. Compar-isons of the two groups are shown in table 1. There was a trend towardslower scores among group O in the social function (p�0.09) and bodilypain (p�0.06) domains. The O group also had a trend towards increasephysical function (p�0.07) However, there was a significantly worsegeneral health score in the O group (p�0.003).

CONCLUSION: Group O patients reported significantly worse gen-eral health than group R, despite being younger and having a trendtowards more physical function and less bodily pain.

CLINICAL IMPLICATIONS: The physiologic basis for impairmentO vs R and age should be taken into consideration when interpretingSF-36 quality of life in patients listed for LT.

DISCLOSURE: Leonardo Seoane, None.

INCIDENCE OF UNDETECTED LUNG NEOPLASMS IN EX-PLANTS OF LUNG TRANSPLANT RECIPIENTS: EXPERIENCEOF A SINGLE CENTERDeborah J. Levine MD* Luis Angel MD Andres Pelaez MD ScottJohnson MD John Calhoon MD Stephanie Levine MD University ofTexas Health Science Center San Antonio, San Antonio, TX

PURPOSE: Many pre-lung transplant recipients with end-stage lungdisease are at high risk for lung cancer. Evidence of lung cancer has beenconsidered a contraindication to lung transplantation mainly because of

TABLE 1

Obstructive Restrictivep

Value

Age (years) 42 � 18 56 � 10 �0.01BMI (kg/m2) 21.4 � 4.3 26.8� 2.5 �0.01Borg scale dyspnea with exercise 5.2� 2.3 5.8 � 2.5 0.93Exercise O2 sat 87 � 8 79 � 10 �0.016-min walk distance (ft) 1143 �

4211196 �

2840.11




the risk of dissemination secondary to immunosuppression post trans-plant. Experience is therefore limited on how patients with carcinomaprogress post transplantation. The purpose of this study was to assess thefrequency and spectrum of lung cancer found incidently at time ofpneumonectomy for transplantation at our center.

METHODS: We reviewed the charts of all lung transplant recipients atthe University of Texas Health Science Center, San Antonio. Patientdemographics including age, sex, indication for transplant, and smokinghistory were collected. Explant pathologic reports and pre-transplantradiographic studies were evaluated.

RESULTS: There was 232 lung transplants performed on 229 patientsfrom 11/1987 to 4/2005 (37 bilateral and 196 single). There were 120males and 109 females. Mean age at time of transplant was 50 years. Fiverecipients (2.2%) were found to have carcinoma in the explanted lung. Asignificant increase in the proportion of smokers and women in therecipients with carcinoma was found. There was no radiographic evidenceof possible neoplasm on CT Scan within 6 months prior to transplant oron chest radiograph on the day of transplantation. See Table 1.

CONCLUSION: Discovering previously undetected neoplasms in theexplanted lung of transplant recipients is an uncommon phenomenon.Although many recipients listed for transplantation are at high risk forlung cancer (diagnoses of emphysema and usual interstitial pneumonitis),those at highest risk are those who also have a significant smoking history.

CLINICAL IMPLICATIONS: Patients listed for lung transplantationoften wait for greater then two years for a graft. The evaluation includingchest radiographs and CT scans are often performed prior to or at the timeof listing. In patients who are at highest risk for developing primary lungcarcinomas, repeat CT scan screening should be considered shortly beforetransplantation.

DISCLOSURE: Deborah Levine, None.

SURVIVAL AFTER WEST NILE VIRUS MENINGOENCEPHALI-TIS IN A LUNG TRANSPLANT RECIPIENTDale C. Lien MD* Justin G. Weinkauf MD Kathleen B. Jackson RN PamBrown RN Andrea Taskinen RN Neil Skjodt MD University of Alberta,Edmonton, AB, Canada

PURPOSE: Although the majority of West Nile Virus (WNV) infec-tions are asymptomatic, severe neurologic injury and death may occur.Immunosuppressed lung transplant recipients are potentially at higherrisk. However, the probability of developing severe disease after exposure,the clinical presentations, and the outcomes for lung transplant recipientscontracting WNV are not well known.

METHODS: We report one case of community acquired WNVinfection in a lung transplant recipient who survived severe meningoen-cephalitis but with permanent neuromuscular impairment. The patientwas a 48 year old male 2.5 years post bilateral transplant for idiopathicpulmonary fibrosis on immunosuppression with tacrolimus, mycophena-late, and alternate day prednisone. He was a farmer in rural westernCanada in a highly endemic area of WNV in the summer of 2003.

RESULTS: He initially presented with fever, malaise and headache,and over the course of 5 days went on to develop confusion, decreasedlevel of consciousness, and coma. Investigations included a series of 4computerized tomographic head scans over 23 days which were normal.MRI was not done because of loose sternal wires. Lumbar punctureshowed a lymphocytic pleocytosis with mildly elevated protein andnegative WNV IgM. Initial WNV IgM in blood 5 days afer onset ofsymptoms was negative but became positive 14 days after symptomsbegan. The patient remained comatose on life support for nearly 3 monthsbefore neurologic recovery began. He received no specific treatmentexcept initial empiric therapy with intravenous acyclovir in case of Herpessimplex encephalitis, and withholding of immunosuppression for 1 weekfollowed by reinstitution at lower dosages. One year after presentation hehas normal mentation but continues to have severe muscle weakness anddyscoordination limiting mobiity. Lung function remains unchanged frombaseline levels.

CONCLUSION: This case illustrates that lung transplant recipientseven though immunocompromised, may recover from severe WNVmeningoencephalitis.

CLINICAL IMPLICATIONS: This case also emphasizes that pro-longed life support may be required and that recovery may be incomplete.

DISCLOSURE: Dale Lien, None.

Medical Education12:30 PM - 2:00 PM

COMPETENCY IN CHEST RADIOGRAPHY: A COMPARISONOF MEDICAL STUDENTS, RESIDENTS AND FELLOWSLewis A. Eisen MD* Abhijith Hegde MD Jeffrey S. Berger MD MangalaNarasimhan DO Roslyn F. Schneider MD Beth Israel Medical Center,New York, NY

PURPOSE: Accurate interpretation of chest radiographs (CXR) isessential since house officers are required to make clinical decisions basedon their readings. We sought to evaluate CXR interpretation competencyat different levels of training and to determine if specific factors areassociated with successful interpretation.

METHODS: Participants (n�145) from a single teaching hospital werethird year medical students (MS) (n�25), internal medicine (IM) interns(n�44), residents (n�60) from the departments of IM and radiology, andfellows (n�16) from the divisions of cardiology and pulmonary/criticalcare. Participants reported their confidence in interpreting CXR on a scaleof 0-10. They also reported their interest in a pulmonary career andperceived adequacy of CXR training. Ten conventional CXR were se-lected from the teaching file of the IM Department. The CXR includedone normal radiograph and three examples of emergencies (pneumotho-rax, misplaced central line and pneumoperitoneum). Participants wereasked to record the most important diagnosis. Two investigators indepen-dently scored each CXR on a scale of 0-2.

RESULTS: The median interpretative score was 11 out of 20. Anincreased level of training was associated with an increased score (MS8, intern 10, resident 15, fellow 15, p�0.001). Self-reported confi-dence (0-10) in interpreting CXR also increased (MS 4.0, intern 4.5,resident 6.0, fellow 6.0 p�0.001). Certainty was significantly corre-lated with interpretative score (r�0.606, p�0.001). IM interns andresidents interested in a pulmonary career scored 14 while those notinterested scored 11 (p�0.037). Radiology residents were more con-fident (7.0 vs. 5.0, p�0.021) and scored higher (18 vs. 11, p�0.001)than IM residents. Pneumothorax, misplaced central line and pneu-moperitoneum were diagnosed correctly 9%, 26% and 46% of the time,respectively. Only 20 of 131 (15%) participants felt that their CXRtraining was sufficient.

CONCLUSION: We identified several factors associated with success-ful CXR interpretation - level of training, field of training and confidence.Although interpretation improved with training, important diagnoses wereoften missed.

CLINICAL IMPLICATIONS: More training in CXR interpretation isrequired with an emphasis on emergencies.

Table 1: Data of Five Lung Transplant Recipients WithUndetected Lung Carcinoma

Case

Age/

Sex

Indication

for

Transplantation

Smoking

History

Type of

Neoplasm

Grade of

Neoplasm

Pre-Transplant

CXR CT Scan

6 months

Prior to

Transplantation

Survival

Post

Transplantation

1 60 M Emphysema Yes Adenocarcinoma

(poorly

differentiated)

Stage 1 Negative Dead -14 months

2 43 F Emphysema Yes Adenocarcinoma Stage 1 Negative Dead-36 months

3 53 F Emphysema Yes Bronchoalveolar

Carcinoma

Stage 1 Negative Dead-4 months

4 59 F UIP Yes Small Cell Carcinoma Stage 1 Negative Dead-1 day

5 45 F �-one

anti-trypsin

Yes Adenocarcinoma

(Invasive)

Stage 1 Negative Alive -

32 months




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DISCLOSURE: Lewis Eisen, None.

PUBLICATION OF RESEARCH UNDERTAKEN IN A CANA-DIAN TEACHING CENTRE: A REVIEW BY A RESEARCH ETH-ICS BOARDRichard I. Hall MD* Cecilia DeAntueno Queen Elizabeth II HealthSciences Centre, Halifax, NS, Canada

PURPOSE: Reporting of results from clinical investigations is animportant component of the ethical conduct of research. We conducted areview of the publication record of all protocols submitted to our ResearchEthics Board (REB) for the periods 1995-1996.

METHODS: Protocols for studies closed by the principal investigator(PI) were identified from the REB database. We identified the local PI,the sponsor, and the phase of clinical investigation. For each publication,we identified publication authors, publication title, journal, and whether arandomised clinical trial or not. For data analysis Systat V10 was utilised.p�0.05 was taken as statistically significant.

RESULTS: We identified 110 unpublished studies and 85 publica-tions (44%). The median time to publication was 32.5 mos (975days)(mean 33.1�17.8 mos) and the median number of subjectsenrolled per study was 329. For unpublished studies, subject recruit-ment was reported for 45 studies. In these studies there was a medianof 2 subjects recruited by local investigators per study. Physiciansauthored 79/85 publications (93%) and were the principal investigatorsin 89% (173/195) of studies. Publication by sponsor is given in theTable. Of the 85 published studies, results could be described aspositive findings in 72 (85%). Of 13 negative published trials, 11 weresponsored by the pharmaceutical industry, one by the health authority,and one by a federal granting agency.

CONCLUSION: Publication of research results was unacceptable, lesslikely to occur if sponsored by the pharmaceutical industry, and morelikely to occur if reporting positive findings. Calls for public registration ofclinical trials appear warranted.

CLINICAL IMPLICATIONS: Publication of research results is anethical obligation of researchers and failure to publish results isconsidered by some to represent scientific misconduct. In additionfailure to publish scientific results violates the social contract researchsubjects undertake when they participate in research and mis-informs public policy through failure to provide adequate informationupon which to base guidelines and perform meta-analysis. Ourresults suggest much further education around these issues isrequired.

DISCLOSURE: Richard Hall, None.

SURVEY OF CURRENT PRACTICES IN PULMONARY ANDCRITICAL CARE FELLOWSHIP ORIENTATION PROCE-DURESMaria R. Lucarelli MD* Catherine Lucey MD John Mastronarde MDThe Ohio State University, Columbus, OH

PURPOSE: The purpose of this survey was to identify current practicesin fellow orientation procedures.

METHODS: A 10 question survey was sent via email to currentpulmonary and critical care medicine program directors identified in theAmerican Thoracic Society (ATS) web registry. The survey sought toidentify common characteristics of fellow orientation programs includingduration, content and educational methods.

RESULTS: Of the 141 deliverable email addresses, 87 responded(61.7%). Of the programs who responded, 86% had a formal fellows’orientation. The mean time frame spent in fellow orientation was 5-10hours in didactic sessions and 0-5 hours in wet labs. Only twenty-fourprograms (28%) spent more than 15 hours in didactic sessions while noprograms spent more than 15 hours in wet labs. The most commondidactic topics were bronchoscopy in 69 programs (80.2%), pulmonaryfunction testing in 63 programs (73.3%) and orientation to hospitalservices in 63 programs (73.3%). The least commonly covered topics weremoderate/deep sedation in 38 programs (44.2%) and intubation in 39programs (45.3%). The most common use of wet labs was for bronchos-copy training in 60 programs (81.1%) and ventilator management in 45programs (60.8%). Thirty-seven responding programs (43%) used simu-lators in fellow orientation. The most frequently used simulator was abronchoscopy simulator in 31 programs (36%). The majority of programdirectors did not offer formal wet lab or simulator training, relying insteadon on-the-job training experiences during their fellowship.

CONCLUSION: This survey demonstrates that early fellowship train-ing experiences differ across programs in terms of duration, content andmethodology. Given the variability in skill level exhibited by enteringfellows and understanding the importance of procedural competence topatient safety, an early standardized approach to clinical and proceduraltraining can assure that entering fellows possess the requisite cognitiveand psychomotor skills to safely embark on training in the critical carearena.

CLINICAL IMPLICATIONS: Establishing competency earlier infellow training, has the potential to decrease medical errors and procedurerelated complications.

DISCLOSURE: Maria Lucarelli, None.

QUALITY OF EDUCATION IN THE INTENSIVE CARE UNIT: ASUBSET ANALYSISJason M. Golbin DO* Robert Bruno DO Gerald Bahr MD Bushra MinaMD Lenox Hill Hospital, New York, NY

PURPOSE: The ICU rotation at our hospital is often described as themost valuable educational experience in the internal medicine residency.Previously presented data demonstrated that this educational enhance-ment cannot be measured. We performed a subset analysis of this data toevaluate disparity among individual ICU topics.

TABLE.

SponsorPublication

Yes No % Success

PharmaceuticalCompany

60 72 46

Local HealthAuthority

11 34 24*

Federal GrantingAgency

11 1 91*

Charity 3 0 100Other 0 3 0

*p�0.05 vs Pharmaceutical Company


Medical Education, continued


METHODS: A question bank of over 100 multiple-choice questionswas created based on the ABIM Critical Care topics. All questions werereviewed independently by two board-certified intensivists. Interns andresidents rotating through the ICU completed a randomized 25 questionpre-test within the first 2 days of the month, and a randomized 25question post-test within the last 2 days of the month (allowing fordifferent call schedules). No changes were made in the standard ICUcurriculum, which allows for a daily teaching conference, and twice-dailyattending-led bedside rounds.

RESULTS: See Table 1.CONCLUSION: The above results demonstrate a wide variance in the

testable medical knowledge gained during the ICU rotation. While theseresults did not achieve statistical significance, likely secondary to smallsample size, there was a trend towards significance in many categories. Webelieve that this illustrates a number of points: (a)In topics commonlyencountered in our ICU (sepsis, DKA, and weaning), residents had ameasurable increase in testable knowledge. (b)In topics not emphasized inour ICU (APACHE and PA catheters), residents did not demonstrate anincrease in testable knowledge. (c)In topics emphasized throughout theinternal medicine residency curriculum (Ethics and Acid-Base/Electro-lytes), residents maintained an excellent fund of knowledge.

CLINICAL IMPLICATIONS: We believe that this information canbe used to identify weaknesses and strengths in our ICU curriculum, andwill allow us to modify that curriculum to further enhance residents’testable knowledge.

DISCLOSURE: Jason Golbin, None.

Occupational and Environmental12:30 PM - 2:00 PM

THE DEGREE OF CO-MORBIDITY OF SILICOSIS AND PUL-MONARY TUBERCULOSIS AMONG EX-MINEWORKERS OFTHE FORMER HOMELAND OF TRANSKEI, SOUTH AFRICA.AN X-RAY BASED STUDYBanwari Lal Meel MD* Ruchika MEEL MB, BCh University of Transkei,Umtata, South Africa

PURPOSE: This study was done to determine the degree of co-morbidity of silicosis and pulmonary tuberculosis in ex-mineworkers,measure distribution of the conditions in different age groups and to

determine the length of service in the mines in relation to the diseasestates.

METHODS: Between 28th May 1997 and 27th May 1999, 2080former mineworkers were examined at the “Benefit Examination Clinic”in the Pulmonology unit of Umtata General Hospital (UGH). The mininghistory of each attendee was recorded and an identification form com-pleted. The form was either signed or fingerprinted by the miner. Afterphysical examination, a chest radiograph was taken. The radiographs weresent to an independent radiologist, experienced in Occupational LungDiseases, for assessment. These were rated according to InternationalLabor organization (ILO) guidelines.

RESULTS: The age of those studied ranged from 35 to 70 years (mean51.6 years) and their length of service in the mines ranged from 1 to 48years. On radiological examination 5.5% showed only silicosis and 28.4%had silicosis with pulmonary tuberculosis (Relative risk�5.08, �2 � 27.3,p�0.01). Among subjects up to 35 years 9.1% had mild, 10.6% marked,and 1.5% severe silicosis. A probable diagnosis was made on 9.1% of thecases. The least number of afflicted was seen in the 36 to 45 year agegroup (21.2%). Surprisingly, most number of cases were in those 35 yearsor less (30.3%). About half (48.4%) the silicotic subjects had worked in themines between 11 to 20 years.

CONCLUSION: Pulmonary TB is 5- times higher in silicotic than innon-silicotic subjects.

CLINICAL IMPLICATIONS: These findings will help clinicians,epidemiologists, compensation authorities and policy makers in under-standing of the silicosis problem in this region of South Africa.

DISCLOSURE: Banwari Lal Meel, None.

PREVALENCE OF ASBESTOS EXPOSURE OF THE MINE-WORKFORCE FROM TRANSKEI, SOUTH AFRICABanwari L. Meel MD* Ruchika Meel MB, ChB University of Transkei,Umtata, South Africa

PURPOSE: To determine the prevalence of asbestos exposure amongthe mine workforce from Transkei.

METHODS: Between May 1997 and May 2000, 2,027 ex-mineworkerswere examined at the Benefit Examination Clinic, a clinic located in thechest section of Umtata General Hospital (UGH), the teaching hospital ofthe University of Transkei, Eastern Cape, South Africa. A structuredquestionnaire with 17 questions were prepared and posted to 644randomly selected ex-mineworkers. Four hundred and six (63%) dulycompleted questionnaires were received, which were later, compiled andanalyzed with the help of Epi Info6 computer programme.

RESULTS: Of the 644 questionnaires posted, 406 were returned. Ofthem 81(20 %) has had exposure to asbestos. Half the number 41(50%) ofthose exposed was between 40-59 years old. Among those who had beenexposed, 8(10%) were smokers, 63(78%) asthmatics, and 56(69%) had ahistory of tuberculosis. Seventy- three (90%) complained of deteriorationof health.

CONCLUSION: One fifth of the mine workforce has had exposure toasbestos.

CLINICAL IMPLICATIONS: These findings will help compensationauthorities, policy makers, and clinicians in understanding of the asbestosproblem in this region of South Africa.

DISCLOSURE: Banwari Meel, None.

EXHALED BREATH CONDENSATE IN ASBESTOS EXPOSUREDaniela Pelclova MD* Zdenka Fenclova MD Petr Kacer PhD MarekKuzma PhD Jindriska Lebedova MD Pavlina Klusackova MD MarieBalikova PhD Tomas Navratil PhD Dept. Occupational Medicine,Charles University, Prague, Czech Republic

PURPOSE: To analyse exhaled breath condensate in subjects exposedto asbestos in the past, as experimental studies in animals have shownincreased lipid peroxidation. Isoprostanes, leukotrien B4 and cysteinylleukotriens have not yet been studied in humans exposed to asbestos.

METHODS: Thirteen persons were examined, mean age 71.4 years,previous exposure to asbestos 25.5 years on average. Five subjects werediagnosed asbestosis as occupational disease, 8 had pleural hyalinoses.Control group was represented by 10 subjects, mean age 66.3 years,without occupational history of fibrogenic dusts exposure.Lung functionswere measured, isoprostaglandin F2alpha; (8-isoprostane) was analyzedby HPLC/MS; leukotrien B4 by SPE, and leukotriens C4, D4, and E4using LC/MS. Cotinine in urine was detected to confirm the smoking

Selected ABIMTopic

Pre-TestPercentageCorrect (%) n

Post-TestPercentageCorrect (%) n

PercentChange(�/-%)

PulmonaryArteryCatheterization

12.5 8 15.3 11 �2.8

Acid-Base /ElectrolyteDisorders

50.0 12 72.7 11 �22.7

COPD/Asthma 72.7 11 80.0 10 �7.3Nutrition in the

Critical CarePatient

33.3 6 32.5 8 -0.8

DKA /HyperosmolarComa

50.0 10 77.7 9 �27.7

Sepsis 23.0 13 70.0 10 �57.0APACHE 14.2 7 11.1 9 -3.1Medical Ethics

in the ICU85.7 7 88.8 9 �3.1

GI Bleed 60.0 5 88.8 9 �28.8Weaning 22.2 9 53.8 13 �31.6


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status. Student t-test and correlation coefficient were used for statisticalcomparison of the groups.

RESULTS: Mean level of 8-isoprostane in persons exposed previouslyto asbestos and controls was 60�20 and 37 �15 pg/mL, respectively.Different values in exposed and control groups were detected (p�0.91).Mean levels of leukotriens B4, C4, D4, and E4 in exposed and controlswere 42�23; 96�40; 11�5; 17�7 and 38�15; 98�47; 20�11; 23�11pg/mL, respectively. In asbestos-exposed persons the concentration of8-isoprostane correlated with TLCO/Hb (p�0.96) and leukotriens B4(p�0.99), D4 (p�0.99), and E4 (p�0.99).

CONCLUSION: In preliminary results, 8-isoprostane seems to beimportant parameter in asbestos-exposed persons. Leukotriens levels didnot differ in exposed and control groups, however in subjects withasbestos exposure leukotriens B4, D4, and E4 were positively correlatedwith 8-isoprostane.

CLINICAL IMPLICATIONS: The level of 8-isoprostane in theexhaled breath condensate might be a useful marker of oxidation stressalso in asbestos-exposed subjects; besides that leukotriens B4, D4, and E4seem to play a role. Acknowledgement: IGA NR/8107-3.

DISCLOSURE: Daniela Pelclova, None.

MARKERS IN BREATH CONDENSATE IN PATIENTS WITHOCCUPATIONAL ASTHMA AND RHINITISJindriska Lebedova MD Pavlina Klusackova MD Petr Kacer PhD MarekKuzma Daniela Pelclova MD* Tomas Navratil PhD Zdenka Fenclova MDDepartment of Occupational Medicine, 1st Medical Faculty CharlesUniversity, Prague, Czech Republic

PURPOSE: Specific provocation tests are used to confirm diagnosis ofoccupational asthma or rhinitis. Decreases of FEV1 or nasal flow areconsidered to be main markers of positivity. Analysis of breath condensatebrings more information for monitoring processes in airways during thesetests.

METHODS: Six patients (average age 38.7 years) with suspicion onoccupational asthma (OA) and rhinitis (OR) and four controls (average age53.8 years) were examined. Total immunoglobuline E (IgE), bloodeosinophils, spirometry, rhinomanometry, non-specific bronchoprovoca-tion test, specific bronchoprovocation tests with occupational allergenswere performed. Leukotrienes C4, D4, E4 from breath condensate wereanalyzed by HPLC/MS, leukotriene B4 on solid phase extraction. Studentt-test and correlation coefficient were used for statistical analysis.

RESULTS: Occupational asthma was finally diagnosed in three pa-tients, occupational rhinitis in three patients. In patients with OA, OR andcontrols IgE levels were 828.3 vs. 564.0 vs. 34.8 mg/l; FEV1 80.3 vs. 95.6vs. 109.0 % predicted values; leukotrienes on admission B4 43.3 vs. 2.6 vs.46.3 pg/mL; C4 114.0 vs. 54.7 vs. 85.0 pg/mL; D4 17.0 vs. 10.7 vs. 35.5pg/mL; E4 20.0 vs. 13.7 vs. 28.3 pg/mL. Significant changes in FEV1(p�0.05) were found between asthmatics and controls.Breath condensateleukotrienes were analysed also before specific test and at the time ofmaximal decrease of FEV1 or nasal flow during the test: OA patients - B4(53.7 vs. 56.7 pg/mL), C4 (121.7 vs. 198.0 pg/mL), D4 (17.0 vs. 17.0pg/mL), E4 (21.3 vs. 21.0 pg/mL), OR patients - B4 (13.0 vs. 17.3 pg/mL),C4 (266.3 vs. 257.3 pg/mL), D4 (19.3 vs. 17.0 pg/mL), E4 (17.3 vs. 15.6pg/mL). No significant correlations were found.

CONCLUSION: Maximum decrease of FEV1 during specific testswith occupational allergens in our small group of patients does not to seemto correspond with elevation of markers of obstruction in breath conden-sate.

CLINICAL IMPLICATIONS: Changes in obstruction markers inbreath condensate probably precede or follow decrease of FEV1. Thesepossibilities will be tested in further provocation tests measurements.Acknowledgement: IGAMZCR NR8109-3/2004.

DISCLOSURE: Daniela Pelclova, None.

XENON DIFFUSING CAPACITY DETECTS ABNORMAL GASEXCHANGE IN A RAT MODEL OF PNEUMONITIS CAUSED BYSTACHYBOTRYS CHARTARUM SPORE INHALATIONNishard Abdeen MD* Greg Cron PhD Albert Cross PhD Thomas RandPhD Steven White MS Giles Santyr PhD Carleton University, Ottawa,ON, Canada

PURPOSE: Xenon diffusing capacity, a novel noninvasive technique ofmeasuring gas exchange analogous to carbon monoxide diffusion capacity,

was evaluated in a rat model of pnemonitis caused by intratrachealinstillation of Stachybotrys chartarum spores.

METHODS: The xenon diffusing capacity was defined analogously tothe carbon monoxide diffusing capacity as the product of a gas transfertime or time constant of uptake into lung parenchyma (determined byhyperpolarized 129 Xenon dynamic spectroscopy) and alveolar volume-(determined by hyperpolarized 129 Xenon magnetic resonance imaging).The xenon diffusing capacity was compared in a group of normal anddiseased rats with histologically proven pneumonitis caused by intratra-cheal instillation of Stachybotrys chartarum spores.

RESULTS: The xenon diffusing capacity for lung parenchyma wassignificantly reduced in a group of 6 rats with pneumonitis caused byintratracheal instillation of Stachybotrys chartarum spores relative to agroup of 6 normal rats(29�/-11 mL/min/mmHg and 66�/-10 mL/min/mmHg, p�0.05). Gas transfer times and lung volumes were signifi-cantly reduced for the diseased rats (22�/-3 ms and 11�/-2mLrespectively)relative to normal rats (35�/-8 ms and 16 �/-2 mLrespectively).

CONCLUSION: Xenon diffusing capacity is an effective at detectinggas exchange abnormalities on a millisecond time scale in a rat model ofpneumonitits.These results support further evaluation of xenon diffusingcapacity in characterization of experimental lung disease.

CLINICAL IMPLICATIONS: Xenon diffusing capacity quantifiesgas exchange abnormalities on a much shorter (millisecond) time scalethan the carbon monoxide diffusing capacity. The method may prove to bea useful adjunct to the carbon monoxide diffusing capacity in lung diseasescharcaterized by a gas diffusion abnormalitities.

DISCLOSURE: Nishard Abdeen, Product/procedure/technique thatis considered research and is NOT yet approved for any purpose.Hyperpolarized 129 xenon spectroscopy and MR imaging.

LONG-TERM RESPIRATORY DISORDERS IN CLAIMERSWITH EXPOSURE TO CHEMICAL WARFARE AGENTS (CWA):REVIEW OF METHACHOLINE CHALLENGE TEST (MCT) RE-SULTSAbbas Nemati MD* Mahdi Rahmati MD Ali Moghimi MD ArteshUniversity of Medical Sciences, Tehran, Iran

PURPOSE: It is well documented that inhalation of sulfur mustardcauses injury of the respiratory system. While all of the reports and surveysthoroughly document long-term pulmonary effects after significant expo-sure to mustard, there is no direct evidence that addresses the issue oflong-term respiratory effects in individuals who were exposed to very lowlevel of mustard and suffered no acute respiratory tract injury. The aim ofthis study is to evaluate the MCT findings in the veteran claimingexposure to CWA during Iran-Iraq war.

METHODS: We studied 395 subjects which were selected among allthose who were in chemically contaminated areas with chemical warfareagents (CWA) and had been registered for an annual checkup. Back-ground data were collected. All subjects underwent diagnostic bronchos-copy and biopsy which was performed by one specialist. In all patientsMCT, according to ATS guidelines, performed.

RESULTS: Subjects were 395 men with the mean age of 41.46 (SD,5.43) years which exposed to CWA averagely 18.7 (SD, 1.74) years ago.132 patients (33.3%) had positive MCT. Results of MCT did not relate tothe cigarette smoking (p�0.82), length time after exposure (p�0.88), age(p�0.36), bronchospic findings (p�0.36) and the presence of interstitialfibrosis (p�0.71). Kappa coefficient of the results of bronchoscopy andMCT in determining patients with airway disorders was not significant(p�0.36).

CONCLUSION: This study shows that a major proportion (33%) ofpatients exposed CWA show airway hypersensitivity in their MCT whichdoes not relate to any underlying factor, though it is not a diagnosticfinding. In addition the results of bronchoscopy and MCT are not inconcordance with each other.

CLINICAL IMPLICATIONS: About one third of patients exposedCWA show airway sensitivity.

DISCLOSURE: Abbas Nemati, None.


Occupational and Environmental,continued


DOES PROTECTIVE MASK (M40) INCREASE REACTIVE AIR-WAY DISEASE IN MILITARY ACTIVE DUTY WITH EXERCISEINDUCED BRONCHOSPASMPedro F. Lucero MD* Patrick Perkins MD Michael J. Morris MD BrookeArmy Medical Center, San Antonio, TX

PURPOSE: To determine whether the M40 protective chemical gasmask (M40 mask) increases bronchial airway hyperreactivity in militaryactive duty soldiers with exercise induced bronchospasm (EIB). The pointof prevalence of EIB in the US Army is 7% and many of these soldiers arecapable of performing their exertional military duties. However, it isunclear how soldiers with EIB will perform when they are required to usethe M40 mask for prolonged periods. Furthermore, there are anecdotalconcerns of increased EIB exacerbations when these individuals wear theM40 mask.

METHODS: Active duty soldiers were screened in the Pulmonaryclinic for EIB. Diagnostic criteria for EIB included a history of exertionaldyspnea, normal baseline spirometry and a positive methacholine chal-lenge test � 4mg/ml. Subjects who participated in the study completedexercise spirometry breathing room air. A repeat exercise spirometry wasperformed two days later with the subject wearing a full face M40 mask.A matched number of participants with no history of EIB or otherpulmonary disorders were included in the control group. The FEV1 postexercise challenge testing (ECT) with and without the M40 mask wascompared in both subject and control groups.

RESULTS: Nine subjects with EIB and 3 controls were evaluated.Both the subjects and controls underwent baseline (ECT) with andwithout the M40 mask. The FEV1 post ECT was compared and there wasno statistical difference in both groups with or without the M40 mask. Oneof the nine subjects with EIB had a positive ECT while wearing the M40mask.

CONCLUSION: Our pilot study revealed that soldiers with EIB whoexercised wearing the M40 mask infrequently had bronchospasm exacer-bations.

CLINICAL IMPLICATIONS: Our results support the US Armyretention standards of soldiers with EIB. Because one subject did have apositive ECT while wearing the M40 mask we recommend screening ECTwhile the protective mask is worn in soldiers with EIB retained on activeduty.

DISCLOSURE: Pedro Lucero, None.

AIR POLLUTION IN A SMALL MICHIGAN COMMUNITYRachna B. Reddy* Elizabeth Busdicker Sridhar P. Reddy MD Port HuronNorthern High School, Port Huron, MI

PURPOSE: The objective of this study was to assess the effects of airpollution on emergency room (ER) visits for respiratory problems andschool absences over a period of 90 days.

METHODS: Air Quality Index (AQI) is a simple aggregate measure ofair quality used by the Michigan Department of Environmental Quality(DEQ) to document the quality of air. It measures Particulate Matter,Ozone, Sulfur Dioxide, Nitrogen Dioxide, and Carbon Monoxide. AQIlevels range from 0-500, with 500 being the worst possible air quality. AQIlevels, ER visits for respiratory problems, and school absences wererecorded daily from October 2004 to January 2005.

RESULTS: Data was charted with no lag, with a one-day lag, two-daylag, and a three-day lag. A Pearson Coefficient of Correlation wasperformed and was best with a two-day lag for ER visits. The data fromthe two-day lag was separated into quartiles by AQI values. The AQI levelsin the highest quartile ranged from 66-80, and in the lowest from 20-35.The average number of ER visits in the highest AQI quartile (poor airquality) was greater than in the lowest quartile(20.5 visits vs. 12.8 visits perday; p value of 0.09. School absences did not show a significant difference.

CONCLUSION: In conclusion there was a trend for the number ofrespiratory-related ER visits to be greater when the air quality was poor.

CLINICAL IMPLICATIONS: These results have implications for asmall community in allocating resources for health care utilization basedon real time simple air pollution measures. The results suggest a need forincreased health care personnel in the emergency room two days subse-quent to poor air quality.

DISCLOSURE: Rachna Reddy, None.

RADIOLOGIC PATTERN OF PULMONARY DISEASE ASSOCI-ATED WITH MYCOBACTERIUM INTRACELLULARE-AVIUMIN HOT TUB USERS (HOT TUB LUNG)Viktor Hanak MD* Jay Ryu MD Thomas Hartman MD Mayo ClinicFoundation, Rochester, MN

PURPOSE: The purpose of this study was to evaluate the radiologicfeatures of Hot Tub Lung disease.

METHODS: The CT scans of 15 patients (13 high resolution and 2conventional CT scans) were evaluated for the distribution and extent ofnodules, irregular lines and ground glass attenuation.

RESULTS: Nodules were present in 11/15 cases. They were bilateraland symmetric in 9 and bilateral and asymmetric in 2. In 9 cases there wasa diffuse distribution of the nodules in the cephalocaudal plane with acentrilobular distribution in the transaxial plane. In the other 2 cases, thenodules had an upper lung distribution in the cephalocaudal plane and arandom distribution in the transaxial plane. In 5 cases the nodules werewell-defined and in 6 cases poorly defined. Ground glass attenuation wasseen in 11/15 cases, and was bilateral and symmetric when present. Theground glass attenuation was diffuse in the cephalocaudal plane with arandom distribution in the transaxial plane in 10/11 cases. In the other 1case the areas of ground glass attenuation had lower lung predominancewith a random distribution in the transaxial plane. In 6 cases the areas ofground glass attenuation involved �40% of the lungs and in 5 involved �40% of the lungs. Both the nodules and ground glass attenuation werepresent in 7 cases (nodules only were present in 3 patients; ground glassonly present in 3 patients). One patient had nodules, areas of ground glassattenuation and irregular linear opacities. Irregular linear opacities werepresent in only 1 case. They were bilateral and asymmetric with asubpleural and lower lung predominance and involved �10% of the lungs.In 7 cases expiratory images were obtained and all showed evidence of airtrapping.

CONCLUSION: The patterns of centrilobular nodules, ground glassattenuation and air trapping are very similar to findings of subacutehypersensitivity pneumonitis.

CLINICAL IMPLICATIONS: In cases where the CT findings sug-gest hypersensitivity pneumonitis, hot tub lung should also be a diagnosticconsideration.

DISCLOSURE: Viktor Hanak, None.

ANTI-GLOMERULAR BASEMENT MEMBRANE ANTIBODY-NEGATIVE, GOODPASTURE-LIKE ALVEOLAR HEMOR-RHAGE SYNDROME IN YOUNG WOMEN WITH METHAM-PHETAMINE USE AND MANUFACTURECarl A. Kaplan MD* Michael S. Plisco MD Ashok Palagiri MD SaintLouis University School of Medicine, Saint Louis, MO

PURPOSE: Illicit substances, such as cocaine, are associated withalveolar hemorrhage. Anti-Glomerular Basement Membrane (GBM) Dis-ease and Goodpasture Syndrome with alveolar hemorrhage are rareimmunologic diseases that are associated with a number of risk factors,and without treatment have significant mortality rates. Methamphetamineuse is a growing public health concern, and its manufacture is common inregions of the United States. Methamphetamine has not previously beenassociated with alveolar hemorrhage. This study addresses the associationwith alveolar hemorrhage and methamphetamine.

METHODS: A single institution retrospective case study from anurban university tertiary care hospital and referral center. A systematicreview of pathology reports and database of cases with alveolar hemor-rhage.

RESULTS: A total of two cases (n � 2), both 22 year-old females, wereadmitted with frank hemoptysis and acute respiratory failure. The medicalhistory was significant for substance abuse, tobacco abuse and both wereassociated with the use and manufacturing of methamphetamine. Bron-choalvelar lavage demonstated alveolar hemorrhage in both, with increas-ingly bloody lavage fluid. Urinalysis was bland with normal creatinines.The open lung biopsy demonstrated, in both, primarily alveolar hemor-rhage, with one associated with capillaritis with areas of organization.Immunofluorescence revealed prominant linear staining of the alveolarbasement membranes for immunoglobulin IgG and complement C3, asdid the glomerular basement membranes on the renal biopsies. Both wereserum anti-GBM antibody negative. Plasmapheresis was performed inaddition to the administration of parenteral corticosteroids, with resolu-tion of the acute respiratory failure. There were no recurrences.




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CONCLUSION: This study demonstrates the association of an Anti-GBM negative, Goodpasture-like Alveolar Hemorrhage Syndrome withMethamphetamine, its manufacture, or related to a component of man-ufacturing. Further studies are necessary to elucidate this new association.

CLINICAL IMPLICATIONS: This study raises a new serious publichealth concern with the increase appearance of the manufacturing and useof methamphetamine in the Midwest region of the United States. This isa new association based on a Medline Search from 1966 – 2005 foralveolar hemorrhage, anti-GBM disease, Goodpasture syndrome, andmethamphetamine.

DISCLOSURE: Carl Kaplan, None.

Outcomes Assessment12:30 PM - 2:00 PM

UPDATED MORTALITY PROBABILITY MODEL (MPM-III)Thomas L. Higgins MD* Daniel Teres MD Wayne Copes PhD BrianNathanson PhD Maureen Stark MS Andrew Kramer PhD BaystateMedical Center/Tufts University School of Medicine, Springfield, MA

PURPOSE: The Mortality Probability Model on ICU admission(MPM0-II), developed on an international sample of 12,610 patientstreated in 1989-90, is used by Project IMPACT as a benchmarking tool,but no longer calibrates. We updated the model based on 2001-2004patient data.

METHODS: Project IMPACT data on 124,855 patients age�18 andeligible for MPM scoring were randomly split into development (60%)and validation (40%) samples and analyzed using logistic regression.Independent variables considered were MPM-II variables, patient loca-tion and lead time prior to ICU admission and code status at the time ofICU admission. Discrimination was assessed by area under the ROCcurve (AUC) and calibration by graphic display and Hosmer-LemeshowGoodness of Fit (HL-GOF) C-statistics.

RESULTS: Observed hospital mortality was 13.8%. The MPM0-IIImodel includes MPM0-II variables and several interaction terms. Leadtime and pre-ICU location did not influence outcome. Addition of a“zero-factor” term for patients with no risk factors other than ageimproved calibration. Coefficients are in the table, and improved calibra-tion can be seen in the figure. Validation set HL-GOF�10.94, p�0.36and ROC AUC�0.823.

CONCLUSION: MPM0-III is well calibrated to current clinical dataand requires collecting only one additional term (code status).

CLINICAL IMPLICATIONS: Use of MPM0-III will allow moreaccurate comparisons of actual versus expected outcomes based on patientcondition at the time of ICU admission.

DISCLOSURE: Thomas Higgins, Consultant fee, speaker bureau,advisory committee, etc. Dr. Higgins serves on the Cerner Critical CareTransformation Council (advisory committee).

Variable Coefficient

Constant -5.397338Coma-stupor 2.032949HR �150 bpm 0.4286778SBP � 90 mmHg 1.578148Chronic Renal 0.4041341Chronic GI 2.078154Metastatic Neoplasm 3.187064Acute Renal 0.7026929Dysrhythmia 0.8247331Cerebrovascular Incident 0.4103774GI Bleed -0.1593359Intracranial Mass 1.838082Age (in years) 0.0387999CPR w/i 24hr 1.499682Mech. Ventilation 0.891268Medical/Unscheduled Surgical Admission 0.916912Zero Factors -0.4025265Full Code -0.8016462SBP x MV Admit -0.1620224Age x Coma -0.0074014Age x SBP�90 -0.0092765Age x ChronicGI -0.0225957Age x Mets -0.0328078Age x CardDys -0.0100795Age x ICM -0.0168818Age x CPR -0.0112155




MORTALITY PROBABILITY MODELS (MPM0-III) FOR SPE-CIALIZED PATIENT POPULATIONSBrian Nathanson PhD Wayne Copes PhD Maureen Stark MS AndrewKramer PhD Daniel Teres MD Thomas L. Higgins MD* BaystateMedical Center/Tufts University School of Medicine, Springfield, MA

PURPOSE: The Mortality Probability Model on ICU admission(MPM0) is used by Project IMPACT as a benchmarking tool. A recentupdate (MPM0-III) has been validated and shown to perform well on alarge dataset. New MPM models based on specific patient subsets havebeen constructed to improve assessment with specialized ICU popula-tions.

METHODS: Project IMPACT data from 2001-2004 for 124,855patients eligible for MPM scoring treated in 135 ICUs were randomly splitinto design (60%) and validation (40%) samples. Logistic regressionmodels were developed to predict hospital mortality from MPM0-IIIvariables for patients in each of the following subgroups: ComplexCardiovascular, Trauma, Elective Surgery, Medical, Neurosurgery andOther Emergency Surgery. Discrimination was assessed by area under theReceiver Operator Characteristic (ROC) curve and calibration by HosmerLemeshow Goodness of Fit (HL-GOF) C-statistics. We compared ICU-specific Standardized Mortality Ratios (SMRs) and associated confidenceintervals (CIs) from MPM0-III to those based on the Subgroup models,using the validation sample.

RESULTS: The six Subgroup models had good calibration and dis-crimination on the validation sample (Table 1-performance on validationdataset). MPM0-III and Subgroup model SMRs and CIs were in substan-tial agreement (overall agreement 94.8%, Kappa Statistic 0.88; p-val-ue�0.001). Important SMR differences were observed for some unitswith an atypical case mix or when a unit’s CI bordered on significance.

CONCLUSION: The MPM0-III Subgroup models calibrate well onspecialized populations and complement the general MPM0-III model forbenchmarking.

CLINICAL IMPLICATIONS: MPM0-III Subgroup models are use-ful when ICU case mix is atypical or SMR performance is near thesignificance boundary. Subgroup models will also be valuable in studies ofspecific patient subsets.

DISCLOSURE: Thomas Higgins, Consultant fee, speaker bureau,advisory committee, etc. Dr. Higgins serves on the Cerner Critical CareTransformation Council; Grant monies (from industry related sources);Dr. Nathanson received grant funding from Cerner.

THE ICU DISCHARGE SCORE TO EVALUATE THE RISK OFREADMISSIONMichael De Cubber MD* Marta Trabbach MD Francesca Garcia LizanaMD Christian Melot MD Jean-Louis Vincent MD Erasem Hospital,Brussels, Belgium

PURPOSE: To determine the clinical and laboratory features ofpatients who are readmitted to the ICU after discharge, and to use theseto develop a score to predict risk of readmission.

METHODS: In this observational cohort study in a mixed, 31-bed,medico-surgical intensive care unit, 226 consecutive adult ICU admissionswere included during a 13-week period (excluding patients admitted foruncomplicated postoperative surveillance).Variables related to epidemiol-ogy, past history, clinical and lab data were recorded. Data were analyzedby univariate regression analysis. Continuous variables were transformedin categorical variables using the threshold obtained by a Lowess smooth-ing function. The categorical variables were entered into a multiplelogistic regression model. The coefficients of the regression were used tocompute the score for each significant item. A p � 0.05 was consideredsignificant.

RESULTS: Of 226 admissions during the study period, 34 (17.4%)patients died in the ICU. The mean length of ICU stay was 6.4 days. Atotal of 42 patients (22%) were readmitted. The score developed from thestatistical analysis of the 272 variables includes 8 simple variables with amaximum score of 41 (Table). The area under the receiving operatingcharacteristic (ROC) curve was 0.74.

CONCLUSION: This simple score, based on routinely collectedvariables, can help to evaluate the risk of readmission to the ICU afterdischarge.

CLINICAL IMPLICATIONS: ICU readmission is associated withworse outcomes. Identifying patients at risk of readmission may preventpremature ICU discharge, may promote the use of increased surveillancesuch as intermediate care unit or telemetry on the floor, and may helpprepare the patient, the relatives, and the heath care professionals for thepossibility of readmission.

DISCLOSURE: Michael De Cubber, None.

DATA MINING THE ELECTRONIC MEDICAL RECORD TOEXAMINE OUTCOMES IN THE EMERGENCY DEPARTMENTPatricia B. Cerrito PhD* Dave Pecoraro University of Louisville, Louis-ville, KY

PURPOSE: To use data mining techniques on the electronic medicalrecord (EMR) in the Emergency Department (ED) with the intent ofimproving care while reducing costs.

METHODS: All patient records for a 6-month period were examined.All records with an initial complaint related to shortness of air or relatedwere extracted for a total of 1329 patient records. There were 53,000�charges ordered for these patients in the ED. The data mining techniquesof text analysis, transactional time series, and association rules were usedto examine the data.

RESULTS: A total of 187 patients were discharged to ICU after the ED,with 25 of the 187 originally triaged as non-urgent. In contrast, only 2 out of626 discharged home were triaged as emergent. Although there is nostandardization in the language of initial patient complaints, there is a generalgrouping of ten different complaints as listed in the table. Bronchitis andasthma require a similar amount of time in ED treatment; COPD requires anextra 100 minutes of treatment time on average compared to the other twoconditions. Patients complaining of shortness of air were tracked into a heartprotocol, receiving tests of Troponin and CBC; or were tracked into arespiratory protocol, receiving oxygen and mini-nebulizer treatment. Therewas 87% confidence that glucose testing was associated with EKG and CBC,a 70% confidence that it was associated with Troponin test, but almost noassociation with SOA treatments.

CONCLUSION: Data mining the EMR can provide useful informa-tion that can be used to improve care while reducing costs. There issufficient variability in treatment for patients with similar complaints thatthe variability can be examined and reduced while developing optimaltreatment patterns.

CLINICAL IMPLICATIONS: Once the variability in treatment isdocumented, it can be examined to develop standardized protocols forpatient complaints. Optimal paths of care can be developed. Specificprotocols can also reduce the time needed to treat patients in the ED.

Subgroup

Model

Complex

Cardiovascular Trauma

Elective

Surgery Medical

Neuro-

surgical

Other

Emergency

Surgery

Sample Size

H-L statistic

p Value

ROC AUC

3434

10.38

0.41

0.87

4248

9.17

0.52

0.90

9812

16.44

0.09

0.79

26633

12.20

0.07

0.79

2298

6.01

0.81

0.85

3605

11.63

0.31

0.79

Variable Score

Presence of decubitus ulcer 12Hyperleukocytosis or inflammatory syndrome

(WBC � 17,000/mm3 or CRP � 20 mg/dL)6

Maximal sequential organ failure assessment (SOFA)score � to 9

6

Paroxysmal atrial fibrillation or need for anti-arrhythmicmedication

4

Chronic obstructive pulmonary disease (COPD)or asthma requiring chronic treatment

4

Morbid obesity or parenteral nutrition or decompensateddiabetes

4

Hypoalbuminemia (serum albumin �3.5 g/dL) 3Alteration of mental status, polytrauma or notable

physical dependence2


Outcomes Assessment, continued


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DISCLOSURE: Patricia Cerrito, Grant monies (from sources otherthan industry) NIH grant #1UC1HS014897-01, ED Information Systems-Kentucky & Indiana Hospitals, Dave Pecoraro, PI, Patricia Cerrito, co-PI.

ASSESSMENT OF ACUTE PHYSIOLOGIC AND CHRONICHEALTH EVALUATION AND THE SIMPLIDIED PHYSIO-LOGIC SCORES IN A POST-TRAUMATIC SURGICAL INTEN-SIVE CARE UNITMeurant Francois MPH* Hopital Kirchberg, Luxembourg, Luxembourg

PURPOSE: The Acute Physiologic and Chronic Health Evaluation(APACHEII ) has been extensively used in Intensive Care Unit (ICU)setting over the past 10 years ,as has been the Injury Severity Score (ISS)using an anatomical descriptive scoring . The Simplified Acute PhysiologyScore( IGSII ) belongs to a new generation of scoring systems : its maininnovation is that the different parameters and their weighting are derivedfrom statistical analysis. However the accuracy of APACHE II and IGSIIscoring systems have to date not been specifically studied in general traumasurgical patients(TSP).To assess whether the APACHE II and IGS II scoresand their derived predictors of risk of death(ROD)are applicable to TSP?.

METHODS: During a16 month period TSP admitted to our ICU hadAPACHE II and IGSII scores with their derived ROD calculated.Receiver Operating Characteristic (ROC) curves and Goodness-of-Fit testwere used to assess the accuracy of the scores.

RESULTS: 62 TSP were included over 93 total trauma patients(median ISS score was 16.0, range 11 to 43), there were 10 in-hospitaldeaths from haemorrhage. The median APACHE II score was 12.0( range0 to 40) with a mean ROD of 17.0 � 19.6%. The median IGSII was 22.0( range 0 to 60) and its derived mean ROD was 15.0 � 19.2%. The areaunder the ROC curves was 0.850 for the APACHE II and 0.858 for theIGS II demonstrate a good discrimination. The goodness-of-fit testindicated that both scores were well calibrated (P �0.1 for APACHE IIand P �0.25 for IGSII). Standardised mortality ratio was 0.65 fromAPACHE II and 0.86 from IGSII.

CONCLUSION: The APACHEII and IGSII scores are both reliableand accurate in post-traumatic patients. Bleeding appeared as a poorprognostic factor.

CLINICAL IMPLICATIONS: The IGSII scoring, using actually ineuropean ICU, could be applied in all of critical intensive care patients,including traumatics patients, improving quality of job.

DISCLOSURE: Meurant Francois, None.

Pediatric Chest I12:30 PM - 2:00 PM

EFFECTS OF PREVENTION OF ASPIRATION DURING RSVBRONCHIOLITISDean Edell MD* Douglas Savino MD Vikram Khoshoo MD WestJefferson Medical Center, Marrero, LA

PURPOSE: To evaluate the effects of prevention of aspiration, with the use ofthickened feeds, during RSV bronchiolitis in previously healthy infants.

METHODS: Previously healthy infants with RSV bronchiolitis, whowere hospitalized, were divided into two categories: those given regularfeeds (Control group, n�30) and those who received feeds thickened withrice cereal as a proven strategy for prevention of aspiration(Study group,n�44). All received similar conservative management with oxygen, IVfluids and bronchodilators. Control and Study groups were matched forage, sex, duration of illness, acidosis, oxygen saturation and respiratoryrate. All infants underwent followup every two weeks after discharge fromthe hospital.

RESULTS: The duration of hospital stay was longer (p�0.05)in theControl group(4.9 days) as compared to the Study group(3.2 days). Thepercentage of infants requiring mechanical ventilation was higher(p�0.05) in Control(13%) versus Study group(2%). At one year followup27% of Study and 43% of Control patints were being treated for recurrentwheezing (p�0.05).

CONCLUSION: Use of thickened feeds during RSV bronchiolitis,with a view to prevent aspiration, is associated with shorter hospital stay,

reduced need for mechanical ventilation and lower incidence of reactiveairway disease.

CLINICAL IMPLICATIONS: The use of thickened feeds duringRSV bronchiolitis is a simple intervention to prevent the subsequent shortand long-term morbidity.

DISCLOSURE: Dean Edell, None.

EPIDEMIOLOGY OF WHEEZING INFANTS REFERRED TO ATERTIARY MEDICAL CENTERHeather Huxol MD Kimberly Kim MD Ron Morton MD Nemr S. EidMD* University of Louisville, Louisville, KY

PURPOSE: Persistent or recurrent wheezing is a common cause forreferral to pediatric pulmonology. These patients require a detailedwork-up to elicit the etiology of wheezing as they often represent adiagnostic dilemma. Objective: To examine the components of thediagnostic course typically taken in these infants and the primary diag-noses given. To compare the epidemiology of patients referred forwheezing with the two most common diagnoses, gastroesophageal reflux(GER) and asthma.

METHODS: A retrospective review was performed on 56 infants,mean age 10 months; range 2- 31 months, referred for recurrent orpersistent wheezing. All of these patients had infant pulmonary functiontests. The majority of patients had chest x-rays, pH probe studies, andupper GI series. A few others had modified barium swallow studies,allergy testing, and sweat chloride tests depending on the clinical presen-tation.

RESULTS: The most common diagnoses were GER and asthma.Asthma, both as a primary diagnosis or with secondary diagnoses, wasfound in 40/56 or 71% of patients. GER, alone or with other diagnoses,was found in 27/56 or 48% of patients. There was no difference betweenthese two groups regarding a parental history of asthma, prematurity, orNICU stay. There was no difference in family size. There was nodifference in reported cases of bronchiolitis or pneumonia between thetwo groups. Environmental smoke exposure was slightly more common inthe GER group. More patients with asthma had pets versus those withGER. A history of breastfeeding was less common in the asthma group.More patients with asthma had attended daycare versus those with GER.A clinical history of reflux was much more common in the GER group.

CONCLUSION: Although wheezy infants constitute a heterogeneousgroup of patients, the most common diagnosis in this cohort is asthma andgastroesophageal reflux.

CLINICAL IMPLICATIONS: The aspects of epidemiology mosthelpful in distinguishing the asthma patients versus the GER patientsincluded clinical history of reflux, history of breastfeeding, history ofdaycare attendance, and history of eczema.

DISCLOSURE: Nemr Eid, None.

THE 24-HOUR TUBERCULIN TEST: A COMPARISON WITHTHE 48-HOUR AND 72-HOUR READINGS AND ITS PREDIC-TIVE VALUEAlfredo A. Yap MD* Olivia C. Go MD University of Santo TomasHospital, Manila, Philippines

PURPOSE: This study was done to determine the value of the 24-hourtuberculin test (TT), its comparison with the currently recommended 48-and 72-hour readings, and the factors which may affect it.

METHODS: A 0.1 ml 5 TU PPD was administered using the MantouxMethod. Induration was measured at 24, 48 and 72 hours. An induration�8mm at 72 hours defined a positive test. The subjects were 230 children,6-15 years old, from Bukidnon, Southern Philippines, who were notpreviously diagnosed or treated for tuberculosis (TB), never had a TT andhad no condition/s that may cause anergy.

RESULTS: Among 230 subjects,117(50.8%)had positive tests at 72hours. The mean (SD)induration size (mm) was significantly larger at 72hours [9.48 (5.65)] than at 48- [8.17 (5.23)] and 24 hours [5.81 (3.7)],respectively. A positive correlation existed between the induration sizes atthe three periods. At 24 hours, the presence of any induration had asensitivity of 96.58%, specificity of 51.33% and positive predictive value(PPV) of 67.26%; an induration �4mm (half the cut-off),had PPV of81.15%; an induration �8 mm had a sensitivity of 34.18% , but 100%specificity and PPV;an induration �8mm had a NPV of 59.74%; anyinduration associated with chest x-ray (CXR) suggestive of tuberculosis,


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among other factors, had a PPV of 98.18%.The absence of an indurationat 24 hours had a negative predictive value (NPV) of 93.55%.

CONCLUSION: Any induration at 24 hours may increase with time.At 24 hours, any induration has a low specificity, high sensitivity, and lowPPV; induration �4mm(half the cut-off point) has high PPV; induration�8mm has high specificity, low sensitivity, and high PPV; �8mm has lowNPV; any induration associated with CXR suggestive of tuberculosis hashigh PPV;the absence of any induration has high NPV.

CLINICAL IMPLICATIONS: This study suggests that the tuberculintest be read at 72 hours whenever possible. However, when pressed fortime, the 24-hour TT may be utilized with caution.

DISCLOSURE: Alfredo Yap, None.

LUNG DEPOSITION OF QVAR (HFA134A-BDP) IN NEWBORNINFANTS WITH BRONCHOPULMONARY DYSPLASIA (BPD)Myrna B. Dolovich* David Millar MB, BCh Lori Sterling RN Rod RhemBSc Andrew P. Bosco BSc Haresh Kirpalani MB, BCh McMasterUniversity, Hamilton, ON, Canada

PURPOSE: Aerosol delivery to ventilated newborns is known to bepoor. CFC beclomethasone dipropionate (BDP) pMDI has been refor-mulated as an HFA134a solution (QVAR, 3M Pharmaceuticals, London,ON) with a demonstrably lower mass median aerodynamic diameter(MMAD) of 1.1 �m and geometric standard deviation (GSD) 2.5 than theCFC aerosol. We hypothesised that an aerosol with these propertieswould result in increased delivery to the peripheral lung with a greatertotal pulmonary deposition. Aim: To investigate the total pulmonarydeposition following inhalation of radiolabelled HFA 134a BDP inventilated neonates.

METHODS: Data expressed as mean(sd). Eight ventilated neonateswith BPD, 40.3 (10.9) days old at time of study, with a mean corrected ageof 32.2 (1.65) weeks post-gestation) were enrolled. Babies weighed 823.5(222.7)g at birth and 1182.9 (188.3)g at time of study. Vital signs weremonitored throughout the study. One dose of radiolabelled BDP (186(57)�Ci in 47 (14)�g BDP) was given via a Neonatal Ventilator AerosolDelivery System (NVADS, Trudell Medical Inc, London, ON), a tubespacer with low dead-space connectors to interface to the ventilatorcircuit. Posterior images of the lungs and lateral head were obtained over10 min using a GE Starcam gamma camera. Tissue attenuation factors foreach baby were obtained using a phantom.

RESULTS: O2 saturation was unchanged during delivery of the aerosol(predose: 90.8 (5.2)%; dosing: 89.5 (5.1)%; post-dose: 91.6 (4.2)%). Mostof the radiolabelled drug was captured in the NVADS (80.0 (13.1)%) andcircuit tubing and connectors. Lung deposition was 1.27 (0.95)% of therecovered emitted dose ex-actuator or 8.63 � 7.39% of the dose ex-spacer.These percentages translated into an average deposited lung dose of 0.6�gBDP.

CONCLUSION: These values are similar to prior work with CFCformulations of salbutamol and appear to show no advantage in the totaldose of HFA134a BDP delivered to these ventilated neonates.

CLINICAL IMPLICATIONS: Clinical trials would need to be un-dertaken to determine if even this low deposition efficiency could providea beneficial clinical outcome.

DISCLOSURE: Myrna Dolovich, Grant monies (from industry relatedsources); Study funded by 3M Pharmaceuticals Canada.

SERIAL EVALUATION OF PULMONARY FUNCTION LONG-TERM AFTER LUNG CONTUSIONJan Sulc MD* Jan Bruthans MD Karel Dlask MD Karel Cvachovec MDMichal Andrlik PhD Jiri Kofranek MD Kardiocentrum, University Hos-pital Motol, Prague, Czech Republic

PURPOSE: Lung contusions (LC) in children are frequent findingsafter road accidents. Possible residual lesions may potentially influencelong-term lung development. Study on serial evaluation of pulmonaryfunction in identical subjects has not published yet.

METHODS: Forty four chidren injured at the age of 10.0�4.0 (ranged2.3-17.5) yrs were diagnosed and treated for LC. These subjects werestudied serially 2.0�1.8 (ranged 0.1-6.6) yrs and later again 8.4�3.3(ranged 0.8-12.6) yrs after injury (when only 21 subject were accessible).The same protocol was used in both studies: static lung volumes by bodyplethysmography, lung elasticity using esophageal balloon technique andairway patency (by body plethysmography and flow-volume curves). 29/44were ventilated by conventional CMV 13.9�14.0 (ranged 2-70) days,

FiO2 0.50�0.2 (ranged 0.3-0.4). The following findings were detected:pneumo- or hemothorax (n�6), sepsis (n�18), ARDS (n�6) and/orribs/clavicle fractures (n�14). No previous history of chronic lung diseasewas ascertained.

RESULTS: Normal lung size (both in 1st and 2nd study, respectively),i.e., TLC 97�12 and 102�12% predicted, N.S.) was found. Normalairway patency (PEF 99�21% vs 105�23% predicted, resp., P�0.04 aswell as MEF25/TLC 92�32% vs 87�22% predicted, resp., N.S.) was alsofound over the years. No signs of hyperinflation were also found in bothstudies. Initial finding of stiffer lung normalized in the 2nd study: lungrecoil at 100% TLC decreased from 123�30% to 119�31% predicted,resp., N.S.).

CONCLUSION: In conclusion, despite serious lung injury duringchildhood the next favourable lung development till early adolescence wasconfirmed.

CLINICAL IMPLICATIONS: Children who recovered after a lungcontusion will not suffer from significant late pulmonary dysfunction.

DISCLOSURE: Jan Sulc, None.

LUNG FUNCTION TEST OF TOLUENE ABUSERS AMONGURBAN STREET CHILDREN AGES 7 TO 18 YEARS OLDFatima B. Pogoy MD* Teresita S. de Guia MD Philippine Heart Center,Quezon City, Philippines

PURPOSE: Toluene, an industrial solvent in adhesive compound is themost commonly abused inhalant among street children in Metro Manila.This study aims to determine the physiologic effects of inhaling toluene onthe respiratory function of the study population.

METHODS: General health status was assessed by history, physicalexamination and a questionnaire with emphasis on the respiratory symp-toms. Spirometry using a Microloop (Micro Medical Limited) was per-formed using the standards of the American Thoracic Society.

RESULTS: Thirty one (31) street children, 26 (84%)males, 5 (61%)females, with a mean age of 14�/-2 years were included. The meanduration of drug use is 2.6 �/- 2.5 years with a frequency of 23 �/- 20 hrper week. The most common respiratory symptoms in this series includedyspnea (38.7%, cough (35.5%), rhinorrhea (29%)and choking (12.9%).Results of spirometric studies showed 13 (41.9%)subjects with low FVCvalues � 80% of predicted indicative of restrictive ventilatory pattern inpatients who tested positive for toluene in the blood. FEV1 values were allnormal (mean FEV1 89�/- 14.9%). There was a statistically significantcorrelation between the duration/frequency of inhalant abuse with tolu-ene levels in the blood (p�0.04) and urine (p�0.006).

CONCLUSION: This study has shown a positive correlation betweentoluene abuse by inhalation and the development of restrictive ventilatorypattern which is directly related to the frequency and duration of tolueneinhalation.

CLINICAL IMPLICATIONS: Solvent abuse is popular among chil-dren and young adults. Sniffing the fumes causes the hunger, pain andloneliness to be numbed for a moment providing escape from realities oflife. It is now well recognized that solvent abuse not only can result insudden death but also cause pathological changes in the lungs. It istherefore, the aim of this study to investigate the effects of Tolueneexposure on the pulmonary function of these children.

DISCLOSURE: Fatima Pogoy, Other Philippine Foundation for LungHealth Research and Development, Inc.research and Development, Inc.

CHRONIC INHALED CORTICOSTEROIDS DO NOT AFFECTSEVERE ACUTE ASTHMA EXACERBATIONS IN CHILDRENChristopher L. Carroll MD* Anita Bhandari MD Aaron R. Zucker MDCraig M. Schramm MD Connecticut Children’s Medical Center, Hart-ford, CT

PURPOSE: Chronic therapy with inhaled corticosteroids (ICS) isknown to reverse and suppress airway inflammation and can also increaseairway responsiveness to beta-adrenergic agonists. We theorized that thechronic use of ICS would be associated with shorter duration of hospital-ization in severely ill children with status asthmaticus.

METHODS: An eight-year retrospective chart review (April 1997 toMay 2005) was conducted of all children greater than two years oldadmitted to the ICU with a primary diagnosis of status asthmaticus.Baseline demographics and outcome measures were compared betweenchildren receiving and not receiving ICS prior to admission.


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RESULTS: During the study period, 241 children were admitted to theICU for status asthmaticus, and 107 (44%) were receiving chronic ICS atthe time of admission. Chronic ICS use was associated with asthmaseverity (NIH asthma classification), previous hospitalization for asthma(79% vs. 45%, p�0.01) and public insurance status (67% vs. 53%,p�0.03). However, ICS use had no effect on hospital or ICU length ofstay, type and duration of treatments received, or the rate of recovery.When examining subsets of patients, including children with persistentasthma and those who received intravenous terbutaline, there was also noimprovement in outcomes with the use of chronic ICS. However, childrenwith persistent asthma were less likely to receive supplemental therapywith non-invasive positive pressure ventilation (5% vs. 15%, p�0.03) ifthey were receiving chronic ICS.

CONCLUSION: The chronic use of inhaled corticosteroids does notappear to reduce ICU length of stay or improve response to beta agonistsin severely ill children with status asthmaticus.

CLINICAL IMPLICATIONS: Although useful preventively, thechronic use of ICS does not appear to affect the course of acuteexacerbations in pediatric patients.

DISCLOSURE: Christopher Carroll, None.

CLASSIFICATION OF ASTHMA SEVERITY AMONG STEROID-NAıVE PEDIATRIC SUBJECTS PREVIOUSLY RECEIVINGSHORT-ACTING BETA2-AGONISTS: DO THE GUIDELINESNEED REVISITING?Bradley Chipps MD Joseph Spahn MD Christine Sorkness PharmDAmanda Emmett MS Laura Sutton PharmD Paul M. Dorinsky MD*GlaxoSmithKline, Research Triangle Park, NC

PURPOSE: According to national/international asthma guidelines,subjects with asthma can be classified into one of 4 categories (intermit-tent, or mild, moderate, or severe persistent) based upon lung function,symptoms, and albuterol use. Guideline criteria for mild asthma based onsymptomatology or rescue use is broad, suggesting that they may notdefine a distinct group of patients.

METHODS: This analysis evaluated 276 subjects previously receivingshort-acting beta2-agonists alone from 5 completed 12-week trials inwhich subjects received placebo. Subjects were initially stratified bybaseline PEF �80% or �80% predicted and further stratified bysymptoms and/or albuterol use on �2 days/wk, 3-6 days/wk or 7 days/wk.

RESULTS: For subjects with PEF �80% and symptoms/albuterol use1-2 days/wk, the majority of weeks were spent in intermittent (76%) ormild (11%) categories, based on overall assessment of asthma severity. Bycontrast, for subjects with PEF �80% and symptoms/albuterol use 7days/wk, approximately 51% of weeks were spent in the moderatecategory. When subjects with PEF �80% and symptoms/albuterol use 3-6days/wk were considered, subjects who would be classified with mildpersistent asthma using current guidelines, approximately 34% of weekswere spent in moderate or severe categories. Furthermore, subjects withPEF �80% and symptoms/albuterol use on 3-6 days/wk, spent only 36%of weeks in intermittent or mild categories and those with PEF �80% anddaily symptoms/albuterol spent only 20% of weeks in intermittent or mildcategories.

CONCLUSION: This analysis clearly demonstrates that asthma sever-ity cannot be determined in many pediatric subjects by discrete, point-in-time assessments of lung function, albuterol use or symptoms. Moreimportantly, these observations suggest that the current classificationsystem for persistent asthma needs to be re-evaluated as many pediatricsubjects who meet current guideline criteria for mild persistent asthmawould appear to be more appropriately classified as having moderate orsevere persistent asthma.

CLINICAL IMPLICATIONS: These data highlight the importanceof ensuring that pediatric patients are carefully monitored and receiveappropriate maintenance therapy for asthma control.

DISCLOSURE: Paul Dorinsky, Shareholder I am a GSK shareholder;Employee I am a GSK employee.

ROUTINE TRACHEAL ASPIRATES: ROLE IN THE MANAGE-MENT OF RESPIRATORY TRACT INFECTIONSJeff McQuade RRT Andrew Braude MD Lily Yang RRT* BloorviewMacMillan Children’s Centre, Toronto, ON, Canada

PURPOSE: The lower respiratory tract is considered to be sterile tobacteria in healthy humans. The insertion of a tracheostomy tube results

in the lower respiratory tract becoming colonized with bacteria. Mechan-ical ventilation enhances the severity of these risk factors. The ability topredict the likely organism and initiate earlier appropriate empiricantibiotic therapy should improve the client’s outcome. To date there is noconsidered standard approach to attempting to predict specific organismsor to predicting a specific antibiotic choice for lower respiratory tractinfections in patients with a tracheostomy who may or may not bemechanically ventilated.Our hypothesis is that regular tracheal swabs willdetect the likely causative organism in lower respiratory tract infections inpredisposed tracheotomized patients. This knowledge will improve anti-biotic choice and reduce morbidity and mortality.

METHODS: For this study, 17 patients with chronic tracheotomies, 9of whom were mechanically ventilated were selected. Periodic trachealaspirates were obtained for bacterial culture and resistance profile tostandard antibiotics. Clinically, when a determination of a lower respira-tory tract infection was made, an antibiotic was chosen based on physicianpreference. At the same time a tracheal aspirate was obtained prior to theinitiation of antibiotics.

RESULTS: If Pseudomonas Aeruginosa was present as a colonizingorgainsm in the tracheal aspirate done when well, it was always present inheavy growth when the patient was ill. Thus making the choice ofantibiotic one which would be effective against this organism.With respectto other gram negative and positive isolates, no apparent correlation couldbe found necessitating empiric coverage for these organisms at times ofclinical infection.

CONCLUSION: Knowlege of colonizing tracheal organisms in pa-tients compromised with a tracheostomy tube and/or mechanically venti-lated is valuable in that Pseudomonas Aeruginosa, if present, should beempirically covered for when clinical infection occurs. Thereafter no otherprediction of infecting organisms could be drawn.

CLINICAL IMPLICATIONS: At times of clinically documentedinfection, the prior knowledge of tracheal aspirate microbiology was oflimited application for appropriate antibiotic choice.

DISCLOSURE: Lily Yang, None.

THE EFFECT OF APNEA ON SLEEP ARCHITECTURE ININFANTS WITH GENETIC OR METABOLIC DISEASEWish Banhiran MD* Chulaluck Techakittiroj MD Teeradej KuptanonMD Narong Simakajornboon MD Tulane University School of Medicine,New Orleans, LA

PURPOSE: Several studies have shown that infants with genetic ormetabolic disease have increased incidence of both central and obstruc-tive apnea. However, those studies have not assessed the effect of sleepapnea on sleep architecture. Since apnea and associated hypoxemia andhypoventilation can lead to sleep fragmentation due to respiratory arous-als, we evaluated the effect of apnea on sleep architecture in thispopulation.

METHODS: A retrospective review of polysomnographic record-ings was performed in infants with genetic or metabolic disease andnormal control infants who were referred to our sleep laboratory from1999-2004. All infants underwent an overnight polysomographic stud-ies. Any infants with significant lung diseases or infants who were onrespiratory stimulants, or supplemental oxygen were excluded from thestudy.

RESULTS: Thirty three infants met the criteria for entry into theanalysis; 17 infants with metabolic or genetic disease [S] and 15age-matched controls [C]. The average apnea index of infants withgenetic or metabolic disease was 23.9�6.8/hr; 58.8 % (10/17) hadpredominately central apnea and 41.2 % (7/17) had predominatelyobstructive apnea. Infants with genetic or metabolic disease hadsignificant lower average SpO2 (95.6�3.4 %[S] vs. 99.1�0.9[C];P�0.05) and higher average EtpCO2 (44.6�5.7 mmHg[S] vs.38.7�4.9[C]; P�0.05) during sleep. However, there was no significantdifference in the sleep efficiency (73.1�12.8%[S] vs. 78.6�5.5[C];P�NS), percentage of REM sleep (54.3�16.2%[S] vs. 53.0�8.0[C];P�NS) and NREM sleep (42.2�14.3%[S] vs. 43.5�8.2[C]; P�NS)between infants with genetic or metabolic disease and control. Analysisof the respiratory arousals revealed that only 11.6 % of apnea in infantswith genetic or metabolic disease was followed by arousals.

CONCLUSION: It is concluded that apnea in infants with genetic ormetabolic disease is not associated with significant changes in sleep




architecture. It is speculated that the intact sleep architecture despite thepresence of central and obstructive apnea may be due to blunted arousalresponse in these infants.

CLINICAL IMPLICATIONS: Infants with genetic or metabolicdisease may be at risk of developing significant adverse events from sleepapnea.

DISCLOSURE: Wish Banhiran, None.

THE USE OF SPIROMETRY AND IMPULSE OSCILLOMETRYIN THE DIAGNOSIS OF VOCAL CORD DYSFUNCTION IN THEPEDIATRIC PATIENTShannon Boudreaux MD* Khalilah Lewis-Brown MD Glenn HildrethRRT Kevin D. Maupin MD University of Florida Department of Pediat-rics/ Sacred Heart Children’s Hospital, Pensacola, FL

PURPOSE: The diagnosis of paradoxical vocal cord dysfunction issuggested by the patient’s clinical history. It is definitively made byobserving the vocal cords via flexible laryngoscopy/bronchoscopy. Para-doxical vocl cord dysfunction can also be suggested by a flat inspiratorylimb of the spirometry flow-volume loop. An increase in airway resistancevia impulse oscillometry may also suggest paradoxical vocal cord dysfunc-tion. The purpose of this study was to evaluate the usefulness ofspirometry and impulse oscillometry in the diagnosis of pardoxical vocalcord dysfunction.

METHODS: We retrospectively reviewed patient charts with a diag-nosis of paradoxical vocal cord dysfuntcion that were seen in our PediatricPulmonary Clinic over a 6-month period. We reviewed fourteen charts forthe following parameters; sex, inspiratory limb of the flow-volume loop,and airway resistance via impulse oscillometry. The diagnosis had beenmade by flexible fiberoptic bronchoscopy performed on all the patients.

RESULTS: Five(35.7%) of the patients were male and nine(64.3%) ofthe patients were female. All of the patients had a normal inspiratory limbof the flow-volume loop. All of the patients had a normal RAW.

CONCLUSION: In this study, the inspiratory limb of the flow-volumeloop and the airway resistance via impulse oscillometry were both normal.

CLINICAL IMPLICATIONS: The inspiratory limb of the flow-volume loop and the airway resistance via impulse oscillometry are notuseful in the disgnosis of paradoxical vocal cord dysfunction. The diagnosisshould only be made by fiberoptic laryngoscopy/bronchoscopy.

DISCLOSURE: Shannon Boudreaux, None.

PHYSIOLOGICAL RESPONSES COMPARATION AND REPRO-DUCTIBILITY OF SIX MINUTE WALKING TEST IN CYSTICFIBROSIS AND NORMAL CHILDRENCristiane C. Coelho MA* Dorcas C. Almeida BA Gisele C. Oliveira BARoberta C. Pinto BA Ivana M. Oliveira MA Evanirso S. Aquino BSUni-BH, PUC MInas-Betim, Belo Horizonte, Brazil

PURPOSE: The aim of this study was to investigate pulmonary andcardiovascular responses during the six minute walking test (6MWT) incystic fibrosis and normal children and to assess the test-retest of 6MWTin the studied population.

METHODS: The subjects recruited were distributed in two groups:cystic fibrosis (CF) and normal group (NG). The study consisted thetest-retest of 6MWT by comparing performance on two consecutive6MWT in both groups. The children had a rest of 30 minutes between thetests. The responsiveness of the 6MWT was determined by assessing theability of the test to detect changes in exercise capacity. The variablesanalyzed were distance walked during the test, heart rate overload (% ofHR), oxygen saturation (SpO2) and Borg score.

RESULTS: A total of 28 children were recruited in this study, 18 boysand 10 girls. The mean age was 11.53 �2,60 and 10,72�2,88 years for CFand NG respectively. The mean values for lung volumes were (FEV1�86.34�27.11; FRC�94.85�25.19) for CF and (FEV1�100.99�8.92;FRC�112.26�15.56) for NG. The comparison between the groupsshowed that the distance walked (CF�577.57�60.22 NG�673�55.32;p�0.0004) and Borg score(CF�9.92�2.32 CN�12.42�2.4; p�0.01)were statistically different. However, there were no differences in %HR(CF�72.46�9.15 NG�72.54�12.19; p�0,85) and SpO2(CF�94.07�5.16 CN�96.28�2.12; p�0.13) between the groups. Thetest-retest in cystic fibrosis group showed a significant increase in the walkdistance in the second test (p�0.012), the others variables analyzed didnot change. In the normal children group just the Borg Score had asignificant increase in the second test (p�0,019).

CONCLUSION: There was no difference in heart rate overload in the6MWT in cystic fibrosis and normal children. However, the cystic fibrosischildren had a lower perception of exercise intensity and walked concern-ing underwear distances when compared with normal children.

CLINICAL IMPLICATIONS: The 6MWT can be applied in cysticfibrosis children as in normal children, however, the cystic fibrosischildren has to be previously familiarized with the test.

DISCLOSURE: Cristiane Coelho, None.

Pediatric Chest II12:30 PM - 2:00 PM

ELECTRICAL ACTIVITY OF THE LARYNGEAL CONSTRICTORAND DILATOR MUSCLES DURING CENTRAL APNEAS IN THENEWBORN LAMBNathalie Samson MS* Francois Moreau-Bussiere MS Joelle Rouillard-Lafond MD Jean-Paul Praud MD Universite de Sherbrooke, Sherbrooke,PQ, Canada

PURPOSE: A complete active glottal closure in inspiratory position ispresent throughout 90% of central apneas in the preterm newborn lamb,partly preventing the post-apneic desaturation. However, results of theliterature (Hutchison A, 2002) suggest that some induced neonatal apneasare characterized by an active laryngeal opening by contraction of thedilator muscles of the larynx. Thus, the goal of this study is to test thehypothesis that the larynx is actively open during some induced andspontaneous central apneas in newborn lambs.

METHODS: Ten full-term lambs were chronically instrumented forrecording electroencephalogram, eye movements, electrocardiogram,SaO2, nasal flow, subglottal pressure. In addition, the electrical activity(EMG) of the diaphragm, a laryngeal constrictor (thyroarytenoid muscle,TA, n � 4) and two laryngeal dilators (cricothyroid muscle, CT, n � 7 andposterior cricoarytenoid muscle, PCA, n � 7) was recorded. Polysomno-graphic recordings were performed in non-sedated lambs, using ourcustom-made radiotelemetry system to study both induced and sponta-neous apneas on two different occasions.

RESULTS: The results show a continuous TA EMG throughout 73%of all induced central apneas, and during the first two thirds of 89% of allspontaneous central apneas (mostly after a sigh). TA EMG was inter-rupted by CT EMG alone or with PCA EMG in 13% of all spontaneousand induced central apneas. The presence of the CT and/or PCA EMGduring induced central apneas was consistently associated with both a fallof the subglottal pressure to atmospheric pressure and a decrease in lungvolume below the preceding end-expiratory lung volume.

CONCLUSION: In conclusion, a few central apneas in newborn lambsare characterized by both an active closure and opening of the larynx,occurring sequentially.

CLINICAL IMPLICATIONS: Active opening of the glottis is asso-ciated with a fall of the subglottal pressure, which consequently leads to adecreased in lung volume during central apnea.

DISCLOSURE: Nathalie Samson, None.

COMPARISON OF DIFFERENT PROTOCOLS OF INSPIRA-TORY MUSCLES INCREMENTAL TEST IN NORMAL CHIL-DRENCristiane Cenachi-Coelho MA* Lıdia M. Barreto BA Maria Fernanda F.Correa BA Rose A. Miranda Figueira BA Evanirso S. Aquino BScUni-BH, PUC Minas-Betim, Belo Horizonte - MG, Brazil

PURPOSE: To evaluate the applicability and acceptability of threedifferent protocols of inspiratory muscles incremental test in normalchildren.

METHODS: The children recruited were aleatory submitted to threeinspiratory muscles incremental tests (IMT). JOHNSON et al (IMTI),JONG et al (IMTII) e NICKERSON E KEENS (IMTIII). Each protocolwas performed with 24 hours between them. The inspiratory musclesendurance was performed 30 minutes after the IMT conforming, and wasdefined, as the time the subject was able to sustain breathing against aninspiratory pressure load equivalent to 80% of the maximal tolerated loadin the IMT.




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RESULTS: A total of 24 children completed the study, 13 boys and 11girls. The mean age was 10,4�2,1 years. The mean values for lungvolumes were withing normal limits. There were no statistically significantbetween initial and final heart rate, breathing frequency, oxygen satura-tion and dyspnea score; the time of the test; inspiratory muscles endur-ance comparing the three tests studied. However, the children wereunable to sustain the maximal load in the (IMTIII) so they did not do theinspiratory muscles endurance. About the Borg score and the sustainedload the results showed IMTI � IMT II� IMTIII (p� 0,001) and IMTII � IMTIII � IMTI (p� 0,001) respectively. IMTIII was the onlyprotocol witch the children did not achieve the maximal load during thetest.

CONCLUSION: The results suggest that the IMT II protocol dem-onstrated better applicability and acceptability in normal children ascompared with IMTI and IMTIII.

CLINICAL IMPLICATIONS: The best inspiratory muscles test toevaluate the inspiratory muscles endurance in normal children was IMTIIbecause it does not underestimate the maximal load sustained.

DISCLOSURE: Cristiane Cenachi-Coelho, None.

NIL NOCERE: ACQUIRED RESTRICTIVE THORACIC DYS-TROPHYFrancis Robicsek MD Alexander A. Fokin MD* Peter N. Kane MD ChadR. Swan MD Heineman Medical Research Laboratories, Carolinas Med-ical Center, Charlotte, NC

PURPOSE: In 1995, Haller reported on a peculiar group of adoles-cents suffering from a condition coined “acquired Jeune’s syndrome,”later also known as “Acquired restrictive thoracic dystrophy” (ARTD). Allthese patients underwent pectus excavatum repair at an early age, afterwhich their chest failed to grow adequately and became rigid with severelyrestricted respiratory function.

METHODS: To shed light on the cause of this heretofore unknowndisease, we have studied clinically five patients with ARTD and coordi-nated our findings with the scarce literary data available on the subject.

RESULTS: All the patients whose data were available presented withsevere respiratory impairment. Evidently, in the course of their pectusrepair their costal cartilages from the second rib down were radicallyextirpated, including their medial and lateral centers of growth. Some ofthe operative reports and all of our imaging studies also indicated that theperichondrial strips were sewn together behind the sternum to maintainits corrected position (Fig. 1). As a result, the patient developed a rib cagethat remained infantile in size, odd in appearance and failed to rise ininspiration or fall when the patient exhales.

CONCLUSION: Performing repair of pectus excavatum the waydescribed above is a grave mistake and should be avoided. We alsodisagree with those who suggest that the best way to avoid ARTD is todelay pectus repair to the age when the chest is already fully developed.As our experience of 300 patients operated at a very early childhoodshows, the operation may be safely performed at any age, given appro-priate operative plan and technique.

CLINICAL IMPLICATIONS: The sparing of the growth plates andsynovial joints of the ribs during cartilage resection preserves growthpotential of the thoracic cage, prevents the development of acquiredrestrictive thoracic dystrophy after pectus excavatum repair and allowssurgical correction of chest wall deformities to be done at early age.

DISCLOSURE: Alexander Fokin, None.

HIGH FREQUENCY CHEST WALL OSCILLATION IMPROVESOUTCOMES IN CHILDREN WITH CEREBRAL PALSYPenny M. Overgaard RN Peggy J. Radford MD* Phoenix Children’sHospital, Phoenix, AZ

PURPOSE: Children with cerebral palsy (CP) have an increased risk ofrecurrent pneumonia from impaired airway clearance. Ineffective cough,poor oral secretion control, reduced mucociliary function from recurrentinfections and chest wall abnormalities contribute to poor airway clear-ance. Improving airway clearance may reduce the number of pneumonias.There is very little information regarding the value of high frequency chestwall oscillation (HFCWO) in this population.

METHODS: We performed a retrospective quality assurance reviewon 13 children with CP, follow0ed in our pediatric pulmonary clinic, whouse HFCWO to enhance airway clearance.

RESULTS: Of the 13 children with CP, 5 are females, 8 males. Threechildren have tracheostomies, 7 have gastrostomy buttons. Hospital andclinic charts were reviewed to determine the number of emergency room(ER) visits and hospitalizations for respiratory problems including pneu-monia and asthma. Calls were made to families to assess HFCWO usageand parental satisfaction. Parent recall and patient records documented 8hospitalizations and 5 ER visits 1 year before HFCWO. Parents reportedfrequent illnesses requiring multiple antibiotics, 1 child missed 50 days ofschool, and another required increased oxygen use. After using HFCWO,5 hospitalizations and 1 ER visit were documented. Parents reported lessrespiratory illnesses, less antibiotic use, and 1 child had a 58% reductionin missed school days. Six of the children have used HFCWO for morethan 1 year; seven for at least 6 months. The average minutes of HFCWOuse per day calculated from the hour meter was 41.3 minutes for 11patients; information was not available on 2. Parental satisfaction withHFCWO was high with 9 parents expressing improvement in their child’shealth and quality of life.

CONCLUSION: This retrospective analysis would suggest that there isbenefit from HFCWO use in children with CP by declines in respiratoryillnesses, antibiotic use, missed school days, hospitalizations and ER visits.

CLINICAL IMPLICATIONS: A controlled, prospectively designedstudy would be able to provide more scientific support for the use of thevest in this population.

DISCLOSURE: Peggy Radford, None.

THE MEASUREMENT OF RESPIRATORY MUSCLE FUNCTIONIN ADOLESCENT IDIOPATHIC SCOLIOSISRupali Bansal MD* Narong Simakajornboon MD Salvador CangiamellaRRT Robert C. Beckerman MD Michael Kiernan MD Tulane University,Department of Pediatrics, New Orleans, LA

PURPOSE: Restrictive lung disease is the most commonly reportedpulmonary abnormality in adolescents with idiopathic scoliosis(IS). Thereis limited data on respiratory muscle function in IS. Since spinal deformityand decrease in lung volumes may lead to reduction in respiratory musclestrength, we studied these relationships.

METHODS: Between 1999-2004, we retrospectively studied pre-operative IS. All performed spirometry, lung volumes and respiratorymuscle assessments. Degree of scoliosis was measured radiographically bythe Cobb Angle(CA). The following parameters were analyzed:CA,FEV1,FVC,FEV1/FVC,FEF 25-75,MVV,PImax,PEmax,and staticlung volumes. Neuromuscular disease,lung disease patients and incom-plete records were excluded.

RESULTS: Seventy four IS met the criteria for the study. The averageage was 13.8� 2.1 years. Cobb Angles(CA) ranged between 23° and 84°,mean 50.7� 13.6°. Patients were divided into two groups, CA � 45° (M),and CA � 45° (S).]. There were significant differences in FVC(97.9�14.9(M) vs 84.5�14.6%(S), P�0.05) and PEmax (85.4�22.5(M) vs64.9�28.3%(S), P�0.05. between M and S groups. However, there wereno significant differences in PImax, MVV or ERV between the twogroups. Using linear regression analysis, there was a strong negativecorrelation between CA and FVC (r� -0.36; p � 0.002). There was a


Pediatric Chest II, continued


correlation approaching significant between CA and PImax (r� -0.23; p �0.05). But there were no significant correlations between the CA andPEmax, MVV, or ERV.

CONCLUSION: FVC is the most sensitive marker of abnormal lungfunction in adolescents with idiopathic scoliosis. Respiratory musclefunction, such as PEmax is significantly decreased in moderate to severeIS. But there is also a trend toward significant correlation between PImaxand the degree of spinal curvature.

CLINICAL IMPLICATIONS: We speculate that the rib cage defor-mity and secondary respiratory muscle dysfunction in these patientsimpairs the ability to generate normal inspiratory and expiratory pressures.Assessment of respiratory muscle function may be a useful additional toolin adolescents with IS who are evaluated preoperatively for spinalstabilization procedures.

DISCLOSURE: Rupali Bansal, None.

RELATIONSHIPS BETWEEN RESPIRATORY FUNCTION ANDSPINAL CHARACTERISTICS IN PATIENTS WITH SEVERE MO-TOR AND INTELLECTUAL DISABILITIES SYNDROMENaoki Mori MS* Hajime Kurosawa MD Azuma Hiramoto MD KayomiMatumoto MS Yuko Sano MS Emiko Fukuda PhD Hiromi Fujii PhDMasahiro Kohzuki MD Dep. of Int. Med. and Reha. Tohoku Univ.Graduate School of Medicine, Sendai, Miyagi, Japan

PURPOSE: Severe motor and intellectual disabilities syndrome(SMIDS) is a term used to describe a heterogeneous group of disorderswith severe physical disabilities and profound mental retardation. Patientswith SMIDS have spinal deformity in high incidence, and showed tomultiple scoliosis curve pattern. The purpose of this study is to examinethe correlation between spinal characteristics (including scoliosis curvepattern and respiratory function.

METHODS: Thirty patients with SMIDS (M:F 18:12, Age, 33.5 �12.1, means � SD)who were studied. All subjects were severe cerebralpalsy, and were unable to sit independently. Spinal deformity weremeasured by Cobb Method (Cobb angles :CA) and Nash & Moetechnique (vertebrae rotation grade :VRG). Scoliosis curve pattern weredivided into three groups(thoracic, thoracolumbar and lumbar ) accordingto the different apical vertebrae by X-ray image. We measured tidalvolume&, respiratory frequency observed during tidal breathing at staticsupine posture.

RESULTS: CA and VRG, both were inversely correlated with tidalvolume (CA:r�-0.71, p�0.01,VRG:rs�-0.59, p�0.01). CA and VRG,both were correlated with respiratory frequency(CA: r�0.67, p�0.01,VRG:rs�0.56, p�0.01). However, We did not find significant differencesof respiratory function among curve patterns in patient with SMIDS.

CONCLUSION: These results suggest that the spinal deformityrestrictively affect respiratory patterns in patients with SMIDS. Scoliosiscurve pattern did not affect respiratory function.

CLINICAL IMPLICATIONS: To care to prevent spinal deformitiesespecially in CA and VRG is very important in terms of maintainingrespiratoy function.

DISCLOSURE: Naoki Mori, None.

DELAYED SLEEVE RESECTION OF DISTAL LEFT MAINBRONCHUS CRUSHING INJURY IN A CHILD AFTER SHORTCOURSE OF STEROIDAL TREATMENT: CASE REPORTAlden H. Kirk MD* Giorgio M. Aru MD Fermin Romero MD Universityof Mississippi - Division of Cardiothoracic Surgery, Jackson, MS

PURPOSE: We report for the first time on the delayed repair of adistal bronchial injury (BI) in a child, treated with steroids prior todefinitive surgical repair.

METHODS: An 8 year old child, run over by a truck, developed a leftsided tension pneumothorax treated with a chest tube. Ten days later shewas transferred to us for atelectasis of the left lung. The initial air leak hadresolved and a flexible bronchoscopy showed bronchial disruption of thevery distal left main stem bronchus. We planned a delayed repairconsidering that the injury in the distal left main bronchus carried a highrisk of pneumonectomy during an early surgical repair for possiblefriability of the bronchial biforcation. She was discharged on low dosesteroids and after 2 weeks a limited sleeve resection of the distal left mainstem bronchus was performed through the left 4th intercostal space . Fouryears later, she is doing well and has a normal CXR.

RESULTS: In children the incidence of BI is very rare due to theelasticity of the tissues. Most injuries occur in the proximity of the carina.It was the initial delay in the diagnosis, as well as the clinical stability of thepatient, that led us to the consideration of using low dose steroids in anattempt to limit the inflammation and stenosis of the involved bronchus.Whether or not the use of low dose steroids contributed to less scarringand a successful repair cannot be stated from a single case and should befurther investigated.

CONCLUSION: We conclude that in selected cases of BI, a shortcourse of low dose steroids can reduce the inflammation related totrauma, allow some healing, and possibly reduce the amount of scarring.

CLINICAL IMPLICATIONS: The option of using a short course oflow dose steroids when presented with a late diagnosis of tracheobronchialinjury should be considered.

DISCLOSURE: Alden Kirk, None.

CONTINUUM OF CARE: THE ROLE OF TEACHING PRO-GRAMS IN THE PROVISION OF CARE TO VENTILATOR-ASSISTED INDIVIDUALS IN URBAN AND RURAL REGIONSOF QUEBECRita Troini MA* McGill University Health Centre, Montreal, PQ, Canada

PURPOSE: To present how the use of teaching programs cancontribute to standardizing the care of ventilator-assisted individuals(VAI’s) across hospitals, rehabilitation centers and regions to whichVAI’s return once discharged home. The National Program for HomeVentilatory Assistance (NPHVA) is a university-based program respon-sible for providing respiratory equipment and related homecareservices to an adult and pediatric population requiring long-termmechanical ventilation. Diagnoses include neuromuscular diseases,Ondine’s syndrome, amyotrophic lateral sclerosis and high spinal cordinjury. The NPHVA provides services to all regions of Quebec over avast demographic area. In an effort to provide VAI’s with the same careacross all regions, the NPHVA developed teaching programs coveringtopics related to each VAI’s illness, treatments and equipment. Theseprograms are used in the training of patients, families, health carepartners and frontline community health workers involved in the careof the patient at home. Binders personalized to each VAI’s needs areprovided.

METHODS: We analyzed patient/family satisfaction surveys and otherquality indicators to identify key elements contributing to the success ofthe NPHVA in providing homecare services to VAI’s in urban and ruralregions of Quebec.

RESULTS: Three key elements were identified: 1) Teaching/trainingprovided to the patient/family and frontline community health workers; 2)Regular home visits; 3) Timely exchange of information between theprogram’s clinical specialists and frontline community health workersproviding care to the patient in their region.

CONCLUSION: The use of teaching programs contributes to an openexchange between all health care partners involved in the care of VAI’sand can contribute to improving the continuity of care and the quality oflife of this patient population.

CLINICAL IMPLICATIONS: The training and dissemination ofinformation to frontline health care workers in conjunction with contin-uous exchange of clinical and technical information between university-based centers of expertise and community workers may prevent needlesshospitalizations of VAI’s due to lack of knowledge and training in homeventilator management and associated therapies.

DISCLOSURE: Rita Troini, None.

THE EVOLUTION AND CURRENT STATUS OF RESPIRATORYTECHNOLOGY DEPENDENT CHILDREN IN MANITOBARaquel J. Consunji-Araneta MD* Karen Wachnian RN Diane LauderRRT University of Manitoba, Winnipeg, MB, Canada

PURPOSE: To describe the demographic and clinical characteristics ofand type of respiratory technology utilized by respiratory technologydependent children (RTDC) in Manitoba (1982-2005).

METHODS: Demographic and clinical data (age, sex, underlyingcondition) were collected retrospectively together with specific informa-tion regarding respiratory technology utilized (oxygen, tracheostomy,




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non-invasive or invasive ventilation – continuous or nocturnal) and currentlocation/situation.

RESULTS: In 1982 the first ventilated child was sent home on anLP3 ventilator. The establishment of the Pediatric Sleep Program in1989 contributed to more children requiring ventilator support. Ma-jority of the 115 children dependent on respiratory technology since1982 have been managed at home. Ventilatory support was discontin-ued in twenty-nine patients and thirteen were successfully decannu-lated. Seventeen children have been transitioned to the Adult Pro-gram. Mortality rate is 16.5% (19/115). The current population ofRTDC in Manitoba consists of 11 children ventilated by tracheostomyand 20 who receive support non-invasively at home; another 15children have tracheostomy tubes only and 17 receive oxygen supple-mentation. Only two tracheostomized/ventilated and 2 tracheos-tomized children remain in hospital. One patient on BiPap supportremains admitted (requiring other therapies). Patients’ underlyingconditions were classified as neuromuscular diseases, central nervoussystem disorders, spinal injuries, craniofacial syndromes, chronicrespiratory diseases (BPD, BOOP) and others (tracheomalacia,trauma, etc). Tracheostomized/ventilated children require on average1-2 hospitalizations/year while children with tracheostomy tubes or O2only are admitted 0-1 times/year. All patients managed at home areassessed at least 2-4 times/year at the Technology Dependent Chil-dren’s Clinic.

CONCLUSION: Majority of RTDC children in Manitoba have beenand are successfully cared for at home.

CLINICAL IMPLICATIONS: Advanced medical technology anddevelopments in critical care have increased the number of childrenwith chronic medical conditions that are dependent on respiratorytechnology. Together with a well-structured Home Care Program,dedicated efforts of Respiratory Therapists, Pediatric nurses andSpecialists, majority of these patients can be managed effectively in thehome setting.

DISCLOSURE: Raquel Consunji-Araneta, None.

LUNG PROTECTIVE STRATEGY DURING MECHANICAL VEN-TILATION OF PEDIATRIC PATIETNS WITH ARDS IS ASSOCI-ATED WITH REDUCED INCIDENCE OF CHEST TUBES IN-SERTION FOR PNEUMOTHORACES BUT WITH INCREASEDINCIDENCE OF CHEST TUBES INSERTION FOR PLEURALEFFUSIONSMichael P. Miller MD* Mayer Sagy MD Schneider Children’s Hospital,New Hyde Park, NY

PURPOSE: To test the hypothesis that the overall incidence of chesttubes insertion for pneumothoraces in pediatric ARDS patients hasdecreased with protective lung strategy (PLS) during mechanical ventila-tion (MV) while the incidence of chest tubes insertion for pleural effusionshas increased.

METHODS: We retrospectively reviewed charts of pediatric ARDSpatients who required a minimum PEEP level of 8 cm of water. Data ofpatients treated in our PICU during years 1992 – 1993 (pre-PLS) werecompared with those of years 2000-2003 (post-PLS). Pre-PLS was definedas a period during which unlimited peak airway pressures (PIP) wereallowed during MV and the tidal volumes used were ranging between 10ml/kg and 20 ml/kg. Post-PLS was characterized by MV with smaller tidalvolumes (6-10 ml/kg) and by PIP values not exceeding 40 cm of water.

RESULTS: Twenty seven patients were studied in the pre-PLS periodand 59 patients in the post-PLS period. The incidences of chest tubesinsertion was 55% (15 out of 27) and 19% (11 out of 59), respectively(p�0.05). In the pre-PLS period, 14 out of the 15 chest tubes (93%) wereinserted for pnemothoraces evacuation and 1 (7%) for evacuation ofpleural effusion. In the post-PLS period 5 of the chest tubes (45%) werefor pnumothoraces and 6 (55%) for pleural effusion (p�0.05).

CONCLUSION: The overall incidences of tube thoracostomy forpneumothoraces and for pleural effusions with PLS implementation hassignificantly decreased and increased, respectively.

CLINICAL IMPLICATIONS: Our study supports the clinical theorythat the ‘Starling resistor’ principles for pressure relationship within lungunits could explain why the high pre-PLS airway pressures could preventpulmonary exudates (effusions) but not pneumothoraces and vice versa.

DISCLOSURE: Michael Miller, None.

SIGNIFICANT IMPROVEMENT IN SPIROMETRY AFTER STEMCELL TRANSPLANTATION IN ONE DUCHENNE MUSCULARDYSTROPHY PATIENTZhiping Li RRT Yubiao Guo MD* Xiaoli Yao MD Cheng Zhang MDCanmao Xie MD Department of Pulmonary & Critical Care Medicine,the First Affiliated Hospital, Guangzhou, Peoples Rep of China

PURPOSE: To describe the pattern of lung function abnormality andto investigate the changes in spirometry before and after autologushematopoietic stem cell transplantation in one duchenne muscular dys-trophy (DMD) patient.

METHODS: Lung function was measured by maximum expiratoryflow-volume loops and whole body plethysmography in one 14-yr oldDMD patient before and three months after stem cell transplantation.

RESULTS: Lung function test was characterized by restrictive patternmanifested by lung volume reduction and increased FEV1/FVC due tomuscular weakness. Before stem cell transplantation, the FVC, FEV1 andMVV were 1.4L, 1.4L and 59.5L respectively. 3 months after stem celltransplantation, the patient’s FVC, FEV1 and MVV were significantlyincreased to 2.12L, 2.12L and 118.0L respectively.

CONCLUSION: Although genetically modified myoblast transplanta-tion remains controversial for DMD, a significant change in spirometrywas found in this DMD patient after stem cell transplantation.

CLINICAL IMPLICATIONS: Spirometric measurement provides asimple and useful means of assessing disease progression in DMD patientsand should be considered when stem cell transplantation is planning.Fur-thermore, since DMD characterized by gradually developing muscularweakness, pulmonary physical rehabilitation should focus on the trainingof respiratory accessory muscles.

DISCLOSURE: Yubiao Guo, None.




THE BENEFIT OF ROUTINE CHEST RADIOGRAPHY IN THEPEDIATRIC PATIENT AFTER FLEXIBLE FIBEROPTIC BRON-CHOSCOPYSusie N. FitzHarris MD* Khalilah Lewis-Brown MD Kevin D. MaupinMD University of Florida Department of Pediatrics/Sacred Heart Chil-dren’s Hospital, Pensacola, FL

PURPOSE: Flexible fiberoptic bronchoscopy in pediatric patients isconsidered to be a low risk procedure with minimal complications. Thepurpose of this study was to evaluate the usefulness of routinely perform-ing chest radiography after flexible fiberoptic bronchoscopy with bron-choalveolar lavage in the pediatric patient.

METHODS: We retrospectively reviewed the charts of 51 pediatricpatients that had undergone flexible fiberoptic bronchoscopy with bron-choalveolar lavage. We reviewed the charts for the following parameters:age, diagnosis for which the procedure was performed, chest radiographyfindings and for any complications that occurred during the procedurethat necessitated stopping the procedure.

RESULTS: Patients’ ages ranged from 1 month old to 19 years old. Thediagnosis were chronic cough(11), cystic fibrosis(4), foreign body evalua-tion(2), hoarseness(2), persistent atelectasis(3), recurrent pneumonia(2),stridor(20), tracheomalacia(1), tracheostomy evaluation(1), tuberculo-sis(2), upper airway obstruction(1), and vocal cord dysfunction(2). 50 ofthe patients had chest radiographs and 1 patient had a chest CAT scan.The chest radiographs and the CAT scan revealed no complications oracute changes from flexible fiberoptic bronchoscopy with bronchoalveolarlavage. There were no complications that necessitated stopping of theprocedure and all procedures were completed.

CONCLUSION: This study has shown that chest radiography in pediatricpatients undergoing flexible fiberoptic bronchoscopy with bronchoalveolar lavage,4with no intraoperative complications that necessitated the procedure to bestopped, had no clinical usefulness or benefit for the patient.

CLINICAL IMPLICATIONS: Chest radiography should not beroutinely performed after uncomplicated flexible fiberoptic bronchoscopywith bronchoalveolar lavage. It is not cost effective, adds no benefit topatient management, and exposes the pediatric patient to unecessaryradiation.

DISCLOSURE: Susie FitzHarris, None.

C-FIBER BLOCKADE INFLUENCE NON-NUTRITIVE SWAL-LOWING IN NEWBORN LAMBSCharles Duvareille PhD* Philippe Reix MD Carole Langlois Julie Ar-senault MS Patrick Letourneau MS Theophile Niyonsenga PhD NathalieSamson MS Jean-Paul Praud MD Centre Hospitalo-Universitaire deSherbrooke, Fleurimont, PQ, Canada

PURPOSE: Non-nutritive swallowing (NNS) is especially important inthe neonatal period for clearing secretions and gastro-pharyngeal reflux,and has been associated with neonatal apneas. One previous study hasreported that systemic C-fiber blockade (CFB) inhibits induced swallow-ing in adult guinea pigs (Jin, Y et al, Am J Respir Crit Care Med. 1994).The aim of our present study was to investigate the effects of CFB onapnea and NNS frequency, and on the coordination between NNS andphases of the respiratory cycle in newborn lambs.

METHODS: Eight CBF and 7 control lambs were chronically instru-mented for recording electroencephalogram, eye movements, diaphragmand thyroarytenoid muscle activity, nasal airflow and electrocardiogram.CFB was induced by subcutaneous injection of capsaıcin (30mg/kg). Allexperiments were conducted in non-sedated lambs at 4 days of age, usinga custom-made radiotelemetry system.

RESULTS: CFB lambs spent more time in active sleep than controls(15 � 4% vs. 9 � 3%, p � 0,03). Apnea frequency was not significantlydifferent between CFB and control lambs, whatever the state of alertness(p between 0.2 and 0.8). NNS frequency was higher in CBF than controllambs (32 � 8/h vs. 20 � 10/h, p � 0.01) in QS. Finally, systemic C-fiberblockade had no effect on the coordination between NNS and phases ofthe respiratory cycle, whatever the state of alertness.

CONCLUSION: Our results suggest that C fibers inhibit NNS, buthave no effect on the coordination between NNS and phases of therespiratory cycle in the neonatal period. Moreover, C fiber blockade hasno effect on apnea frequency.

CLINICAL IMPLICATIONS: such studies may prove to be impor-tant in the use of capsaicin agonists or antagonists in the treatment ofvarious conditions, including swallowing difficulties.

DISCLOSURE: Charles Duvareille, None.

A CHRONIC PNEUMOTHORAX AND FITNESS TO FLYGraeme P. Currie MD* Annie Kennedy MB, ChB Ed Paterson MB, BChStephen Watt MB, ChB Aberdeen Royal Infirmary, Aberdeen, UnitedKingdom

PURPOSE: Without definitive intervention, individuals with an un-treated pneumothorax should not participate in commercial flying.Whether this advice applies to patients with a long-standing pneumotho-rax is uncertain. We report two adults with persistent pneumothoraceswho underwent further investigation to determine the safety of doing so.

METHODS: Following clinical assessment, both subjects had chestcomputerised tomographic (CT) imaging and underwent a hypoxic chal-lenge test (breathing 15% oxygen). The individuals then proceeded tocabin altitude simulation in a hypobaric chamber.

RESULTS: Case 1 - Chest CT showed a small left pneumothorax(estimated volume 110 millilitres). During a hypoxic challenge test, theoxygen saturation fell to 90%. During cabin altitude simulation, the patientremained asymptomatic and oxygen saturation fell to 90%. He was consid-ered fit to fly and has completed over a dozen transatlantic flights withoutdifficulty.Case 2 - Chest CT showed a loculated right sided pneumothorax(estimated volume 250 millilitres) and during a hypoxic challenge test, theoxygen saturation fell to 93%. An altitude chamber test was tolerated withoutsymptoms and the oxygen saturation fell to a minimum of 92%. She wastherefore considered fit to fly in commercial aircraft.

CONCLUSION: Some patients with a closed chronic pneumothoraxcan fly without adverse consequences.

CLINICAL IMPLICATIONS: This risk should be determined afterthorough assessment incorporating chest CT, a hypoxic challenge test andsimulation of flying at altitude in a decompression chamber with closemonitoring of symptoms and oxygen saturation.

DISCLOSURE: Graeme Currie, None.

PREVALENCE OF EMPHYSEMA-LIKE CHANGES OF THELUNGS AMONG YOUNG HEALTHY ADULTS, AND AMONGTHOSE WITH SIMILAR PHYSIOGNOMY TO PATIENTS WITHPRIMARY SPONTANEOUS PNEUMOTHORAX: A THORACO-SCOPIC EVALUATIONKayvan Amjadi MD* Eef Vanderhelst MD Brigitte Velkeniers MD MarcNoppen MD Queen’s University, Kingston, ON, Canada

PURPOSE: To thoracoscopically determine the prevalence of emphysemalike changes (ELCs) among young healthy adults, and among healthy individualswho are age, gender, height, weight and smoking habit-matched to patients withdiagnosis of primary spontaneous pneumothorax (PSP).

METHODS: We performed bilateral thoracoscopic evaluation of thelungs in healthy individuals who were referred to us for thoracoscopicthoracic sympathectomy. Presence of ELCs, age, gender, height, weight,smoking habits, and pulmonary function tests were documented. Com-parisons of these parameters were made between ELC-positive andELC-negative individuals. Participants were enrolled into a registry,allowing long-term follow-up (6 years). Individuals were then matched toa group of 12 PSP patients (all male, mean age 29.9, range 17 – 43, meanheight � standard deviation (SD); 1.79 � 0.07 meters, mean weight �SD; 68.7 � 9.9 kilogram, mean body mass index (BMI) � SD; 21.3 � 2.7,smoker/non-smoker 0.6). Prevalence of ELCs among healthy individualswith matched characteristics was evaluated.

RESULTS: Analysis was performed on 250 consecutive cases (male/female 0.4, mean age � SD; 29 � 10 years). ELCs were observed in15/250 (6%) individuals (male/female 6/9, mean age 25.3, range 15 – 51).Compared to ELC-negative group, ELC-positive individuals had a signif-icantly lower body mass index (BMI) (20.7 � 2.4 vs. 22.7 � 3.4; P �0.027), whereas all other parameters were similar. ELCs tended to bemore prevalent among smokers; however, statistical significance was notachieved (P � 0.76). Similarly, in the matched group, ELCs wereobserved in 6/101 (6%) individuals. During 6 years of follow-up, none ofthe ELC-positive individuals has developed pneumothorax.

CONCLUSION: Thoracoscopically, ELCs were present in 6% ofyoung healthy adults with no underlying lung disease. Low BMI (� 22)appears to play an important role in the development of ELCs.

CLINICAL IMPLICATIONS: Given that far less than 6% of thepopulation develops PSP, we hypothesize that ELC’s in PSP population isat least in part due to their physiognomic features and not the obligatorycause of pnemothorax.

DISCLOSURE: Kayvan Amjadi, None.


Pediatric Chest II, continued Pleural Disease12:30 PM - 2:00 PM


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DIAGNOSTIC VALUE OF TUMOR MARKERS CEA, CA 125, CA15-3 AND NSE LEVEL DETERMINATION IN THE SERA ANDPLEURAL FLUIDS IN PATIENTS WITH MALIGNANT PLEU-RAL EFFUSIONSSamrad Mehrabi MD* Mohammad Ali Ghayyumi MD Abbas GhaderiPhD Mehrnoush Doroudchi PhD Kurdisatn University of Medical Sci-ences, Sanandaj, Iran

PURPOSE: The aim of this study was to evaluate the individual and combined

diagnostic utility of four tumor markers in patients with pleural effusion.METHODS: Pleural and serum levels of carcinoembryonic antigen

(CEA), carbohydrate antigen 15-3 (CA 15-3), neuron specific enolase(NSE) and cancer antigen 125 (CA 125) were assayed prospectively in 77patients with pleural effusion (40 malignant and 37 benign).

RESULTS: Using the cutoff values of 29.7 U/ml for CA 15-3, 10.36�g/L for NSE, 2.95 �g/L for CEA and 50.65 U/ml for CA 125 in serumand cutoff values of 21.11 U/ml, 5.21 �g/L, 3.60 �g/L and 1196.67 U/mlfor pleural fluid CA 15-3, NSE, CEA and Ca 125 respectively, thesensitivity (%) and specificity (%) of these tumor markers for differenti-ating malignant from benign effusions were as follows: in serum CA 15-359.5/63.5, NSE 38.9/63.6, CEA 47.2/81.8 and CA 125 50/48.5; and inpleural fluid CA 15-3 70/83.3, NSE 68.4/75, CEA 47.4/85 and CA 12548.6/70.6. The highest specificity in the diagnosis of pleural malignancywas obtained with combination of CA 15-3 in serum, and CA 15-3 andNSE in pleural fluid and also with combination of CA 15-3 in serum, andCA 15-3, NSE and CEA in pleural fluid and was 100%.The bestcombination of tumor markers which revealed 100% specificity and 100%PPV with 76.5% sensitivity could be obtained by measurement of CA 15-3in serum and pleural fluid plus NSE in pleural fluid.

CONCLUSION: The findings of this study suggest that a combinationassay of tumor markers in addition with pleural fluid cytology can use asa diagnostic test in diagnosis of malignant pleural effusion.

CLINICAL IMPLICATIONS: The use of combination of CA15-3/NSE/CEA determination in pleural effusion coulld reduce the need forinvasive measures in undiagnosed exudative pleural effusions.

DISCLOSURE: Samrad Mehrabi, None.

ANALYSIS OF 112 CONSECUTIVE CASES OF THORACIC EM-PYEMA OVER A 19-YEAR PERIODBasil Varkey MD Manish Joshi MBBS* Veterans Affairs Medical Centerand Medical College of Wisconsin, Milwaukee, WI

PURPOSE: To analyze pathogenesis, bacteriology, drainage methodsand outcomes of thoracic empyema in one institution over a nineteen yearperiod. (1986-2004).

METHODS: Retrospective review of medical and microbiologyrecords of thoracic empyema (culture positive pleural fluid and /or pus)and analysis of patient demographics, pathogenesis, bacteriology, drainagemethods and outcome.

RESULTS: One hundred and twelve cases (culture � � 107, pus � 5) ofempyema were identified. The patients were predominantly men over 45 yrsof age (45-65 yrs�52%, �65yrs �42%). Most common pathogenetic factorswere post pneumonic in 66(60%) and post thoracotomy in 18(16%). Sixtypercent of the empyemas were community-acquired and the remaining werehospital- acquired. The 107 culture positive cases yielded 154 bacterialisolates. Pleural fluid isolates showed only aerobes in 80 cases (74.8%)anaerobes alone or with aerobes in 27 cases (25.2%). The most commonaerobes were staphylococci (38.6% of aerobic isolates) and streptococci(31.0%) followed by gram negative bacilli (17%) and Streptococcus pneu-moniae (6.7%).The most common anaerobes isolated were Bacteroides(28.5% of anaerobic isolates), Fusobacterium (17%), peptostreptococcus(14.2%), diptheroids 4(11.4%) and micro-aerophilic streptococci (8.5%). Inall cases appropriate antibiotics were given. The initial drainage procedureemployed was closed chest tube in 91 patients (20 required subsequentsurgical procedures) and thoracotomy in 13 patients. Eight patients weredrained by thoracentesis alone. Eighty one (72.3%) patients were cured, 9patients (8%) died of empyema and 22 patients (19.6 %) with co-morbidconditions died while empyema was active.

CONCLUSION: Most empyemas are postpneumonic and in a quarterof cases anaerobes are the causative microbes. Closed chest tube drainageis effective in most cases but additional surgical procedures may beneeded in 20%. Mortality due to empyema was 8%; however a largernumber of patients with co-morbid conditions died.

CLINICAL IMPLICATIONS: Information on patient demographics,pathogenetic mechanisms, bacteriology, treatment and outcome of empy-ema from this large series may be useful in devising better treatment andimproving outcome.

DISCLOSURE: Manish Joshi, None.

A RETROSPECTIVE ANALYSIS OF THE MANAGEMENT OFPARAPNEUMONIC EMPYEMAS IN A COUNTY TEACHING FA-CILITY FROM 1992-2004Glena Cheng MD* Janine R. Vintch MD Harbor-UCLA Medical Center,Torrance, CA

PURPOSE: To characterize how patients with empyemas are managedinitially at our facility and to determine how “less aggressive” treatments(no drainage, repeat thoracentesis, tube thoracostomy) affect short term

Operating Characteristics of Each Tumor Marker andCombinations of Tumor Markers in Patients With

Pleural Effusion

Tumor Marker Cutoff

%

Sensitivity

%

Specificity

%

PPV

%

NPV

%

Accuracy

Serum

CA 15-3 29.07 59.5 63.6 64.7 58.3 61

NSE 10.36 38.9 63.6 51.1 46.2 49

CEA 2.95 47.2 81.8 42.6 26.1 37

CA 125 50.65 50 48.5 53 47.2 50

Pleural Fluid

CA 15 -3 21.11 70 83.3 82.4 71.4 76

NSE 5.21 68.4 75 74.3 69.2 72

CEA 3.60 47.4 85.3 78.3 59.2 65

CA 125 1196.67 48.6 70.6 42 34.5 39

CA 15-3�NSE 57.5 91.9 88.5 66.7 74

CA 15-3 in serum � 71.4 86.4 87 70.4 78

CA 15-3 in pleural fluid

CA 15-3 in serum � 76.2 77.3 76.3 77.3 77

NSE in pleural fluid

CA 15-3 in serum �

CA 15-3 and CEA in pleural

fluid

80 88.9 88.9 80 84

CA 15-3 in serum � CA 15-3

and NSE in pleural fluid

76.5 100 100 77.8 87

CA 15-3 in serum � CA 15-3,

NSE and CEA in pleural

fluid

80 100 100 81.3 89


Pleural Disease, continued


outcomes (inpatient mortality and need for a second intervention) com-pared to “more aggressive” treatments (intrapleural fibrinolytics, video-assisted thoracoscopic surgery, or other surgery). We will also assess iffewer patient co-morbidities, earlier diagnosis, earlier antibiotic treat-ment, and consulting appropriate services improve mortality.

METHODS: A retrospective chart analysis was performed in a countyteaching hospital in Los Angeles, California on seventy-two adult inpa-tients with parapneumonic empyemas. Mortality and need for secondintervention rates were calculated and compared with data published inthe 2000 American College of Chest Physicians Consensus Statement onthe management of parapneumonic effusions using Fisher’s exact tests.Comparisons were made between empyema survivors and non-survivorsusing t-tests and chi-squared tests.

RESULTS: All 72 patients were managed with “less aggressive” initialtreatments. There were no difference in mortality when our patients werecompared to the literature’s “less aggressive” group (6% vs. 9%, P�0.40, RR 0.6,95% CI: 0.23-1.62) or “more aggressive” group (6% vs. 3%, P�0.29, RR 1.8, 95%CI: 0.64-5.23). There was no difference between the second intervention rate ofour patients and the “less aggressive” group (47% vs. 43%, P�0.47 RR 1.1, 95%CI: 0.86-1.42) although there was a difference when compared to the “moreaggressive” group (47% vs. 11%, P�.0001, RR 4.5, 95% CI: 3.20-6.31). Therewere no differences in number of patient co-morbidities, time of diagnosis, timingof antibiotic treatment, or number of services consulted when survivors andnon-survivors were compared.

CONCLUSION: Patients with empyemas at our hospital are treatedwith “less aggressive” initial treatments and have a higher second inter-vention rate when compared to patients described in the literature whowere initially managed with “more aggressive” treatments.

CLINICAL IMPLICATIONS: Given these findings, it would beworthwhile to evaluate the impact of treating empyemas with “moreaggressive” initial interventions at our institution.

DISCLOSURE: Glena Cheng, None.

PROTEIC PROFILE OF PLEURAL EFFUSIONS SECONDARYTO TUBERCULOSIS AND MALIGNANCYLeila Antonangelo MD Francisco S. Vargas MD Eduardo H. GenofreMD Lisete R. Teixeira MD Milena M. Acencio BS Marcia Seiscento MDEvaldo Marchi MD Roberta K. Sales MD* Pulmonary Division, HeartInstitute (InCor), University of Sao Paulo Medical Sc, Sao Paulo, Brazil

PURPOSE: To evaluate the proteic profile of tuberculous and neo-plastic pleural effusions.

METHODS: Pleural fluid and pleural-serum ratio (PSR) of total protein andeletrophoretic (EF) albumin, alpha, beta and gamma globulin were analysedfrom 403 patients having tuberculosis (200) or malignant pleural effusions(203).Univariate analysis was applied to compare the results between the groups.Significant difference was considered for a p�0.05.

RESULTS: The results are expressed in median with p value.

CONCLUSION: Total proteins and their subsets were significantlyhigher in the pleural effusion due to tuberculosis as compared to themalignant, suggesting a more intense inflammatory response in thetuberculous group.

CLINICAL IMPLICATIONS: These data may colaborate in thedifferentiation between the tuberculous and malignant pleural effusions.

DISCLOSURE: Roberta Sales, None.

CORRELATION OF WHITE BLOOD CELLS (WBC) WITHPLEURAL FLUID PH VALUES COLLECTED IN HEPARINIZEDAND NON-HEPARINIZED SYRINGESAli H. Debek MD* Mohammad Khatib PhD Ghassan Jamaleddine MDAhmad Husari MD Pierre Bou-Khalil MD American University of Beirut- MC, Beirut, Lebanon

PURPOSE: In a previous study done at our institution, we reported astatistically significant decrease in pleural fluid pH when samples weredelayed up to two hours after collection. The aim of this study is toinvestigate the effect of WBC on pleural fluid pH values measured atvarious time intervals.

METHODS: This is a prospective study at an academic tertiarymedical center. From 40 consecutive (n�40) thoracentesis, 1ml of pleuralfluid was collected anaerobically in each of six 3 ml syringes. Threesyringes were coated with heparin. Samples in each syringe type (hepa-rinized (H) and non-heparinized (NH)) were processed for pleural fluidpH measurements at time 0 (T0), one hour (T1) and two hours (T2) postcollection. All specimens were preserved at room temperature until themeasurements were carried out in duplicates by a calibrated blood gasanalyzer. In addition, WBC count was determined at T0 by an automatedWBC counter.

RESULTS: With the heparinized syringes, there was a statisticallysignificant negative correlation between pleural fluid pH and WBC at T1and T2. With the non-heparinized syringes, there was a statisticallysignificant negative correlation between pleural fluid pH and WBC only atT2.(table 1).

CONCLUSION: Our data showed an effect of WBC on pleural fluidpH measurement. For pleural fluid samples collected in non-heparinizedsyringes, there is up to two hours time before the WBC will have its effecton pH measurements. While for pleural fluid samples collected inheparinized syringes, the effect of WBC on pH measurements starts atone hour after collection of pleural fluid sample.

CLINICAL IMPLICATIONS: It is advisable to process pleural fluidfor pH measurements no later than one hour of collection when usingheparinized syringes, and up to two hours when using non heparinizedsyringes.


COMPARISON BETWEEN PLEURAL FLUID PH MEASURE-MENTS OF SPECIMENS COLLECTED IN HEPARINIZED VER-SUS NON-HEPARINIZED SYRINGESAli H. Debek MD* Pierre Bou-Khalil MD Ghassan Jamaleddine MDNadim Kanj MD Mohammad Khatib PhD American University of Beirut-MC, Beirut, Lebanon

PURPOSE: Pleural fluid pH measurement is an important tool forcharacterizing the type of pleural fluid, establishing a diagnosis, andguiding clinical management. The current standard and widely acceptedpractice is to collect pleural fluid samples for pH measurement inheparinized syringes and to instantaneously process these samples at roomtemperature. We conducted a prospective study to investigate the changesin pleural fluid pH measurements collected in heparinized versus nonheparinized syringes and processed at various time intervals while thesamples are preserved at room temperatur.

METHODS: This is a prospective study in an academic tertiarymedical center. From 50 consecutive (n�50) thoracentesis, 1ml of pleuralfluid was collected anaerobically in each of six 3 ml syringes. Threesyringes were coated with heparin. Samples in each syringe type (hepa-rinized (H) and non-heparinized (NH)) were processed for pleural fluidpH measurements at time 0 (T0), one hour (T1) and two hours (T2) postcollection. All specimens were preserved at room temperature until the

Tuberculosis Malignancy

Protein (mg/dl) 5.4 (4.9 – 5.7) 4.3 (3.7 – 4.9) *PSR-Protein 0.69 (0.65 – 0.73) 0.61 (0.54 – 0.65) *Albumin-EF 2.63 (2.35 – 2.9) 2.5 (2.1 – 2.8) *PSR-Albumin 0.77 (0.71 – 0.83) 0.77 (0.64 – 0.77) *�1 globulin-EF 0.23 (0.2 – 0.3) 0.2 (0.14 - 0.23) *PSR-�1 globulin 0.62 (0.54 – 0.7) 0.53 (0.41 – 0.62) *�2 globulin-EF 0.47 (0.4 – 0.6) 0.3 (0.2 – 0.4) *PSR-�2 globulin 0.52 (0.46 – 0.6) 0.36 (0.28 – 0.43) *� globulin-EF 0.8 (0.62 – 0.9) 0.6 (0.46 – 0.71) *PSR-� globulin 0.69 (0.6 – 0.77) 0.52 (0.41 – 0.63) *� globulin-EF 1.14 (0.9 – 1.4) 0.7 (0.52 – 0.9) *PSR � globulin 0.64 (0.57 – 0.7) 0.55 (0.46 – 0.65) *

* p�0.05

Table 1

Type of syringe & time r p

H - T0 0.16 0.32H - T1 0.34 0.03H - T2 0.45 0.003NH - T0 0.13 0.42NH - T1 0.26 0.10NH - T2 0.264 0.001




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measurements were carried out in duplicates by a calibrated blood gasanalyzer.

RESULTS: Pleural fluid pH values were significantly (p�0.05) lowerwhen collected in heparinized versus non-heparinized syringes at all timeintervals (T0: pH(H)�7.37�0.10 vs. pH(NH)�7.39�0.10, T1:pH(H)�7.37�0.11 vs. pH(NH)� 7.39�0.11, T2: pH(H)�7.37�0.12 vs.pH(NH)�7.38�0.11). With heparinized syringes, there was a significant(p�0.05) decrease in pleural pH values only at T2 versus T1. There wereno significant changes in pleural pH values over time with the non-heparinized syringes.

CONCLUSION: There were statistical differences in the values ofpleural pH when using heparinized versus non-heparinized syringes.Inheparinized syringes, the pleural pH values decreased at two hours butnot at one hour post collection, therefore it is advisable to process pleuralfluid for pH measurements no later than one hour of collection whenusing heparinized syringes.

CLINICAL IMPLICATIONS: for serial pleural pH measurementsthe same type of syringes (either heparinized or non-heparinized) shouldbe consistently used and samples collected in heparinized syringes can beprocessed up till one hour of collection.


DOES STORAGE TIME AND TEMPERATURE INTERFERE INTHE ADENOSINE DEAMINASE MEASUREMENT IN PLEURALEFFUSIONS?Leila Antonangelo MD* Francisco S. Vargas MD Luciana P. AlmeidaPharmD Milena M. Acencio BS Fabrıcio D. Gomes BS Roberta K. SalesMD Marcia Seiscento MD Lisete R. Teixeira MD Pulmonary Division,Heart Institute (InCor) and Department of Pathology of Univer, SaoPaulo, Brazil

PURPOSE: To evaluate the interference of pre-analytic factors asstorage time and temperature in pleural fluid adenosine deaminase (ADA)measurement in pleural effusions.

METHODS: 27 pleural effusions obtained from patients with neo-plasm (20) or tuberculosis (07) were analyzed. The pleural effusions werecollected into tubes containing EDTA. The ADA determination wasrealized 1, 3, 7, 10 and 28 days after the toracocentesis and the sampleswere stored at 4°C (refrigerator) or -20°C (freezer). The ADA determinedimmediately after the pleural collection (T1) was used as gold standart tothe comparison with the results obtained from the other times. The ADAactivity was determined by the modified Giusti method. Statisticalanalysis: The Wilcoxon test was used to compare T1 with the resutsobtained at 1, 3, 7, 10 and 28 days, for both temperatures. We used thePearson coefficient to evaluate the correlation between T1 and the othertimes evaluated.

RESULTS: Pleural ADA from T1 was 36.45 U/L (23.2 � 55.1). We donot observe differences statistically significant between this measurementwith those obtained from 1, 3, 7, 10 and 28 days, for both temperatures(4°C or -20°C). The correlations between T1 and the other times weresuperior to 0.90 until the tenth day for both temperatures, with a tendencyof decreasing around the 28th for the temperature of 4°C (r� 0.86) or-20°C(r�0.83).

CONCLUSION: ADA levels are stable for at least 28 days in samplesof pleural fluids if they were maintained refrigerated (4°C) or freezed(20°C).

CLINICAL IMPLICATIONS: Considering that samples of pleuraleffusion can be sended to ADA determination many hours after thetoracocentesis or that frequently we have to confirm ADA results, weconsider safe to quantify this enzyme until at least 28 days after thecollection, if the samples were maintained at refrigerator or freezer.

DISCLOSURE: Leila Antonangelo, None.

RELATIONSHIP BETWEEN METALLOPROTEINASE AND EX-UDATIVE PLEURAL EFFUSIONSAn Chang Hyeok MD* Kim Yu Jin MD Kyung Sun Young MD Lee SangPyo MD Park Jeong Woong MD Jeong Seong Hwan MD Gachon MedicalSchool Gil Medical Center, Incheon, South Korea

PURPOSE: Residual pleural thickening is common complication oftuberculous pleurisy and sometimes in parapneumonic effusion. The aimof this study was assess the expression of MMP-1 and –9 and TGF-�, andthen compared with amount of pleural fluid at the first time of detectionand the end of follow-up.

METHODS: Patients with newly diagnosis of pleural fluid was en-rolled from June 2004 to January 2005. MMP-1, MMP-9 and TGF-� weredetermined by ELISA in plasma and pleural fluid. The amount of pleuralfluid and pleural thickening were measured on the simple chest PA films.

RESULTS: The study included 39 patients with pleural effusion.Twenty-three was tuberculous, 7 parapneumonic effusion, 7 malignanteffusion, and 2 transudates. The patients with malignant effusion(meanage 62�15 years) was more older than of tuberculos(40�18)(p�0.028).MMP-1 concentrations of parapneumonic effusion(9.6�8.5 pg/mL) wassignificantly higher than other pleural fluid(tuberculous 3.9�2.3,p�0.012; malignant 2.7�1.7, p�0.016, transudate 1.8�0.2, p�0.094).MMP-9 of parapneumonic effusion(383.6�410.0 ng/mL) was also signif-icantly higher than other pleural fluid(tuberculous 74.0�68.7, p�0.002;malignant 62.1�61.0, p�0.007, transudate 40.0�42.4, p�0.058). Intuberculous effusion, the absortion of pleural fluid or thickening wassignificantly increased in accordance with lower concentration of MMP-1(p�0.011).In parapneumonic effusion, higher concentration of MMP-1,the amount of pleural fluid at the fist detection was significantlylarger(p�0.014), but there was no correlation with absortion of pleuralfluid or thickening. There was no correlation between TGF-� and pleuralfluid or thickening.

CONCLUSION: Inconclusion, elevated MMP-1 and –9 expressionwas found in parapneumonic pleural effusion. The concentration ofMMP-1 was correlated with amount or absortion in several exudativepleural effusion.

CLINICAL IMPLICATIONS: MMP-1 could be implicated in theresolution of pleural fluid or residual pleural thickening in tuberculouspleurisy and in the production of pleural fluid in parapneumonic effusion.

DISCLOSURE: An Chang Hyeok, None.

VIBRATION RESPONSE IMAGING (VRI): A NEW MODALITYFOR EVALUATION AND FOLLOW-UP OF PLEURAL EFFU-SION (PE)Ram Mor MD* Tatiana Boikaner MD Avi Man MD Zipi Yemini IgalKushnir MD Joel Greif MD Pulmonary Institute, Tel Aviv Med Center,Tel-Aviv, Israel

PURPOSE: Imaging is essential for confirmation of PE, especiallyprior to taping. Chest X-ray (CXR) cannot be done effectively at bedsideand involves radiation. Ultrasound requires expensive equipment andspecial skills. Follow-up of patients after drainage usually involves re-peated radiation for weeks or months.The VRI system constructs adynamic lung image from vibrations produced by airflow. The vibrations,hence the image, are altered by the airway and parenchymal abnormali-ties. The vibration energy from 40 sensors, attached to the back, isprocessed during breathing cycles and creates a dynamic image. Thepresence of fluid as well as compression and displacement of the lungs byPE are easily detected by this method. Changes in the amount of pleuralfluid can be seen in successive VRI recordings. To evaluate this noveltechnology in the monitoring of PE compared to conventional CXR.

METHODS: We analyzed the VRI of 10 patients (6 males) with avg.69.7 yrs with PE. The presence of PE was confirmed by a standard CXR;one case of large PE (� 2 Lit.), 6 with moderate PE (1–2 Lit.) and 2 withsmall PE (� 1 Lit.). Repeated CXR and VRI were obtained followingdrainage in all cases.

RESULTS: The characteristic VRI image of PE showed a meniscusshape in the lower lobe(s) and absence of vibration response (VR) in thearea of the pleural fluid. Absence of VR was correlated to the region of PEas determined by the CXR in 9/10 (90%) patients. Following treatment,VRI images showed increased vibration response in the drained area in all10 cases, which corresponded with CXR clearing. The decrease in fluidlevel after drainage was evident in all the VRI recordings.

CONCLUSION: The VRI provides a simple, bedside, radiation-freeapproach to follow the course of pleural effusion; thereby, improving thecost effectiveness of bedside evaluation and follow up.

CLINICAL IMPLICATIONS: The VRI provides a simple, radiation-free approach to follow the course of pleural effusion; thereby, improvingthe cost effectiveness of bedside follow up.

DISCLOSURE: Ram Mor, None.




CAN PLEURAL FLUID DENSITY MEASURED BYHOUNSFIELD UNITS(HU) ON CHEST CT BE USED TO DIF-FERENTIATE BETWEEN TRANSUDATE AND EXUDATE?Vijay A. Rupanagudi MD* Ashwini Sahni MD Karthikeyan KanagarajanMD Hima Kona MD Daniel Contractor MD Padmanabhan Krishnan MDConey Island Hospital, Brooklyn, NY

PURPOSE: Density of lesions as measured by hounsfield units onchest CT is used to characterize the nature of thoracic lesions as solidversus cystic versus calcific. The aim of the study was to see if density ofpleural effusion as measured by HU on chest CT could be used todifferentiate transudative versus exudative pleural effusion; a non-invasivetechnique not being used for this purpose at this time.

METHODS: 38 patients with pleural effusion who had thoracentesisdone and had chest CT were identified and evaluated retrospectively.Pleural fluid was classified as transudate or exudate using light’s criteri-a.Pleural fluid density using hounsfield units was calculated on CT chestas a mean of fluid density taken at four rectangular areas as shown in thefigure.

RESULTS: 17 patients had transudative effusion with mean(�SD) HUof 7.8(5.6). 21 had exudative effusion with mean(�SD) HU of 17.5(7.4).Based on the results 15 HU was used as cut off to differentiate betweentransudative and exudative effusion.

CONCLUSION: HU on CT of more than 15 can be used tocharacterize a pleural effusion as an exudate. Transudative effusions forthe most part have HU less than 15. However HU �15 can be seen inexudative pleural effusions. Therefore this technique cannot be used todifferentiate transudative from exudative pleural effusion when HU is�15.

CLINICAL IMPLICATIONS: In patients with HU �15 further workup is indicated and will include thoracentesis and possibly pleural biopsy.In patients with HU �15 thoracentesis is indicated only when the clinicalpicture indicates that the pleural effusion cannot be explained by disor-ders that cause transudative effusion.

DISCLOSURE: Vijay Rupanagudi, None.

ACUTE PLEURAL-PULMONARY ALTERATIONS AFTER CABG(CORONARY ARTERY BYPASS GRAFT)Marcelo A. Vaz MD* Daniela B. Mont’alverne Maria I. Feltrim Lisete R.Teixeira MD Francisco S. Vargas MD Heart Intitute (InCor), Universityof Sao Paulo Medical School, Sao Paulo, Brazil

PURPOSE: Evaluate the changes over pulmonary mechanics andpleural effusion in the first six days after CABG.

METHODS: We analyze FVC, Maximum Inspiratory Pressure(PImax), Maximum Expiratory Pressure (PEmax) daily until the 6th dayafter CABG, and Atelectasis and pleural effusion (X-ray and CT) on the6th day after CABG. It was studied 60 patients consecutively after CABG.Lower lobe atelectasis at X-ray was scored (0 � no atelectasis; 1 �plate-like atelectasis; 2 � atelectasis of a single segment; 3 � atelectasis ofmore than one segment; 4 � lobar atelectasis). Pleural effusion on X-raywas scored (0 � no pleural effusion; 1 � blurring of the costo-phrenicangle; 2 � effusion occupying one to two intercostal spaces; 3 � effusionoccupying more than two intercostal spaces). Pleural effusion volume oncomputerized tomography was estimated through the formula d 2 x l 2,




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where d � greatest depth of the effusion on a single CT image and l �greatest length of the effusion. Were considered significant p�0.05.

RESULTS: Were observed a decline in PImax, PE max and FVC in the1st day after CABG, with a slow recovery over the first six days after theCABG (Graphic1). On X-Ray there were a high frequence of atelectasis(70% of the patients)and pleural effusion (83% of the patients), and CTscan revealed a greater amount of atelectasis(92%), when compared withX-ray. The estimated volume of pleural effusion on the 6th day afterCABG was 73.72 �/- 188.31 ml (rigth side) and 258.72 �/- 400.62 ml (leftside).

CONCLUSION: CABG induces a deep decline of strength andvolumes (bigger than 50% of decline)acutelly after the surgery. Thisprocedure will leave an amount of pleural effusion and atelectasis on the6th day after the surgery.

CLINICAL IMPLICATIONS: Despite we do not observe majorcomplications after CABG, these procedure may be harmful for patientswith pulmonary impairment, or lung disease before the surgery.

DISCLOSURE: Marcelo Vaz, None.

Pulmonary Function Testing: ExerciseTesting12:30 PM - 2:00 PM

EXERCISE CAPACITY IN CLINICALLY STABLE HIV PATIENTSAS A FUNCTION OF HIGHLY ACTIVE ANTIRETROVIRALTHERAPYWilliam W. Stringer MD* Mallory D. Witt MD Michelle Cao MD RoseSandoval Kathy E. Sietsema MD Los Angeles Biomedical Institute atHarbor-UCLA Medical Center, Torrance, CA

PURPOSE: Exercise capacity is reported to be reduced in HIVinfection, but the cause (s) remains unclear. Highly Active Antiretroviraltherapy (HAART) has markedly improved longevity and health status forHIV infected patients, however, these drugs are associated with diverseside-effects which could independently decrease exercise function, in-cluding nucleoside reverse transcriptase inhibitor (NRTI) -related mito-chondrial toxicity. We hypothesized that patients on HAART with ele-vated resting blood lactate levels (La, �2.2, EL) would have lowerexercise capacity on cardiopulmonary exercise testing, as compared toART treated patients with normal resting lactate levels (NL), or HIVinfected non-ART treated controls (NoH).

METHODS: Therefore, we compared exercise capacity (as measuredby peak oxygen uptake, VO2) in these three groups during cycle ergom-etry. We studied 29 clinically stable HIV� infected subjects (27M/2F)without co-morbid conditions which would affect exercise function.

RESULTS: Mean CD4 count for the group was 477 (134, Mean(SD))cells/mm3 [EL 418 (94), NL 583 (237), NoH 478 (159]. Lean mass wasmeasured by DEXA. Demographics, resting La concentration and PeakVO2 are shown in the table.

CONCLUSION: Among all three groups peak VO2 and peak VO2/kgwere low relative to expected for normal subjects, however, they did notdiffer significantly with respect to HAART status or resting lactate level.

CLINICAL IMPLICATIONS: It appears that reduced exercise ca-pacity is characteristic of HIV infection, regardless of HAART status orresting La values, and could reflect deconditioning or other factors.Thisstudy was supported by NIH # R21DK063644 and M01 RR00425.

DISCLOSURE: William Stringer, None.

THE VALUE OF CARDIO-PULMONARY EXERCISE TESTING(CPET) IN THE DETECTION OF CARDIAC DISEASE IN RE-SPIRATORY IMPAIRED (RI) PATIENTSBohdan M. Pichurko, FCCP MD* J. Trosell RRT D. Luneack RRT C.Rubner RRT A. Pichurko Providence Hospital and Medical Centers,Southfield and Novi, MI

PURPOSE: Cardiovascular disease (CVD) in respiratory impairedpatients is a likely co-morbidity since key risk factors (e.g. tobacco use,age) are shared. As symptoms of dyspnea and chest tightness arenon-specific, underlying CVD may too long remain undiagnosed; to thepatient’s detriment. To determine the diagnostic value of CPET alone andas an addition to conventional cardiac exercise testing in detecting CVD inRI pts, we performed the following experiment.

METHODS: 92 subjects, (50M, 42F) were evaluated for persistentdyspnea by CPET utilizing a stationary bicycle and watt-ramp protocol.Each had a known respiratory disorder (COPD, asthma, sarcoid, RADS)under treatment. 68 of these were also cardiac stress tested over the sameinterval; with 56 patients considered “low-risk for ischemia”. CPETanalysis was performed without knowledge of cardiac test results.

RESULTS: 81 subjects exhibited a reduced work capacity (�85% ofthe VO2max pred.) with 65 (80%) exhibiting a pattern of respiratorylimitation (Breathing reserve �15%; O2sat �89%; FEV1 �15% decline)at peak exercise. 16 (20%) manifest a CV limitation (VO2 AT �40% ofVO2max; reduced O2/pulse). Of the latter CV-limited group, 10 (63%)tested “low-risk for ischemia”. All 16 patients underwent re-evaluationincluding medication changes and/or catheterization.

CONCLUSION: Respiratory impaired patients appear to be at risk forundetected concurrent cardiovascular disease. Even when utilized, conventionalcardiac testing (combining exercise with ultrasound or scintiographic imaging)may overlook non-ischemic CVD. CPET, a metabolically based assessment ofglobal cardiovascular function/oxygen delivery, is sensitive to non-ischemic car-diac dysfunction that may evade conventional cardiac stress testing.

CLINICAL IMPLICATIONS: Respiratory impaired patients pose particu-lar challenges to clinical suspicion and diagnosis of concurrent cardiovasculardisease by conventional cardiac testing modalities. CVD due to hypertension,valvular dysfunction, and primary myocardial disorders may evade cardiac stresstesting that principally targets ischemia. A high index of suspicion for concurrentCVD coupled with selective use of CPET may help detect significant cardiovas-cular impairment and may lead to improved treatment.

DISCLOSURE: Bohdan Pichurko, FCCP, None.

GAS EXCHANGE ASSESSMENT AT REST AND DURING EXER-CISE IN PATIENTS WITH EISENMENGER SYNDROMEEdgar G. Bautista MD* Ma. Luisa M. Guerra MD Tomas Pulido MDEfren Santos MD Silvio A. Namendys MD Jose L. Sandoval MD GerardoRojas MD David Mendoza MD Julio Sandoval MD Instituto Nacional deCardiologıa “Ignacio Chavez”, Mexico City, Mexico

PURPOSE: To assess gas exchange and distribution of ventilation inEisenmenger syndrome patients at rest and while performing submaximalexercise at an altitude of 2240 mts above sea level.

METHODS: 93 patients with Eisenmenger syndrome due to ASD 49p, VSD27p, PDA 20p; 74 females, 19 males. Age 36�14(20-73)yo, height 1.53�0.1 m,weight 59�17 Kg. PAP 98�27 mmHg, PaO2 50�8 mmHg, V-A shunt QsQt%14.9�5, Hb gr/dl 17.7�4.2. Gas exchange (GE) was assessed in 70 p at roomair(ra),FiO2 1 (100%) and at the end of exercise (e). Independent student t test;p�0.05 * was considered as significative when compared to ra values alsoregression analysis with SPSS 10 was applied to data.

RESULTS: Spirometry; FEV1 mls. 1877�646; FEV1% 70�18, FEVI/FVC% 78�14, FEF% 56�30. GE is presented in table 1. A trend to

N Age

La

(Rest) BMI

Peak

VO2

Peak

VO2/kg

Peak

VO2/kg

(y) (mmol) kg/m2 (l/min) (ml/min/kg) (ml/min/lean kg)

EL 10 45 (6) 2.58 (.49)* 25.3 (3.9) 1.73 (0.48) 22.8 (5.9) 29.6 (6.3)

NL 9 46 (3) 1.17 (.30) 24.8 (2.8) 1.69 (0.48) 23.5 (7.0) 31.4 (7.5)

NoH 10 41 (7) 1.51 (.68) 24.0 (4.0) 1.73 (0.41) 25.4 (6.0) 32.5 (6.4)

*�P�0.01 for differences between groups




decrease in PaO2 and pH was observed at the end of exercise although notstatistically significant. Distribution of ventilation and gas exchange betweenrest r and submaximal exercise e (mets 1.60�0.5 to 3.45�1 )as follows :VE;Minute ventilation 10.2L�3.3 to 22L�7.2 *, AV Alveolar Ventilation5.5L�1.9 to 12.8�4.4 *, VO2 mls/min; Oxygen consumption 230�64 to514�130 *, VCO2mls/min; CO2 production 218�65 to 528�146 *.

CONCLUSION: Despite severe Pulmonary Arterial Hypertension anda significant right to left shunt, the change in paO2 during exercise isremarkable low even with a significant change in VO2. As it is alsoremarkable the preservation of pH and paCO2 with such an increase inVE and VA. We consider that the ventilatory pump may contributesignificantly to the ability of these patients to perform exercise even indisadvantage conditions, as it is high altitude.

CLINICAL IMPLICATIONS: No limitation to perform regular activi-ties and even light exertion could be recomended in this group of patients.More data is needed about the impact of long term exercise on the disease.

DISCLOSURE: Edgar Bautista, None.

EXERCISE PERFORMANCE AND VENTILATION IN CO2–RICH ATMOSPHERE IN COAL MINEMatjaz Flezar MD* Mitja Kosnik MD Marjan Bilban MD UniversityHospital Golnik, Golnik, Slovenia

PURPOSE: Long-term exposure to high CO2 in coal mine environmentcould lead to diminished exercise performance, acid-base changes and otherhealth effects. CPET testing and blood gas analysis during the work at the headof coal mine excavation would provide an accurate estimate of true workplace-related impact on physical performance and health status.

METHODS: We performed lung function testing (spirometry and singlebreath DlCO), blood gasses and modified Masters step test in 76 coal miners,that worked at least 10 years in a row as a head-excavation miners. CPETparameters were measured using portable metabolic analyzer. Tests wereperformed in duplicates: every subject underwent the same procedure outand in a coal mine – approximately 430 m under the ground level. CO2 in acoal mine was continuously monitored and mean value of was 1.21%. Pairedtests were used for presentation of results.

RESULTS: There was no chronic acid-base disorder. pO2 of arterialblood, spirometry values and DlCO after exercise in and out of the coalmine were not significantly different. Ventilation in the coal mine waselevated with an average increase of 11%. Increase in ventilation wasmainly due to increase in tidal volume. Increase in heart rate was lowerduring exercise and oxygen consumption was 11% less in the mine (samelevel of exercise). Anaerobic threshold did not differ.

CONCLUSION: No lung function of blood gas deficit was noted intested coal miners. Exercise performance in coal mine atmosphere wasnot affected by increase in ventilation. Lower oxygen consumption duringthe same level of exercise in a coal mine could be due to more efficientskeletal muscle recruitment or unknown influence of other atmosphereconditions on sceletal muscle performance.

CLINICAL IMPLICATIONS: Physical work in a coal mine withincreased CO2 levels of average 1.21% is not associated with chronic oracute respiratory and muscular changes.

DISCLOSURE: Matjaz Flezar, None.

ARM EXERCISE AND LOWER LIMB EXERCISE CAPACITIESARE SIMILAR IN PATIENT WITH SEVERE COPDCastagna Olivier MD* IMNSSA, Toulon, France

PURPOSE: In patients with COPD, upper limb solicitation was important indaily activity. However, very few studies concerning upper limb physiologicaladaptation during exercise was available. The purpose of this study was to assessand compare the upper limb and lower limb capacities in severe COPD patientsduring incremental and constant load exercises.

METHODS: Ten COPD patients with homogenous age and severe air flowlimitation (age 65 � 6.1 [SD]yr; FEV1: 35% � 5% predicted) and ten healthycontrol (age 63 � 5.3 [SD]yr; FEV1: 102 � 4% predicted) subjects were studied.

RESULTS: at peak exercise, maximal values of load, VO2, RER, VE,and HR were significantly lower in patient with COPD, compared withhealthy controls for both conditions(p�0.001). On the opposite, nosignificant difference was observed between arm and leg for theseparameters in COPD patients. For both conditions (arm vs. leg), mechan-ical efficiency (ME) was significantly lower in patients with COPD than incontrol subjects (20.97 % � 2.33 % and 25.90 % � 3.30 % for arm ; 20.91% � 2.92 % and 27.38 % � 3.03 % for leg, p� 0.001). In both

populations, ME of the lower limb was comparable to that of the upperlimb. In COPD patients within homogenous and sever air flow limitation,during upper-limb exercise, as observed in previous study, we noted thatexercise capacity was relatively more preserved than during leg exercise.

CONCLUSION: To explain this situation, we hypothesized that a part of theupper limb mass muscle is relatively less deconditioned compared to lower limband could explain why maximal workload values are relatively well preservedduring arm exercise. Furthermore, it’s seems to be possible that a level of exercisewas reached beyond which the VO2 could not be increased.

CLINICAL IMPLICATIONS: improvements in upper-limb strengthor endurance resulting from training could lead to improved overallfunctional capacity and ability to perform activities of daily living.

DISCLOSURE: Castagna Olivier, None.

PARAMETERS OF RESPIRATORY FUNCTION AS INDICATORSOF AEROBIC CAPACITY ATHLETE’SNenad Ponorac MD Amela Matavulj MD* Nikola Grujic MD ZvezdanaRajkovaca MD Pedja Kovacevic MD Medical School, Department forPhysiology, Banjaluka, Bosnia-Herzegovina

PURPOSE: The term aerobic capacity represents the sum of aerobicmetabolic processes in human organism. It is the bases of the physicalworking capacity. Parameters of respiratory function are very informativeand appropriate for aerobic capacity researching. The purpose of thisstudy was to check possibilities of using respiratory parameters as theindicators of aerobic capacity in athletes and to check differences inregard to non- athletes [1, 2]. The goals were: 1.Analyses of respiratoryfunction parameters in various sports athletes 2.Comparison with valuesobtained in non-athletes.

METHODS: This study included 67 athletes (rowers, soccer’s, andjudo) and 28 non-athletes. Respiratory parameters (maximal voluntaryventilation / Ve, respiratory volume / RV and breathing frequency / Fr)were measured during determination VO2max, direct method.

RESULTS: Results obtained show statistically higher Ve values inrowers (142 L/min) in regard to soccer’s (123 L/min) and judo (111L/min). Successfully rowing requires high anaerobic capacity and soeffective maximal voluntary ventilation.

CONCLUSION: These results express the grater values of Ve andother parameters too, in athletes in regard to non-athletes. Reason forthese results is just process of training. Other parameters of respiratoryfunction were not useful for determination the aerobic capacity.

CLINICAL IMPLICATIONS: These parameters are limitation fac-tors for physical activities only in patients with obstructive and restrictivediseases.

Table 1. Data at Peak Exercise.

Arm Crank Leg Cycle

Controls COPD Controls COPD

PMA, watts 94�12.65† 54�8.54* 162�21.50 58�10.33*

V;�S�UP6(.O2 , ml.min-1. 1597�168.† 1054�67* 2190�271 1109�116*

RER 1.15�0.04 1.09�0.03* 1.14�0.05 1.08�0.03*

V;�S�UP6(.E , l.min-1. 61.8�6.2† 28.9�3.21* 77.2�9.53 31.6�4.06*

V;�S�UP6(.E / MVV, % 60.2�4.8† 88.6�1.6* 74.9�5.8 95�2.1*

VT, l. 1.64�0.13† 0.92�0.18* 1.95�0.23 0.98�0.17*

fb, breaths min-1. 37.8�2.9† 31.5�3.4* 39.8�3.34 32.5�3.3*

HR, beats min-1. 156�5.7 117�6* 157�5.1 125�8.8*

Table 2:Values are means � SE; V;�S�UP6(.O2, O2 consumption;V;�S�UP6(.CO2, CO2 excretion; RER, respiratory exchange ratio;V;�S�UP6(.E, minute ventilation; MVV, maximal voluntary ventilation;VT, tidal volume; fb, frequency of breathing; HR, heart rate; † p�0.05arm vs leg; * p�0.05 COPD patients vs control.


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DISCLOSURE: Amela Matavulj, None.

Pulmonary Hypertension12:30 PM - 2:00 PM

ENVIRONMENTAL TOBACCO SMOKE AND HEALTH STATUSIN PATIENTS WITH PULMONARY ARTERIAL HYPERTENSIONHubert Chen MD* Mark D. Eisner MD Carla M. Teehankee BA Paul D.Blanc MD Teresa De Marco MD UCSF, San Francisco, CA

PURPOSE: We sought to quantify environmental tobacco smoke(ETS) exposure among patients treated for pulmonary arterial hyperten-sion (PAH), and to determine whether ETS exposure is related to healthstatus in these patients.

METHODS: We enrolled consecutive patients referred to a tertiarycare center for PAH. Criteria for inclusion were elevated meanpulmonary artery pressure (MPAP) �25 mmHg by right heart cathe-terization and medical stability on PAH therapy for �3 months. ETSexposure was assessed using a validated passive smoke exposurequestionnaire, as well as by urine cotinine. Exercise capacity wasassessed by six-minute walk (6MW) distance. Disease-specific quality-of-life was assessed using both the 20-item Airways Questionnaire(AQ20) and Minnesota Living with Heart Failure Questionnaire(MLHFQ).

RESULTS: We analyzed 91 patients with the following character-istics: mean age 49�13 yrs; 70% female; mean MPAP 50�14 mmHg;WHO class I-II (42%), III (51%), and IV (7%). Forty (44%) patientsreported exposure to ETS. Urine cotinine was positive in 45 (57%) of79 tested. Self-reported ETS exposure correlated significantly withurine cotinine level (r�0.42, p�0.0003). There was no significantcorrelation between self-reported ETS exposure and either 6MWdistance (p�0.26) or quality-of-life (AQ20: p�0.80; MLHFQ:p�0.83). Similarly, there was no significant association between urinecotinine positivity and either 6MW distance (p�0.14) or quality-of-life(AQ20: p�0.77; MLHFQ: p�0.90).

CONCLUSION: ETS exposure is common among patients treated forPAH, however, its relationship with exercise capacity and quality-of-liferemain uncertain.

CLINICAL IMPLICATIONS: Patients on PAH therapy should beencouraged to avoid ETS exposure until stronger evidence regarding itseffects are available.

DISCLOSURE: Hubert Chen, None.

FUNCTIONAL CHANGES OF RESPIRATORY MUSCLES INPULMONARY HYPERTENSIVE RATSFrances De Man BSc* Brechje van Beek-Harmsen BSc Anton Vonk-Noordegraaf PhD Willem van der Laarse PhD VU University MedicalCentre, Amsterdam, Netherlands

PURPOSE: Patients with pulmonary hypertension have impairedrespiratory muscle function. We investigated whether functional changesof inspiratory and expiratory muscles (diaphragm, external and internalintercostal muscles) are similar.

METHODS: Six male Wistar rats (body weight 180g) were injectedsubcutaneously with 40 mg monocrotaline (MCT) per kilogram bodyweight. Another six rats were age-matched controls. The animals weresacrificed after 2 or 4 weeks. During anesthesia the intercostal musclesand diaphragm were dissected. Calibrated histochemical methods wereused to determine muscle fiber cross-sectional area (CSA), maximum rateof oxygen consumption (VO2max), myoglobine (Mb) concentration andthe number of capillaries per fiber. Statistical analyses were performedwith the use of 2 way Analysis of Variance.

RESULTS: The diaphragm shows a significant decrease in VO2max xCSA ((P�0.0001) and a decrease in Mb x CSA (P�0.01) after 2 weeks.The number of capillaries per fiber was constant. The external intercostalmuscle shows a significant decrease of VO2max x CSA (P�0.0001) and adecrease in Mb x CSA (P�0.0001) after 4 weeks. The number ofcapillaries per fiber was constant. The internal intercostal muscle shows,however, a significant increase of VO2max x CSA (P�0.0001), a decreaseof Mb x CSA (P�0.01) and a decrease in number of capillaries per fiber(P�0.05).

CONCLUSION: The internal intercostal muscles show a trainingeffect after 4 weeks of MCT, whereas there is reduced maximum poweroutput in the diaphragm and external intercostal muscles. The resultssuggest that a reduction of lung compliance causes shortening of the fibersin the diaphragm and the external intercostal muscle and stretch of theinternal intercostal muscles, which are known regulators of muscleatrophy and hypertrophy, respectively.

CLINICAL IMPLICATIONS: Functional changes of respiratorymuscles in pulmonary hypertensive patients may be muscle-dependent.

DISCLOSURE: Frances De Man, None.

PULMONARY VENO-OCCLUSIVE DISEASE IN ASSOCIATIONWITH CREST SYNDROME (LIMITED SCLERODERMA): CLIN-ICAL, RADIOLOGIC, HEMODYNAMIC AND PATHOLOGICCHARACTERIZATIONWilliam T. Mansfield MD* Linda Allred RN Thomas E. Van der KlootMD Joel A. Wirth MD Maine Medical Center, Portland, ME

PURPOSE: Pulmonary Arterial Hypertension (PAH) is a rare diseasesometimes associated with collagen vascular diseases, usually LimitedScleroderma (CREST Syndrome). Pulmonary Veno-occlusive Disease(PVOD) is an uncommon subtype of PAH with a particularly poorprognosis. PVOD is usually idiopathic, however it has also been associatedwith chemotherapy exposure and rheumatic diseases. PVOD has rarelybeen associated with CREST Syndrome, however few clinical data existconcerning this connection. We present clinical, radiographic, hemody-namic and pathologic data on two patients with PVOD and associatedCREST Syndrome.

METHODS: Two patients managed at our institution for PVOD withconcomitant CREST Syndrome were studied via retrospective chartanalysis. All available clinical, radiographic, hemodynamic, and pathologicdata were reviewed.

RESULTS: Two female patients (aged 63 and 71 years) were diagnosedwith CREST Syndrome (8 and 20 years) prior to onset of pulmonaryhypertension symptoms or diagnosis. Both were treated with nifedipine,prednisone, and cyclophosphamide for scleroderma, and warfarin, oxygenand epoprostenol for PAH. One received sitaxsentan prior to epoprostenolinitiation. Both presented with dyspnea, (WHO Class III), accentuated P2heart sound, RV heave, and II/VI tricuspid regurgitation murmurs. Bothwere seropositive for anticentromere antinuclear antibodies (titres: 1:1280and 1:2048). Thoracic CTs demonstrated very mild interstitial LungDisease (ILD). PFTs showed mild reductions in TLC with markedreductions in DLCO. Right heart catheterization showed: mean PAP 53and 63 mmHg, PCWP 14 and 7 mmHg, CO 3.1 and 2.2 L/min, MVO2 44and 37%, RAP 14 and 9 mmHg, respectively. Clinical courses werenotable for rapid clinical deterioration (death within several weeks)characterized by progressive right heart failure, pleural effusions and


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pulmonary edema when given epoprostenol. Autopsies demonstratedPVOD without significant ILD in both cases.

CONCLUSION: PVOD and CREST Syndrome are two relatively rareconditions which may co-exist. The association carries a particularly poorprognosis in these cases, marked by clinical deterioration upon initiationof epoprostenol.

CLINICAL IMPLICATIONS: Clincians should consider PVOD inpatients with scleroderma and pulmonary hypertension, particularly ifthoracic CT scanning suggests ILD.

DISCLOSURE: William Mansfield, Grant monies (from industryrelated sources) Encysive, LP Myogen Biopharmaceutical; Product/pro-cedure/technique that is considered research and is NOT yet approved forany purpose. sitaxsentan.

SECONDARY PULMONARY HYPERTENSION IN GERIATRICPOPULATIONSotir Polena MD Eirene Mamakos MD* Anwar Hague MD ChristosIakovou MD Rick Conetta MD Rajen Maniar MD Flushing HospitalMedical Center, Flushing, NY

PURPOSE: Pulmonary hypertension (PH) is a disease with a very poorprognosis. Although primary PH remains a rare pathology, PH related toother diseases is being diagnosed quite often. Chronic respiratory disor-ders, hypoxia, thromboembolic events, valvular disorders, systolic anddiastolic dysfunction etc have all been listed as potential pathologies thatcan lead to the development of the secondary PH. One of the reasons forthe increased prevalence of the secondary PH is attributed to the agingpopulation. The aim of our study is to identify the etiological factors(comorbidities) that contribute to the development of the secondary PHin geriartric population.

METHODS: We conducted a retrospective analysis of 153 elderlypatient charts after an echocardiografic study, which identified moderatepulmonary hypertension (�50mm Hg). The medical charts were reviewedin detail, data from the echo-lab and findings from the computerizedtomography (CT) of the chest were analyzed.

RESULTS: The study population consisted of elderly patients (meanage 76.8) 66% male and 44 females. Systemic hypertension was found tobe present on 72 % of the patients (110). Two (1.3%) patients were foundto have severe mitral valve dysfunction. Left atrium and left ventriculediameter was enlarged in 75% (115) of the patients. Moderate to severesystolic dysfunction (EF�30%) was recorded in 28% (43) of the patientsand dyastolic dysfunction in 17% (26). CT findings were categorized innormal findings, airway disease, interstitial/ inflammatory changes, andpulmonary embolisms (PE), respectively 12%, 20%, 68%, 11%. In a fewCT’s combined interstitial changes with pulmonary embolism were found.

CONCLUSION: The etiology of secondary pulmonary in geriartricpopulation is mainly attributed to systemic hypertension, interstitial/inflammatory pulmonary disorders, systolic and diastolic dysfunction.History of airway disease, PE, and valvular dysfunction are also important.

CLINICAL IMPLICATIONS: Aggressive treatment of cardiopulmo-nary disorders in geriartric population can delay or even stop thedevelopment of the secondary PH.

DISCLOSURE: Eirene Mamakos, None.

ESTABLISHING A MINIMALLY IMPORTANT DIFFERENCE IN6-MINUTE WALK DISTANCE AND SF-36 AMONG PATIENTSWITH PULMONARY ARTERIAL HYPERTENSIONClaire Gilbert* Martin C. Brown Joseph C. Cappelleri PhD Tamiza ParpiaPhD Stephen P. McKenna PhD Pfizer Ltd, Sandwich, United Kingdom

PURPOSE: There are currently no guidelines or standards to helpphysicians determine whether or not the treatment provided to patientswith pulmonary arterial hypertension (PAH) results in a clinically impor-tant benefit. This study was undertaken to define the level of change inexercise capacity, as measured by the 6-minute walk distance (6MWD),and functioning and well-being, as measured by the SF-36, that isclinically meaningful in patients with PAH: a minimally important differ-ence (MID).

METHODS: Data from a 12-week sildenafil study were used toevaluate an MID for 6MWD and the physical functioning, role-physical,social functioning, and vitality domains of the SF-36 in patients with PAH,using the following distribution-based approaches: Effect Size (ES),Standard Error of Measurement (SEM), and Standard Error of the

Difference (Sdiff). The total population enrolled in the study, includingthe placebo- and the sildenafil-treated groups, was used for these analyses.

RESULTS: An MID was established for each of the end points basedon the average of the distribution-based estimates (Table). These esti-mates are a point change in score for the SF-36 and a change in distancewalked in meters for the 6MWD.

CONCLUSION: A wide range of estimates were obtained for each endpoint using three distribution-based methods to explore a minimallyimportant change. The average of these was then taken as an MID valuefor each end point. This is the first clinical investigation to establish anMID for key SF-36 domains and 6MWD in patients with PAH. Furtherwork incorporating the patient and clinical perspective of change usinganchor-based methods would complement and supplement the findingsreported here.

CLINICAL IMPLICATIONS: The analyses and results presentedhere may be useful in establishing clinical guidelines to determine theeffectiveness of PAH therapies objectively.

DISCLOSURE: Claire Gilbert, Shareholder Pfizer Ltd; EmployeePfizer Ltd.

OUTCOMES OF INVESTIGATING PULMONARY ARTERY HY-PERTENSIONVinay K. Sharma MBBS* Karim Djekidel MD Graduate Hospital,Philadelphia, PA

PURPOSE: With increasing use of echocardiography, an increasingnumber of patients are being identified as having pulmonary arteryhypertension (PAH). In patients with normal systolic left ventricular (LV)function, extensive work up is often performed, even in patients in whoma comprehensive history, physical examination and chest radiograph doesnot suggest an underlying diagnosis. This descriptive study investigates thecharacteristics of these patients and the outcomes of diagnostic testing.

METHODS: Pulmonary consult sheets over a period of 4 years werereviewed, and patients with newly diagnosed PAH, by echocardiography,identified. Patients with a likely etiology for PAH on history or examina-tion were excluded from the study. Medical records were then reviewedand the following data abstracted: patient demographics, co-morbidconditions, medications taken, and results of echocardiography, chest CTscan, PFT, polysomnogram, serologies for connective tissue disorders, andtests for pulmonary embolism (PE) (ventilation-perfusion scan or PEprotocol chest CT).

RESULTS: Twenty-six patients were included in the study. Twenty(77%) were women. Mean age was 66 (�11) years and 19 (73%) werehypertensive. The mean pulmonary artery systolic pressure was 60 (�12)mmHg and LVH was present in 19 (73%). An average of 3.5 diagnosticstudies were done. Three of 22 chest CT scans were abnormal: 2 withinterstitial lung disease and one with severe emphysema. One of 18 PEstudies was abnormal. Nine of 12 polysomnograms revealed obstructivesleep apnea. Two of 12 serologies were abnormal. 23 patients had PFTs:16 had minor abnormalities, 4 had severe restriction and one severeobstruction. Five (19%) had relatively normal studies except for elevatedPAP on echocardiography. Seven (27%) patients had LVH and no otherabnormality that adequately explained PAH. Six (23%) patients had LVHand OSA.

CONCLUSION: The prevalence of hypertension and LVH was unex-pectedly high in our cohort of PAH. Except for polysomnograms, theother studies had poor diagnostic yields.

CLINICAL IMPLICATIONS: LVH with diastolic dysfunction maybe the underlying etiology in a significant proportion of patients withPAH.

DISCLOSURE: Vinay Sharma, None.

Minimally Important Differences for Pre-specified SF-36 Domains and 6MWD

Outcome MID Range of estimates

SF-36 physical functioning 11 3.8-20.9SF-36 role physical 21 8-40.5SF-36 social functioning 16 5.2-33.1SF-36 vitality 13 4.3-256MWD (m) 39 12.7-77.9


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BOSENTAN THERAPY IN PATIENTS WITH PULMONARY HY-PERTENSION SECONDARY TO CONGENITAL HEART DIS-EASE (EISENMENGER PHYSIOLOGY)Michele D’Alto PhD* Berardo Sarubbi PhD Carmine D. Vizza PhDEmanuele Romeo MD Giuseppe Santoro MD Paola Argiento MD MariaG. Russo MD Raffaele Calabro MD Chair of Cardiology, SecondUniversity, V. Monaldi Hospital, Naples, Italy

PURPOSE: To evaluate safety, tolerability, clinical and haemodynamicimpact of bosentan, an orally administered endothelin-1 antagonist, inpatients with pulmonary hypertension due to congenital heart disease(Eisenmenger syndrome).

METHODS: Twelve patients with ES (5M, 7F, mean age 33.6�8.7)were treated with oral bosentan (62.5 mg x 2/die for the first month andthen 125 mg x 2/die). Patient clinical status, liver enzymes, WHOfunctional class, resting oxygen saturations, 6 min walk test and transtho-racic echocardiography were assessed at baseline and at 1, 3 and 6 month.Haemodynamic evaluation with cardiac catheterization was performed atbaseline and at 6 month follow-up.

RESULTS: At baseline 10 patients were in III and 2 in IV WHOfunctional class. Six had ventricular septal defect, 3 single ventricle, 2atrio-ventricular canal, 1 truncus arteriosus. All 12 patients welltolerated bosentan, but in 2 patients we reduced the maintenance dosefrom 125 mg x 2/die to 62.5 mg x 2/die for a transient elevation of liverenzyme (1 patient) and transient leg oedema (1 patient). After sixmonth therapy, oxygen saturation at rest (78.3�9.3% vs 85.8�5.6%;p�0.05) and after 6-min walk test (64.4�8.8% vs 73.5�12%; p�0.05),the distance travelled in the 6-min walk test (321�101 vs 445�45 m;p�0.05) and Borg’s index (5,9�1.4 vs 3�2.3; p�0.05) significantlyimproved. A significant change of total pulmonary indexed resistances(19.1�9.5 vs 9.3�5.3 WU, p�0.05), arterial pulmonary indexedresistances (15.2�7.2 vs 7.62�4.7 WU, p�0.05) and systemic-to-pulmonary blood flow ratio (0.74�0.34 vs 1.36�1.14, P�0.05) wasobserved suggesting an improvement of pulmonary haemodynamics.At six month follow-up 5 patients were in II, 6 in III and 1 in IV WHOfunctional class.

CONCLUSION: Bosentan treatment was safe and well tolerated inadults with ES after a mid-term follow-up (6 months of oral therapy).Oxygenation, functional status and pulmonary haemodynamics of patientsimproved with minimal side effects.

CLINICAL IMPLICATIONS: Bosentan is useful in the managementof the Eisenmenger syndrome in adults but larger clinical investigation arenecessary.

DISCLOSURE: Michele D’Alto, None.

EFFICACY AND SAFETY OF PULMONARY REHABILITATIONIN PATIENTS WITH PULMONARY HYPERTENSION: PRELIM-INARY RESULTSMaria Carrillo MD* Cheryl A. Szymanski RN Sandy K. Truesdell MSNLisa D. Stagner DO Kevin M. Chan MD Henry Ford Hospital, Detroit,MI

PURPOSE: Pulmonary rehabilitation(PR) is recommended for pa-tients with pulmonary hypertension (PH) but little is known about itsefficacy and safety. We evaluated the outcomes of our PR patients withpulmonary arterial hypertension(PAH)and pulmonary hypertension asso-ciated with lung disease(PHLD).

METHODS: Patients enrolled in our single center PR programdiagnosed with these conditions were reviewed. Demographics, outcomesand Chronic Respiratory Disease Questionaire(CRDQ)data were ana-lyzed and compared.

RESULTS: 8 patients with PAH(2 IPAH, 4 CTEPH, 1 PSS, 1 Druginduced) and 12 with PHLD(7 COPD, 2 IPF, 1 Sarcoidosis, 2 OSA)wereidentified. The PAH group was all female and slightly younger(63�13)than the PHLD(68�12)group(8F, 4M). The number of exercise ses-sions(24�13 vs 25�8), days to complete therapy(72�14 vs 65�17),pre-6MW distance(260m�79 vs 264m�100), supplemental O2(3L�2.14vs 2.8�1.9), and WHO Symptom Class(3.5�0.76 vs 3.4�0.55) weresimilar. 4/8 PAH patients completed PR; 2 expired while enrolled, 1developed knee pain, 1 had symptomatic PVCs during exercise. 8/12PHLD patients completed PR; 1 expired, 1 received a lung transplant, 2were lost to follow up. 6 MW distance improved post PR in the combinedgroup of PH patients from 268m�105 to 351�47(p�0.006). CDRQ datarevealed improvement in Dyspnea(17.6�2.7 to 22.1�4), Fatigue(14.6�5to 19.2�4), and Mastery(21�2.3 to 24�3).

CONCLUSION: Pulmonary rehabilitation improves 6MW distanceand CRDQ Score(Dyspnea, Fatigue, Mastery Domains)in Class III-IVpulmonary hypertension patients. The high severity of illness in the PAHgroup lead to low program completion. Earlier referral to PR may bebeneficial.

CLINICAL IMPLICATIONS: Pulmonary rehabilitation improvesphysical conditioning and overall “well being”. It is an effective and safetreatment for patients with PH.

DISCLOSURE: Maria Carrillo, None.

WARFARIN MANAGEMENT IN PULMONARY ARTERIAL HY-PERTENSION IS SIMILAR BETWEEN BOSENTAN, PLACEBO,AND SITAXSENTANTerrance Coyne MD* Richard Dixon PhD Encysive Pharmaceuticals,Houston, TX

PURPOSE: Warfarin, commonly used in pulmonary arterial hyperten-sion (PAH) is a difficult therapy to use, requiring frequent and ongoingmonitoring to achieve safe and effective anticoagulation, with dosinginfluenced by changes in diet as well as drugs. As an inducer of CYP2C9,bosentan (BOS), a twice daily, nonselective ETRA, interacts with themetabolism of warfarin. As an inhibitor of CYP2C9, sitaxsentan (SITAX),a once daily, highly ETA selective ETRA, also interacts with the metab-olism of warfarin. Here, we report on the management of warfarin froma multi-center, placebo (PBO)-controlled study, STRIDE-2.

METHODS: STRIDE 2 included SITAX 100mg once daily, 50mgonce daily, PBO, and an open-label, efficacy rater blinded, arm of BOSBID. BOS was dosed according to label. The protocol recommended thatpatients (pts) on warfarin randomized to SITAX or PBO were, at studyentry, to have a single reduction in warfarin dose of 80%, followed byusual management. Pts on warfarin at study entry and randomized to BOSdid not have warfarin dose adjusted. Warfarin doses at endpoint and thetotal number of dosing changes in the 18 week trial were assessed.

RESULTS: 47% of pts were on warfarin at study entry. Results for wk18 mean warfarin dose and mean number of dose changes per pt areshown in Table 1.

CONCLUSION: Warfarin dose was higher in BOS pts and lower inSITAX pts than PBO, consistent with expectations. Nonetheless, warfarindosing changes were equally frequent for pts treated with BOS, SITAX, orPBO, indicating no meaningful difference in management complexity.

CLINICAL IMPLICATIONS: Warfarin is a difficult therapy to useand requires frequent and continuous monitoring. The management ofwarfarin in patients with PAH is similar between no ETRA therapy andthe use of either bosentan or sitaxsentan.

DISCLOSURE: Terrance Coyne, Employee Encysive Pharmaceuti-cals; Product/procedure/technique that is considered research and is NOTyet approved for any purpose. Sitaxsentan.

Hemodynamics

PAH PHLD

Echo PASP(mmHg) 79�19 60�17 p�0.04RV diameter(cm) 3.06�0.7 2.11�0.5 p�0.009mPAP(mmHg) 52�16 32�4 p�0.04PVR(WU) 12.7�7

Treatment Groups (n)

PBO(33)

SITAX50mg(26)

SITAX100mg

(27)BosentanBID (29)

Warfarin dose at wk 18(mg/d; mean � sd)

3.7 � 2.7 2.8 � 1.2 2.1 � 1.0 5.1 � 2.9

Mean # of changes inwarfarin dosing per pt

1.6 1.8 1.8 1.7




RESPONSE OF PATIENTS WITH PULMONARY ARTERIAL HY-PERTENSION THAT DO NOT QUALIFY FOR TREATMENTWITH BOSENTAN TO TREATMENT WITH BOSENTANZoheir Bshouty MD* University of Manitoba, Winnipeg, MB, Canada

PURPOSE: To asses the response of patients with underlying pulmo-nary arterial hypertension who do not qualify for treatment with bosentanto treatment with bosentan.

METHODS: Fifteen patients (8 females and 7 males) with underlyingpulmonary arterial hypertension who did not qualify for treatment withbosentan [3 with chronic thromboembolic disease (CTED), 2 withcongenital and valvular disease (CVD), 3 with interstitial lung disease andsevere fibrosis (ILD), and 7 with connective tissue disease and severefibrosis (CTD�FIB)] where treated with bosentan. Bosentan was startedat 62.5 mg PO BID and increased to 125 mg PO BID after 4 weeks. Onepatient with CTED was started on dual therapy with bosentan andsildenafil. Primary end points where 6-minute walk distance and NYHAfunctional class. Patients were assessed at baseline, 3 and 6 months.

RESULTS: The overall 6-minute walk distance at baseline, 3 and 6 months(Mean�SE, meters) were 262.2�36.76, 357.4�38.60, and 366.3�44.92 respec-tively. Individual as well as group data (CTED, CVD, ILD, CTD�FIB) areshown in Figure 1. Overall NYHA class dropped from an average of 3 to 2.2 bothat 3 and 6 months. All patients tolerated the treatment well. Two patientsrequired a reduction in dose down to 62.5 mg PO BID.

CONCLUSION: Patients with underlying pulmonary arterial hyper-tension that do not qualify for treatment with endothelin receptorantagonists may still benefit from treatment.

CLINICAL IMPLICATIONS: More RCT are needed to assess theresponse to treatment in wider groups of patients with underlyingpulmonary arterial hypertension.

DISCLOSURE: Zoheir Bshouty, None.

TREATMENT OF PORTOPULMONARY HYPERTENSION WITHORAL SILDENAFILShiraz A. Daud MD* Murali M. Chakinala MD Washington University inSaint Louis, St Louis, MO

PURPOSE: Pulmonary arterial hypertension (PAH) in the setting ofportal hypertension, or Porto-pulmonary Hypertension (PPHTN), has anestimated prevalence of 3.5% to 12.5% in patients referred for livertransplantation. Complications of cirrhosis such as encephalopathy, highcardiac output state, and thrombocytopenia have made treatment withprostanoids challenging. Furthermore, Bosentan is contraindicated inchronic liver disease and severe pulmonary hypertension is a contraindi-cation to liver transplantation. We report our experience with oralSildenafil monotherapy in PPHTN.

METHODS: This is a case series of three patients with PPHTN treated withoff-label Sildenafil. Secondary causes of pulmonary hypertension were excluded.Laboratory and hemodynamic data, New York Heart Association functional class,and six-minute walk distance (6MWD) were obtained at baseline and aftertreatment for an extended period with Sildenafil.

RESULTS: All three patients had improvements in their hemodynam-ics and 6MWD. Functional improvement was evident in all three patients.During the 31 patient-months of follow-up, there were no directlyattributable side effects or complications of Sildenafil.

CONCLUSION: Sildenafil is a safe and effective pulmonary vasodila-tor for patients with PPHTN.

CLINICAL IMPLICATIONS: Because conventional PAH therapiesare potentially problematic in the setting of cirrhosis, sildenafil should beconsidered as a chronic therapeutic choice in PPHTN and may serve as a“bridge” to liver transplantation.

DISCLOSURE: Shiraz Daud, None.

TREATMENT OF SECONDARY PULMONARY ARTERIAL HY-PERTENSION WITH ENDOTHELIN RECEPTOR BLOCKADESatyendra Sharma MBBS* Roger Philipp MD Tarik Kashour MD Uni-versity of Manitoba, Winnipeg, MB, Canada

PURPOSE: Secondary pulmonary arterial hypertension (SPAH) isan adverse outcome of a variety of systemic disorders. These includecollagen vascular diseases, chronic thromboembolism, human immu-nodeficiency virus (HIV), portal pulmonary hypertension and otherdiseases. Progression of SPAH may persist despite stabilization of thecausative disease and contributes to the poor quality of life andunfavorable survival in these patients. Treatment of the underlyingcause and oxygen supplementation may alleviate symptoms, but nospecific therapy to treat SPAH currently exists. Endothelin receptorblockade with bosentan has been shown to be beneficial therapy in thetreatment of primary pulmonary hypertension but efficacy of thistherapy in SPAH has not been established.

METHODS: Retrospective review of patients followed through our clinic.RESULTS: We describe a case series of six patients with disparate

causes of SPAH, who benefited from endothelin receptor blockade

Patient 1 Patient 2 Patient 3

Duration of sildenafil therapy 9 months 7 months 15 months

Dose of sildenafil 50mg QID 50 mg TID 50 mg TID

Pre Post Pre Post Pre Post

PASP (mm) 96 85 94 57 90 85

PADP (mm) 40 28 52 24 40 33

mPAP (mm) 60 50 66 38 60 51

mRAP (mm) 20 3 29 0 23 5

CO (L/min) 2.0 7.7 2.7 4.5 3.5 4.0

CI (L/min) 1.1 3.9 1.3 2.2 1.8 2.2

PCWP (mm) 16 7 N/A* 3 N/A* 7

PVR (dynes/sec/cm5) 1760 447 N/C 622 N/C 880

PaO2 sat% 34 67 47 73 58 68

6MWD (ft) 375 875 ND# 1350 250 1500

NYHA Class 4 3 4 1 4 1

Hemoglobin (g/dL) 11 10.4 16.1 17 12.5 14.6

Platelets (103 /mcl) 24 49 72 95 39 48

PASP � pulmonary arterial systolic pressure, PADP � pulmonaryarterial diastolic pressure, mPAP � mean pulmonary arterial pressure,mRAP � mean right atrial pressure, CO � cardiac output, CI � cardiacindex, PCWP � pulmonary capillary wedge pressure, 6MWD � sixminute walk distance, NYHA � New York Heart Association,

Patient 1 Patient 2 Patient 3

Age 56 59 53

Gender F M M

Etiology of cirrhosis cryptogenic alcohol Hepatitis C,

alcohol

Child-Pugh class B B B

Complications EV,GV,

portal vein thrombosis,

thrombocytopenia

EV, thrombocytopenia Encephalopathy,

thrombocytopenia

Symptoms at

presentation

Progressive breathlessness, lower

extremity edema, syncope

Progressive

breathlessness, syncope

Exertional

breathlessness,

syncope

EV � esophageal varices, GV � gastric varices




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therapy. The causes of SPAH in this series included collagen vasculardisease (scleroderma 1, systemic lupus erythematosis 2), chronicthromboembolic disease (2) and granulomatous vasculitis from sar-coidosis (1). Therapy with bosentan led to symptomatic improvement,shift in New York Heart Association functional class and walkingdistance in all patients. 6 minute walk test demonstrated an increasefrom a mean of 151.67�69.30 meters at baseline to 314.83�89.09meters following average 14 months of bosentan treatment. Pulmonaryarterial pressure decreased in most but not in all six patients on followup echocardiogram.

CONCLUSION: The patients in this series very likely improvedsecondary to the antiproliferative effects of bosentan on pulmonaryvasculature.These patients were treated with multiple therapies in-cluding calcium channel blocker and anticoagulation. Although, cal-cium channel blockers and anticoagulation may have contributed to thetherapeutic effect in these patients, they have not been shown toimprove exercise capacity or functional class in advanced pulmonaryhypertension.

CLINICAL IMPLICATIONS: This case series makes a compellingargument for a systematic, controlled study of endothelin receptorantagonists in patients with SPAH.

DISCLOSURE: Satyendra Sharma, None.

Respiratory Failure Outcomes12:30 PM - 2:00 PM

FACTORS ASSOCIATED WITH FAVORABLE LTACH DIS-CHARGE OUTCOMESLinda L. Wolfenden MD* Grant T. Anderson BA Nancy E. Clardy MSNNancy V. Murrah RN Emir Veledar PhD Emory University, Atlanta, GA

PURPOSE: Long term acute care hospitals (LTACHs) can continuethe care for high risk patients who are deemed medically stable to leavean ICU. Little is known about the type and frequency of dischargedestinations from LTACHs. Factors such as age, prior debility andnumber of comorbidities are significantly associated with survival todischarge from LTACHs. We sought to understand the factors associatedwith a favorable discharge outcome, beyond survival.

METHODS: A prospective, observational medical record review andsurvey. Inclusion criteria: ICU patients with principal diagnosis of respi-ratory insufficiency or failure, referred to the Emory LTACH pulmonaryservice for ventilator and tracheostomy weaning. Exclusion criteria: prioradmission to LTACH. A favorable outcome was defined as any dischargedestination other than re-admission to an acute care hospital, hospice ordeath.

RESULTS: 62 patients enrolled. Mean age: 60.5 �/- 16.3 years; 51.6%female; 53.2% non-white race; 27.4% active smokers. ICU indicationswere as follows: 29.0% CNS disease; 19.3% post-operative; 16.1% acutelung injury; 12.9% MSOF; 9.7% cardiac disease; 6.5% chronic lungdisease; 6.5% other. The distribution of discharge destinations was asfollows: 27.4% acute rehabilitation facility; 25.8% readmission to acutecare hospital ICU; 22.6% subacute rehabilitation facility; 14.5% home;6.5% died; 3.2% nursing home. See table.

CONCLUSION: Most (68%) patients in our study experienced afavorable discharge outcome. Younger age, more education, history ofprior independence and absence of renal disease were all statisticallysignificant factors associated with a favorable discharge outcome. Lowerinitial ICU albumin; lower initial LTACH albumin and lower initialLTACH hemoglobin; and higher initial LTACH creatinine were allsignificantly associated with unfavorable discharge outcomes. A significantminority of patients (26%) required re-admission to the acute carehospital ICU.

CLINICAL IMPLICATIONS: Most patients experienced a favorableLTACH discharge outcome. Factors associated with favorable ICUoutcomes (age, history of renal disease, albumin, creatinine, hemoglobin)are also associated with favorable LTACH outcomes in our study. Moreresearch is needed to determine what factors within the LTACH coursecan improve patient outcomes.

DISCLOSURE: Linda Wolfenden, None.

OUTCOME OF CHRONIC VENTILATED PATIENTS TRANS-FERRD TO A STEP-DOWN RESPIRATORY CARE CENTER INTAIWANFung J. Lin MD* Chang-Yi Lin MD Pei-Jan Chen MD Hsu-Tah Kuo MDMacKay Memorial Hospital, Taipei, Taiwan ROC

PURPOSE: The aim of the study was to investigate the outcome ofprolonged ventilated patients after their transferal from intensive careunits (ICU) to the step-down respiratory care center (RCC) in Taiwan.

METHODS: This was a retrospective observational study in a step-down RCC. Adult patients who was admitted to RCC from October 2000to September 2001 were eligible for the study. Admission criteria of RCCincluded age �17 years old, MV for �14 days, arterial oxygenation�60mmHg with the fraction of inspired oxygen (FiO2)�0.55, andpositive end-expiratory pressure of �10 cmH2O. The primary outcomewas the survival in the RCC and after discharge from the RCC.

RESULTS: Total 224 cases were eligible for the survey, and108(48.2%) patients were successfully liberated in the RCC. Those whofailed weaning had a longer stay in the ICU and RCC (25.1 vs. 20.9 days,and 31.4 vs. 18.6 days with p�0.05). After discharge from the RCC,another 4.9% of the failed patients were weaned within the one year.Patients who failed weaning in RCC had a shorter survival time (5.2 vs.10.4 months, p�0.05) and a lower one-year survival (23.6% vs. 44.6%,p�0.05).

CONCLUSION: Patients who were transferred to RCC were still incritical condition, and 25% of these patients died during their stay in theRCC. However, a step-down RCC cound offer a continual care of thesepronlonged ventilated (PMV) patients who could not be weaned when in

FactorFavorable(N � 42)

Unfavorable(N � 20)

pValue

Demographicsmean age –years 56.3� 15.4 69.3� 14.8 0.0023High school

graduate36 (86%) 11 (55%) 0.0411

Female gender 22 (52%) 10 (50%) 0.8608White race 22 (52%) 7 (35%) 0.1998Never smoker 18 (43%) 5 (25%) 0.1736Past Medical

HistoryPrior

independence31 (74%) 9 (45%) 0.0441

History of renaldisease

7 (17%) 8 (40%) 0.0449

ICU day onealbumin (g/dL) –

mean2.80� 0.85 2.31� 0.58 0.0296

creatinine (mg/dL)– median

0.95 1.3 0.0502

hemoglobin (g/dL)– median

12.1 11.75 0.2802

ICU LOS (days) –median

30 27 0.133

LTACH day onealbumin (g/dL) –

mean2.37 �/- 0.5 2.03 �/- 0.5 0.0125

creatinine (mg/dL)– median

0.75 1.0 0.0320

hemoglobin (g/dL)– median

10.75 9.9 0.0157

LTACH LOS(days) – median

24 13 0.010




ICU with a reduced cost and resource. Establishing a functional positionof step-down RCC in selected PMV patients can be cost-effective.

CLINICAL IMPLICATIONS: Early transfer of stable PMV patientsto RCC can be cost-effective.

DISCLOSURE: Fung Lin, None.

FACTORS AFFECTING WEANING AND SURVIVAL OUT-COMES IN PATIENTS ON PROLONGED MECHANICAL VEN-TILATIONDebapriya Datta MD* Paul Scalise MD Manchester Hospital, Manches-ter, CT

PURPOSE: Literature is limited on weaning and survival outcomes inpatients on prolonged mechanical ventilation (PMV), which is defined asventilatory support �21 days . The objective of this study was todetermine factors affecting weaning and survival outcomes in patients onPMV.

METHODS: We retrospectively studied patients on PMV admitted forweaning to a regional weaning center over a 3-year period. The followingdata was abstracted from records: patients’ age, sex, precipitating cause ofrespiratory failure, duration of ventilatory support (Dvs), percent idealbodyweight (%IBW), body mass index (BMI), serum albumin, prealbu-men, BUN, serum creatinine (Cr), creatinine clearance (CrCl), hemoglo-bin (Hb), WBC count, total lymphocyte count (TLC) and serum TSHlevels. Outcomes noted were liberation from PMV, defined as being offventilatory support for � 7 days and survival (alive at discharge or not).Multivariate analysis was used to determine relation between studiedparameters and outcome. Chi square test was used to test statisticalsignificance, with p � 0.05 being deemed statistically significant.

RESULTS: Of 202 patients studied, 48% were males. Mean age was66.3�16 years. Cause of respiratory failure was cardiovascular surgery in27%; other surgery in 14.5%; COPD in 21%; pneumonia in 9%; ARDS in6%; neurological disease in 18.5% and CHF in 4%. Mean Dvs was 60.8days (range 21-680 days). Sixty-seven percent were liberated from PMV;33% failed to wean. Seventy-one percent survived to discharge. Dvs � 12weeks was associated with better weaning outcome. Table 1 depictsstudied parameters in liberated patients and patients that failed to wean.On multivariate analysis, factors associated with adverse impact onliberation were: COPD as cause of respiratory failure, longer Dvs, lowerCrCl. Factors associated with adverse survival outcome were CHF andCOPD as causes of respiratory failure, higher Cr and lower TLC.

CONCLUSION: Multiple factors affect weaning and survival out-comes in patients on PMV.

CLINICAL IMPLICATIONS: More studies are needed to developscreening criteria for selection of appropriate patients on PMV foradmission to weaning facilities.

DISCLOSURE: Debapriya Datta, None.

PREDICTORS OF ABILITY TO WEAN FROM PROLONGEDMECHANICAL VENTILATION SIX MONTHS AFTER DIS-CHARGE FROM A MEDICAL INTENSIVE CARE UNITLeslie A. Hoffman PhD* JiYeon Choi MSN Thomas H. Miller PhD KeikoKobayashi MSN Thomas G. Zullo PhD Michael P. Donahoe MDUniversity of Pittsburgh School of Nursing, Pittsburgh, PA

PURPOSE: To examine predictors of ability to wean from mechanicalventilation (MV), functional ability and health-related quality of life(HRQoL) in patients who required prolonged mechanical ventilation(PMV) (� 7 days) six months after Medical Intensive Care Unit (MICU)discharge.

METHODS: Consenting patients (n�145) completed questionnairesrating their functional ability (Health Assessment Questionnaire [HAQ])one week before MICU admission (baseline), MICU discharge, 1 and 6months post discharge and HRQoL (SF-36) at baseline, 1 and 6 months.Proxy responses of family members were used when patients could notrespond.

RESULTS: At 6 months, 60.7% patients were living. Survivors were55.7% female, 59.8� 16.7 yrs of age and on MV for 23.4� 22.5 days atMICU discharge. Complete sets of questionnaires were obtained from52% patients for SF-36 and 72% for HAQ. At baseline, no differenceswere seen in SF-36 or HAQ scores. Patients on MV exhibited a statisticallysignificant interaction between MV and Time (p�.034) with higher HAQscores (worse functional ability) at 1, but not 6 months. SF-36 physicalcomponent scores were lower (worse ratings) at 1 (p�.003), but not 6months. No significant changes were seen in SF-36 mental componentscores. Using logistic regression, cormobidity was identified as a signifi-cant predictor of ability to wean from MV following MICU discharge(71.4% cases correctly predicted). Age, gender, APACHE III, baselineHAQ and SF-36 scores were not identified as significant predictors.

CONCLUSION: PMV survivors rate HRQoL similarly 6 months afterMICU discharge, regardless of ability to wean from MV. Those notweaned from MV were more compromised in functional ability at 1, butnot 6-months. Cormorbidity was the best predictor of ability to weanfollowing MICU discharge.

CLINICAL IMPLICATIONS: Inability to wean from PMV does notappear to influence ratings of HRQoL 6 months after MICU discharge.Potential reasons include changes in reference point (expectations) or lackof instrument sensitivity. Cormorbidity significantly influences ability towean following MICU discharge.

DISCLOSURE: Leslie Hoffman, None.

TIME TO WEAN AFTER TRACHEOTOMY IN CRITICALLY ILLPATIENTSDenise P. Veelo MD Dave A. Dongelmans MD Johanna C. Korevaar PhDMarcus J. Schultz PhD* Academic Medical Center, Amsterdam, Nether-lands

PURPOSE: To estimate time to wean from mechanical ventilationafter tracheotomy in critically ill patients.

METHODS: Prospective observational study in translaryngeally intu-bated mechanically ventilated patients that received a tracheostomyduring their stay in an academic ICU.

RESULTS: Approximately 7% of all ICU-patients required a trache-ostomy. Significant more tracheotomies were performed in neurosurgical/neurology patients and patients who were acutely admitted to the ICU(14% and 12%, respectively). Patients after cardiac arrest as the reason forthe present ICU-admittance were tracheotomized in 15%. Tracheotomywas performed at a median time of 8 days (interquartile range, 4-13) afterICU-admittance. Within one week after tracheotomy, the probability ofhaving breathed spontaneously without assist of the mechanical ventila-tor � 4 hours/day was 89%, 78% for � 8, 72% for � 12, and 60% for �24 hours/day. By day 28, the probability of having breathed spontane-ously � 4 hours/day was 98%, 97% for � 8, 94% for �12 and 93% for �24 hours/day. Mean time to wean after tracheotomy was 5 days (2-11) forall patients. At day 7, 77% of the neurosurgery/neurology patients, 66% ofcardiopulmonary surgery patients and 63% of the cardiology patients, butonly 41% of surgical patients and 34% of medical patients were weanedcompletely from the mechanical ventilator.

CONCLUSION: Time to wean completely from mechanical ventila-tion after tracheotomy differs among the separate ICU-patient groups.

CLINICAL IMPLICATIONS: After tracheotomy, the majority ofpatients are quickly able to breathe spontaneously without assist of themechanical ventilator for several hours/day.

TABLE 1—Studied Parameters in Patients Liberatedand Failed-To-Wean

Parameters Liberated Failed

Age (years) 66�7 68�15Dvs (days) 51�32 61�66BMI (kg/sqm) 27�8 26�8% IBW 121�36 119�36Protein (gm/dL) 5.9�0.8 5.5�0.8Albumen (gm/dL) 2.6�0.5 2.5�0.5Prealbumen (mg/dL) 20�7 20�8BUN (mg/dL) 29�21 32�17Cr (mg/dL) 0.8�0.9 0.8�0.8CrCl (ml/min) 69�34 61�32Hb (gm/dL) 10�1.4 10�1.3WBC 10�5 10�3TLC (cells/cumm) 1672�1060 1597�995TSH (mU/L) 4.2�9 3.9�11


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MEASUREMENT OF BRAIN NATRIURETIC PEPTIDE LEVELSIN PATIENTS WITH RESPIRATORY FAILURE DUE TOCHRONIC OBSTRUCTIVE PULMONARY DISEASEChristopher R. Powers MD* Daniel R. Ouellette MD Brooke ArmyMedical Center, Fort Sam Houston, TX

PURPOSE: The measurement of serum BNP levels is advocated in theacute evaluation of patients with dyspnea as an aid leading to the diagnosisof congestive heart failure. The presence of elevated serum BNP levels inother groups of patients with acute respiratory disease would limit theusefulness of serum BNP measurement. Additionally, elevated serumBNP levels in patients with respiratory failure due to COPD might suggesta role for right heart failure in these patients.

METHODS: Enrolled patients had a new or existing diagnosis ofCOPD and were admitted to the intensive care unit (MICU at theenrolling institutions ) with acute respiratory failure and no evidence ofacute left or right heart failure or myocardial ischemia. Enrolling institu-tions included Brooke Army Medical Center (BAMC) and Wilford HallMedical Center (WHMC). The control population consisted of clinicallystable patients with COPD enrolled in the outpatient setting. Measure-ments included brain natriuretic peptide (BNP), transthoracic echocar-diogram, and pulmonary function testing when medically stable. ICUpatients had competing diagnoses such as pneumonia, ischemia, conges-tive heart failure, or thromboembolic disease ruled out by appropriateclinical testing within the standard of care.

RESULTS: Seven inpatients were enrolled with an average BNP levelof 320.4 were enrolled during this initial phase of the study. These sevenpatients were compared to seven stable COPD outpatients with moderateto severe COPD whose average BNP level was 21.4. Statistical analysiswas performed using the Student t-Test for independent samples and aone tailed test of hypothesis was significant at the 0.05 level with a P valueof 0.033.

CONCLUSION: BNP levels are significantly elevated in patient’s withmoderate to severe COPD who are hospitalized in the intensive care unitwith respiratory failure during an acute COPD exacerbation.

CLINICAL IMPLICATIONS: Elevated serum BNP levels in patientswith respiratory failure due to COPD suggest a role for right heart failurein these patients. Further research is needed to determine possibletreatments for ongoing right ventricular strain due to severe COPD.

DISCLOSURE: Christopher Powers, None.

Respiratory Infections: Bronchitis andPneumonia12:30 PM - 2:00 PM

COMPARATIVE EVALUATION OF THE EFFICACY, SAFETYAND TOLERABILITY OF EXTENDED-RELEASE (ER) CEFU-ROXIME AXETIL TABLETS 500 MG (ONCE DAILY) AND CE-FIXIME TABLETS 200 MG (TWICE DAILY) IN PATIENTS WITHACUTE TONSILLOPHARYNGITIS: A PILOT STUDYAnish A. Desai MD* U Venkatesan MD G S. Kadam MD Ashish S.Gawde MD Vidyagauri P. Baliga PhD Glenmark Pharmaceuticals Ltd,Mumbai, India

PURPOSE: A new Extended –Release(ER) formulation of Cefuroximeaxetil 500 mg tablets has been recently developed. This pilot study wasundertaken to compare the efficacy, safety and tolerability of this newformulation and Cefixime tablets in patients with acute tonsillopharyngitis.

METHODS: Adult patients(n�100) with a clinical diagnosis of acutepharyngotonsillitis, fulfilling the selection criteria were enrolled in thisprospective, multicentric, randomized, assessor-blind, comparative pilotstudy after obtaining their informed consent. Patients were randomized toreceive either 500 mg ER- Cefuroxime axetil tablets once–daily orcefixime 200 mg tablets twice daily for 10 days. Efficacy outcomesincluded monitoring of clinical and bacteriological response at end oftherapy. Safety and tolerability were assessed by monitoring adverseevents and laboratory parameters.

RESULTS: A total of 96 patients completed the study with 4 drop-outs(2 from each group) being lost to follow-up. There was a significantdecline in mean scores of sore throat, dysphagia, tonsillar erythema,pharyngeal or tonsillar exudate and tender anterior cervical nodes frombaseline at end of treatment in both groups. However, difference betweengroups was not statistically significant. Cure was observed in 91.7%patients in ER-Cefuroxime axetil group and 93.7% patients in cefiximegroup at end of study (p�0.05). Bacteriological response was observed insimilar number of patients in both groups(ER-Cefuroxime axetil(95.8%);Cefixime (97.9%)) at end of therapy. Similar incidences of mild tomoderate adverse events mostly gastrointestinal in nature were reportedin both groups(ER-Cefuroxime axetil 6% & cefixime - 8%). No abnor-malities were detected in the laboratory parameters.

CONCLUSION: ER-Cefuroxime axetil tablets once daily were com-parable in efficacy, safety and tolerability to Cefixime tablets twice daily inpatients with acute tonsillopharyngitis.

CLINICAL IMPLICATIONS: Once-daily ER-Cefuroxime axetil is abetter therapeutic option than twice daily cefixime tablets in patients withacute tonsillopharyngitis on account of its dosage convenience.

DISCLOSURE: Anish Desai, None.

ASSESSMENT OF THE EFFICACY AND SAFETY OF SINGLE-DOSE EXTENDED-RELEASE (ER) CEFUROXIME AXETIL INADULT INDIAN PATIENTS WITH ACUTE EXACERBATIONSOF CHRONIC BRONCHITIS (AECB)Anish A. Desai MD* A B. Mishra MD G Bhatia MD R S. MurlidaharnMD G S. Kadam MD Ashish S. Gawde MD Vidyagauri P. Baliga PhDGlenmark Pharmaceuticals Ltd, Mumbai, India

PURPOSE: Cefuroxime axetil possesses activity against Streptococcuspneumoniae Moraxella catarrhalis and Hemophilus influenzae and hasbeta-lactamase stability. It is therefore useful in the treatment of acuteexacerbations of chronic bronchitis. An extended-release (ER)preparationof cefuroxime axetil has been recently formulated. The present studyevaluated the efficacy, tolerability and safety of this new ER- formulationof Cefuroxime in adult Indian patients with AECB.

METHODS: Adults patients(n�125) with clinically and radiologicallyconfirmed AECB were enrolled in this prospective, multicentric , openlabel, non-comparative Phase III study after obtaining informed consent.The study was approved by the respective Institutional Review Boards.Patients fulfilling the selection criteria received 1g. ER-Cefuroxime axetilonce-daily for 10 days. Efficacy outcomes included clinical and bacterio-logical response at the end of therapy. Safety was assessed by monitoring.

RESULTS: Following therapy with ER –Cefuroxime, there was asignificant reduction in body temperature, chills, dyspnea, chest pain byDay 3 which further improved on Day 10. There was a significantimprovement in the quantity, consistency, nature and odour of sputum,intensity of cough and ausculatory findings by Day 3 which was sustainedtill the end of study. The effects of therapy on primary outcome measuresare depicted in Table 1. Adverse events were reported by only 12% of thestudy population.

CONCLUSION: ER-Cefuroxime axetil 1g. once daily was effectiveand safe in the treatment of AECB.

CLINICAL IMPLICATIONS: ER-Cefuroxime axetil 1g. once daily isa useful therapeutic option in the treatment of Acute exacerbations ofChronic bronchitis.

DISCLOSURE: Anish Desai, None.

Table 1—Effect of Therapy With ER-Cefuroxime Axetilin Patients With AECB

Clinicalresponse

% ofpatients

Bacteriologicalresponse

% ofpatients

Cure 71.8% Clearance 64.5%Improvement 25.8% Partial clearance 28.3%Failure 2.4% Failure 3.2%Not-evaluable - Colonization/Not evaluable 4%


Respiratory Failure Outcomes, continued


THE EFFECT OF DISEASE SEVERITY ON CLINICAL OUT-COME WITH ACUTE EXACERBATION OF CHRONIC BRON-CHITIS PATIENTS TREATED WITH GEMIFLOXACINI. Morrissey MD* T.M. File Jr. MD L.A. Mandell MD G.S. Tillotson MSG.R. Micro Ltd., London, United Kingdom

PURPOSE: Gemifloxacin is approved to treat acute bacterial exacer-bations of chronic bronchitis (AECB). Patients with AECB associated withCOPD and a history of recurrent acute episodes can be difficult to treat.Data from 10 AECB clinical trials were analysed for number of exacer-bations in last year (NELY), disease duration, history of asthma or chronicbronchitis.

METHODS: Clinical response (success/failure) at end of therapy(EOT), follow-up Clinical response at end of therapy (EOT), follow-upand long follow-up (LFU, �2/52) was evaluated. Comparators wereclarithromycin, levofloxacin , trovafloxacin , amoxycillin-clavulanate ,ceftriaxone/cefuroxime and ofloxacin.

RESULTS: See Table.CONCLUSION: These data support the utility of gemifloxacin in

AECB. Improved success at FU and LFU suggests that use of gemifloxa-cin may reduce time before next exacerbation with COPD patients.

CLINICAL IMPLICATIONS: Combined COPD/Respiratory medi-cal histories show higher clinical success with gemifloxacin at FU andLFU.

DISCLOSURE: I Morrissey, Grant monies (from industry relatedsources) Oscient; Shareholder Oscient; Employee Oscient; Consultantfee, speaker bureau, advisory committee, etc. Oscient.

THE EFFECT OF COMPUTERIZED ORDER SETS ON QUAL-ITY INDICATORS FOR HOSPITALIZED PATIENTS WITHCOMMUNITY ACQUIRED PNEUMONIAKathryn Wood MPH Allyson Mirabella MD* Jonathan Gottlieb MDThomas Jefferson University, Philadelphia, PA

PURPOSE: Evaluate the impact of a computerized order set on theadherence to core measures in patients with Community AcquiredPneumonia (CAP).

METHODS: Study was conducted as a retrospective chart review at atertiary care academic medical center with mandatory computerizedphysician order entry (CPOE). Study population was defined as all adultpatients admitted between December 2003 and October 2004 whosephysicians used a standardized CAP order set. Controls were matched onage and gender over the same time period from patients without use of aCAP order set but within DRG 89 or 90. The groups were compared onfive core measures: oxygenation assessment, pneumoccocal vaccination,smoking cessation counseling, and time to blood culture and antibiotics.Length of stay, appropriateness of antibiotic, and admitting services werealso compared.

RESULTS: The records of 20 order set and 20 controls were ab-stracted. Combining all CAP indicators, use of the order set was associatedwith a significantly greater proportion of quality indicators than controls(60% vs. 40%, p�0.0017). Use of order sets was associated with greaterproportion of every quality indicator, although differences were not

significant for individual indicators. Proportion of patients receivingappropriate antibiotics (85% vs.75%) and length of stay were not signifi-cantly different between the two groups.

CONCLUSION: Patients whose physicians used the CAP order setwere more likely to receive appropriate care.

CLINICAL IMPLICATIONS: Use of order sets combined withCPOE may help improve standardization of care and compliance withguidelines established by regulatory agencies. Due to the small size of thestudy population, the insignificant differences in individual core measuresmay not accurately predict larger populations. These findings shouldencourage the support of order set utilization within existing CPOEsystems.

DISCLOSURE: Allyson Mirabella, None.

COMPARATIVE EFFICACY OF ORAL AND SEQUENTIAL IN-TRAVENOUS/ORAL MOXIFLOXACIN IN THE TREATMENT OFCOMMUNITY ACQUIRED PNEUMONIA (CAP) IN THE VERYELDERLY (AGE >�75 YEARS)Antonio Anzueto MD* Daniel Haverstock MS Frank Kruesmann PhDShurjeel Choudhri MD Univ. of Texas Health Sci. Ctr., San Antonio, TX

PURPOSE: To evaluate the efficacy and safety of sequential IV/PO andPO moxifloxacin (MXF) versus that of comparator (COMP) antibiotics invery elderly (�75 years old) patients with CAP.

METHODS: Data were pooled from all global, randomized, controlledtrials of IV/PO (5 trials) and PO (5 trials) of MXF in the treatment of CAP.The pooled data were used to determine the clinical success rates andadverse event rates in the very elderly for both MXF and COMP-treatedpatients. The comparators were clarithromycin and amoxicillin in the POstudies and trovafloxacin, levofloxacin, ceftriaxone � azithromycin andamoxicillin/clavulanate � clarithromycin in the sequential IV/PO studies.

RESULTS: Of the 908 very elderly patients identified in the pooledanalysis, 215 (114 MXF, 101 COMP) received PO and 693 (349 MXF, 344COMP) received sequential IV/PO therapy. Of these, 158 PO-treated (84MXF, 74 COMP) and 497 IV/PO-treated (248 MXF, 249 COMP) patientswere valid for the primary efficacy analysis. Clinical success rates in IV/POstudies were 90% (222/248) for MXF vs. 83% (206/249) for COMP (95%CI 0.3%, 12%). For PO studies clinical success rates were 95% (80/84) forMXF vs. 86% (64/74) for COMP (95% CI 0.7%, 18.6%). Adverse andserious adverse event rates were similar in MXF- and COMP-treatedpatients.

CONCLUSION: Both IV and PO moxifloxacin were highly efficaciousand safe in treating community acquired pneumonia in the very elderlyand overall cure rates were significantly better in moxifloxacin treated-patients than those achieved with the comparator regimens.

CLINICAL IMPLICATIONS: Moxifloxacin appears to have excellentefficacy when used as empiric monotherapy for the treatment of CAP invery elderly patients.

DISCLOSURE: Antonio Anzueto, Employee Dan Haverstock, FrankKruesmann, Shurjeel Choudhri; Consultant fee, speaker bureau, advisorycommittee, etc.

RESISTANCE PHENOTYPES OF STREPTOCOCCUS PNEU-MONIAE AND CLINICAL OUTCOME OF RESPIRATORYTRACT INFECTIONS TREATED WITH GEMIFLOXACINIan Morrissey PhD Thomas File MD* Lionel Mandell MD Glenn S.Tillotson MS SUMMA Healthcare, Akron, OH

PURPOSE: Gemifloxacin (GEM) is a potent fluoroquinolone withexcellent activity against respiratory tract infection (RTI) pathogens,including S. pneumoniae (SP). Pooled data from 17 phase III clinical trialsfor GEM with community-acquired pneumonia, acute bacterial sinusitis& acute exacerbation of chronic bronchitis patients (pts.

METHODS: 530 Pts where SP was the sole pathogen & SP suscepti-bility known, were evaluated.Clinical success at end of therapy (EOT) &at follow-up (FU, approx. 1-3 weeks after treatment) was studied. Maincomparators (CMP) were cefuroxime (61 pts), amoxicillin-clavulanate (37pts), trovafloxacin (34 pts), cefuroxime & clarithromycin (28 pts), levo-floxacin or clarithromycin (11 pts). Percentage success based on suscep-tibility to penicillin G (Pen) and/or macrolides (Mac) is shown (Table, S �susceptible, NS � non-susceptible, R � resistant, N � pts/group).

RESULTS: See Table.


Respiratory Infections: Bronchitis andPneumonia, continued


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CONCLUSION: GEM showed good clinical success against all resis-tance phenotypes. These data support the use of GEM in the treatment ofRTI, especially where MacR SP prevails.

CLINICAL IMPLICATIONS: The emergence of antibacterial resis-tance may effect empirical therapy, gemifloxacin has been shown to beeffective against resistant phenotypes of th emost common bacterialrespiratory pathogen.

DISCLOSURE: Thomas File, Consultant fee, speaker bureau, advi-sory committee, etc. TF & LM are consultants to Oscient.

DOES TELITHROMYCIN EXHIBIT IMMUNOMODULATORYPROPERTIES IN CHRONIC AIRWAY INFLAMMATION?Maysah S. El-Deen MD Abdalla A. Abu Hussein MS* Gamal A. El-KholyMD Amany Abouzeid MD Tanta Int’l Cardiothoracic Vascular Center,Tanta, Egypt

PURPOSE: The role of telithromycin in the treatment of respiratorytract infections is well established. However, telithromycin seems to haveimmunomodulatory properties in chronic airway inflammation, includingthe inflammatory allergic condition bronchial asthma. The aim of this trialwas to establish whether our clinical observation of an extended 1-2months treatment with telithromycin in patients with chronic inflamma-tory airway disorder is beneficial.

METHODS: Open comparative clinical trial with male and femalepatients aged 18-65 years with persistent cough, chronic obstructivebronchitis (with and without acute exacerbations), COPD or bronchialasthma. We compared post-treatment symptomatic relief and peak flowmeter results with baseline recordings, while monitoring for adverseevents, including abnormal laboratory values.

RESULTS: 84 patients (46 males, 38 females, age 37.3 � 8.4 years)were enrolled. After 60 days of treatment (47.3 � 3.2 days), symptomaticrelief and improved spirometry were significantly better (p�0.05) thanbaseline recordings. The main adverse events were diarrhea and dizziness.

CONCLUSION: Telithromycin may have a role in the treatment ofchronic airway inflammatory conditions including bronchial asthma. Thismay be explained by its high tissue penetration characteristic, and theincreasing evidence that atypical respiratory pathogens (Mycoplasmapneumonia, Moraxella catarrhalis, and Legionella pneumophila), againstwhich telithromycin is reportedly active, play a major role in the patho-genesis and prognosis of chronic inflammatory airway disorders.

CLINICAL IMPLICATIONS: Extended treatment with telithromy-cin may provide further benefits to patients with chronic airway inflam-mation, especially where atypical respiratory pathogens are suspected.

DISCLOSURE: Abdalla Abu Hussein, None.

PATIENT RISK FACTORS IN COMMUNITY-ACQUIRED PNEU-MONIA INFECTIONS OUTCOME FOLLOWING TREATMENTWITH GEMIFLOXACINI Morrissey MD T.M. File Jr. MD L.A. Mandell MD* G.S. Tillotson MSMcMaster University, Hamilton, ON, Canada

PURPOSE: Respiratory fluoroquinolones are important agents in themanagement of patients with community-acquired pneumonia (CAP).

Gemifloxacin is a new potent fluoroquinolone with excellent activityagainst CAP pathogens.

METHODS: Pooled data from 5 phase III CAP gemifloxacin clinical trialswere evaluated. Patients were grouped based on risk factors indicated in theIDSA guidelines [Mandell et al.2003 CID 37:1405]. Clinical response(success or failure) at end of therapy (EOT) & at follow-up (FU, approx. 1-3weeks after treatment) was studied. Main comparators for CAP patients werecefuroxime & clarithromycin (322 patients), trovafloxacin (282 patients) &amoxicillin-clavulanate (156 patients).

RESULTS: Percent success is shown in table (AB, antibiotics, COPD,chronic bronchitis and obstructive lung disease, HD, heart disease,*includes patients that did not score a response at FU and were countedas clinical failure).

CONCLUSION: These data support the use of gemifloxacin in the treatmentof CAP, especially where the patient has recognised IDSA risk factors.

CLINICAL IMPLICATIONS: Although gemifloxacin showed lower% success than comparator against CAP patients with no defined riskfactor, gemifloxacin was considerably more successful than comparatoragainst patients associated with risk factors. This advantage was even moreprominent at FU than at EOT. Patients with other comorbidities such asrenal failure or malignancy were not recruited in sufficient number foranalysis.

DISCLOSURE: LA Mandell, Grant monies (from industry relatedsources) Oscient; Shareholder Oscient; Employee Oscient.

CARDIO-PULMONARY MEDICAL HISTORY AND THE EF-FECT ON CLINICAL OUTCOME OF COMMUNITY-ACQUIREDPNEUMONIA INFECTIONS TREATED WITH GEMIFLOXACINI. Morrisey MD T.M. File Jr. MD L.A. Mandell MD G.S. Tillotson MS*Oscient, Waltham, MA

PURPOSE: Gemifloxacin is a potent new fluoroquinolone with excel-lent activity against community-acquired pneumonia (CAP) pathogens.

METHODS: Pooled data from 5 phase III CAP gemifloxacin clinicaltrials were evaluated. Patients were grouped based on cardio-pulmonarydisease and medical history (CPD). Clinical response (success or failure)at end of therapy (EOT) & at follow-up (FU, approx. 1-3 weeks aftertreatment) was studied. Main comparators for CPD patients were cefu-roxime & clarithromycin (97 patients), trovafloxacin (66 patients) &amoxicillin-clavulanate (55 patients).

RESULTS: Percent success is shown in the table (* includes all 3 CPDgroups in table plus patients with a medical history of angina, pulmonaryheart disease, cardiomyopathy, cardiac murmurs, tachycardia or myocar-dial infarction).

CONCLUSION: Although in general ,gemifloxacin showed slightlylower success than pooled comparators against CAP patients , gemifloxa-cin showed higher success rates than comparator against CPD patient-s.This difference was greater at FU than at EOT.

CLINICAL IMPLICATIONS: These data support the use of gemi-floxacin in the treatment of CAP, especially where the patient has a historyof CPD.

Phenotype Treatment

% Success (N)

EOT FU

All SP GEM 92.5% (321) 88.8% (321)CMP 90.4% (209) 86.0% (207)

PenS GEM 93.3% (252) 88.9% (252)CMP 91.0% (166) 86.0% (164)

PenNS GEM 89.7% (68) 88.2% (68)CMP 88.4% (43) 86.0% (43)

MacS GEM 93.0% (256) 88.3% (256)CMP 92.0% (175) 86.2% (174)

MacR GEM 90.3% (62) 90.3% (62)CMP 81.3% (32) 83.9% (31)

PenR & MacR GEM 85.7% (28) 85.7% (28)CMP 82.4% (17) 82.4% (17)

RiskFactor Treatment

% Success (number of patients)

EOT FU

CAP All Gemifloxacin 86.9% (1166) 80.9% (1164)Comparator 87.2% (933) 81.6% (928)

Prior AB Gemifloxacin 86.9% (291) 82.1% (291)Comparator 86.6% (262) 79.0% (262)

Diabetes Gemifloxacin 87.6% (129) 82.2% (129)Comparator 86.6% (82) 77.8% (81)

COPD Gemifloxacin 85.6% (181) 77.3% (181)Comparator 83.7% (190) 73.7% (190)*

HD Gemifloxacin 88.8% (356) 82.9% (356)Comparator 86.0% (299) 79.9% (298)




DISCLOSURE: GS Tillotson, Grant monies (from industry relatedsources) Oscient; Shareholder Oscient; Employee Oscient; Consultantfee, speaker bureau, advisory committee, etc. Oscient.

FLUOROQUINOLONE AS 2ND CHOICE THERAPY IN NOSO-COMIAL PULMONARY COMPLICATIONS AFTER RESECTIONFOR LUNG CANCERCosimo Lequaglie MD* Gabriella Giudice MD Centro di RiferimentoOncologico Basilicata, Rionero in Vulture, Italy

PURPOSE: To value the effect of quinolone therapy in lung cancerresected patients with nosocomial pulmonary infection.

METHODS: A multicentric study is reported on 38 complicatedpatients and submitted to pulmonary resection for cancer after prophy-laxis with cephalosporin. The patients developed a microbiological testedpulmonary infection after resection procedure. A history of chronicbronchopulmonary disease was present in 26 cases, bronchial asthma in 4.The isolated pathogens on bronchoalveolar lavage were Haemophilusinfluenzae (n° 15), Streptococcus pneumoniae (n° 11), Moraxella ca-tarrhalis (n° 3), Mycoplasma pneumoniae (n° 7), Chlamydia pneumoniae(n° 1) and Legionella pneumophila (n° 1). A quinolone, the Levofloxacin,was employed to the dosing of 500 mg IV twice day for 10 days.Thepatients have been observed for 10 days by the basal find of nosocomialinfection after pulmonary resection. The basal sputum results positive in8 cases as also to the first control at 4th day of therapy, without presenceof pathogens at the 2nd test. The basal bronchoalveolar lavage resultspositive in the remainders 30 cases as also in 4th day, and it has beenpositive at the 2nd test in alone 2 cases, but with reduction of the bacterialcount. All the isolated pathogens were sensitive in vitro to Levofloxacin.

RESULTS: There was a clinical improvement with resolution of thesymptoms in 36/38. Eradication was in 34 cases about the pathogen incause and a presumed eradication in 2 ones: in the remainders 2, thepartial eradication in 1, while in the last one there was a colonization. Fivepatients had diarrhea for about 5 days, 3 headache for 2 days of which 1with nausea and 1 asthenia for 6 days.

CONCLUSION: On the escort of the microbiological finds theeffected therapy has allowed to not only reach the microbiologicaleradication but also a clean improvement of the symptoms with reductionof the postoperative hospitalization.

CLINICAL IMPLICATIONS: The clean improvement of the symp-toms with reduction of the postoperative hospitalization increased reducesthe costs of admission.

DISCLOSURE: Cosimo Lequaglie, None.

PENETRATION OF AMPHOTERICIN B IN HUMAN LUNG TIS-SUE AFTER SINGLE LIPOSOMAL AMPHOTERICIN B INFU-SIONCosimo Lequaglie MD* Franco Fraschini PhD Germana Demartini PhDFranco Scaglione PhD Centro di Riferimento Oncologico Basilicata,Rionero in Vulture, Italy

PURPOSE: To investigate the tissue levels and distribution of ampho-tericin B in lung after i.v. administration of liposomal amphotericin B(L-AmB) in patients with lung cancer resected.

METHODS: We enrolled 18 adult (�18 ys) patients with primary orsecondary lung cancers. All patients were informed about the prospectivestudy. There were 12 males and 6 females, both sexes ranging in weightfrom 53 to 86 kg, and in age from 28 to 65 years. L-AmB was administeredby 1 hour single infusion at fixed doses of 1,5 mg/kg, and it wasadministered from 10 to 25 hours before the surgery. The starting and theend points of infusion were noted, the same for arterial and vein ligatures,and the end point of pulmonary tissue sample collection. Moreover, 10 mlof blood sample at the artery closure were collected. L-AmB was assayedin blood and lung tissue by an HPLC validated method of Bekersky et all

(Shimadzu LC-9A pump, SPD-6A detector, CR-4A data processor,Simmetry Shield RP8 water column).

RESULTS: The blood levels after 10 to 16 hours from the end of infusion (n°6) ranged from 3.4 to 2.1 mg/l-gr, while the tissue levels ranged from 0.9 to 1.59mg/l-gr; 18 to 22 hours after blood infusion (n° 6) levels ranged from 1.8 to 0.9mg/l-gr; 23 to 25 hours after infusion (n° 6) blood and the tissue levels rangedfrom 1.8 to 0.98 mg/l-gr and 1.48 to 2.38 mg/l-gr.

CONCLUSION: These data support the consistent lung tissue diffu-sion of L-AmB in patients with lung cancers. The L-AmB plasmaconcentration was gradually decreasing in all the cases.

CLINICAL IMPLICATIONS: The relationship between these datacan effort the best choice of drug in possible fungal infections as for aprophylactic employment for lower dosage and for lower collateral sideeffects.

DISCLOSURE: Cosimo Lequaglie, None.

RESPONSE TO ITRACONAZOLE IN PATIENTS WITH MEDIAS-TINAL GRANULOMATalaat A. Al Shuqairat MD* University of Missouri-Columbia, Columbia, MO

PURPOSE: Mediastinal Granuloma is an uncommon cause of amediastinal mass. It is thought to be due to Histoplasma infection.Surgical resection is advocated to prevent the possible progression ofmediastinal granuloma to fibrosing mediastinitis. Antifungals are alsothought to be helpful. We evaluated the role of itraconazole in treatmentof patients with mediastinal granuloma.

METHODS: We evaluated five patients with mediastinal granulomawho were seen in the pulmonary clinic at the University of Missouri-Columbia Hospital over the last three years. The patients were 30.6 � 9.9years of age, and 3 of them were females. The diagnosis of mediastinalgranuloma was confirmed by biopsy in all patients. Three patients weretreated with Itraconazole (200 mg once a day). One patient had surgicalresection only, and another patient had resection followed by treatmentwith Itraconazole. Patients were followed up for at least four months.Fungal stains and cultures were negative for all patients. Two patients hadpositive Histoplasma antibodies.

RESULTS: Four months after starting therapy, patients receivingitraconazole alone were asymptomatic and they had almost total resolutionof the mediastinal mass. The patient who had surgical resection did nothave any recurrence on follow up. The patient who had resection followedby Itraconazole treatment had partial improvement. None of the patientstreated with Itraconazole had liver function derangements. The mostcommon side effect was diarrhea.

CONCLUSION: Despite lack of evidence for active Histoplasmainfection, patients with mediastinal granuloma responded well to treat-ment with Itraconazole. The medication was effective, safe and well-tolerated. Itraconazole should be considered as the first line of treatmentfor mediastinal granuloma.

CLINICAL IMPLICATIONS: Patients hwo have Mediastinal Gransuloma,whether diagnosed by biopsy or clinically, may have no evidence of a previousHistoplasma infection. Such patients would still respond to Itraconazole treat-ment, without the need for surgical resection of the mass.

DISCLOSURE: Talaat Al Shuqairat, None.

Respiratory Infections: Challenges12:30 PM - 2:00 PM

MICROORGANISMS RESPONSIBLE FOR FAILURE OF MACRO-LIDE TREATMENT OF ACUTE EXACERBATION OF CHRONICBRONCHITIS: RESULTS OF BRONCHOSCOPIC CULTURESRobert P. Baughman MD* University of Cincinnati, Cincinnati, OH

PURPOSE: Macrolide therapy is associated with clinical failure insome cases of acute exacerbation of chronic bronchitis (AECB). While themost likely reason for failure is resistant pathogens, there is little reliablemicrobiologic information in these patients. We have previously demon-strated that protected brush sample (PBS) provides the most reliableculture information in AECB (Baughman, R. P. et al. J Bronchology2000;7:221-5). We used this technique to evaluate patients who failedazythromycin treatment for AECB.

CPD group Treatment

% Success (Number of patients)

EOT FU

CAP All Gemifloxacin 86.9% (1166) 80.9% (1164)Comparator 87.2% (933) 81.6% (928)

ALL CPD* Gemifloxacin 88.8% (356) 82.9% (356)




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METHODS: Patients with a history of COPD and a clinical courseconsistent with AECB who had been treated with azythromycin and hadpersistent symptoms were evaluated. All patients underwent bronchos-copy with a PBS taken from the lower respiratory tract. The specimen wassent for semi-quantitative cultures. Patients were then treated with fivedays of moxifloxacin and repeat bronchoscopy was performed. No patienthad been hospitalized in the prior six months.

RESULTS: Thirteen patients have been studied. Eleven patients hadone or more bacteria identified in the initial PBS specimen. Sevenpatients had at least one bacteria growing at �1000 colony forming units(cfu)/ml from the initial PBS specimen. S. aureus was isolated in five(38%) of the initial PBS cultures. The S. aureus was sensitive to oxacillinin 4/5 case, ciprofloxacin 4/5 cases, and trimethoprim/sulfamethoxazole in5/5 cases. Only one S. aureus was sensitive to erythromycin. After five daysof moxifloxacin, no respiratory pathogens were identified in the repeatPBS specimen.

CONCLUSION: Significant bacterial infection was identified in pa-tients with persistent symptoms despite azythromycin therapy for theirAECB. Among the pathogens was S. aureus. Treatment with a moxifloxa-cin was associated with clearance of the micro organism.

CLINICAL IMPLICATIONS: Patients with repeated AECB infec-tions and previously treated with macrolide therapy are at risk for multidrug resistant bacteria, including S. aureus.

DISCLOSURE: Robert Baughman, Grant monies (from industryrelated sources) Bayer/Schering Plough; Consultant fee, speaker bureau,advisory committee, etc. Bayer/Schering Plough.

NOSOCOMIAL PNEUMONIA AND ANTIBIOTIC RESISTANCEPrashant S. Borade MD* Daniel K. Lee MD Department of RespiratoryMedicine, Ipswich Hospital, Ipswich, Suffolk, England, United Kingdom

PURPOSE: The emergence of antibiotic resistant pathogens poses asignificant threat to patients with nosocomial pneumonia. It is thereforeimportant to evaluate the relationship between hospital-acquired patho-gens and antibiotic resistance.

METHODS: A prospective study was conducted in 100 consecutivepatients with hospital-acquired infections admitted to the intensive careunit of which 46% had clinical, laboratory, and radiological evidence ofnosocomial pneumonia.

RESULTS: Isolated pathogens consisted of Klebsiella spp. (29%),Pseudomonas spp. (16%), Acinetobacter spp. (13%), Staphylococcusaureus (11%), Escherichia coli (10%), Enterobacter spp. (9%), methicil-lin-resistant S. aureus (2%), and Candida spp. (9%). Details of antibioticresistance are shown in Table 1. Mortality was 33% in patients withnosocomial pneumonia.

CONCLUSION: Antibiotic resistance in hospital-acquired pathogensis significant.

CLINICAL IMPLICATIONS: Patients with nosocomial pneumoniaremain at risk from antibiotic resistant pathogens.

DISCLOSURE: Prashant Borade, None.

DETECTION OF HISTOPLASMA CAPSULATUM ANTIGEN INBRONCHIAL ALVEOLAR LAVAGE SPECIMENS BY IMPROVEDANTIGEN DETECTION ENZYME-LINKED IMMUNOASSAYLawrence J. Wheat MD Ann M. Le Monte BS Chadi Hage MD* KennethS. Knox MD Debra Blue-Hnidy MD Thomas E. Davis MD IndianaUniversity School of Medicine, Indianapolis, IN

PURPOSE: Detection of H. capsulatum antigen by Enzyme-linkedImmunoassay (EIA) is well documented, and an improved 2nd generationassay exhibits increased sensitivity and specificity for urine and serumspecimens as compared to the original EIA. The purpose of this study isto compare sensitivity for detection of antigen in bronchial alveolar lavage(BAL) specimens in the 2nd generation vs. original H. capsulatum antigenassay.

METHODS: BAL specimens previously submitted for H. capsulatumantigen detection were evaluated concurrently in the new 2nd generationvs. original immunoassays.

RESULTS: Of the 39 BALs tested, 14 were positive in the 2ndgeneration assay vs. 10 in the original assay. For the positive specimens,the median antigen level was 4.15 EIA units in the 2nd generation vs. 1.36EIA units in the original assay.

CONCLUSION: Testing of BAL samples for H. capsulatum antigenmay aid in rapid diagnosis. Sensitivity of antigen detection in BALs wasgreater in the 2nd generation assay.

CLINICAL IMPLICATIONS: Bronchoscopy with BAL for His-toplasma antigen determination offers an adjunctive method for rapiddiagnosis of pulmonary histoplasmosis. Improvements in the antigenimmunoassay increase its sensitivity for diagnosis.

DISCLOSURE: Chadi Hage, None.

ENDOBRONCHIAL ASPERGILLOMA: A RETROSPECTIVECASE REVIEWDoyun Kim MD* Yoonsu Chang MD Hyungjung Kim MD Chulmin AhnMD Department of Internal Medicine Yonsei University College ofMedicine, Seoul, South Korea

PURPOSE: As compared to aspergilloma which is usually developedafter complication of tuberculosis in Korea, endobronchial aspergilloma isa rare disease entity and clinical findings and natural course is not wellknown. We retrospectively analyze the clinical, radiological, and broncho-scopic finding and treatment options in patients confirmed as endobron-chial aspergilloma.

METHODS: From 1993 to 2005, eight patients were identified withendobronchial aspergilloma in Yongdong Severance hospital. We re-viewed medical records for analysis of clinical, radiological, and broncho-scopic finding, and treatment options and result. All cases are confirmedas endobronchial aspergillosis by bronchoscopic biopsy and pathologicalfinding. The patients ranged in age from 46 to 67 (mean 55.3). There are3 males and 5 females.

Table 1Antibiotic Resistance in Hospital-acquiredPathogens.

Klebsiellaspp.

Pseudomonasspp.

Acinetobacterspp. S. aureus

Amikacin 40% 39% 32%Cefazolin 55%Cefoperazone 71%Cefotaxime 60%Ceftazidime 46% 46% 36%Ceftriaxone 48% 79% 45%Ciprofloxacin 68% 79% 73% 70%Cloxacillin 60%Co-amoxiclav 76% 15%Piperacillin 25%


Respiratory Infections: Challenges,continued


RESULTS: All patients were symptomatic when hospitalization. Mostcommon symptome is hemoptysis (100%), cough (63%), sputum (25%),chest discomfort (25%), and general weakness (13%). Most commonunderlying diseases were pulmonary tuberculosis (75%), bronchiectasis(25%), and small cell lung cancer (13%). Bronchoscopic finding is typicaland more diagnostic than radiological findings. Seven out of eight caseshad endobronchial aspergilloma in upper lobe bronchus. The location ofendobronchial aspergilloma were right upper lobe bronchus (50%), leftupper lobe bronchus (25%), left upper lobe lingular bronchus (13%), andlower lobe bronchus (13%). Endobronchial aspergilloma was developedright upper lobectomy stump site in a lung transplanted patient. Recur-rent and moderate to large amount of hemoptysis was common, seriousand unique symptoms. Five patients were surgically managed and theprognosis was good. A patient who refused surgery showed intermittenthemoptysis. Endobrochial aspergilloma in transplanated case and a casewith acute pneumonia, DM and end stage renal disease was aggravated toinvasive aspergillosis and patients were expired.

CONCLUSION: Endobronchial aspergilloma is unique form of as-pergillosis followed by pulmonary tuberculosis and most common symp-tom is recurrent hemoptysis. Surgery is choice of treatment in immu-necompetent patient.

CLINICAL IMPLICATIONS: Aspergillus organism in patient whohad previous pulmonary tuberculosis occasionally forms endobronchialaspergilloma.

DISCLOSURE: Doyun Kim, None.

CYTOPATHIC CHANGES OF HERPES SIMPLEX VIRUS INMECHANICALLY VENTILATED PATIENTS: WHAT DOES ITMEAN?Howard S. Weiss DO* Peter Spiegler MD Maritza L. Groth MDWinthrop University Hospital, Mineola, NY

PURPOSE: Herpes Simplex Virus(HSV) causes tracheobronchitis andpneumonitis in critically ill patients. The characteristic endobronchialappearance is mucosal ulceration and membrane formation. We describea series of critically ill patients with a normal endobronchial exam andcytopathic changes of HSV.

METHODS: We reviewed all bronchoscopies performed in mechan-ically venilated patients in the medical ICU between October 2003 andMarch 2005 for evidence of mucosal lesions and cytopathic changes ofHSV. Data including age, cause of respiratory failure, duration ofmechanical ventilation and hospitalization prior to diagnosis, and level ofHSV-1 IgG and IgM antibody(Ab)titers were recorded.

RESULTS: Of 52 bronchoscopies performed, 7 subjects with cyto-pathic changes of HSV were identified (13.5%) and one with broncho-scopic features of HSV. This patient was immunosupressed and wasexcluded. The average age was 64.9 yrs (49-84 yrs). The duration ofventilation prior to diagnosis was 9.4d (0-14) and of hospitalization was15.1d (8-47). HSV-1 Ab titers were obtained in 4 of 7 subjects. The HSV-1IgG Ab was elevated in 4 of 4 subjects(100%)with an average level of31.0(normal�0.90). The HSV-1 IgM Ab titer was elevated in 2 of 4subjects with an average level of 1.3 of those with elevated levels(normal�0.91). Respiratory failure (RF) was due to pneumonia oratelectasis in all but one patient, who had microscopic polyangiitis. Fivepatients received therapy with acyclovir. No specific clinical features wereseen in the subjects with HSV cytopathic changes compared to the rest ofthe sample.

CONCLUSION: Cytopathic changes of HSV without obvious airwayor parenchymal involvement are common in critically ill ventilatedpatients. To our knowledge, this has not been previously described in RFdue to pneumonia or atelectasis. All cases occurred in fall and wintermonths (October to February).

CLINICAL IMPLICATIONS: The significance of HSV cytopathicchanges in critically ill ventilated adults and whether antiviral treatment isbeneficial remains unknown. This may represent true herpes infection orthat of another etiologic agent. Further studies are indicated to definewhether treatment is necessary.

DISCLOSURE: Howard Weiss, None.

DEVELOPMENT OF SURFACE OF PROTEIN CHIP FOR CHLA-MYDIA PNEUMONIAEWoo J. Kim MD* Jong Seol Yuk PhD Se-Hui Jung Ji Hyun Sung SungJoon Lee MD Seung-Joon Lee MD Kwon-Soo Ha PhD KangwonNational University, Chunchon, Kangwon-do, South Korea

PURPOSE: Chlamydia pneumoniae is an important pathogen whichis etiologic agent of acute and chronic infection. The diagnosis ofchlamydial infection is based on serology. Current gold standard ofdiagnosis is MIF(microimmunoflurescence), but it is subjective andtime-consuming. Recently, protein microarray using SPR(surface plas-mon resonance) sensor is suggested to be a method for detection ofinfection. For development of protein chip for diagnosis of chlamydialinfection, we investigated the morphology of surface with AFM(atomicforce microscopy) on gold chip and detected interaction betweenantibody for Chlamydia pneumoniae and EB(elementary body) immo-bilized on surface by wavelength shift using SPR sensor.

METHODS: For surface antigen, EBs of Chlamydia pneumoniaeLKK1 were purified after they were grown in Hep-2 cells. For chipsurface, gold arrays on glass slides were prepared and cleaned withNH4OH/H2O2/H2O at 80°C for 10 min. Charged arrays were pre-pared by PDDA(polydiallyldimethylammonium chloride) which has apositive charge and PSS(poly(sodium 4-styrenesulfonate) which hasnegative charge. After immobilization of chlamydial EB on PDDAsurface and PSS surface, we investigated the surface using atomic forcemicroscopy. After immobilization of EB of Chlamydia pneumoniae onsurface, antibody for Chlamydia was applied on chip. We monitoredthe SPR wavelength-shift to detect antigen-antibody interaction usingself-assembled SPR sensor.

RESULTS: The chlamydial EBs on positively charged PDDA werevisible on surface by atomic force microscopy but EBs on PSS surfacewere not detected. SPR wavelength increased after interaction of antibodyfor Chlamydia pneumoniae with EBs immobilized on charged goldsurface. The wavelength-shift was correlated with concentration of anti-gens.

CONCLUSION: We identified surface immobilization of EBs on goldsurface with charged arrays and antigen-antibody interaction on gold chip.More researches are needed to apply to clinical implication.

CLINICAL IMPLICATIONS: It may possible that protein chipwould be used to diagnosis the atypical pneumonia using SPR sensor.

DISCLOSURE: Woo Kim, None.

BACTERIAL DIFFERENTIATION BY ION MOBILITY SPEC-TROMETRY: FIRST RESULTS OF A PILOT STUDYPattrick Litterst Michael Westhoff MD* Lutz Freitag MD Vera RuzsanyiPhD Jorg I. Baumbach PhD Lungenklinik Hemer, Hemer, Germany

PURPOSE: Early diagnosis and specification of bacterial airway infec-tion is of importance, especially in patients who are at high risk forrespiratory failure, invasive or non-invasive ventilation and a prolongedhospital stay.

METHODS: Ion mobility spectrometer (IMS) coupled to a multi-capillary-column (MCC) identifies and quantifies volatile metabolitesdown to the ng/L- and pg/L-range of analytes within less than 500 s andwithout any pre-concentration. The IMS investigations are based ondifferent drift times of swarms of ions of metabolites formed directly in airat ambient pressure. Head space over selected microbiological cultureswas directly sampled for IMS-chromatograms.

RESULTS: In this in-vitro study IMS-chromatograms of differentbacteria (Staphylococcus aureus, Staphylococcus epidermidis, Streptococ-cus pneumoniae, Streptococcus agalactiae, Haemophilus influenzae,Klebsiella pneumoniae, Escherichia coli, Serratia marcescens, Pseudomo-nas aeruginosa, Enterobacter cloacae) and Candida albicans were ob-tained. The selected bacteria and Candida albicans could be defined anddistincted by different metabolites.

CONCLUSION: Ion mobility spectometry seems to provide a tool forprecise bacterial analysis. The results of this pilot study have to be provedby an in-vivo study, especially in patients with airway infections asCOPD-exacerbation and pneumonia.

CLINICAL IMPLICATIONS: A future aspect might be the imple-mentation of an “IMS –beside-test” for the rapid diagnosis of airwayinfection including bacterial differentiation.

DISCLOSURE: Michael Westhoff, None.




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CURRENT KNOWLEDGE AND PRACTICE TO DIAGNOSE PA-TIENTS WITH SEVERE COMMUNITY-ACQUIRED PNEUMO-NIA ADMITTED TO THE ICUMarcos I. Restrepo MD* Antonio Anzueto MD Eric M. Mortensen MDJacqueline A. Pugh MD Mark L. Metersky MD Patricio Escalante MDRichard G. Wunderink MD Bonita T. Mangura MD on behalf ChestInfections Network VERDICT/STVHCS/UTHSCSA, San Antonio, TX

PURPOSE: Community acquired pneumonia (CAP) is a commonproblem in clinical practice. Different recommendations regarding typeand degree of diagnostic testing in patients admitted to the intensive careunit (ICU) are found in CAP guidelines from various professionalsocieties. Our aim was to document the diagnostic procedures thatclinicians use to assess patients with CAP admitted to the ICU.

METHODS: Self-administered survey to assess physician preferencesabout CAP diagnostic approach in patients admitted to the ICU. Surveywas generated based on literature review and committee consensusregarding diagnostic tests for CAP patients admitted to the ICU. Sub-group analysis was performed comparing academic practitioners vs.non-academic practitioners, and whether they work in an open ICU vs.closed ICU. The survey was e-mailed to ACCP members (in Chestinfections and Critical Care network) in 2004.

RESULTS: A total of 393 questionnaires (19% of submitted) werereturned. The most common diagnostic methods used by clinicians wereblood cultures (97%), sputum gram stain (83%), sputum culture (85%),Legionella urinary antigen (77%) and endotracheal aspirate (76%). Aca-demic practitioners (n�182) ordered more endotracheal aspirates (79%vs. 68%; p�0.03), Legionella cultures (37% vs. 27%; p�0.05), but lessserologic tests for atypical pathogens (34% vs. 46%; p�0.03) thannon-academic practitioners (n�203). Practitioners working in a closedICU (n�159) ordered more blood cultures (99% vs. 93%; p�0.01), andLegionella sputum cultures (39% vs. 26%; p�0.01) than those working inan open ICU (n�224). No other statistical significant differences wereobserved between groups for other diagnostic methods.

CONCLUSION: Important differences were found in academic versusnon-academic practitioners, and open ICU versus closed ICU situations regard-ing the diagnostic methods use in clinical practice for patients in the ICU withCAP. Current clinical practice guidelines for CAP diagnosis are applied differ-ently according to type of practitioners and the setting where they work.

CLINICAL IMPLICATIONS: Differences in clinician practice pref-erences in regard to diagnosis of CAP patients in the ICU should be takeninto account for future, clinical, educational and research studies.

DISCLOSURE: Marcos Restrepo, None.

PULMONARY MANIFESTATIONS IN MALARIAUmashankar Mishra MD* Gandharva Ray MD M.K.C.G. Medical Col-lege, Berhampur, India

PURPOSE: Malaria is still the major killer in developing countries like India.In recent years respiratory system is being recognized as one of the majormanifestations of falciparum malaria. It is very important to recognize that thepulmonary involvement is due to malaria to institute treatment to reducemorbidity and mortality. Our study was to detect the incidence of pulmonaryinvolvement in malaria and its impact on outcome.

METHODS: Our study included 150 cases of slide positive malaria.Out of these 72(48%) Plasmodium vivax, 54(36%) Plasmodium falciparumand 24(16%) were mixed infections. The patients were thoroughlyinvestigated for involvement of respiratory system. Besides routine hema-tological and biochemical investigations E.C.G. and chest x-ray were donein all patients. Patients having ARDS and acute pulmonary edema weresubjected to echocardiography, haemodynamic monitoring by Swam-Ganz catheter and oxymetry. These patients were treated in ICU withmechanical ventilatory support with high concentration of inspired oxygenand use of Positive End Expiratory Pressure.

RESULTS: Out of 150 cases of malaria 45 patients presented withrespiratory symptoms in the form of cough (80%), dyspnoea (40%),expectoration (32%), chest pain (18%) and haemoptysis (4%). The clinicalpresentations were in the form of bronchitis (23 cases), pneumonia(8cases), acute pulmonary edema (2 cases), ARDS (7 cases), pulmonarytuberculosis (3 cases) and respiratory muscle fatigue (2 cases). Out of the45 cases with respiratory symptoms 42 (93.4%) had falciparum malaria.Four out of 7 patients of ARDS and both the 2 patients with acutepulmonary edema died.

CONCLUSION: Malarial atypical respiratory presentations are higherthan reported in the literature. P. falciparum malaria is responsible for

most of the respiratory manifestations. Acute pulmonary edema andARDS have high-grade mortality in spite of intensive care.

CLINICAL IMPLICATIONS: Patients of high fever with respiratorysymptoms should have always blood slide examination for malarialparasites in endemic areas and prompt antimalarial therapy should bestarted to save life.

DISCLOSURE: Umashankar Mishra, None.

Sepsis and Shock: Treatment12:30 PM - 2:00 PM

EFFECTS OF AUTOTRANSFUSION ON MICROVASCULARPERFUSION USING PASSIVE LEG-RAISING IN PATIENTSWITH SEPTIC SHOCKPeter E. Spronk PhD* Daniel F. Faber MD Johannes H. Rommes PhDGelre Hospitals (Lukas site), Apeldoorn, Netherlands

PURPOSE: Passive leg raising (PLR) can be used effectively to treathypotension associated with hypovolemia. Shock is associated with im-pairment of microvascular flow. We investigated the microvascular re-sponse to PLR in patients with shock.

METHODS: Patients who were admitted to the ICU with septic shock(defined by MAP�60 mm Hg and sepsis according to standard criteria) wereassessed for sublingual microvascular perfusion by orthogonal polarization spec-tral (OPS) imaging before and 1 minute after PLR (45 degrees upward).Perfusion was estimated using a semi-quantitative microvascular flow index(MFI) in small (diameter 10-25 �m), medium (25-50 �m), and large-sized(50-100 �m) capillaries (0�no flow; 1�sludging (0 – 0,5 mm/s), 2�moderateflow (0,5 – 1,0 mm/s), 3�high flow (1,0 – 3,0 mm/s)).

RESULTS: Ten patients (2 female, 8 male; mean age 67 years) partici-pated in this study. Mean APACHE-II score was 23 (range 13-33). Meanlactate levels were 3.5 mmol/l. MAP and CVP inceased after PLR (table).Microvascular flow increased in parallel in most patients, i.e. flow increasedpredominantly in small microvessels, while flow in the larger microvesselsremained relatively preserved. In 4 patients, microvascular flow hardlyimproved after PLR. Also, after infusion of fluids until CVP was above 10, in3 of those 4 patients flow had still not normalized. After giving 0,5 mgnitroglycerin iv as described before, flow normalized in all cases.

CONCLUSION: Changes in sublingual microvascular perfusion afterPLR reflect the recruitment of blood from the venous leg pool in shockpatients. Microvascular flow improves by volume infusion in most cases.Some patients may require additional infusion of nitroglycerin to activelyopen the microvascular system.

CLINICAL IMPLICATIONS: OPS imaging may be a valuablebed-side tool for assessing optimal fluid resuscitation.

DISCLOSURE: Peter Spronk, None.

USE OF VASOPRESSIN FOR SEPTIC SHOCK IN A NONMONI-TORED SETTINGManoj L. Karwa MBBS Kaye Hale MD* Montefiore, Bronx, NY

PURPOSE: To review cases of septic shock treated outside the intensive careunit (ICU) setting with a fixed non-titratable continous infusion of vasopressin,determining its effects on survival, hemodynamics, and any adverse effects.

METHODS: With permission from our IRB, we conducted a retro-spective review of all patients that received vasopressin infusion for septicshock, between the dates of January 1, 2003 and December 31, 2003. In

MAP(mean,

mm Hg)

CVP(mean;

mm Hg)

MFIsmall

microvessels

MFImedium

microvessels

MFIlarge

microvessels

Before PLR 50 4 0,8 1,9 2,8After PLR 57 8 1,7 2,6 3,0

P�0,05 P�0,01 P�0,01 P�0,05 P�0,05




a tertiary care academic medical center. Values were expressed aspercentages and means (standard deviation).

RESULTS: Of 193 patients that received vasopressin infusion, 29 patientswith septic shock were identified as having been treated outside the ICU.They had the following characteristics Age of 74.7 years (16.1), 45% male,45% were intubated, APACHE II score 20.1 (7.2), and 52% of the cases haddo not resuscitate orders in place. 19 (65%) of these patients had survived thehospitalization. All received a non-titrating infusion of 0.04 units/minute ofvasopressin the average duration of which was 64.8 (54.8) hours. Systolicblood pressure had increased by 25.7% from 82.7 mmHg at onset to101-mmHg post 48 hours infusion. Mean arterial pressure had increased by21% from 60.9 to 78 mmHg. Serum Lactate decreased from 1.7 at onset to0.84 at end of the infusion period, BUN from 43.9(33) to 27.8(21), and serumcreatinine from 1.7 (1.6) to 1.3 (1.5). 10.3% patients died during the infusion.Bradyarrythmias and tissue necrosis were not observed in any of the cases.

CONCLUSION: For patients with septic shock who do not meet admissioncriteria to the ICU, therapy for with a non-titrating dose of vasopressin may be anadditional therapy utilized on the regular hospital ward.

CLINICAL IMPLICATIONS: Vasopressin at a fixed dose of 0.04units for use in patients with septic shock who do not otherwise meetcriteria for admission into the ICU may have significant implications onthe utilization of resources such as cardiac and hemodynamic monitoring,as well as nursing resources.

DISCLOSURE: Kaye Hale, None.

ACTIVATED PROTEIN C INFUSION MIMICS ANTIOXIDANTEFFECTS ON HYPOXIA-INDUCED MICROVASCULAR INJURYSonja D. Bartolome MD* Alan J. Casillan John G. Wood PhD Steven Q.Simpson MD Amy R. O’Brien-Ladner MD University of Kansas School ofMedicine, Kansas City, KS

PURPOSE: Hypoxia induces an inflammatory cascade that results ininjury to the microvasculature. Specifically, leukocyte adhesion to theendothelium begins, and leukocyte emigration and vascular leak follow.The mechanism of hypoxia related injury is incompletely understood, butinvolves oxidant stress. Infusion of antioxidants has been shown to preventhypoxia induced microvascular injury. Activated protein C is reported tohave anticoagulant and anti-inflammatory properties. Its protective role isbest described during sepsis. However, it has been utilized, with somesuccess, in experimental models of ischemic injury. Our experiments aredesigned to characterize the effects of activated protein C on themicrovasculature during systemic hypoxia and compare them to those ofa potent antioxidant, alpha-lipoic acid.

METHODS: Experiments utilize intravital microscopy of the intact ratvenular bed. Five groups were utilized: saline control, activated protein Cinfusion alone (100mcg/kg bolus), hypoxia alone (10% O2), simultaneoushypoxia � activated protein C infusion, and hypoxia � alpha lipoic acid.Measurements of leukocyte adherence (# per 100um venule), leukocyteemigration (# per 4000 um2), and venular leak by fluorescein isothiacy-anate-labeled albumin (Fi/Fo) are reported below.

RESULTS: � SEM.CONCLUSION: Activated protein C infusion and antioxidant infusion

prevent hypoxia-related microvascular injury as evidenced by measure-ments of leukocyte adherence, leukocyte emigration and vascular leak.

CLINICAL IMPLICATIONS: This similarity may reflect a commonmechanism of action. This work is important because the understanding ofthe hypoxia-induced inflammatory cascade is essential to a plethora ofdisease states, such as myocardial infarction, sepsis, ARDS and trauma.Further characterization of the effects of activated protein C in hypoxicinjury could lead to new therapeutic use.

DISCLOSURE: Sonja Bartolome, None.

DATA FROM THE TOP TEN ENROLLING COUNTRIES CON-TAINED IN THE PROGRESS (PROMOTING GLOBAL RE-SEARCH EXCELLENCE IN SEVERE SEPSIS) REGISTRY DEM-ONSTRATES VARIATIONS IN TREATMENT AND HIGHMORTALITY RATESKonrad Reinhart* Jean-Louis Vincent Graham Ramsay Claudio MartinEliezer Silva Richard Beale Frank M. Brunkhorst Mitchell Levy GregoryMartin Mary Ann Turlo Samiha Sarwat Jonathan Janes Universitasklini-kum Jena, Jena, Germany

PURPOSE: PROGRESS is an international, prospective, observationalregistry on severe sepsis patients in Intensive Care Units.

METHODS: Patients diagnosed with severe sepsis (suspected onproven infection � �1 acute sepsis induced organ dysfunction[s]) wereincluded; there were no exclusion criteria. Data were entered fromparticipating institutions via secured website. An independent advisorycommittee governs PROGRESS. Software development and websitemaintenance are funded by Eli Lilly.

RESULTS: Results As of 3/11/05 there were 11,925 patients in theregistry with 8,456 from the top 10 enrolling countries. (Table #1).

CONCLUSION: Management of severe sepsis varies across geo-graphic regions and mortality rates are high. The similarity of ROC curvesprovides support for the validity of the database and are independentpredictors of death despite these variations.

CLINICAL IMPLICATIONS: More research is necessary to explorethe reasons for differing patient management and outcomes.

DISCLOSURE: Konrad Reinhart, Consultant fee, speaker bureau,advisory committee, etc. Speaker is a member of the PROGRESS advisorycommittee.

EVALUATION OF THE MANAGEMENT OF SEPSIS IN THEEMERGENCY DEPARTMENTMaria I. Rudis PharmD* Kathy L. Rowland PharmD Jill M. HaraPharmD Philip Bretsky PhD Mark Hollinger RN Kathryn Challoner MDEd Newton MD USC School of Pharmacy, Los Angeles, CA

PURPOSE: The 2004 Surviving Sepsis Campaign Guidelines (SS-CG)emphasize the importance of early aggressive sepsis treatment toreduce mortality. We sought to determine compliance with the SSCG inpatients(pts) with sepsis in the ED, specifically the timeliness and extentoffluid administration and antimicrobial therapy, the use of earlygoal-directed therapy (EGDT), and the nature of vasopressor use.

METHODS: Retrospective cohort of consecutive pts with an EDdiagnosis of’sepsis’ in ourlarge, urban, county, level I trauma center from12/03-5/04. Pts wereexcluded if age�18yrs,had arequirement for imme-diate surgery, DNR status or were incarcerated.

LeukocyteAdherence

LeukocyteEmigration

VascularLeak

Normoxia 1.6 � .5 2.6 � .19 .14 � .04Hypoxia 14.5 � 1.2 12.3 � 2.2 .82 � .14Activated protein C 2.0 � .8 3.1 � .4 .19 � .05Activated protein

C � hypoxia4.4 � 1.5 3.5 � .3 .25 � .14

Alpha-lipoicacid � hypoxia

0.6 ��0.4 2.3 � .3 .10 � .04

Germany

n

1436

Argentina

n

1326

Brazil

n

921

Canada

n

889

India

n

841

Malaysia

n

684

Australia

n

679

US

n

671

Mex

n

516

Philippines

n

493

ICU Mortality 38% 46% 56% 32% 37% 56% 22% 33% 39% 41%

APACHE II

(mean)

27 23 23 24 20 24 21 26 22 24

�2 OD 90% 75% 93% na 90% 93% 91% 87% 93% 94%

Vent use 89% 79% 92% 90% 64% 99% 89% 76% 95% 76%

Vasopres. 93% 69% 75% 64% 59% 89% 88% 76% 90% 79%

Fluid resuscitation 95% 86% 94% na 63% 93% 86% 84% 97% 67%

Albumin 4.5% 9% 10% na 37% 29% 53% 19% 32% 14%

Low dose

steroids

46% 30% 59% 38% 29% 11% 30% 29% 30% 25%

Renal replacement 33% 12% 21% 14% 15% 22% 26% 18% 13% 17%

DroAA 5% 2% 7% 8% 4% 2% 8% 27% 11% 2%

Unfx heparin* 63% 59% 55% 73% 8% 34% 61% 30% 10% 8%

Low mole. Wt.

Heparin*

48% 14% 45% 14% 21% 16% 16% 32% 58% 17%

*Sum may exceed 100% due to possibility of sequential treatment


Sepsis and Shock: Treatment, continued


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RESULTS: After excluding 23 pts who did not meet inclusion criteriafromall ptswith sepsis (n�107), our cohort consisted of 84 pts with a meanage of 50.2� 19.6 yrs and 49% males. The ethnicity reflects thatofourgeneral ED population (62% latino, 18% caucasian, 11% Asianand9%African American). Mean volume of IV fluid administered in thefirst 6h in the ED was 1951 � 1644 ml, with the majority of pts(60.7%)receiving 1-3.5 L. Mean time to antibiotic administration fromtimeofpresentation (4.7 � 4.3 h) or from physician evaluation (2.3 � 2.9 h)exceeds the recommended 1 h by the SSCG. Vasopressorswere given to26 (30.9%) pts, with the majority receiving dopamine(25.0%) and nore-pinephine (6%) as first line agents. No pt was managed using EGDT.Mean LOS in the ED,ICU and hospital were 21.6 �18.6h, 8.9 � 13.8d,and 13.6 � 18.3 d, respectively.

CONCLUSION: ED management of pts with sepsis does not currentlymeet the parameters as set by SSCG. Assessment of 28-day mortality maydetermine impact of ED treatment of septic pts.

CLINICAL IMPLICATIONS: Interventions to optimize compliancewith SSCG are needed in the ED.

DISCLOSURE: Maria Rudis, None.

INDEPTH DATABASE OF SEVERE SEPSIS PATIENTS SHOWSFEWER CARDIAC EVENTS IN DROTRECOGIN ALFA (ACTI-VATED) PATIENTS VS PLACEBO PATIENTSDarell Heiselman DO* Stephen Lowry MD Jean-Francois Dhainaut MDPierre-Francois Laterre MD Roland Schein MD Michael Seneff MDJean-Pierre Sollet MD Antonio Artigas MD Jonathan Janes Frank BoothMD Andreas Sashegyi PhD Michael Cobas Meyer MD Akron GeneralMedical Center, Akron, OH

PURPOSE: This study was done to better understand treatment risksand benefits of drotrecogin alfa (activated) (DrotAA).

METHODS: A blinded, independent clinical evaluation committeeevaluated all serious adverse events (SAEs) within INDEPTH, a 4459patient integrated database of five clinical trials of patients with severesepsis. Trials were conducted by a single sponsor (Eli Lilly and Company).We report the incidence of cardiac serious adverse events in placebotreated patients (n�1231) and in those treated with DrotAA (n�3228).

RESULTS: SAEs were characterized as occurring either during thestudy drug infusion period or during the 28-day survival observationperiod. Sepsis-related clinical outcomes and sepsis-related deaths werenot considered SAEs unless attributable to study drug. Despite highersurvival in DrotAA, overall SAEs rates were similar in both groups.Observed rates for MI and arrhythmia were significantly lower duringinfusion period and at 28 days.

CONCLUSION: These data show a possible association betweenDrotAA administration and a reduced rate of cardiac events in patientswith severe sepsis.

CLINICAL IMPLICATIONS: Further investigation may be justified.DISCLOSURE: Darell Heiselman, Consultant fee, speaker bureau,

advisory committee, etc. Advisory panel fee.

AUTONOMIC NERVOUS SYSTEM-BASED EARLY GOAL DI-RECTED THERAPY IN THE TREATMENT OF SEVERE SEPSISAND SEPTIC SHOCK: PRELIMINARY EVIDENCEWilliam C. Shoemaker MD Adam Colombo DO Joseph Colombo PhD*Department of Science and Technology, Bucks County CommunityCollege, Newtown, PA

PURPOSE: To investigate the clinical efficacy of early goal-directedtherapy based on autonomic nervous system (ANS) monitoring (non-invasive, simultaneous, independent measures of sympathetic (SNS) andparasympathetic nervous system (PSNS) activity) in patients with severesepsis and septic shock.

METHODS: 208 severe sepsis and septic shock patients were studiedin an urban, level 1 university-run trauma service.: ANS monitoringmeasured the sequential patterns of SNS and PSNS activity immediatelyafter admission to the emergency department (ED). Also measurednoninvasive hemodynamic patterns, including: cardiac index (CI) bybioimpedance, as well as HR, and mean arterial pressure (MAP) toevaluate cardiac function, pulse oximetry to reflect changes in respiratoryfunction, and transcutaneous oxygen (PtcO2) to reflect tissue perfusion/oxygenation.

RESULTS: In all patients autonomic balance (the ratio of SNS toPSNS activity) was markedly abnormal. These patients also had low MAP,CI, and PtcO2/FiO2 values associated with increased HRV that reflectincreased autonomic activity. Patients with improved or restored ANSearly in their ED stay, all survived; while the latter admission to ED hadmixed results. ANS balance was not well-correlated with HR, BP, and CI.

CONCLUSION: In nonsurvivors, severe sepsis and septic shock wereassociated with pronounced ANS imbalance. Survivors had relativelynormal ANS balance. Patients that first presented poor ANS balance hadbalance improved due to therapy, also survived.

CLINICAL IMPLICATIONS: Shows a correlation between thecondition of severe sepsis and septic shock patients and their autonomicbalance.

DISCLOSURE: Joseph Colombo, Shareholder Joe Colombo, PhD is ashare holder and part owner of Ansar, Inc.; Employee Joe Colombo is theExecutive VP and Medical Director of Ansar, Inc.

Sepsis: The Faces of Sepsis12:30 PM - 2:00 PM

PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DIS-EASE ARE AT HIGHER RISK OF SEPSISDavid A. Hasselbacher MD* David M. Mannino MD Rolando BergerMD University of Kentucky, Lexington, KY

PURPOSE: Although studies have been completed examining thecause of death and rates of sepsis in patients with chronic obstructivepulmonary disease (COPD) no study has been completed examiningCOPD as a risk factor for sepsis. The goal of our study was to prospectivelyexamine COPD as a risk factor for sepsis.

METHODS: Data from the Atherosclerosis Risk in Communities(ARIC) study (a prospective study of 15,792 U.S. adults age 45-65 yearsold) were used in this analysis, with up to 11 years of follow-up dataavailable. A diagnosis of COPD was made using modified GOLD criteria(we added a “restrictive” category consisting of people with an FEV1/FVC � 70% and an FVC � 80% predicted). Episodes of sepsis orpneumonia were obtained using diagnostic codes (ICD-9 codes 038 and480-487, respectively) from hospital discharge. Out of 15,586 patientsanalyzed there were 136 documented cases of sepsis. A logistic regression,controlling for age, sex, cigarette smoking, body mass index, education

Table 1

VariableDrotAAN�3228

PlaceboN�1231 p Value*

Infusion Period: All SAE: N (%) 199 (6.2%) 78 (6.3%) NSAll bleeding Arrhythmia w/o MI 37 (1.15%) 30 (2.44%) 0.0015All non bleedingMyocardial

Infarction11 (0.34%) 10 (0.81%) 0.04

Death at 28 Days following anyInfusion Period SAE

87/199 (43.7%)† 47/78 (60.3%)† 0.013

MI/ Thrombotic All stroke/other arterial thromboticevents28 DayObservation Period:All SAE: N (%)

425 (13.2%) 170 (13.8%) NS

Arrhythmia w/o MI 54 (1.67%) 43 (3.49%) �0.001Arrhythmia without MIMyocardial

Infarction17 (0.53%) 15 (1.22%) 0.014

0ther ? Death at 28 days YesDeathat 28 Days following any SAE

137/425 (32.2%)† 72/170 (42.4.3%)† 0.02

†In these rows only, the denominator for the calculation of percent-age mortality is the number of patients at that time point with anSAE.


Sepsis and Shock: Treatment, continued


level, family income was completed using the SUDAAN software package.A second regression model added hospitalization for pneumonia to theabove noted variables.

RESULTS: The table depicts the classification of lung disease withincidence of sepsis, pneumonia, odds ratio for sepsis with 95% confidenceintervals (controlling for the factors noted in the methods) and odds ratiofor sepsis when controlled for pneumonia. Pneumonia was a very strongpredictor of sepsis (odds ratio 22.7, 95% CI 14.5, 35.4).

CONCLUSION: Patients with GOLD stage 2 or higher COPD andthose with restrictive disease had an increased risk for sepsis in this cohort.After controlling for pneumonia, the risk was attenuated, and onlysignificant in patients with restrictive disease.

CLINICAL IMPLICATIONS: These findings suggest that most, butnot all, of the increased risk of sepsis among patients with COPD is relatedto their increased risk of developing pneumonia.

DISCLOSURE: David Hasselbacher, None.

SEVERE SEPSIS IS ASSOCIATED WITH AN APOPTOSIS-MEDI-ATED DECREASE IN HEPATIC BACTERIAL CLEARANCEAlix Ashare MD* Timur Yarovinsky PhD Martha Monick MS GaryHunninghake MD University of Iowa, Iowa City, IA

PURPOSE: The development of liver disease during the course ofsepsis is associated with increased mortality. We hypothesized thatworsening liver function would result in decreased bacterial clearance andbe associated with increased dysfunction of other organs and increasedmortality.

METHODS: Mild and severe sepsis were generated in C57BL/6 micevia intratracheal inoculation with 103 or 104 organisms of Pseudomonasaeruginosa, respectively. To evaluate bacterial clearance by the liver,portal vein and right ventricle bacterial concentrations were measuredusing quantitative real-time PCR with primers specific for P. aeruginosa.Liver and cardiac injury was assessed by ALT and CK levels. Organapoptosis was evaluated with a caspase-3 activity assay. Levels of IL-1 betaand TNF-alpha were measured by ELISA. To inhibit apoptosis, a subsetof mice was pre-treated with the caspase inhibitor z-VAD-fmk.

RESULTS: Mild and severe sepsis resulted in 20% and 60% mortalityat 36 hours, respectively. Mild sepsis triggered a short but significanthepatic inflammatory response and some liver injury that returned tobaseline by 24 hours. Effective bacterial clearance was not lost in thismodel. Severe sepsis caused a prolonged hepatic inflammatory responseand liver injury that continued to worsen over time. Effective bacterialclearance was eventually lost in this model and was associated withincreased injury to other organs, as well as increased mortality. Pretreat-ment with z-VAD-fmk resulted in preservation of hepatic bacterialclearance and increased survival 24 hours after infection with the severesepsis model.

CONCLUSION: We conclude that liver injury in sepsis is associatedwith decreased bacterial clearance, increased end-organ damage, andmortality. Inhibition of apoptosis preserves hepatic bacterial clearance andimproves survival.

CLINICAL IMPLICATIONS: This study suggests that bacterialclearance by the liver may be an important determinant of the outcome ofsepsis.

DISCLOSURE: Alix Ashare, None.

AUTONOMIC AND HEMODYNAMIC ACTIVITY IN SEPSISWilliam C. Shoemaker MD Charles C. Wo BS Payman Fathizadeh MDJoseph Colombo PhD* Department of Science and Technology, BucksCounty Community College, Newtown, PA

PURPOSE: The aim is to evaluate early hemodynamic patterns ofpatients with severe sepsis and septic shock and compare/contrast theeffects of sepsis as a primary etiologic event versus sepsis as a secondarycomplication after trauma, surgery etc. with simultaneously monitoredsympathetic (SNS) and parasympathetic nervous system (PSNS) activitiesmeasured by the variability of the heart rate (HR) and respiratory rate(RR).

METHODS: Level 1 university-run trauma service in a public hospi-tal.Non-invasively monitored the early hemodynamic patterns in 208severely septic patients beginning shortly after admission to the emer-gency department (ED). Simultaneously, monitored and compared thespectrum of HR and RR variability patterns, as markers of autonomicactivity, with temporal hemodynamic patterns in 73 of these septicpatients. The HR variability was measured to evaluate the low frequencyarea (LFa), which reflects SNS. The high frequency area (RFa) isindicative of PSNS activity. The LFa/RFa, reflects the relationship of SNSto PSNS. Concurrent noninvasive hemodynamic monitoring consisting of:a) cardiac output by bioimpedance, HR, and mean arterial pressure(MAP) to reflect cardiac function, b) pulse oximetry (SapO2) to reflectchanges in pulmonary function, and c) transcutaneous oxygen (PtcO2)indexed to the FiO2 as a marker of tissue perfusion/oxygenation.

RESULTS: Non-survivors had higher LFa and RFa values than thesurvivors did. The increased RFa preceded the increases in LFa innon-survivors and a higher percentage of sympathetic activity. Thesechanges were more marked when measured before sedation and painmedication. In survivors, these patterns were associated with increasedcardiac index (CI), and HR, normal MAP, SapO2, and normal tissueperfusion indicated by PtcO2/FiO2 ratios. Nonsurvivors had relativelynormal CI, hypotension, tachycardia, poor tissue perfusion, borderlineSapO2, and reduced oxygen delivery.

CONCLUSION: In the period immediately after ED admission ofpatients with sepsis increased ANS activity was observed more pro-nounced in non-survivors. This activity was associated with increased HR,MAP, and CI, and a tendency toward reduced tissue perfusion/oxygen-ation.

CLINICAL IMPLICATIONS: Established relation between hemo-dynamic variables and the ANS balance of Sepsis patients.

DISCLOSURE: Joseph Colombo, Shareholder Joe Colombo, PhD is ashareholder and part owner of Ansar, Inc.; Employee Joe Colombo is theExecutive VP and Medical Director of Ansar, Inc.

RISK FACTORS FOR CANDIDEMIA: COMPARISON BETWEENMEDICAL AND SURGICAL INTENSIVE CARE UNIT PATIENTSStephen B. Heitner MD* Glenn Eiger MD Robert Fischer MD Emma C.Scott MD Aba Somers MD Albert Einstein Medical Center, Philadelphia,PA

PURPOSE: Candidemia is a potentially lethal and common infection inthe intensive care unit (ICU). A number of risk factors for invasivecandidiasis have been identified in previous studies. Our objective is todetermine if there is a difference in the risk factor profile of medical ICU(MICU) and surgical ICU (SICU) patients.

METHODS: A retrospective analysis was conducted at a large com-munity-based teaching hospital. Subjects had positive blood cultures forCandida species and were admitted to the MICU and SICU over atwo-year time period. Patients with known malignancies or other immu-nocompromising states were excluded. Demographic variables, SimplifiedAcute Physiological Score (SAPS), and known risk factors for candidemiawere compared between MICU and SICU patients. Chi-square analysisand independent-sample t-tests were applied.

RESULTS: Forty-three patients were included for analysis. MICUpatients had significantly higher SAPS scores (57.8 vs. 41.1, p� 0.005.).

Lung Disease N%

Sepsis%

PneumoniaOR forSepsis

OR controlledfor Pneumonia

Gold Stage 3 & 4 281 3. 6 12.8 4.2(2.0-9.1) 1.9(0.8-4.4)Gold Stage 2 1491 1.7 4.3 2.3(1.3-3.8) 1.7(0.9-2.9)Gold Stage 1 1688 0.6 2.1 0.9(0.5-1.9) 0.8(0.4-1.7)Gold Stage 0 2192 0.9 4.2 1.5(0.9-2.6) 1.5(0.8-2.5)Restrictive 1325 2.2 1.7 3.3(2.0-5.5) 2.4(1.4-4.2)Normal 8609 0.5 0.9 1.0 1.0


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SICU patients had a greater number of antibiotic days (42 vs. 18.38,p�0.001) and received a larger number of antibiotics (4.68 vs. 3.04,p�0.002). SICU patients were on mechanical ventilation longer (19.37 vs.8.5 days, p� 0.02) and had longer hospital stays (56.7 versus 35.3 days,p�0.03). SICU patients tended to have greater frequencies of other riskfactors including parenteral nutrition and central venous catheters. Therewas no difference in mortality rate between the two populations.

CONCLUSION: Significant differences exist between MICU andSICU patients who develop candidemia. The observed trend in our studyis that SICU patients had higher frequencies of traditional risk factors,while MICU patients had worse physiological indices.

CLINICAL IMPLICATIONS: Traditional risk factors for the devel-opment of candidemia need further analysis to determine whether theyare equally applicable to both MICU and SICU patients.

DISCLOSURE: Stephen Heitner, None.

MYCOBACTERIUM TUBERCULOSIS AN UNUSUAL YETHIGHLY FATAL CAUSE OF SEPTIC SHOCKRaquel Nahra MD* Sergio L. Zanotti-Cavazzoni MD Anand Kumar MDCooper University Hospital, Camden, NJ

PURPOSE: To describe a group of patients with septic shock caused byM. Tuberculosis and compare their outcomes to those of patients withseptic shock caused by other microorganisms.

METHODS: Data was extracted from a multicenter database withinformation from the records of 2731 patients with septic shock. Patientswith septic shock caused by M. Tuberculosis were identified by positiveblood or multi-site cultures.

RESULTS: A total of 2731 patients with septic shock were studied.Eleven patients (0.4%) had septic shock caused by M.Tuberculosis (MTBgroup). In the MTB group, the mean age was 44.2 (�19.5) years, meanAPACHE II score was 26 (�8), 36% were males and 64% were females.Comorbid conditions included; alcohol use 54%, non-HIV immunosupre-sive diseases 36.4%, and diabetes mellitus 18.2%. None of these patientshad documented HIV. Overall mortality in the MTB group was 81.8 %,and mean length of stay in the ICU was 12.7(� 17.1) days. Inapropriateinitial antimicrobial coverage based on culture results was given to fivepatients (45.5%) in the MTB group. When compared to patients withseptic shock caused by other microorganism (OTH group), patients inMTB group were younger (44.27(�19.5) years vs 62.66 (�16.4)) yearsp � 0.0002), and more likely to have alcohol use as a comorbidity (54.4%vs 13.8 %, p� 0.0013). Patients in the MTB group were more likely toreceive inappropriate initial antimicrobial therapy than patients in theOTH group (45.5% vs 18.6%, p�0.0039). Patients in the MTB group hada higher mean ICU LOS (12.21 days vs 8.1 days ), had a higher overallmortality (81.8% vs 56.2% , p � 0.12 ), and were more likely to develophepatic failure (p 0.0039).

CONCLUSION: M. Tuberculosis is an uncommon cause of septicshock. However, when it occurs it is associated with increased morbidityand mortality and a significant delay in institution of appropriate antitu-berculous treatment.

CLINICAL IMPLICATIONS: Mycobacterium Tuberculosis shouldbe thought of as a possible cause for septic shock in apropriate clinicalsituations.

DISCLOSURE: Raquel Nahra, None.

Sleep Disorders: Other Than Sleep Apnea12:30 PM - 2:00 PM

QUANTIFYING MICROSLEEP TO ASSESS SLEEPINESSAllen J. Blaivas DO* Rajeshri Patel MD Kenneth Antigua David HomHormoz Ashtyani MD UMDNJ-New Jersey Medical School, Newark, NJ

PURPOSE: The qualitative presence of microsleep during the Multi-ple Sleep Latency Test (MSLT) has been shown to correlate with anincreased incidence of subjective complaints of sleepiness, tiredness,accidents/near accidents, and gap driving. However, there is no data as tohow to quantify microsleep and effectively incorporate it as a diagnostictool in the measurement of sleepiness. The purpose of this study is to

integrate microsleep to the MSLT score and determine if it improves thecorrelation between the MSLT and symptomatic sleepiness.

METHODS: The charts of 54 patients who had an MSLT score ofgreater than 5 minutes and the presence of microsleep on at least one napwere reviewed. If microsleep was present in a given nap it was used as asurrogate for sleep onset. This MSLT plus microsleep score (MSLT�)was then averaged into the total sleep latency and compared with theMSLT score to determine if it improves correlation with the ESS.

RESULTS: Using the Spearman correlation the MSLT� improved theassociation between ESS when compared to MSLT (r�0.106 versusr�0.063), but the results were not statistically significant. Of note, boththe MSLT and MSLT� were only weakly correlated to the ESS.

CONCLUSION: The addition of microsleep onset to the MSLT scoreas a quantitative assessment tool failed to significantly enhance thecorrelation between subjective and objective accounts of sleepiness,beyond the improvement seen in the MSLT value by the simple presenceof microsleep alone.

CLINICAL IMPLICATIONS: The use of microsleep as a marker ofexcessive daytime sleepiness has been previously demonstrated, as has itsqualitative presence as an enhancement to the MSLT score. Its clinicalsignificance in daily life also can not be overstated, as it has been labeledas contributory in multiple large accidents and catastrophes. This studyattempted to determine its exact implication on the way sleepiness isquantified; however the “holy grail” of accurately correlating objectivesleep propensity to symptomatic excessive daytime sleepiness continues toelude us.

DISCLOSURE: Allen Blaivas, None.

THE CLINICAL SIGNIFICANCE OF SPONTANEOUS AROUS-ALS INDEX (SAI) DURING POLYSOMNOGRAPHYJoe G. Zein MD* Maroun M. Tawk MD Tarek Dernaika MD Gary T.Kinasewitz MD William C. Orr PhD The University of Oklahoma, HealthSciences Center, Oklahoma City, OK

PURPOSE: Sleep arousals are important for reestablishing a patentairway subsequent to an obstructive event and to protect against pro-longed hypoxemia. Spontaneous arousals (SA) are also considered amongthe clinical indicators of upper airway resistance syndrome (UARS). Weexamined the frequency and clinical significance of SA in patients referredfor evaluation of obstructive sleep apnea (OSA).

METHODS: This was a retrospective study of 118 consecutive adultpatients presenting for polysomnography from October 2002 till March2003. A multivariate logistic regression was constructed with the rate ofSA as the dependent variable. Apnea Hypopnea Index (AHI), Sleepefficiency (SE), mean SaO2, and stage 1 were independent variables.Arousals were defined according to the American Academy of SleepMedicine established criteria. Data are presented as mean � SEM.

RESULTS: The mean total recording time was 396�6 with a totalsleep time of 308�10 min. An increased SAI (�10/hr) was present in 20


Sepsis: The Faces of Sepsis, continued


patients (19%). Age, gender, Epworth Sleepiness Scale, sleep onsetlatency, periodic limb movement index were similar in patients with highand normal SAI. A higher SAI was associated with a higher AHI (57.8�6vs.32.5�3; p�0.0002)(r�0.4; p�0.05), a lower SE (57�3 vs. 77�2%;p�0.002), a higher stage 1 sleep (11.5�1.2 vs. 6.5�0.6 %; p�0.0003) anda lower mean SaO2 (90.4�0.8 vs.92.1�0.4; p�0.04). There was a trendtowards a higher respiratory arousal index (35�5 vs. 25�3; p�0.1) andhypoxemia (time SaO2�90%) (72�15 vs. 43�8; p�0.09) with a higherSAI. In the multivariate analysis, a higher SAI was associated withincreased AHI (OR�7.6; 95 CI:2.7-34.7). In the high SAI group, while onCPAP , SAI improved from 17�2 to 3.2�1.2 events /hour (p�0.001), andcorrelated significantly with the improvement in AHI (r�0.6; p�0.05).

CONCLUSION: High SAI is a marker of severe sleep apnea andcorrelates with the AHI.

CLINICAL IMPLICATIONS: The SAI variable does not add appre-ciably to the available clinical information except when the SAI is highwith substantially lower AHI, which would increase the index of suspicionfor the presence of UARS.

DISCLOSURE: Joe Zein, None.

OVERNIGHT PULSE RATE RECORDING AS A SCREENINGTEST FOR SLEEP DISTURBANCESHeloisa Glass PhD Maria Margarete d. Zembrsuski MS Ana Paula G.Garay Maria Alice M. Neves Laercio M. Valenca MD* Hospital dasForcas Armadas/Universidade Catolica de Brasilia, Brasilia, Brazil

PURPOSE: It is well known that arousals are often associated withtachycardia. Because polysomnography is costly as a screening test, westudied the correlation between the pulse rate obtained from overnightoximetry with polysomnographic parameters of sleep efficiency andfragmentation.

METHODS: Polysomnography and pulse oximetry (Healthdyne Tech-nologies, model 920M) were recorded simultaneously in 31 patients, 13women and 18 men, referred for sleep studies. Highest, lowest and meanpulse rate, standard deviation and frequency distribution of pulse ratewere correlated with parameters related to sleep efficiency and fragmen-tation using ANOVA. For frequency distribution 25 beats intervals (�50;50-74; 74-99; 100-124; 125-149; 150-174; 175-199; �200) were used.

RESULTS: Age of the patients ranged from 14 to 77 years (mean 47,52�- SD 15,91). Body mass index was 27,42 � 4,44 (range of 17,78 – 39,96kg/m2). The statistical analysis indicated that highest pulse rate and rate�100/min as a percentage of total recording time are good predictors of alow sleep efficiency (F� 4,841; p�0,008). On the other hand, none of thevariables tested can predict arousals, microarousals, reduced REM orreduced delta sleep.

CONCLUSION: Our data show that tachycardia diagnosed by pulseoximetry can predict low sleep efficiency but not sleep arousals. Never-theless, further studies can disclose other variables, which can be used inthe construction of a model for screening of disturbed sleep.

CLINICAL IMPLICATIONS: Low sleep efficiency is associated withtachycardia during sleep. This observation increases the usefullness ofpulse oximetry as a screening tool for disturbed sleep.

DISCLOSURE: Laercio Valenca, None.

DOES SLEEP SPINDLE FREQUENCY AND DENSITY DIS-CRIMINATE BETWEEN THE VARIOUS TYPES OF EPILEPSY?Juliana C. Rajter MD* Sigmund G. Jenssen MD Han C. Ryoo PhD SivaK. Ramachandran MD Drexel University College of Medicine, Philadel-phia, PA

PURPOSE: During stage 2 sleep the thalamic reticular neurons releaseGABA, allowing sleep spindles to emerge at an oscillatory frequency of12-14 Hz.There is evidence from from thalamic kindling in cats thatspindle oscillations develop into seizures in corticothalamic systems. Fromcomputer modeling it is hypothesized that that there is cortical transfor-mation of one of every 2 or more spindle waves to a spike component ofspike and wave discharges and the other replaced by a slow wave1. Thismodel predicts the evolvement of spindle waves to seizures.We ponderedon the predictive relationship between spindle characteristics amongdifferent types of epilepsy and compared them to subjects withoutepilepsy.

METHODS: 7 patients, each, with temporal lobe epilepsy, frontal lobeepilepsy, primary generalized epilepsy and 5 subjects without epilepsywere studied after IRB approval. At the time of EEG recordings 4 out of

5 normals were on benzodiazepines while the rest were on antiepilepticmedications. From the whole night EEG recordings, segments of 300seconds were extracted to assess spindle duration, number of spindles andfraction of spindle time per Epoch of stage 2 sleep by 2 independentscorers blinded to the clinical information. A 2 way ANOVA was used totest the differences between the various frequency categories.

RESULTS: See attached table.CONCLUSION: 1.More spindles were seen in normal subjects. This

represents medication effect on sleep.2. Although mean spindle durationand fraction of spindle time per epoch of stage 2 sleep occurred more intemporal lobe epilepsy, this was not statistically significant. 3.Overallspindle characteristics are not discriminative between the various types ofepilepsy.

CLINICAL IMPLICATIONS: In studying patients with epilepsy inthe sleep laboratory, the morphology of spindles is unlikely to offer cluesto assess either the origin or activity of spike and wave discharges.1. TraubRD, Contreras D et al. Single- column thalmocortical network modelexhibiting gamma oscillations, sleep spindles and epileptogenic bursts.J Neurophysiol. 2005; 93:2194-232.

DISCLOSURE: Juliana Rajter, None.

ADVANCED AUTOMATED ANALYSIS OF HUMAN ELECTRO-ENCEPHALOGRAPHY (EEG) USING MULTIDIMENSIONALMATHEMATICAL ANALYSES OF FREQUENCY CHANGESCOMPARED TO TRADITIONAL RECHTSCHAFFEN ANDKALES (R&K) SCORING OF A KNOWN BIOLOGICAL SLEEPSIGNALRichard K. Bogan MD* Jo Anne Turner MSN Alex Novodvorets MS KobyTodros BS Baruch Levy BS SleepMed, Columbia, SC

PURPOSE: To assess the use of an automated system (Morpheus) inthe analysis of human EEG frequency changes in pre and post severeobstructive sleep apnea using a split night protocol. To correlate adaptivesegmentation and fuzzy logic frequency changes using Markov models totraditional R&K.

METHODS: A total of 23 adults were studied with a diagnosis ofsevere obstructive sleep apnea. Each subject underwent polysomnography(PSG) and received early intervention CPAP therapy during initial study.Only individuals with oxygen saturations greater than 85% and respiratorydisturbance index (RDI) less than 10 episodes per hour during the idealCPAP titration period were included. Fundamental frequency segmentswere measured using Morpheus algorhythms. Sleep states were analyzedusing traditional R&K rules.

RESULTS: Means and standard deviations are reported for 23 adults.RDI pre CPAP was 73.5 (26) with low oxygen saturation of 81%(7). Preand post CPAP periods for the sleep states that reached statisticalsignificance by automated analysis during study time were: highfrequency(HF)�pre 30%(15), post 23%(11); low frequency(LF)� pre3%(4), post 8%(5); mixed frequency-1(MF1)�pre 15%(8), post 25%(7);delta� pre 2%(4), post 4%(5); beta� pre 5%(5),post 2%(2); under 4 Hz�pre 5.2%(7), post 12.6%(5). Significant R&K sleep state results are asfollows as a % of time in bed: sleep efficiency pre� 76%(16), post 84%(9);Stage II pre� 58%(16), post 35%(12); Stages III&IV pre� 4%(8), post15(9); REM pre�4%(9), post 26(11). Signals analyzed but not found to bestatistically significant were: Morpheus mixed frequency 2, theta, alpha,and sigma segments; R&K Stage I.

CONCLUSION: The automated analysis demonstrates a differentmethodogy for analyzing a known biological sleep signal. In this study

Normal GeneralizedTemporal

lobeFrontal

lobe p

Mean spindleduration inseconds (�SD)

0.69�0.24 0.72�0.21 1.47�1.12 0.63�0.21 0.37

Spindle time /epoch instage 2 sleep

0.03�0.02 0.02�0.03 0.05�0.08 0.02�0.01 0.84

Spindle numberper epoch

3.4�3.3 2.8�2.8 2.6�2.2 3.4�1.8 0.37


Sleep Disorders: Other Than Sleep Apnea,continued


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group with severe sleep apnea there was an improvement in sleepmeasures that reflect EEG synchrony comparable to that as measured byR&K.

CLINICAL IMPLICATIONS: A completely automated analysis mayexpand knowledge of sleep states and processes from a high resolutionmultidimensional mathematical perspective thus allowing improved un-derstanding of disease state mechanisms, medical risk, treatment out-comes, and quality of life measures.

DISCLOSURE: Richard Bogan, Shareholder SleepMed Inc.

OPTIMIZATION OF NON-INVASIVE VENTILATION PRES-SURES USING COMBINED OXIMETRY AND CUTANEOUSCARBON DIOXIDE TENSION MONITORINGPrashant N. Chhajed MD* Simone Gehrer Trupti P. Chhajed IngridStrobel Martin Brutsche MD Michael Tamm MD Werner Strobel MDPulmonary Medicine, University Hospital Basel, Basel, Switzerland

PURPOSE: To examine the safety, feasibility and utility of combinedcutaneous carbon dioxide tension (PcCO2) and oximetry monitoring tore-titrate the non-invasive positive pressure ventilation settings in patientswith chronic hypercapnic respiratory failure due to hypoventilation.

METHODS: 12 patients with chronic hypercapnic respiratory failureunderwent complete polysomnography and combined oximetry andPcCO2 measurement (Sentec AG, Switzerland) on the ear lobe. non-

invasive positive pressure ventilation pressures were adjusted with the aimof normalizing PcCO2 or reducing it by 10 to 15 mm Hg. Sensor drift forPcCO2 measurement was calculated to reduce the discrepancy betweenPcCO2 and awake arterial carbon dioxide tension. Epworth sleepinessscore and patient satisfaction with home ventilation was charted on a 10centimeter visual analogue scale before and after the study.

RESULTS: Mean baseline PcCO2 was 45.4 � 6.5 mm Hg and driftcorrected awake PcCO2 was 45.1 � 8.3 mm Hg. IPAP pressures werechanged in nine patients and EPAP in eight patients. Epworth sleepinessscore before and after the study showed no change in five patients, mildimprovement in six patients and mild deterioration in one patient. Sevenpatients had a mild increase and five patients a mild decrease in theirvisual analogue scale score at follow up.

CONCLUSION: Combined continuous PcCO2 and oximetry monitor-ing is feasible and permits the optimization of non-invasive positivepressure ventilation settings in patients with chronic hypercapnic respira-tory failure due to hypoventilation. Continuous PcCO2 monitoring mightserve as an important additional tool to complement diurnal arterialcarbon dioxide tension values.

CLINICAL IMPLICATIONS: A titration study with continuousPcCO2 measurement in patients receiving non-invasive positive pressureventilation can be helpful to optimize the ventilator settings.

DISCLOSURE: Prashant Chhajed, None.

SLEEP-RELATED DESATURATION IN PATIENTS WITH UNI-LATERAL DIAPHRAGMATIC DYSFUNCTIONNorman Wolkove MD* Osama Elkhouli MD Marc Baltzan MD RichardDabrusin MD Mark Palayew MD Mount Sinai Hospital Center, Mon-treal, PQ, Canada

PURPOSE: Benign unilateral diaphragmatic dysfunction or paralysis(BUDDP) is not associated with known malignancy and may be idiopathicor due to previous trauma. BUDDP is generally thought to be of littleclinical significance. Previous studies have been of limited scope, and havenot included sleep studies. We assessed the physiologic and polysomno-graphic findings in 6 patients with BUDDP.

METHODS: Six patients with suspected BUDDP and an elevatedhemi-diaphragm on chest X-ray were identified and studied with chestfluoroscopy and sniff maneuver to quantify diaphragmatic movement(grade1�decreased movement, grade 2 � no movement, grade 3 �paradoxical movement). Additional studies included pulmonary functiontesting (PFTs), PI max, PE max and overnight polysomnography.

RESULTS: Mean age of our patients was 63 years (range 39-73 years).Four patients were male, 3 patients had previous chest surgery. 3 patientswere assessed as grade 1, 2 grade 2 and 1 grade 3. PFTs revealed mildrestriction with mean TLC 78% predicted (70-96%) and 4 patients hadsuperimposed obstruction (FV1/FVC � 75%). PI max and PE max werewithin normal limits (86% and 116% predicted). Mean obstructive apneaindex was 7(0-30), mean RDI was 30 (2-97). Mean RDI during NREMand REM-sleep were 27(1-91) vs. 45 (5-76) (p�0.18). All patientsdemonstrated nocturnal desaturation. Mean lowest saturation duringsleep was 80 %( 66-87%). Mean lowest saturation was 84 %( 70-94%)during NREM sleep and 69 %( 51-81%) during REM sleep. (p�0.0017).Severity of BUDDP was significantly correlated with FEV1, PI max anddesaturation during REM sleep.

CONCLUSION: During the wake state patients with BUDDP may beable to compensate for the unilateral loss of diaphragmatic function.However, during REM sleep, when the accessory respiratory muscles areinhibited, resultant hypoxemia can occur.

CLINICAL IMPLICATIONS: Patients with BUDDP have mildrestrictive lung disease and REM associated desaturation which correlateswith the degree of diaphragmatic dysfunction. The resultant desaturationmay be severe enough to require oxygen supplementation.

DISCLOSURE: Norman Wolkove, None.

PATIENTS WITH PULMONARY ARTERIAL HYPERTENSION(PAH) HAVE POOR SLEEP QUALITYChirag M. Pandya MD* Omar A. Minai MD J. A. Golish MD K.McCarthy MD Cleveland Clinic Foundation, Cleveland, OH

PURPOSE: Sleep disturbances (SD) and severe nocturnal hypoxia ofunclear etiology have been previously reported in patients with PAH. Weperformed sleep studies in PAH patients to evaluate their sleep charac-teristics and to look for possible factors associated with SD or NH.




METHODS: Patients followed at our PAH center who underwentsleep studies were included in the study. Variables analyzed included:apnea-hypopnea index (AHI), arousal index (AI), sleep stages, limbmovements, oximetry, and EKG changes. Patients who spent more than10% of the total sleep time (TST) with an oxygen saturation (SpO2) �90%were considered nocturnal desaturators (ND) and patients with an arousalindex (AI) �10 or sleep efficiency �70% were considered to have SD.

RESULTS: Patients slept an average of 304�66 (mean�SD) min andspent 14�9% (mean�SD) of TST in REM, 9�8 %(mean�SD) in stage1, 66�18%(mean�SD) in stage 2, and 5�6 % (mean�SD) in SWS. Outof the 20 patients, 12 (60%) were nocturnal desaturators. On averagepatients spent 22�27% (mean�SD) of their TST �90% SpO2. Fivepatients spent � 30% of TST �90% SpO2. Of the desaturators 3 patientswere found to have OSA. Eight patients received supplemental oxygenduring polysomnography. The overall arousal index was 19.5�12.8(mean�SD), 11 of 15 (73%) had and arousal index �10, the average sleepefficiency was 76�14% (mean�SD). Five patients had premature ven-tricular contractions. Periodic limb movement index (PLMI) was 24�31.5(mean�SD) and four patients had a PLM arousal index �10. None hadOSA severe enough to be considered a potential cause of their PAH.

CONCLUSION: Patients with PAH may have poor quality or non-restorative sleep due to a variety of factors including PLMs, and nocturnaldesaturation even in the absence of sleep disordered breathing.

CLINICAL IMPLICATIONS: Patients with PAH may have poorsleep quality or non-restorative sleep and nocturnal hypoxia even in theabsence of sleep-disordered breathing.

DISCLOSURE: Chirag Pandya, None.

PNEUMATIC COMPRESSION DEVICES FOR TREATMENT OFRESTLESS LEGS SYNDROMEArn H. Eliasson MD* Walter Reed Army Medical Center, Washington,DC

PURPOSE: Restless legs syndrome (RLS) is a troublesome conditionmanifested by sensory and motor symptoms that disrupt sleep onset orsleep maintenance. RLS is common, occuring with a estimated populationprevalence of 10%. There are no consistently reliable treatment alterna-tives and pharmacological treatments are often associated with unaccept-able side effects. An effective nonpharmacological treatment would be ahighly attractive option.

METHODS: A convenience sample of patients reliably diagnosed withRLS was asked to wear pneumatic compression devices for at least onehour each evening for at least 30 days. Symptoms of RLS severity andrelated quality of life measures were evaluated before and after treatment.RLS severity was measured using a validated 10-item questionnaire.Quality of life indices were scored using the RLS Foundaton Quality ofLife Instrument. Daytime sleepiness was gauged using the EpworthSleepiness Scale (ESS). Patients were asked to track compliance usinglogs.

RESULTS: Of eight patients enrolled (mean age 55 years, range 37 to81, 6 women), one man withdrew due to inability to comply. Of the otherseven patients, all improved regarding RLS severity with three patients(43%) experiencing complete resolution. Mean severity decreased from24/40 to 7/40 (p�0.003). Social functioning improved from 87% to 98%(p�0.05), daily functioning improved from 76% to 94% (p�0.06), sleepquality improved from 30% to 54% (p�0.01), and emotional well-beingimproved from 61% to 88% (p�0.05). ESS did not change significantly,decreasing from 9.9 to 8.6 (p�0.14). Compliance averaged 87% of nights(range 58% to 100%). One patient was able to discontinue previouslyprescribed gabapentin and pramipexole while experiencing improvementin RLS symptoms.

CONCLUSION: Pneumatic compression devices worn for one hourper day over days to weeks improve RLS symptom severity and quality oflife measures. A proportion of patients experience complete resolution ofRLS symptoms.

CLINICAL IMPLICATIONS: Pneumatic compression devices are aneffective treatment alternative for patients with RLS. This nonpharmaco-logical therapy may preclude resorting to medications which may beineffective or have unacceptable side effects.

DISCLOSURE: Arn Eliasson, Other Aircast Industries of New Prov-idence NJ supplied six pneumatic compression devices for use in thisstudy. No other financial incentive or support was received.

RESTLESS LEGS SYNDROME IN PATIENTS WITH CHRONICRENAL FAILURE IS NOT RELATED TO SERUM FERRITIN ORSERUM IRON LEVELSKhalil Ansarin MD* Jafar Shabanpour MD Hasan Argani MD HormozAiromlou MD Tuberculosis and Lung Research Center, Tabriz Universityof Medical Sciences, Tabriz, Iran

PURPOSE: Restless legs syndrome (RLS) is a sleep disorder thoughtto be related to iron stores and dopamine receptors of basal ganglia ofbrain. It occurs more commonly in patients with chronic renal failure(CRF), iron deficiency, and some other conditions. Its incidence in a fewreports of patients with CRF from Asia varies from 1% to 60%. Westudied this syndrome in patients with CRF and analyzed the effect ofvarious parameters possibly involved in the etiology of RLS.

METHODS: We investigated 194 patients (116 males and 78 females)with CRF diagnosed in Tabriz University Hospital using a structuredquestionnaire evaluating details of sleep, RLS, sleep apnea and othersleep disorders, and drug history. Daytime sleepiness was investigatedwith a modified Epworth Sleepiness Scale. Also a detailed laboratoryinvestigation including serum, iron, ferritin, and PTH levels were per-formed.

RESULTS: 56 (28.9 %) patients, 27(23.1 %) men and 29 (37.2%)women had symptoms compatible with RLS. (p� 0.04). There was nosignificant difference on the mean levels of hemoglobin (9.7 � 0.18 versus10.1 � .31; p� 0.71) serum iron (72.2 � 3.63versus 74.3� 6.66; p� 0.87),and serum ferritin (684 � 97.4 versus 519 � 138; p� 0.65) in patientswith CRF who had RLS and those did not. There was a statisticallysignificant difference daytime sleepiness in patient with CRF who did anddid not have RLS ( 5.92�0.76 versus 2.95�0.34; p�0.0001).

CONCLUSION: RLS syndrome is a common disorder in patients withCRF in Asian population of Azarbaydjan province of Iran.. Unlike generalpopulation in patients with CRF presence of RLS has no relationship withserum ferritin, serum iron level, or degree of anemia. These patients hadpoor quality of sleep that is at least partly related to the presence of RLS.

CLINICAL IMPLICATIONS: RLS in patient with CRF is not relatedto serum ferritin or iron levels or degree of anemia and treatment on thisdirection is not expected to be as efficacious as patients without CRF.

DISCLOSURE: Khalil Ansarin, University grant monies Supported bya gran from Tuberculosis and Lung Research Center, Tabriz University ofMedical Sciences, Tabriz, Iran

RESTLESS LEGS SYNDROME IN LUNG TRANSPLANT RECIP-IENTSJose C. Yataco MD* Joseph Golish MD Marie Budev DO Omar MinaiMD Cleveland Clinic Foundation, Beachwood, OH

PURPOSE: Restless legs syndrome (RLS) is a neurologic disorder witha prevalence between 2.5 and 15% in the general population. Among solidorgan transplant recipients, RLS was found in 45% of patients after hearttransplantation in a cross-sectional study. In a prospective study, RLScases disappeared after kidney transplantation in a group of patients onhemodialysis. The goal of this study is to determine the prevalence,severity and risk factors of RLS in a population of lung transplantrecipients.

METHODS: This is a cross-sectional, observational study that re-cruited consecutive patients in the transplant clinic. For the diagnosis andseverity assesment of RLS, we used previously validated questionnairespublished by the international RLS study group (IRLSSG). Demographicdata and possible risk factors were obtained from medical records.

RESULTS: RLS had a prevalence of 47.6% in 42 lung transplantrecipients recruited. Among the RLS patients, 80% had a moderate tosevere disorder based on the IRLSSG. The mean age in RLS patients(46.4 years � 15.5) was similar to the mean age in patients without RLS(46.8 years � 15.6) but there were more women in the RLS group (75%)compared to the non-RLS group (40.9%). Diabetes mellitus had aprevalence of 45.2% in the overall group but the frequency of diabetes didnot reach statistical difference between the two groups (p�0.05). Chronicrenal failure (defined as creatinine clearance � 50cc/hr), was found in42.8% in the overall group but had similar distribution in the RLS andnon-RLS groups (p�0.05).

CONCLUSION: RLS has a high prevalence in lung transplant recip-ients. Diabetes mellitus and chronic renal failure were frequent in lungtransplant recipients but had similar distribution in the patients with orwithout RLS.




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CLINICAL IMPLICATIONS: RLS is common and may have pro-found negative effects in the quality of life of transplant recipients causinginsomnia, fatigue, reduced concentration, decreased motivation, depres-sion and anxiety. Careful selection of therapy is necessary due to thepotential interactions with the numerous medications taken by lungtransplant recipients.

DISCLOSURE: Jose Yataco, None.

THE IMPACT OF SLEEP DISORDERS ON THE ATTENTIONDEFICIT DISORDER IN THE ADULTPART II: THE NON-OSAPATIENTClifford G. Risk MD* Nadine Y. Smith MS Clifford Risk, MD, Marlbor-ough, MA

PURPOSE: Patients with sleep disorders report excessive daytimefatigue, sleepiness, and attention impairment. This study will assess theimpact of sleep disorders (other than sleep apnea) on the attention deficitdisorder in patients who present with a wide spectrum of comorbidneuromuscular disorders, psychological disorders, auditory or readingimpairments, learning impairments, executive function impairments, andorganicity.

METHODS: This study included 64 adult patients who presented to anationally accredited sleep center for the evaluation of a slepe disorderother than obstructive sleep apnea. Scores were obtained for the degreeof attention deficit, insomnia, excessive daytime sleepiness, anxiety,depression, fatigue, and pain, using standard scales of measuring severity.Neuropsyhcological testing of memory and learning was perfomred on asubset of these patients.

RESULTS: Presenting comorbid diagnoses were as follows: Neuro-muscular disease (16), anxiety and mood disorders (22), auditory orreading deficits (5), impaired executive function or memory impairment(15), organic brain injury (6).Sleep diagnoses were as follows: Insomnia(50), hypersomnia (2), periodic limb movements of sleep (2), REMbehavior disorder (1), sleep terrors (1), fatigue/non-restorative sleep(8).Attention deficit was presented in 57 patients (90%), and stronglycorrelated with the severity of insomnia, anxiety and depression; auditoryor reading deficits; memory or learning impairments; and organicity.Neu-ropsychological testing demonstrated significant impairments in auditoryand visual learning and memory. Goal directed therapy undertaken in 15patients, successfully decreased their attention deficit to the normal range.

CONCLUSION: Sleep disorders other than obstructive sleep apneahave a strong impact on the presence of the attention deficit disorder inthe adult. The slepe disorder and the comorbid contributing disordermust both be evaluated and treated to improve the daytime attentiondeficit disorder.

CLINICAL IMPLICATIONS: Sleep specialists should be aware thatevaluation and treatment of insomnia and of other slepe disorders requiresconcurrent assessment of comorbid diagnoses that contribute to theattention deficit presentation. This is best achieved by a multidisciplinarymedical model.


RELATIONSHIP BETWEEN BODY FAT CONTENT AND ARTE-RIAL OXYGEN TENSION IN MILD-MODERATE OBESITYKhalil Ansarin MD* Mariam Nobari Tabrizi Jamal Ghaemmagami BSAliReza Ostadrahimi PhD Mehrnoush Toufan MD Tuberculosis andLung Research Center, Tabriz University of Medical Sciences, Tabriz,Iran

PURPOSE: Hypoxemia in obesity is attributed to gas exchangeabnormality secondary to physical effect of obesity on the FRC and otherlung volumes. However it seems that factors other than the physicaleffects of obesity are contributing to hypoxemia in obesity. We studied therelationship between fat content of mild-moderately obese subjects withtheir lung function changes and arterial oxygen pressure and saturation.

METHODS: We selected 22 ( 2 men and 20 women) otherwise healthyobese subjects (BMI � 35.68 � 3.2 and ages 17 to 60 years) from ObesityClinic of the Tabriz University of Medical Sciences. All subjects com-pleted a structured questionnaire indicating full medical and sleepdisorder history and underwent complete physical examination. All sub-jects had spirometry and lung volume studies (using Jaeger Bodyplethys-mograph, Germany), arterial blood gases(using AVL 995, Austria), pulseoxymetry, capnography, body mass composition analysis (using TanitaTBF215 Analyzer, Japan), and echocardiography with estimation of

pulmonary artery pressure. Matrix Pearson correlation was performed toobtain correlation between parameters.

RESULTS: None of the subjects had CO2 retention. We found asignificant negative correlation between both arterial oxygen pres-sure(PaO2) and saturation (O2Sat)and body fat mass, BMI and body fat %(r� -0.56; p�0.007, r� -0.57; p� 0.008, r � -0.533; p� 0.013 respec-tively) while there was no relationship between PaO2 and PaCO2,FRC%predicted, TLC%predicted, FVC%predicted or BMI. There wasno meaningful relationship between lung function parameters and bodyfat mass or fat % which may be related to a less than severe degree ofobesity in subjects studied.

CONCLUSION: PaO2 and SaO2 in obese subjects are negatively butsignificantly related to fat mass and fat percent of the body which it seemsto be at least partly independent of the effect of the obesity on the physicalchanges of respiratory system and lung function.

CLINICAL IMPLICATIONS: Arterial oxygen tension in obesity maybe related to factors other than physical effect of the obesity on therespiratory system and may be addressed accordingly for therapeuticpurposes.

DISCLOSURE: Khalil Ansarin, University grant monies From TabrizUniversity of Medical Sciences

THE IMPACT OF THE ATTENTION DEFICIT, MOOD, LEARN-ING AND PRAGMATIC DISORDERS ON THE PRESENTATIONOF AN INSOMNIA DISORDER IN THE ADOLESCENTClifford G. Risk MD* Nadine Y. Smith MS Clifford Risk, MD, Marlbor-ough, MA

PURPOSE: Adolescents presenting to a sleep center with a chiefcomplaint of insomnia may suffer from an underlying attention deficit,mood, learning or pragmatic disorder. This study evaluated the presenceof these dual diagnoses, and the effectiveness of patient-based therapeuticprograms to improve the insomnia and comorbid diagnoses.

METHODS: This study included 13 adolescents aged 10-17 whopresented to a nationally accredited sleep center for evaluation of aninsomnia condition. Diagnoses of attention deficit disorder, Asperger’ssyndrome, non-verbal learning disorder, anxiety, and depression wereestablished by prior neuropsychological and psychiatric assessments. Apatient centered learning program was structured to address specificattention and learning deficits and build compensatory strategies forlong term acquisition and memory and learning skills development.Treatment of insomnia included non-pharmacological interventions(sleep hygiene, sleep restriction, relaxation therapies) and pharmaco-logical interventions (hypnotics, benzodiazapines). Treatment formorning sleepiness and attention deficit included, when indicated, awake-promoting agent, and interventions by a speech language pathol-ogist and professional doctoral level education specialist with appro-priate modifications of the academic environment.

RESULTS: Attention deficit disorder was found in 7 adolescents;Asperger’s syndrome and non-verbal learning disorder in 3; obsessivecompulsive disorder, Tourette’s syndrome or an anxiety disordre in 3patients; depression in 3 patients; and leraning disorder in 1 patient.(Some adolescents carried dual diagnoses.) Treatment interventions wereeffective in 6 patients treated by us with respect to an improvement insleep structure and efficiency, and in improved alertness and attentive-ness, and knowledge acquisition.

CONCLUSION: Adolescents presenting with insomnia may sufferfrom significant disordres of attention deficit, pragmatic and specificlearning impairments, or anxiety and mood disorders. Diagnoses anddesign of a therapeutic intervention may improve the sleep disorder andtheir daytime attention and wakefulness impairments, and academicperformance.

CLINICAL IMPLICATIONS: Physicians and parents should beattentive to sleep disorder evaluations in the treatment of the adolescentwith a primary diagnosis of an attention, learning or mood disorder, anda comorbid diagnosis of either insomnia or delayed phase sleep disorder.





ARE OROFACIAL PAIN PATIENTS PRONE TO OROPHARYNXRELATIONSHIP MODIFICATIONS, ALTERED RESPIRATORYPATTERNS OR SLEEP DISORDERS?Florence M. Sekito MS* Lucas N. Lemes MD State University of Rio deJaneiro, Rio de Janeiro, Brazil

PURPOSE: Determine if in orofacial pain patients there are differ-ences of the Mallampatti classification indexes, respiratory upper airwayspreference and intensity flow or sleep problems in relationship to healthycontrols.

METHODS: The study design was transversal, analyzing 145 consec-utive healthy patients enrolled at UERJ Faculty of Dentistry, without anyprevious history of smoking or respiratory disease. The Mallampatti indexwas calculated in layed position according to the traditional description.They were classified by clinical examination in 3 groups according theirmode of breathing: nasal-breathing, oral-breathing, mixed-breathing(turns nasal or oral mode). All patients were submitted to the Epworthsleepiness questionnaire. Their respiratory airflow were measured by theForced Oscillation Technique (FOT), Oscilab-version 2.0, from nose andfrom mouth at a frequency of 5 Hz, to determine the obstruction in nasoand oropharynx.

RESULTS: The Qui-square and Fisher exact tests were used. Nostatistical differences were found in relation to Mallampatti index, respi-ratory patterns and upper airways obstruction between orofacial painpatients and controls. Pain patients had clinical sleepiness determined byEpworth index.

CONCLUSION: Orofacial pain has no effect on tongue position atoropharynx and does not alter patients breathing mode. Orofacial painpatients have sleepiness when compared to controls.

CLINICAL IMPLICATIONS: There was not any reference at theliterature about orofacial pain patients and breathing patterns, respiratoryflow evaluations, sleep disorders or tongue position in relationship tooropharynx. As far as we know this is the first description that neuromus-cular orofacial pain doesn’t cause any influence on these subjects.

DISCLOSURE: Florence Sekito, None.

SLEEP HABITS IN VENEZUELA AND ITS CORRELATIONWITH HEART AND LUNG DISEASEGur Y. Levy MD* Julio Castro MD Juan A. Cardenas MD BenitoRodriguez MD Dolores Moreno MD Ismenia Chaustre MD Arnoldo SotoMD Guillermo Isturiz MD Jose M. Lopez MD Universidad Central deVenezuela, Caracas, Venezuela

PURPOSE: Evaluate sleep habits and disorders among individualsfrom three cities in Venezuela and its correlations with lung and heartdiseases.

METHODS: A self-reported questionnaire sponsored by the Venezu-elan Association of Sleep Medicine, was designed in order to knowsocio-demographic profile, heart and lung diseases, alcohol intake, ciga-rette-smoking habits and sleep medication. Athens insomnia scale andEpworths sleepiness scale were also included. Epworth score was used asa main outcome logistic regression (Forward stepwise), two separatesmodels were performed to rule out overfiting; model A include only thequestions related to somnolence and model B include comorbid condi-tions and baseline characteristics. Significance level was considered as0.05.

RESULTS: 946 questionnaires were analyzed. Age: 10 to 81 (mean36.5) with 59 % of females. 15 % had heart disease, 12 % lung disorders,33 % known as snores, 39 % with ethylic habits, 16 % used sleeping pillsand Epworths scale of 6.7 � 4.4. Sleeping hours of 6.9 � 2.6 and workinghours of 8.2 hours � 2.09. According to the Athens scale, 62 % hadenough sleep time, 76 % had an overall satisfactory quality of sleep, 79 %had no awakening and 89 % had no somnolence.

CONCLUSION: Lung disorders and overall quality of sleep were the

only statistical variables associated to somnolence. The prevalence ofsnores (33 %) and apnea suggestive episodes (4 %) were similar tonumbers reported else were.

CLINICAL IMPLICATIONS: Lungs Diseases seem to be morerelated to somnolence that any other condition.

DISCLOSURE: Gur Levy, None.

Smoking Cessation12:30 PM - 2:00 PM

INITIATING AN INPATIENT SMOKING CESSATION PRO-GRAMJeanne McCabe RN Peter R. Smith MD Kathy A. Garrett-SzymanskiRRT* Rosemarie Samuels RN Latoya Fyffe Michael Bergman MD LongIsland College Hospital, Brooklyn, NY

PURPOSE: Smoking remains a chief avoidable cause of morbidity andmortality in the US. Healthcare organizations should be in the vanguardof efforts to develop smoking cessation programs. Inpatient smokingcessation programs (ISCPs) are often more effective than those in theambulatory setting. One year abstinence rates as high as 70% have beenreported for cardiac patients enrolled in ISCPs. We report our experiencewith initiation of an ISCP at our institution.

METHODS: Our 450 bed, university-affiliated hospital is in northwestBrooklyn. The goal was to provide cessation advice to all hospitalizedsmokers (smoked within the past twelve months) without new hires. Threestaffers, all with other primary responsibilities (Asthma Center coordina-tor, Adult CF Nurse Coordinator, bronchoscopy RN) were trained ascounselors using the 1996 US DHHS guideline. The 5Rs (Relevance,Risks, Rewards, Roadblocks, Repetition) and 5As (Ask, Advise, Assess,Assist, Arrange) were the key concepts learned and the focus for patientcounseling. Understanding nicotine replacement therapy (NRT) and theuse of buproprion were emphasized. A roster of newly admitted smokersis created by the hospital’s case managers each AM and faxed to theSmoking Cessation Center (SCC). Counselors see patients that day.Patients accepting, receive 5-10 minutes of counseling and writtenmaterials. Those declining, receive materials. Charts are stamped, docu-menting smoking cessation counseling. Physicians are encouraged toprescribe NRT and/or bupropion. Nursing staff are informed of theintervention. Monthly contacts via phone or email are attempted forpatients agreeing to follow-up.

RESULTS: The ISCP began 7/04. Outcomes through 3/05 are shownin the table. The project has been publicized widely and has enjoyedbroad support from clinical leadership, providers and administration.

Variable p value

Frequency

Cases (n�75) Controls (n�75)

Mallampatti 0,25 1 13.33% 1 12.00%2 28,00% 2 17.33%3 58,67% 3 70.67%

RespiratoryPattern

0,99 1 62.67% 1 62.67%2 5,33% 2 6.77%3 32,00% 3 30.67%

Upper airwaysobstruction

0.40 1 56,76% 1 63.51%2 43,24% 2 36.49%

Mallampatti level: 1-normal; 2-parcial obstruction; 3- total obstruc-tion

OddsRatio

StdErr z P � z

95% ConfInterval

City 0.855 0,94 -1,40 - 0,159 1,06Age 0,98 0,007 -1,57– 0,116 1,00Gender 1,2 0,25 1,26- 0,205 1,87Smokers 0.88 0,21 -0,49 - 0,619 1,42Alcohol intake (gday) 1,25 0,24 -1,15 - 0,24 1,85Heart disorders 1,14 0,27 -0,57 - 0,56 1,84Lung disorders 1,92 0,50 2,504 - 0,012 3,22Pills 0,96 0,26 -0,13 - 0,89 1,63Hours of sleep 0,88 0,05 -1,81- 0,07 1,00Hours of job 1,05 0,04 -1,10 - 0,26 1,14




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CONCLUSION: Our experience suggests that ISCPs can be imple-mented without additional hires. Success requires broad institutionalsupport, staff commitment based on an understanding of, and passion for,the task, and creative scheduling.

CLINICAL IMPLICATIONS: Wide-scale development of ISCPscould reduce tobacco use in the US especially benefiting those withsmoking-related illnesses resulting in hospital admission.

DISCLOSURE: Kathy Garrett-Szymanski, None.

A COMPARATIVE STUDY OF THE ROLE OF PHYSICIAN AD-VICE AND NICOTINE REPLACEMENT THERAPY IN SMOK-ING CESSATIONAshrafjit S. Chahal MD* Jai Kishan MD Anmol Dhillon MBBS MataKaushalya Hospital, Patiala, India

PURPOSE: Cigarette smoking is the most prevalent modifiable riskfactor for increased morbidity and mortality in the world. The WHOestimates that worldwide 1.1 billion people smoke, representing one thirdof the global population aged 16 years and above. If the present trendcontinues there will be 1 billion deaths due to tobacco during the 21stcentury compared to 100 million deaths during the 20th century. A studywas conducted to evaluate the comparative role of physician advice andnicotine replacement therapy on smoking cessation.

METHODS: A total of 150 smokers were enrolled in the study. Theywere divided into 3 groups of 50 each. One group received physicianadvice, the other nicotine replacement therapy and the third was givenplacebo. Fagerstorm score was used to quantify smoking dependence. Thepatients were followed for 6 months.

RESULTS: Advice alone is as effective as nicotine replacement therapyin smokers who have a Fagerstorm score of 4 to 7. Smokers with aFagerstorm score of 8 or more require more than advice alone.

CONCLUSION: Most of the time, physician advice alone goes a longway in making people quit smoking. In patients with high dependence,nicotine replacement therapy should be used alongwith. The progress apatients makes after intervention is directly related to what stage it was inprior to intervention.

CLINICAL IMPLICATIONS: Considering the enormous hazards ofsmoking, every patient coming in contact of the physician should be askedand advised about smoking.

DISCLOSURE: Ashrafjit Chahal, None.

DOES INTENSIVE SPORT AT SCHOOL HAVE AN IMPACT ONSMOKING IN ADOLESCENTS?Dominique Lauwers MD* Jacques LeComte MD Jean-Pol Quarre MDAnne Hoyez MD Philippe E. Pierard MD CHU Charleroi, Charleroi,Belgium

PURPOSE: It has been suggested that regular sporting practice mighthave a positive impact on smoking habits in young people. We tried toassess this impact in a group of adolescents.

METHODS: Students at the same school, aged 14 to 20 years, werestudied with a questionnaire relative to smoking habits, knowledge oftobacco risks, impact of media and school messages about smoking. Twogroups were distinguished : a sporting department (more than 8 hourssporting per week), and a traditional section (less than 3 hours).

RESULTS: 212 students were examined with a detailed questionnaireand 208 of them were fully completed and relevant : 122 in the sportingsection, 86 in the other group. 70 % of boys and 66 % of girls are nonsmokers in the sporting section, versus respectively 64 and 57 % in theother group. In both groups, 90 % of smokers intend to stop definitely inthe near future. Teaching messages at school are poorly received, butinformation carried by the media is well perceived and tobacco risks aregenerally known but addiction is massively misjudged. When they aresmokers, there is no significant difference of consumption habits between

the 2 groups. The use of drugs or alcoholic consumption is quiteexclusively related with the group of smokers.

CONCLUSION: Intensive sporting practice at school reduces signif-icantly, but moderately, the risk to become a regular smoker.

CLINICAL IMPLICATIONS: Intensive sporting practice at schoolseems to be a useful weapon for tobacco prevention in young people. Butit is also clear that an improved policy and a better information on smokingis needed at school, with particular attention on the risks of addiction.

DISCLOSURE: Dominique Lauwers, None.

SMOKING CESSATION: WHO DESERVES BEHAVIORAL ANDPHARMACOLOGICAL ASSISTANCE?Daiana Stolz MD* Anja Meyer Martin Brutsche MD Jorg Leuppi MDKarl Fagerstrom MD Michael Tamm MD University Hospital Basel,Pneumology, Basel, Switzerland

PURPOSE: To evaluate the appropriateness of the primary health caresystem to support smoking cessation as well as individual patterns forsuccessful quitting.

METHODS: University hospital employees (n�5218) were addressedthrough a two page, 17 questions questionnaire inquiring about past andcurrent smoking behavior. Questions included daily cigarette consump-tion, pack-years, previous quitting attempts, smoking free period, andutilization of pharmacological therapies and counseling.

RESULTS: 2574 (49.3%) questionnaires were returned. 791 subjectsdeclared to have successfully quit smoking. A complete data set wasavailable in 763 cases (mean age 44.4, range 17-68, 227 (29.8% male).Patients remained smoke free for a mean period of 11.8� 9.7 years.Smoking cessation method in these subjects was: cold turkey in 89%;counseling 1.7%; nicotine replacement therapy in 4.5%; bupropion in1.2%; and alternative approaches in 15.4%. On average, 2.4 � 3.02attempts leaded to successful smoking cessation. Smoking cessation wasachieved with one attempt in 53% of the cases, two in 19%, three in 13%,and more than three attempts in 14%, respectively. After two or moreunsuccessful attempts, odds ratio for unsuccessful smoking cessation was2.58 (95% CI 1.94 to 3.45).

CONCLUSION: The majority of the ex-smokers quitted smokingwithout any behavioral or pharmacological support. The chance tosuccessfully quit smoking without any help in a first or second attempt isconsiderable high. Accordingly, more than 50% of smokers have suc-ceeded to quit on the first attempt. The risk for smoking recurrence aftertwo ineffective quit attempts is markedly increased (OR 2.58).

CLINICAL IMPLICATIONS: Behavioral and pharmacological ther-apies for smoking cessation are deemed effective and are supposed to berecommended to all patients who are attempting to quit smoking.However, in reality, the majority of smokers quit smoke without any help.According to our data, assistance should be offered particularly to subjectswhich already performed two unsuccessful attempts to quit.

DISCLOSURE: Daiana Stolz, None.

HABIT AND STIMULATION: ARE THESE IMPORTANT FAC-TORS OF SMOKING DEPENDENCY IN YOUNG PEOPLE?Marija M. Mitic Milikic PhD* Miodrag D. Vukcevic MD SnezanaStojanovic-Ristic MD Milan M. Grujic MD Institute for PulmonaryDiseases and TB, Belgrade, Serbia

PURPOSE: In our previous study we showed that 39360 or 33.3% outof 118 342 students of University of Belgrade are smokers. The aim of thisstudy was to examine the importance of two factors of smoking depen-dency in young people - habit and stimulation by Ohio State University“Why Do You Smoke” questionnaire (WDYSQ).

METHODS: The study included 546 students of University of Bel-grade: 499 (mean age 20.9 � 2.7) at the begging of the study (group A)and 47 (mean age 22 � 1.7) on the forth years of the study (group B). Allof them fulfilled WDYSQ and six factors of smoking dependency werecalculated. Two factors, stimulation and habit were evaluated. Thedifference between the groups A and B was evaluated by student’s t-test.

RESULTS: The means values of stimulation and habit for whole groupof students were 4.55 �1.59 and 4.71 � 1.99 retrospectively. High levelof smoking dependency (score � 11) were found in 24 (4%) students forstimulation and in 36 (7%) for habit There were not established statisti-cally significant differences in the level of habit between groups A (4.7 �2.02 ) and B (4.89 � 2.0), as well as in stimulation between groups A( 4.49 � 1.53) and B ( 5.19 � 1.11).

ISCP 9 Month Outcomes

Total patients seen 635Committed to quit 458 (72.1%)Agreed to follow-up 270 (42.5%)Contacted �1 times 139 (51.5%)Abstinent @ 1-9 mos 75 (54.0%)


Smoking Cessation, continued


CONCLUSION: Stimulation and habit are neither frequent factors ofsmoking dependency nor the factors with the high level of smokingaddiction in young people.

CLINICAL IMPLICATIONS: The subject study was performed onthe young people having not been smoking for many years. These resultsmay help them to give up smoking as well as to find the best way to do it.

DISCLOSURE: Marija Mitic Milikic, None.

EFFICACY OF A COUNTY GOVERNMENT EMPLOYEE BENE-FITS SMOKING CESSATION PROGRAM UTILIZING AN ANTI-CHOLINERGIC INTRAMUSCULAR INJECTION COMBINEDWITH COUNSELINGKirk G. Voelker MD* Lung Associates of Sarasota, Sarasota, FL

PURPOSE: To evaluate the efficacy of a county government employeebenefits smoking cessation program utilizing counseling and an anticho-linergic intramuscular injection.

METHODS: Between January 1 and April 1, 2005 forty-five Sarasotacounty government employees enrolled in a smoking cessation programutilizing an anticholinergic intramuscular injection comprised of scopol-amine and hydroxyzine in conjunction with a dedicated counselingprogram. Patients were supplied with a educational video and booklet atleast one week prior to their office visit. They were also assigned a seriesof “homework” projects to be accomplished prior to their office visit. Onthe day of the office visit, they participated in group counseling lead by aphysician followed by individual counseling and an intramuscular injectionof scopolamine and hydroxyzine followed by 10 days of scopolamine basedoral medication. The patients also received telephone counseling by thephysician and trained counselors including a psychologist for as long asdeemed necessary.

RESULTS: One month success rates were compiled from patientfollow up telephone calls and confirmed by independent postcard evalu-ations returned to the Sarasota county wellness development advisor. Atthe end of one month, 34 of 45 patients(76%)were still smoke free. Thisis in concordance with our previously reported data of an 80% success rateusing this method. It is also consistent with our unpublished data of over500 patients which has yielded a 75% 1 month quit rate.

CONCLUSION: A smoking cessation program utilizing an intramus-cular injection of scopolamine and hydroxyzine in combination withcounseling and close follow up can be extremely effective when added toa governmental employee benefits program.

CLINICAL IMPLICATIONS: By October 2005 we will be able topresent independently verified 1 month smoking cessation data on over100 Sarasota county employees as well as six month data on these 45employees. We will also be able to present safety and efficacy data on over1000 patients and six month follow up data on over 500 patients treated atour clinic.

DISCLOSURE: Kirk Voelker, Shareholder American Medical Inno-vations Stop Smoking Clinics; Product/procedure/technique that is con-sidered research and is NOT yet approved for any purpose. Scopolamineand Hydroxazine are not FDA approved for smoking cessation.

THE KANO TEST FOR SOCIAL NICOTINE DEPENDENCE(KTSND) IN SAMPLES FROM A PHARMACEUTICAL COMPANYChiharu Yoshii MD* Masato Kano MD Yukiko Kawanami MD MasamitsuKido MD Division of Respiratory Disease, University of Occupational andEnvironmental He, Kitakyushu, Japan

PURPOSE: A smoking habit is maintained by psychological andphysical dependence. We developed a new concept, in regard to socialnicotine dependence, which is a part of psychological dependence, andmade a new questionnaire, namely, “The Kano Test for Social NicotineDependence (KTSND)”. The KTSND has ten questions with a total scoreof 30. In order to investigate the validity of the KTSND, we applied it topharmaceutical company employees.

METHODS: We delivered the KTSND to a pharmaceutical companyand received answers from 214 respondents. They consisted of 53 currentsmokers, 49 ex-smokers, and 112 non-smokers.

RESULTS: Total scores of the KTSND were 18.62 � 5.60, 15.00 �6.01, and 12.25 � 5.73 in current smokers, ex-smokers, and non-smokersrespectively. In regard to the subject matter of the questions, that is,“Tobacco is one of life’s pleasures”, “Smokers’ lifestyles may be re-spected”, “Smoking sometimes enriches people’s life”, “Tobacco haspositive physical or mental effects”, “Tobacco has effects to release stress”,

“Tobacco enhances the function of smokers’ brains”, “Doctors exaggeratethe ill effects of smoking”, and “People can smoke at the place whereashtrays are available”, current smokers tended to answer positively(p�0.05). To the question regarding “Smoking itself is a disease”, currentsmokers answered negatively (p�0.05). There was no significant differ-ence among the three groups to the question concerning “Tobacco is apart of culture”.

CONCLUSION: From the results of the KTSND, we found there wasa significant difference between current smokers and ex/non-smokers onsocial recognition and attitude to smoking.

CLINICAL IMPLICATIONS: The KTSND has good possibilities toplay a complementary role vis-a-vis the FTND.

DISCLOSURE: Chiharu Yoshii, None.

Testing Respiratory Function andMechanics12:30 PM - 2:00 PM

INSPIRATORY RESISTIVE LOAD-INDUCED MODIFICATIONOF TROPONIN T IN RAT DIAPHRAGMJeremy A. Simpson PhD* Steve Iscoe PhD Queen’s University, Kingston,ON, Canada

PURPOSE: Although the development of respiratory muscle fatiguehas been well documented, its molecular basis is poorly understood. Wewished to characterize the development of fatigue in rats subjected tosevere inspiratory resistive loading (IRL) and identify IRL-inducedchanges to the diaphragmatic myofilament proteome. We hypothesizedthat inspiratory resistive loading (IRL) would elicit diaphragmatic fatigue(a decrease in the ratio of transdiaphragmatic pressure to integratedphrenic; Pdi/�Phr) due, in part, to modifications to myofilament proteins.

METHODS: We subjected 14 spontaneously breathing anesthetizedrats to IRL until pump failure (decreased pressure generation) at whichpoint we terminated the load and harvested diaphragmatic tissue forproteomic analysis.

RESULTS: IRL elicited a rapid (� 2 min) decrease in Pdi/�Phr whichplateaued until a later decrease at � 42 min; this was followed by centralfailure (decreased minute phrenic activity) and pump failure at � 44 min.One-dimensional western blot analysis of myofilament proteins indicatedchanges only to the fast isoforms of troponin T (TnT), particularly a lossof the dominant isoforms of type IIB fibers. In western blots of serumtaken before and during IRL, we detected the presence of only the fast,not slow, isoform of troponin I, confirming damage to fast-twitch fibers. Inaddition, differential antibody immunoreactivity revealed an altered affin-ity to the other fast TnT isoforms, indicating the presence of a post-translational modification.

CONCLUSION: These results demonstrate for the first time that typeIIB fibers are preferentially injured during inspiratory resistive loadingand that TnT, a key contractile protein, is modified in the diaphragms ofrats subjected to IRL. The exact nature of this modification remains to bedetermined but likely plays an important role in the development offatigue.

CLINICAL IMPLICATIONS: Our results suggest that fatigue andinjury to fast fatiguable fibers alone is sufficient to cause respiratory pumpfailure.

DISCLOSURE: Jeremy Simpson, University grant monies Wm. M.Spear Foundation (funds bequested to Queen’s University for respiratory-related research); Block Term Grant (funds awarded to Queen’s Univer-sity from the Ontario Thoracic Society for respiratory-related research);Grant monies (from sources other than industry) Canadian Institutes forHealth Research and Ontario Thoracic Society.

THE CARDIOPULMONARY EFFECTS OF A CANNABINOID 1RECEPTOR (CB1) AGONIST IS MEDIATED BY THE TRAN-SIENT RECEPTOR POTENTIAL VANILLOID 1 (TRPV1) CHAN-NELSteven G. Smith BSc* Sandra G. Vincent Valerie F. Barrette John T.Fisher PhD Queen’s University, Kingston, ON, Canada

PURPOSE: Anandamide (AEA), a cannabinoid 1 receptor (CB1)agonist, has been suggested to be involved in the pathogenesis of


Smoking Cessation, continued


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hypertension (Lake et al, 1997) and cardiogenic shock (Wagner et al,2001). AEA also binds to transient receptor potential vanilloid 1 (TRPV1)channels (Zygmunt et al, 1999), which are expressed on pulmonaryC-fibers (Michael & Priestley, 1999). The latter are believed to beinvolved in the sensation of inflammation during lung disease (Lee &Widdicombe, 2001), and dyspnea during exercise (Paintal, 1973). In rats,intravenous injection of AEA elicits the pulmonary chemoreflex (apnea,bradycardia and hypotension; Lin & Lee, 2002), which is a C-fibermediated reflex (Coleridge & Coleridge, 1984). However, the role of thetransient receptor potential vanilloid 1 (TRPV1) receptor in this cardio-pulmonary response remains unknown.

METHODS: We measured the responses to AEA in anesthetizedspontaneously breathing TRPV1�/� (wildtype - WT) and TRPV1-/-(knockout - KO) mice. We also measured the response to aerosolized AEAin conscious, chronically instrumented WT and KO mice. Respiratoryfrequency (f) and heart rate (HR) were measured using a whole bodyplethysmograph and telemetry respectively. Vehicle, and AEA (9mM)were aerosolized at 350ml/min.

RESULTS: In anesthetized animals, the reflex pulmonary response toAEA was abolished in TRPV1 KO mice. In conscious mice, a significantbradycardia was observed during nebulization of AEA in the WT mice thatwas abolished in the TRPV1 KOs.

CONCLUSION: We conclude that TRPV1 plays a critical role in thecardiopulmonary reflex response to AEA.

CLINICAL IMPLICATIONS: We speculate that the TRPV1 proteinis a primary molecular mechanism mediating C-fiber reflexes and mayrepresent a therapeutic target for respiratory sensations involving bron-chopulmonary C-fiber afferents.

DISCLOSURE: Steven Smith, None.

RESPIRATORY SYSTEM IMPEDANCE AND NASOPHARYN-GEAL CLOSURE DURING PURSED-LIP BREATHINGYuko Sano MS* Hajime Kurosawa MD Yukio Katori MD ToshimitsuKobayashi MD Kayomi Matsumoto MS Naoki Mori MS MasahiroKohzuki MD Department of Internal Medicine and Rehabilitation Sci-ence, Tohoku University Sc, Sendai, Japan

PURPOSE: To elucidate the mechanics of pursed-lip breathing (PLB),which is a traditional skill to alleviate dyspnea, especially in patients withsevere airflow limitation such as chronic obstructive pulmonary disease(COPD).

METHODS: Twenty healthy volunteers were studied. Of these, in 10subjects (7 women and 3 men), aged 26 to 48 years (39.2 � 7.3 years;mean � SD), total respiratory system impedance (Zrs) was measured, andthe other 10, aged 29 to 77 years (55.0 � 14.9 years), were examined fornasopharyngeal phenomena endoscopically. Informed consent was ob-tained from all the volunteers. Zrs during PLB with or without a noseclipwas measured using the forced oscillation technique at 3 Hz. Zrs wasmeasured through a mouthpiece during quiet normal breathing orthrough a facemask during PLB. To confirm the nasopharyngeal functionduring PLB, endoscopic observation was performed.

RESULTS: Under the condition of wearing a noseclip, PLB signifi-cantly increased the Zrs from 0.37 � 0.15 to 0.87 � 0.34 (kPa/L/min;mean � SD). PLB also increased Zrs without a noseclip, showing similarresults as those with a noseclip. The nasopharynx was widely openedduring normal breathing. However, immediately after the start of PLB,the pharyngeal cavity was completely and strongly closed. This nasopha-ryngeal movement could consistently be observed in all the subjects.

CONCLUSION: These results demonstrated 1) the extent of the oralresistance, and 2) the nasopharyngeal closure, during PLB.

CLINICAL IMPLICATIONS: A noseclip is not necessary duringPLB. Estimation of respiratory impedance during PLB would be helpfulto estimate the dilating force on the small airways.

DISCLOSURE: Yuko Sano, None.

COMPUTED TOMOGRAPHY TO ASSESS RESPIRATORY ME-CHANICS IN TETRAPLEGIC PATIENTSGabi Mueller MS* Claudio Perret PhD Pius Hofer BSc Markus BergerMD Franz Michel MD Swiss Paraplegic Research, Nottwil, Switzerland

PURPOSE: The aim of this study was to evaluate the reproducibility ofcomputed tomography (CT) to assess respiratory mechanics in tetraplegicsubjects. Due to the lack of most expiratory muscles, tetraplegic subjectsshow big differences in respiratory mechanics compared to able-bodied

subjects. To specify these differences, the reproducibility of chest-CT-scans at maximal in- and expiration in tetraplegic subjects was assessed.

METHODS: Eight chronic tetraplegic subjects with motor completelesions between C5 and C8 were tested. All CT-scans were performedtwice in supine position, with a repositioning of the patient in-between. Atmaximal in- and expiration, a topogram of the whole chest and 2 slices atthe bottom plate of vertebral body Th4 and the cover plate of vertebralbody Th9 were recorded. The raw values for diaphragm levitation, lungareas as well as frontal and sagital expansions of the chest were calculatedby visual selection of the areas and distances using ’Osiris’ medicalimaging software. Coefficients of variation (CV) were calculated for thevariation between the first and second measurement of the patients andfor the intra-tester reproducibility of 3 independent testers, analyzingeverything twice.

RESULTS: Mean CV of the 3 intra-tester calculations were 0.2�0.1%for lung areas, 0.6�0.2% for sagital and 0.3�0.1% for frontal distancesand 2.9�1.0% for diaphragm levitation. Mean CV of the patients’ maximalin- and expiration were 3.8�2.6% for lung areas, 2.9�2.0% for sagital and1.3�0.6% for frontal distances and 11.3�2.4% for diaphragm levitation.

CONCLUSION: Our results showed a high intra-tester reproducibilityof the calculated values with CV below 1%. CV of maximal in- andexpiration of the patients were below 4%, indicating the measurementerror which is relevant for the practical use of this method. Concerningdiaphragm levitation, the rather weak reproducibility has to be taken intoaccount.

CLINICAL IMPLICATIONS: Computed tomography provides in-teresting possibilities to assess changes in respiratory mechanics due totraining or degeneration in tetraplegic subjects.

DISCLOSURE: Gabi Mueller, None.

POSTOPERATIVE PULMONARY COMPLICATIONS AFTER AB-DOMINAL SURGERYFayez Bader MD* Peter R. Smith MD Muhammed Baig MD JasonAkulian MD Veronica Brito MD Siddarth Shah MD Michael BergmanMD Antonio Alfonso MD Long Island College Hospital, Brooklyn, NY

PURPOSE: The frequency of, and risks for postoperative pulmonarycomplications (PPCs) after abdominal surgery (AS) are incompletelyunderstood. Definitions of PPCs have been variable and the range ofPPCs reported in the literature is wide (2-19%). In the present study wehave used a definition of PPCs that is clinically relevant in terms ofaffecting key outcomes including morbidity, mortality, and length of stay(LOS).

METHODS: Data for 200 consecutive Pts in 2004 were collected usingCPT codes to identify AS performed at our hospital. PPCs were definedas 2 or more of the following for at least 2 consecutive days, occurringwithin 7 days of surgery: 1) new cough /sputum production, 2) physicalexam c/w segmental or greater atelectasis or pneumonia 3) radiographicfindings c/w segmental or greater atelectasis or pneumonia 4) temp�38 C.Additionally, exacerbation of preexisting lung disease, respiratory failure,and pulmonary embolism defined PPCs. Incentive spirometry is usedroutinely at our hospital after AS. A stepwise multiple logistic regressionmodel was used for statistical analysis.

RESULTS: PPCs occured in 9 of 200 (4.5%) cases (Table I). Therewere no PPCs after laparoscopy. There were no deaths. Risk factors forPPCs identified in univariate analyses are shown in Table II. Nasogastrictubes and a history of cardiac disease independently predicted risk inmultivariate analysis. LOS was statistically greater in patients with PPCs(OR�1.17, 95% CI 1.08-1.27, p�.001).

CONCLUSION: These data suggest a low incidence of PPCs after AS.The reasons for a lower frequency of PPCs reflected by these datacompared to many prior studies are multi-factorial including a moreclinically relevant definition of PPCs, improved technology, and use of lessinvasive techniques (laparoscopy).

CLINICAL IMPLICATIONS: Morbidity and potential mortalityfrom PPCs can be reduced by preoperative risk assessment and appro-priate perioperative management.


Testing Respiratory Function andMechanics, continued


DISCLOSURE: Fayez Bader, None.

CORRELATION ANALYSIS BETWEEN SIX MINUTES WALKDISTANCE AND RESPIRATORY MUSCLES STRENGH ANDRESPIRATORY MUSCLES INCREMENTAL TEST IN COPD PA-TIENTSEvanirso S. Aquino BSc* Fernanda M. e Castro BA Isabel B. Lopes BAThaıs M. Peres BA Cristiane Cenachi-Coelho MA Inacio T. Cunha FilhoMD Uni-BH PUC Minas - Betim, Belo Horizonte, Brazil

PURPOSE: The objective of this study was to correlate the respiratorymuscles strengh(RMS) and respiratory muscles incremental test (RMIT-)with six minutes walk distance (6MWD)in COPD patients.

METHODS: COPD patients in clinically stable condition between 59and 80 years of age were selected if they met following criteria: mild tosevere airflow obstruction according to Global Initiative for ChronicObstructive Lung Disease. All patients were submited to lung functiontest, respiratory muscles strength, assessed by maximal inspiratory mouthpressure and maximal expiratory mouth pressure (PImax and PEmax),respiratory muscles incremental test (RMIT) and 6MWT.

RESULTS: 21 patients were studied (3 women and 18 mens). The mean agewas 71,66� 14,78 years. The results showed the positive correlation betweenInspiratory endurance time assessed by RMIT and 6MWD (r � �0,607 P�0,004), maximal inspiratory and expiratory load evaluated through RMIT with6MWD (r � �0,0598 P � 0,004) and (r � �0,442 P � 0,004)respectively.PImax and PEmax were not statistically significant.

CONCLUSION: The results of the present study demonstrate amoderate and positive correlation between respiratory muscles incremen-tal test and six minutes walk distance.

CLINICAL IMPLICATIONS: The respiratory muscles endurancetraining might contribute to exercise performance evaluated by sixminutes walk distance in patients with chronic airflow limitation.

DISCLOSURE: Evanirso Aquino, None.

CORRELATION BETWEEN INDIRECT METHODS OF THECORPORAL COMPOSITION ASSESSMENT AND RESPIRATORYMUSCLES STRENGTH AND ENDURANCE IN COPD PATIENTSEvanirso S. Aquino BS* Fernanda de M. Resgalla e Castro BA Isabel B.Vasconcellos Lopes BA Thaıs M. Peres BA Inacio T. Cunha Filho MDUNI-BH PUC Minas-Betim, Belo Horizonte - MG, Brazil

PURPOSE: To do a prospective analysis between indirect methods ofthe corporal composition assessment and respiratory muscle strength andendurance in chronic Obstructive Pulmonary Disease (COPD) patients.

METHODS: COPD patients in clinically stable condition wererecruited, and for the control group normal subjects around the sameage and biotype. All the subjects and patients were submitted topulmonary function test (spirometry), maximal respiratory pressures(PImax and Pemax), respiratory muscles incremental endurance test,six-minute walk test (6MWT), skinfold and body mass index (BMI)measurements.

RESULTS: A total of 30 subjects completed the study, 6 women and 24men. They were divided between three different groups: Group A;moderate to severe COPD (n�11); Group B, mild COPD (n�10) andGroup C, control group (n�9). The mean age was ( 69,54 � 10,51years),( 71,1 � 8,13 years), ( 70,11 � 5,86 years) and the mean values for theBMI was ( 24,00 � 3,66 Kg/m2), ( 24,41 � 0,58 Kg/m2) and (27,44 � 1,33Kg/m2) respectively . The results showed that the correlations were notstatistically significant between the anthropometric variables measuredand the strength and endurance of the respiratory muscles.

CONCLUSION: It is a literature consensus that diminish nutri-tional state evidenced through the weight loss causes an impairment ofthe peripheral and the respiratory muscles. Our study did not showedcorrelations statistically significant between the nutritional variablesand the strength and endurance of the respiratory muscles. Otherstudies are necessary with a bigger sample and with subjects withdifferent degrees of nutritional impairment to have a better analysis ofthe correlation between the nutritional state and the respiratorymuscles of the COPD patients.

CLINICAL IMPLICATIONS: There is no correlation between indi-rect methods of the corporal composition assessment and muscle respi-ratory strength and endurance in copd patients with body mass indexlower than 20 Kg/m2.

DISCLOSURE: Evanirso Aquino, None.

THE OXYGEN CONCENTRATIONS DELIVERED BY DIFFER-ENT OXYGEN THERAPY SYSTEMSJuan A. Garcia MD* Donna Gardner RRT David Vines RRT DavidShelledy PhD Richard Wettstein PhD Jay Peters MD University of TexasHealth Science Center at San Antonio, San Antonio, TX

PURPOSE: To test the oxygen concentrations delivered by some of theavailable oxygen therapy systems in normal subjects.

METHODS: Two different groups of ten healthy volunteers partic-ipated in two parts of this study. Nasal cannula (NC) O2 delivery wastested in the first group Simple masks (SM) and non-rebreathing(NRB) masks were tested in the second group. Each subject had a # 8French nasal catheter inserted through a nare with the tip positionedimmediately behind the uvula. The nasal catheter’s proximal end wasconnected to a syringe stopcock “T” piece system with the oxygenanalyzer in line. Oxygen was administrated via the high flow NC(model ref 1600, Salter Labs, Alvin, Ca) at flows 6-15 L/min. For theSM (Hudson RCI, Temecula, Ca), oxygen was administer at 6-12 L/m,and for the NRB mask (Hudson RCI, Temecula, Ca), the flow was 6-15L/min. At each different oxygen flow the subject breathed normally forfive minutes. Using the oxygen sampling system, three gas samples (60mL each) were withdrawn from the pharynx during inspiration anddirected to the oxygen analyzer. The average FiO2 delivered wasrecorded for each one of the oxygen flows administered with thedifferent systems.

RESULTS: Table 1 shows the means � SD for each device. Figure 1shows the comparison between the different devices.

CONCLUSION: The HFNC was able to provide higher mean FiO2than the SM at flows of 6-10 L/min; at 12 L/min the delivered FiO2 wasequal. HFNC compared to NRB mask delivered equal mean FiO2 atflows 8-15 L/min, and was superior at 6 L/min. Both masks will deliver lessvariable FiO2 than HFNC.

CLINICAL IMPLICATIONS: If needed, HFNC can deliver similarFiO2 than NRB mask. Medical personnel should be aware of the highFiO2 variability this system may deliver.When switching from HFNC toSM, a higher O2 flow should be selected to achieve similar deliveredFiO2. The simple rule for estimating delivered FiO2 with different oxygensystems is not accurate.

Table I

PPC Description n

Atelectasis 3Pneumonia / Atelect. 1Resp. Failure 2Pulm. Emboli 2COPD exacerb. 1

Table II—Risk Factors for Post Operative PulmonaryComplications

Risk Factor OR 95% CI p Value

Age 1.04 1.002-1.088 .039Smoking (ever) 4.0 1.10-14.53 .035COPD 9.11 .82-100.97 .072Cardiac disease 5.37 1.40-20.57 .014ASA 4.99 1.50-16.62 .009Anesthesia time 7.13 1.23-41.41 .029Upper abdo incision 8.88 1.06-74.26 .044NG tube 39.97 4.90-326.15 .001Non-pulm complic 4.36 1.03-18.43 .045




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DISCLOSURE: Juan Garcia, None.

TRANSCUTANEOUS CARBON DIOXIDE TENSION AND OXY-GEN SATURATION MONITORING VERSUS ARTERIAL BLOODGAS MEASUREMENTElisa Canturri MD Christian Domingo MD* Manel Lujan MD MiguelGallego MD Amalia Moreno MD Humildad Espuelas RN Merce Gime-nez MD Albert Marın MD Corporacio Parc Taulı, Sabadell, Spain

PURPOSE: To evaluate the precision of a non-invasive digital ear-clipsensor providing continuous transcutaneous (Tc) monitoring of carbondioxide tension (PaCO2) and oxygen saturation (SaO2%) using arterialblood gases (ABG) as the gold-standard technique.

METHODS: Population: patients referred to the Pulmonary FunctionTesting Laboratory of our Institution. Instrumentation: Spirometry wasperformed on the admission day. The ear-clip V-signTM (SenTec) wasplaced and after stabilization, the lecture was performed. While thepatient wore the ear-clip, ABG were performed, the blood was analyzedin two different blood gas analyzers and the mean value was taken as thegold-standard measurement. Statistical evaluation: Student’s t test forpaired data was used to compare the mean values obtained from the Tcand the ABG measurement. A Pearson correlation coefficient (r) wasobtained. Bland-Altman plot was used to detect bias in the readings. Thisevaluation was performed for the whole group and for sub-groupsstratified according to lung obstruction severity and PaCO2 value (nor-mal� 45 mmHg; elevated PaCO2 (�45 mmHg).

RESULTS: 130 patients were included (10 were excluded for calibra-tion problems of the sensor in two consecutive days). Data are given asmean�SD.The subgroup analysis did not show relevant differences. TheBland Altman plot did not show marked dispersion at any values of PaC02.

CONCLUSION: 1) The differences found in the measurements ofPaCO2 and SaO2 with both methods, although statistically significant,were not clinically relevant. 2) Appropriate calibration and stabilizationperiod of the Tc sensor is needed before a measurement is consideredreliable.

CLINICAL IMPLICATIONS: Tc measurement is a reliable methodto determine carbon dioxide tension and oxygen saturation. In many cases,this technique can substitute ABG analysis.

DISCLOSURE: Christian Domingo, None.

THE OXYGEN ADHERENCE MODEL: IMPROVING HOME OX-YGEN USAGEDeborah L. Cullen* Indiana University, Indianapolis, IN

PURPOSE: A handful of studies have pointed to explanations relatedto a patient’s reluctance to wear a cannula or breathe oxygen for 15 hoursa day. Fewer studies have determined strategies aimed at improvingLTOT (Long Term Oxygen Therapy) use. Adherence is not generalizableand may differ with treatment or by condition. Adherence is a dimensionalconstruct and no current explanatory theory or model specific to LTOTexists. LTOT adherence varies between 45-70% therefore an explanatorymodel is needed which addresses patient and treatment factors.

METHODS: An Oxygen Adherence Model was developed whichdefined the variables, processes and barriers present when LTOT and arespiratory disability interact. This hierarchical and tiered model is relatedto established drug adherence constructs, respiratory health behaviortheory, and physiologic variables inherent with chronic respiratory dis-ease.

RESULTS: Adherence will advance as the variables and domains ineach tier are addressed. Tier 1, Chronic Respiratory Disability is definedby symptoms and physiologic deteriorization which is assisted via LTOT.Tier 2, Information Enhancement, is educational as the clinician assiststhe patient and family with understanding LTOT. Interventions andtreatments related to Tier 3, Emotional and Psychological Limitations,should be focused to improving self-efficacy. Tier 4, Reduction ofTreatment Barriers should be approached with the goal of therapeuticeffectiveness.

CONCLUSION: Health behavioral and psychological models explaingeneral adherence behavior and have been effective in guiding interven-tional strategies for many conditions and health promotion. The OxygenAdherence Model can be tested to determine approaches appropriate tolimiting symptoms, improving physical limitations, educating the patient,addressing psychological and emotional variables as well as reducingbarriers to more effective oxygen therapy.

CLINICAL IMPLICATIONS: Chronic disease management includesadherence plans. Most patients find LTOT a complex treatment. Newstrategies and research related to LTOT adherence may assist withimproved LTOT utilization by patients.

DISCLOSURE: Deborah Cullen, None.

STANDARDIZATION AND ENHANCED SAFETY OF EXTER-NAL BATTERY SYSTEMS USED TO OPERATE PORTABLE VEN-TILATORS IN THE HOME CARE SETTING OF THE PROVINCEOF QUEBECBrigitte Fillion RRT* Mc Gill University Health Center, Montreal, PQ,Canada

PURPOSE: The aim of this project was to standardize and enhance thesafety of the clients of the National Program for Home VentilatoryAssistance (NPHVA) using external battery systems to operate theirportable ventilators in the home setting.

METHODS: A partnership was formed between the McGill UniversityHealth Centre’s Biomedical department and the National Program for

Table 1

O2

flow

(L/min)

Nasal

cannula

FiO2 %

(mean �

SD)

Range

FiO2 %

Simple

Mask

FiO2 %

(mean �

SD)

Range

FiO2 %

Non-

rebreather

FiO2 %

(mean �

SD)

Range

FiO2 %

Predicted

FiO2 %

6 54 � 13 35-89 43 � 2.6 38-47 45 � 2.9 40-49 45

8 58 � 14 33-87 41 � 2.6 37-47 57 � 4.6 51-65 53

10 66 � 13 40-88 57 � 3 52-63 68 � 2.3 64-71 61

12 69� 13 37-93 69 � 3.3 64-74 68 � 2.7 64-73 69

15 75 � 13 39-98 Not tested 74 � 2.4 68-77 77

ABG Tc * Mean Difference IC (95%) r *

CO2mmHg

42.16�7.2 40.93�8.4 1.22�4.1 -1.9; -0.50,875

SaO2% 93.46�4.4 94.35�4.4 0.88�3.1 0.3; 1.40,747

* p�0.05

Tier 1 Tier 2 Tier 3 Tier 4

Chronic Respiratory

Disability

Information

Enhancement

Emotional and

Psychological Limitations Treatment Barriers

Symptoms: Dyspnea,

Fatigue, Anxiety,

Depressed Mood

Physiologic

Deteriorization: Arterial

Oxygen Desaturation

Exercise capacity Body

Mass Index Cognitive

status Functional status

Prescription

Knowledge

Treatment

rationale

Technical ability

Motivational

enhancement

Denial Hopelessness

Apathy Misery Isolation

Burden Stigma Fear of

addiction Fear of

dependence Depressed

mood Anger Health

belief conflicts

Poor provider support

Limited clinician

communication Not

practically portable

Expensive

Inconvenient

Duration of treatment

Complexity Life style

interference




Home Ventilatory Assistance to identify Canadian Standard Association(CSA) recommendations regarding external battery systems for portableventilators. Together we evaluated if the battery systems employed by ourpatient population met CSA standards and if these were safe for homeusage. A cost analysis of available battery systems was also undertaken.

RESULTS: The findings demonstrated that there was no standard forcomplete battery systems but only for individual components. Further-more, the analysis of existing battery systems demonstrated that even theindividual components used did not always meet CSA standards makingthe battery systems employed potentially hazardous for clients in thehome setting. The costs analysis of the systems used by the patientpopulation showed that the cost was inordinate compared to the cost of acustom-made external battery system composted with CSA approvedcomponents.

CONCLUSION: This process allowed us to develop a custom-madeexternal battery system that was composed completely of CSA approvedcomponents. In addition a preventive program for lead-acid batteries wasalso developed.

CLINICAL IMPLICATIONS: The use of the custom-made externalbattery systems with CSA approved components has eliminated theincidents associated with the initial systems used by the population. Sinceone year of implementation there has been less reported service callsregarding battery systems.

DISCLOSURE: Brigitte Fillion, None.

RELATIVE SENSITIVITY AND LOWER LIMITS OF NORMALFOR SPIROGRAPHIC MARKERS OF AIRWAY OBSTRUCTIONJames E. Hansen MD* Xing Guo Sun MD Karlman Wasserman MDHarbor-UCLA Medical Center, Torrance, CA

PURPOSE: 1) Develop mean and 95% confidence lower limit ofnormal (LLN) formulae for FEV3/FVC for Black, Latin, and White menand women to supplement the findings of Hankinson et al. 2) Ascertaincomparative variability of FEV1/FVC, FEV3/FVC and FEF25-75 innever-smoking adults and evaluate their utility in measuring the effects ofsmoking on airway obstruction. 3) Develop and use the concept of1-FEV3/FVC to identify airway obstruction.

METHODS: We identified 5938 never-smokers and 3570 currentsmokers with spirometric data meeting American Thoracic Society stan-dards from the NHANES-III nationwide database. In these groups wedeveloped regression formulae for the FEV3/FVC, quantified variabilityand LLN of the FEV1/FVC, FEV3/FVC and FEF25-75 to identifyabnormalities in current-smokers, and evaluated 1–FEV3/FVC as amarker of airflow obstruction.

RESULTS: With normal aging, there were concurrent linear decreasesin FEV1/FVC and FEV3/FVC and increases in 1-FEV3/FVC, the latterattributable to slower emptying of acini with longer time constants. Bymiddle age these spirometric measurements worsened, on average, about20 years earlier in current-smokers. Two-thirds of current-smokers whomanifested airway obstruction had both FEV1/FVC and FEV3/FVCabnormal, while 1/6 had only FEV1/FVC abnormal and 1/6 had onlyFEV3/FVC abnormal. The normal variability of FEF25-75 is greatest andthat of the FEV3/FVC is least. If �80% of mean predicted FEF25-75values were used to identify abnormality, �25% of all never-smokerswould have been falsely identified as abnormal. Using 95% confidencelimits for FEF25-75, only 1% of never-smokers had isolated abnormalFEF25-75 while 42% of 683 smokers without restriction but with reducedFEV1/FVC and/or FEV3/FVC had normal FEF25-75 values (false nega-tives).

CONCLUSION: FEV1/FVC, FEV3/FVC and 1-FEV3/FVC all char-acterize expiratory obstruction well. In contrast, FEF25-75 has an unac-ceptably large proportion of false negatives and false positives.

CLINICAL IMPLICATIONS: Using �80% of mean predicted todefine abnormality is statistically invalid. For valid spirographic assess-ment of airways obstruction, we recommend requiring statistically correctLLN and replacement of the FEF25-75 with the FEV1/FVC andFEV3/FVC.

DISCLOSURE: James Hansen, None.

DETERMINING THE LOWER LIMITS OF NORMAL OF SPIRO-METRIC REFERENCE VALUES FOR ADULT CHINESE INHONG KONGJohnny W. Chan MBBS* Sai-On Ling MBBS Daniel Fong PhD Agnes LaiMS Fanny W. Ko MB, ChB Kam-Sing Tang MBBS Arthur C. Lau MBBSKahlin Choo MBBS Wai-Cho Yu MBBS Moira M. Chan-Yeung MBBSMary S. Ip MD Queen Elizabeth Hospital, Hong Kong, Hong Kong PRC

PURPOSE: Delineation of lower limits of normal (LLN) is importantin the clinical utilization of reference values. In a cross-sectional multi-center study to derive the reference spirometric values of adult Chinese,we compared two methods of its determination in lung function param-eters.

METHODS: The study was carried out between January 2001 andMarch 2003. Healthy non-smoking Chinese subjects were recruited fromthe community by random digit dialing to undergo spirometry in lungfunction laboratories of eight hospitals of Hong Kong. Prediction equa-tions for lung function parameters were developed using multiple regres-sion analysis. LLN were determined by: (1) traditional method assumingconstant difference between the mean and fifth percentile throughout theage range (mean-1.645 residual standard deviation); or (2) distribution-free estimation of age-related centiles described by Healy & Rabash(Annals of Human Biology 1988).

RESULTS: Evaluable data of 1089 (494 males and 595 females)subjects aged 18 to 80 years were analysed. In deriving LLN, distribution-free estimation, when compared with the traditional equation, yieldedbetter approximation to the fifth percentiles. To illustrate, 4.88% vs4.05%, 4.66% vs 3.64% and 4.86% vs 3.85% of men were considered tohave subnormal values of FEV1, FVC and FEV1/FVC ratio respectively.Equations from distribution-free estimation also yielded more stableage-related profiles of LLN. To illustrate, for FEV1, the proportions ofsubjects in four age stratifications who were classified as having subnormalvalues ranged from 3.33% to 6.58%, compared with 0.67% to 7.55%obtained with the traditional method.

CONCLUSION: In determining LLN for spirometric values, thedistribution-free estimation of age-related centiles, compared with an-other traditional method, yielded better proximity to fifth percentiles andmore stable profiles in various age groups.

CLINICAL IMPLICATIONS: Application of distribution-free esti-mation of age-related centiles was more appropriate in this study cohort.

DISCLOSURE: Johnny Chan, Grant monies (from sources other thanindustry) This study was supported by a grant from Hong Kong Pneumo-coniosis Fund Board; Other The study was conducted under the auspicesof Hong Kong Thoracic Society and American College of Chest Physicians(HK and Macau Chapter).

NORMAL REFERENCE VALUES FOR CARDIOPULMONARYEXERCISE TESTING AMONG FILIPINOSLenora C. Fernandez MD* Camilo C. Roa MD Norman Maghuyop MDUniversity of the Philippines, Manila, Philippines

PURPOSE: Performance on cardiopulmonary exercise test (CPET) isinfluenced by genetic, racial and environmental factors. Normal referencevalues derived from Caucasian populations are not deemed appropriate ifCPET is done among non-Caucasian subjects. It is important to establisha set of reference values for the Filipino population. The objectives of thisstudy were to (1) establish the Maximum Working Capacity, Peak oxygenintake (VO2), Peak carbon dioxide output (VCO2), Tidal Volume (TV) fornormal Filipinos during exercise, (2) determine the median perceived rateof exertion using the Borg Scale, and (3) derive prediction equationmodels for Maximum Working Capacity, Peak VO2 , Peak VCO2 andmaximum attained TV.

METHODS: The maximal cardiopulmonary responses were analyzedfor one hundred eighteen healthy sedentary adult Filipino subjects whounderwent CPET using a symptom limited incremental progressive cycleergometer driven protocol. A Vista Mini-CPX Model 17670 was used.Models for predicting VO2 max, VCO2 peak, VT peak, and Work maxwere derived with height, weight, age and sex being screened forsignificance as predictors of the said parameters. Linear and non-linearregression was done.

RESULTS: The maximum working capacity for males was154.21�26.6 watts and 93.02�15.57 watts for females while the peak VO2for males was 4.90�3.11 and 4.56�2.41 liters/minute for females. Thepredictive formulae derived from our study for maximum work capacity,peak VO2, VCO2 and tidal volume had acceptable correlation coefficients




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and performed as well as other published predictive equations based onCaucasian and Asian populations.

CONCLUSION: Cardiopulmonary exercise testing was performed ona community based, healthy, sedentary Filipino population using astandard maximal incremental cycle ergometry protocol. Predictive equa-tion models were derived for Maximum Working Capacity(r2 �0.728),peak VO2 (r2�0.123), peak VCO2(r2�0.648) and TV (r2 �0.579). Thederived predictive formulae performed as well as other published predic-tive equations.

CLINICAL IMPLICATIONS: Differences in response to cardiopul-monary exercise testing among racial populations do exist and normalreference values for different populations should be obtained and utilizedfor proper interpretation of these tests.

DISCLOSURE: Lenora Fernandez, Grant monies (from industryrelated sources) Boehringer-Ingelheim (Philippines) Research MedicalFoundation, Incorporated.

RELIABILITY OF THE ERROR CODE FROM THE BEST TRIALAS AN INDICATOR OF SPIROMETRIC TEST QUALITY USINGAMERICAN THORACIC SOCIETY (ATS) CRITERIAMayuko Fukunaga MD* Shobharani C. Sundaram MD Eugene J. KimMD James Sullivan BA Steve H. Salzman MD Beth Israel MedicalCenter, New York, NY

PURPOSE: Assessment of spirometric test quality is important inthe interpretation of an individual patient’s study, in determining theoverall quality of tests being performed by technologists, and whenusing the data in research. The 1994 ATS criteria for spirometryrequire three acceptable trials, two of which are reproducible. Com-puterized testing equipment often provide a five or six digit error codewhich summarizes whether these criteria have been met. The system inuse at our institution provides an error code that identifies whether thereproducibility criteria have been met, yet reports acceptability onlyfor the designated single best trial. The purpose of this study is todetermine how frequently an error code from the best trial that is bothacceptable and reproducible accurately indicates that all ATS criteriaare met when all trial data are manually reviewed.

METHODS: All spirometric tests performed on black, white orHispanic patients in 2003 and 2004 at Beth Israel Medical Center werereviewed. Tests were performed in a SensorMedics Vmax 6200Autobox (SenorMedics-Viasys, Yorba Linda, CA). The individual trialswere manually reviewed for all spirometric studies that had an errorcode suggesting that ATS criteria for acceptability and reproducibilitywere met.

RESULTS: There were 2416 tests which had an error code indicatingthat the best trial was acceptable and that reproducibility criteria weremet. Among these 2416 tests, 1926 (79.7%) actually had three or moreacceptable trials, 380 (16.0%) had two acceptable trials and 110 (4.6%)had only one acceptable trial.

CONCLUSION: A final report error code which summarizes whetherATS criteria for reproducibility and acceptability were met can bemisleading, unless it also reports how many individual trials meet ATScriteria for acceptability.

CLINICAL IMPLICATIONS: Graphical and numerical data, includ-ing error codes, should be reviewed from all spirometric trials to bestassess test quality prior to the use of the best trial data for interpretationor research.

DISCLOSURE: Mayuko Fukunaga, None.

SAFETY AND ACCURACY OF INHALATION OF CAPSAICINAEROSOLS IN A NORMAL ADULT POPULATIOND A. Sams DO* Thomas Truncale DO Stuart M. Brooks MD Universityof South Florida, Tampa, FL

PURPOSE: A subject’s death at Johns Hopkins, after inhalation ofhexamethonium, led to the FDA discouraging further human researchinvolving inhalation of non-approved medications/drugs. This reportdescribes the safety of inhalation studies using pharmaceutical gradecapsaicin and looks at the results of high pressure liquid chromatography(HPLC) analyses of administered doses compared to their calculatedconcentrations.

METHODS: 35 normal male subjects underwent capsaicin inhala-tion challenges under an Investigational New Drug (IND) protocolapproved by the FDA. Study protocol included the use of pharmaceu-tical grade capsaicin (Formosa Laboratories, Taiwan), subject safetyprocedures, and preparation of capsaicin doses by a registered phar-macist. Serial measurements of spirometry and impulse oscillemetrywere recorded as well as HPLC measurements of administeredcapsaicin doses. Continuous electrocardiography, blood pressure, andoxygen saturation were monitored.

RESULTS: There were no adverse reactions at any dose tested,including the highest capsaicin concentration of 1000 micromoles.Spirometry and oscillemetry did not change. HPLC measurements ofthe administered capsaicin concentrations were significantly lowerthan the calculated doses. The solutions averaged 14.7% lower than thecalculated values (2.2% lower at the highest dose of 1000 micromolesand 28.1% lower at the lowest dose of 0.48 micromoles). Coefficient ofvariation for the doses ranged between 1.7% (125 umol) and 5.4%(0.49 umol). There was stability of prepared capsaicin doses up to 4months.

CONCLUSION: Performance of capsaicin challenges can be con-sidered safe for normal individuals when using pharmaceutical gradecapsaicin and following strict safety procedures. HPLC documentsaccurate capsaicin concentrations for inhalation studies. The actualadministered doses are lower than calculated, and HPLC analysisimproves accuracy and reproducibility and insures the safety of subjectvolunteers.

CLINICAL IMPLICATIONS: Performance of capsaicin challengescan be considered safe, but there is a discrepancy between calculated andactual dosages administered. This brings in to question the accuracy andreproducibility of previously reported data.

DISCLOSURE: D Sams, None.

U.S. BORN ASIAN INDIANS HAVE HIGHER PULMONARYFUNCTION VALUES COMPARED TO IMMIGRANT ASIAN IN-DIANSAhmet S. Copur MD Ashok Fulambarker MD* Mark E. Cohen PhDMonali Patel Sanjay Gill George Chacko RRT Joseph K. Rosman MDFrank Maldonado MD Rosalind Franklin University of Medicine andScience/The Chicago Medical School, North Chicago, IL

PURPOSE: To evaluate differences in pulmonary function betweenUS born Asian Indians and immigrant Asian Indians that might beattributable to environmental and socioeconomic factors.

METHODS: We constructed regression equations to predict forcedvital capacity (FVC), forced expiratory volume in one second (FEV1),and mid-expiratory flow rate (FEF25-75) in 90 male and 90 femalehealthy, non-smoking US born Asian Indians and 160 male and 90female healthy, non-smoking immigrant Asian Indians, using Age andHeight as predictors, as well as these predictors in combination withthe binary country of origin variable. Age range in both groups was18-35. Values were obtained by using a Spirolab spirometer, followingstrict ATS guidelines.

RESULTS: The regression equations for each sex from each country oforigin are shown in Table 1. When data for countries were combined andCountry was considered as an independent variable in the regression,P-values for Country approached significance for Males (0.0655, 0.0958,0.3739) and were significant for females (�0.0001, �0.0001, 0.0925) forFVC, FEV1, and FEF25-75, respectively. As shown in Table 2, US bornsubjects had higher values for all measurements.

CONCLUSION: US Born, Asian Indian men and women had greaterpulmonary function values compared to immigrant Asian Indians. Thesedifferences approached statistical significance for men and were signifi-cant for women.

CLINICAL IMPLICATIONS: The differences in pulmonary functionbetween these groups could be attributed to differences in environmentaland socioeconomic factors.




DISCLOSURE: Ashok Fulambarker, None.

EVALUATION OF THE CORRELATION BETWEEN IMPULSEOSCILLOMETERY (IOS) AND CONVENTIONAL SPIROM-ETERY PARAMETERS IN PATIENTS WITH POSITIVE METHA-CHOLIN CHALLENGE TEST (MCT)Ali Moghimi MD* Abbas Nemati MD Mahdi Rahmati MD Iran Univer-sity of Medical Sciences and Health Care Services, Tehran, Iran

PURPOSE: IOS is a new method for the evaluation of the bronchialairway narrowing. In comparison with conventional spirometery IOS ismore convenient and needs less patient’s cooperation. The aim of thisstudy is to evaluate the correlation between the IOS and spirometeryparameters in patients with positive MCT.

METHODS: 42 patients with respiratory symptoms suggesting asthmaand positive MCT were studied. All of them had performed an IOS testwith MS Jeager device which measures both IOS and spirometeryparameters. After administration of different concentrations of methacho-lin IOS and spirometery parameters were measured. After at least 20%fall in the serial FEV1s, the case considered positive for MCT. The crudeand percent changes for X5, Z5, R5, R20, R central and R peripheral ofIOS and FEV1, PEFR, MMEF, FEF25%, FEF50% and FEF75% weremeasured and compared with each other.

RESULTS: Percent changes of predicted MMEF and FVC were notcorrelated significantly with any IOS parameter mentioned above. Signif-icant correlations between the percent changes FEF25%, FEF50%,FEF75% and PEFR and some IOS parameters was not clinically signif-icant (r � 0.5). Changes in the percent of predicted FEV1 were correlatedwith percent changes of the predicted and crude values of R5 and R20, allwith r � 0.5.

CONCLUSION: This study shows although there are some correla-tions between IOS and spirometery parameters, these are not clinically

significant. It might be because of technical considerations to do a correctIOS test and standardization of that.

CLINICAL IMPLICATIONS: Results of IOS test in determiningairway narrowing have a low correlation with conventional spirometery.

DISCLOSURE: Ali Moghimi, None.

GREATER THAN 12% IMPROVEMENT IN FEV1 OR 25% IM-PROVEMENT IN FEF25-75 AS PREDICTORS OF A POSITIVEMETHACHOLINE CHALLENGEZoheir Bshouty MD* Garth Rodgers RRT University of Manitoba,Winnipeg, MB, Canada

PURPOSE: To assess the sensitivity, specificity, positive and negativepredictive values of greater than 12% improvement in FEV1, or greaterthan 25% improvement in FEF25-75 as predictors of a positive metha-choline challenge in patients with a suspected diagnosis of asthma.

METHODS: 378 patients, 158 females and 220 males, with a sus-pected diagnosis of asthma underwent pulmonary function testing pre andpost bronchodilator administration and a methacholine challenge. Sensi-tivity, specificity, positive and negative predictive values for FEV1,FEF25-75, and either parameter were calculated. Youden Index was alsocalculated to assess the overall best test.

RESULTS: For FEV1, the sensitivity and specificity in predicting apositive methacholine challenge where 42.2% and 79.9% respectively[positive (PPV) and negative predictive values (NPV), 39.6% and 18.4%respectively]. For FEF25-75, the sensitivity and specificity in predicting apositive methacholine challenge where 26.8% and 89.2% respectively(PPV and NPV, 43.7% and 20.4% respectively). When using either FEV1or FEF25-75, the sensitivity and specificity in predicting a positivemethacholine challenge where 47.8% and 78.8% respectively (PPV andNPV, 41.4% and 17%, respectively). The Youden Index for FEV1 was22%, for FEF25-75 was 15.9%, and for either FEV1 or FEF25-75 was26.7%.

CONCLUSION: FEV1 is a more sensitive test in predicting a positivemethacholine test whereas FEF25-75 is a more specific test. The use ofeither criterion improved sensitivity at a small cost in specificity. Based onthe Youden Index either criterion is the best over all test.

CLINICAL IMPLICATIONS: Neither FEV1 nor FEF25-75 aregood predictors of a positive methacholine challenge. The application ofeither test does not improve this predictibility. In patients with suspectedasthma and negative bronchodilator response methacholine challengeshould still be performed to assess the presence of underlying hyperre-active airways disease.

DISCLOSURE: Zoheir Bshouty, None.

THE IMPACT OF CHRONIC LUNG DISEASES ON THE QUAL-ITY OF LIFE OF PATIENTS MEASURED BOTH BY DISEASESPECIFIC AND GENERIC INSTRUMENTSSiu Pui Lam MBBS* Pui Shan Lam MBBS Wai Woon Ho MBBS Ho PuiSo MBBS Wong Tai Sin Hospital, Hong Kong, Hong Kong PRC

PURPOSE: Chronic lung diseases affected the quality of life ofpatients. We aimed to (1) evaluate the health related quality of life(HRQOL) in patients with chronic lung diseases (2) examine the corre-lation among the HRQOL measures.

METHODS: Patients who joined the Pulmonary Rehabilitation Pro-gram between August and December 2004 were included. Pulmonaryfunction, blood gases and 6-min walking test were assessed. HRQOLinstruments included: SF-36 (Hong Kong), St George’s RespiratoryQuestionnaire (SGRQ) and the Functional Impairment Checklist (FIC).

RESULTS: The group consisted of 28 male (60.9.%) and 18 female(39.1%) with a mean age of 74.1 (SD � 9.5, range 39 – 87). The mean

Table 1—Prediction Equations for US Born andImmigrant Asian Indian Men and Women

US Born Asian Indian MenFVC � -3.378 � (0.0426)*HT � (0.0111)*Age R2�0.183FEV1� -1.562 � (0.0317)*HT � (-0.0100)*Age R2�0.1513FEF25-75� -2.909 � (0.0151)*HT � (-0.0504)*Age R2�0.026

Immigrant Asian Indian MenFVC� -4.382 � (0.0498)*HT � (-0.0080)*Age R2�0.2860FEV1�-2.339 � (0.0374)*HT � (-0.0249)*Age R2�0.3224FEF25-75�1.979 � (0.0208)*HT � (-0.0597)*Age R2�0.094

US Born Asian Indian WomenFVC� -2.575 � (0.0329)*HT � (0.0173)*Age R2�0.2875FEV1� -1.272� (0.0243)*HT � (0.0072)*Age R2�0.2081FEF25-75� -30.94 � (0.1716)*HT � (0.3634)*Age R2�0.0257

Immigrant Asian Indian WomenFVC�-0.700 � (0.0223)*HT � (-0.0011)*Age R2�0.1664FEV1� -0.403 � (0.0197)*HT � (-0.0099)*Age R2�0.2074FEF25-75� 1.452� (0.0145)*HT � (-0.0320)*Age R2�0.0813

Table 2—Typical Pulmonary Function Values Derivedfor a 25 Year Old Man With a Height of 1.75 Meters and

a 25 Years Old Woman With a Height of 1.65 Meters.-

TEST

US Born Asian

Indian Men

Immigrant

Asian

Indian Men

US Born

Asian

Indian Women

Immigrant Asian

Indian Women

FVC� 4.35 4.13 3.29 2.95

FEV1� 3.74 3.59 2.92 2.60

FEF25-75� 4.29 4.13 6.46 3.04

Table 1

Total Number of Patients 378

Males (%) / Females (%) 220 (58.2%) / 158 (41.8%)Age [Mean (Range)] 44.5 (16-71)FEV1 � 12% [Number (%)] 96 (25.4%)FEF25-75 � 25% [Number (%)] 55 (14.6%)Positive Methacholine [Number (%)] 90 (23.8%)




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FEV1 was 0.76 (SD 0.46), FVC 1.4 (SD � 0.58) with the FEV1 %predicted 51.2% (SD 24.9). The pulmonary diagnosis included ChronicObstructive Pulmonary Diseases (COPD 72%), chronic asthma (14%) andpulmonary tuberculosis (10%). The SF-36 domain scores were signifi-cantly impaired as compared with the population norms, particularly inphysical functioning (mean: 37.4 vs. 91.8), role physical (mean: 35.9 vs.82.4), general health (mean 37.1 vs. 55.98), vitality (mean 46.7 vs. 60.3)and role emotion (mean: 52.2 vs. 71.7). The norm-based physical compo-nent summary (PCS) was 25.7 (mean � SD 11.1) and mental componentsummary (MCS) was 52.8 (mean � SD 12.6). There was significantcorrelation between SF-36 PCS and FIC scales (FIC-symptom: -0.33, p �0.027; FIC-disability: -0.62, p � 0.001). The SF-36 MCS correlatedmoderately with FIC-disability (-0.39, p �0.008) but not with FIC-symptom and with SGRQ domains. The SGRQ activity domain correlatedmoderately with SF-36 PCS (-0.44, p � 0.15) and FIC domains (FIC-symptom: 0.37, p �0.44; FIC-disability: 0.5, p � 0.005). However, thecorrelation between the other SGRQ domains and SF-36 / FIC was notsignificant.

CONCLUSION: (1)The HRQOL of patients with chronic lung dis-eases was significantly impaired.(2)Moderate correlations existed amongthe different HRQOL instruments.

CLINICAL IMPLICATIONS: Both generic and disease specificHRQOL instruments should be used as in the comprehensive assessmentof patients suffering from chronic lung diseases.

DISCLOSURE: Siu Pui Lam, None.

THE VALUE OF A GOOD QUALITY FORCED EXPIRED FLOWBETWEEN 25% AND 75% OF THE VOLUME (FEF25-75) INDETECTING AIRFLOW OBSTRUCTIONJason L. Williams MD* Marcy F. Petrini PhD University of MississippiMedical Center, Jackson, MS

PURPOSE: To determine whether an FEF25-75 from a good flow-volume loop contour provides any additional information.

METHODS: The total number of tests performed in 2004 by aUniversity Hospital Pulmonary Function Laboratory were retrospectivelyanalyzed. We discarded tests that did not meet ATS standards, duplicatetests, tests from races other than Caucasian or African-American, or age �80 years. The remaining 871 tests were categorized according to obstruc-tion or non-obstruction and the FEF25-75 defined as normal or lowaccording to the NHANES III predictive equations (age � 80 years).

RESULTS: The Table shows the results. Of the 303 tests defined asobstructed by ratio of FEV1 to FVC, SVC (if available) or FEV6, 31% hada normal FEF25-75. Of the 568 non-obstructed tests, 7% had anabnormal FEF25-75. However, only 15 of these tests, or approximately3%, had flow-volume loop contours that provided a reliable FEF25-75.

CONCLUSION: Only 3% of the FEF25-75 provided potentially newinformation. However, this is the expected value for false positives. TheFEF25-75 was normal in 31% of the obstructed tests where it would beexpected to be abnormal.

CLINICAL IMPLICATIONS: Obstruction is generally detected byusing the FEV1/FVC, FEV1/SVC, or the newer FEV1/FEV6 ratio.Analyzing the FEF25-75 does not provide any additional useful informa-tion.

DISCLOSURE: Jason Williams, None.

DO WE REALLY NEED TO CORRECT FOR LUNG VOLUMEWHEN INTERPRETING THE DIFFUSING CAPACITY?Todd Whitman MD David A. Kaminsky MD* University of VermontCollege of Medicine, Burlington, VT

PURPOSE: The diffusing capacity of the lung for carbon monoxide(DLCO) is commonly used as a measure of gas exchange. The DLCO isusually reported as both an absolute number (DLCO) and corrected foralveolar volume (DLCO/VA). However, it remains unclear which one touse in interpretation. To resolve this dilemma we determined whetherabnormal DLCO or DLCO/VA was more closely associated with abnor-mal gas exchange as measured by exercise oximetry.

METHODS: With Institutional Review Board approval, we retrospec-tively reviewed the charts of all patients who had both DLCO and6-minute walk/oximetry testing at our University Pulmonary Clinic over a2-year period. We analyzed the association between abnormal DLCO orDLCO/VA (defined as �75% predicted) and abnormal gas exchange(defined as oxygen desaturation �/� 4%) using Chi-square or Fisher’sexact tests, and calculated sensitivity, specificity, positive and negativepredictive values (PPV, NPV) and likelihood ratios (LR). We alsomeasured the association between DLCO, DLCO/VA and oxygen desatu-ration using Spearman rank correlations.

RESULTS: A total of 93 patients had valid and complete data. Theiraverage age was 66 years, 54% were women and 60% had interstitial lungdisease. The prevalence of oxygen desaturation was 44%. The % predictedvalues of DLCO and DLCO/VA were highly correlated (rho�0.91,p�0.0001), but both correlated only weakly with oxygen desaturation(rho � -0.37, p�0.0003; rho� -0.42, p �0.0001, respectively). LowDLCO predicted desaturation with a sensitivity of 0.95, specificity of 0.29,PPV of 0.51, NPV of 0.88 and LR of 1.34 (p�0.003). Low DLCO/VApredicted desaturation with a sensitivity of 0.90, specificity of 0.38, PPV of0.54, NPV of 0.83 and LR�1.45 (p�0.002). The highest LR (1.91) wasseen for DLCO/VA of patients with restriction (p�0.04).

CONCLUSION: There were no differences in the ability of DLCO orDLCO/VA to predict abnormal gas exchange, but patients with abnormalgas exchange were slightly more likely to have an abnormal DLCO/VAthan DLCO.

CLINICAL IMPLICATIONS: Either the DLCO or DLCO/VA maybe used to assess gas exchange.

DISCLOSURE: David Kaminsky, None.

A SIMPLE MODEL OF PARADOXICAL VENTILATION ANDDIFFUSION-LIMITED GAS EXCHANGEMichael E. Perry MD* Antonio Vila BS Denver Lung, Centennial, CO

PURPOSE: We observed a consistent paradoxical reduction of arterialpCO2 in patients with Adult Respiratory Distress Syndrome (ARDS)whenever we minimized minute ventilation with respiratory rates as low as5/min using 4:1 inverse inspiratory/expiratory (I:E) mode ventilation. Thiseffect was counter-intuitive and its magnitude was a qualitative departurefrom behavior anticipated by deadspace timing effects or other ventila-tion/perfusion (V/Q) mechanisms. We wondered whether incompleteCO2 equilibration between the end-capillary and gas-containing compart-ments could account for our observation.

METHODS: We developed a rudimentary two compartment steady-state model of diffusion-limited gas exchange. The model determines themixed-venous pCO2 value required in the pulmonary capillary to producea diffusion flux across the boundary into the gas compartment equal to themetabolic production of CO2. The arterial pCO2 is in turn determined bystable metabolic production and cardiac output to be some constantamount less than this mixed-venous value. As opposed to V/Q-basedanalysis, there is no restriction that CO2 equilibration be completebetween pulmonary end-capillary (arterial) blood and ‘alveolar’ gas. Ourmodel maintains diffusion across the alveolar boundary proportional to thepartial pressure difference between the mixed-venous blood compartmentand the gas compartment. The gas compartment oscillates in an instan-taneous fashion, partially emptying between end-inspiratory and end-expiratory positions analogous to the ventilatory cycle of the lung. Themodel addresses effects of airway dimension by allowing diffusion onlyduring the maximal volume portion of each oscillation. A reconfigurationtime corrects for the non-square-wave character of physiologic ventilation.

RESULTS: Using a low diffusion co-efficient, inputs of I:E, respiratoryrate and tidal volume yield output patterns which demonstrate the efficacyof inverse I:E ventilation and reproduce the phenomenon of paradoxicalventilation.

CONCLUSION: Paradoxical ventilation may be a consequence of adiffusion-limited gas exchange regimen.

CLINICAL IMPLICATIONS: By directing ventilator strategy inARDS to maximize diffusion transfer, under certain circumstances muchlower ventilator frequencies can be theoretically justified. Lower frequen-cies might limit ventilator-induced lung injury by minimizing lung move-ment.

DISCLOSURE: Michael Perry, None.

Numbers (%) Obstructed Non-Obstructed

FEF Normal 93 (31%) 531 (93%)FEF Low 210 (69%) 37 (7%)




THE ROLE OF FEF50/0.5 FVC RATIO IN THE DIFFERENTIALDIAGNOSIS OF VENTILATORY DISORDERSMarcelo T. Rodrigues PhD* Sergio S. Menna Barreto PhD JussaraFiterman PhD Hospital de Clinicas de Porto Alegre, Porto Alegre, Brazil

PURPOSE: a) to evaluate the contribution of a new coefficient –FEF50/0.5 FVC ratio – from the maximal expiratory flow-volume(MEFV) curve in the differential diagnosis of ventilatory disorders; b) toevaluate the FEF50 / 0.5 FVC ratio in the separation of groups (Normal,Obstructive and Restrictive) of patients; c) to determine cut-off points foreach functional diagnosis and the probability of a diagnosis from anindividual value and to test the correlation between the FEV1 / FVC ratioand FEF50 / 0.5 FVC ratio.

METHODS: After evaluating the MEFV curves of the groups (Nor-mal, Obstructive and Restrictive), we calculated the FEF50 / 0.5 FVCratio and its differences. The whole sample was then divided in twogroups: obstructive and non-obstructive and the analysis of the likelihoodratio (LR) of the FEF50 / 0.5 FVC ratio between them was done.

RESULTS: There were 621 forced expiratory maneuvers performed byadults with a broad range of pulmonary abnormalities and normalsubjects. The FEF50 / 0.5 FVC ratio was different between the groupsNormal (2.10�0.82), Restrictive (2.55�1.47) and Obstructive(0.56�0.29) (p�0,001). It also showed a positive correlation with FEV1 /FVC ratio in the obstructive group (r�0.83). The analysis of the likelihoodratios for the FEF50 / 0.5 FVC showed that values below 0.79 are strongindications of obstructive disorders and above 1.33 almost exclude thisdiagnosis.

CONCLUSION: The FEF50 / 0.5 FVC ratio is a useful parameter inthe differential diagnosis of ventilatory disorders and has positive corre-lation with the FEV1 / FVC ratio.

CLINICAL IMPLICATIONS: Spirometry can provide information inorder to make the diagnosis of a ventilatory disorder. Sometimes,however, the conventional approach cannot be used, and more sophisti-cated resources are necessary, not always available. The FEF50 / 0.5 FVCratio can help in the differential diagnosis of ventilatory disorders.

DISCLOSURE: Marcelo Rodrigues, None.

AIRWAY RESISTANCE IN PATIENTS WITH AIRFLOW LIMITA-TION ESTIMATED BY THE INTERRUPTER TECHNIQUEHajime Kurosawa MD* Katsuhiro Maruta PhD Wataru Hida MD YukoSano MS Kayomi Matsumoto MS Maki Yamakawa MD Junko Niisato MDMasahiro Kohzuki MD Dep Int Med & Reha Sci, Tohoku Univ Sch Med,Sendai, Japan

PURPOSE: Measurement of airway resistance (Raw) requires bodyplethysmography, which makes difficult to monitor in disabled patients.On the other hand, measurement of airway resistance using the ineter-rupter technique (Rint) does not require the big and expencive apparatus,and has been reported in animal models, healthy subjects, pre-schoolchildren, and geriatric patients. However, little is known about Rint inpatients with high airway resistance. In this study, measurements of Rintwas compared those of conventional Raw using body plethysmography inpatients with airflow limitation such as COPD.

METHODS: We studied 7 patients including 5 with COPD (M:F 5:2,age 59 � 6.4 years). Rint was measured using a commercialized system(HI-801, Chest M.I., Tokyo). The algorism of Rint measurement in thissystem is based on a report by Chowienczyk et al. (Eur Respir J 4: 623,1991). Raw were measured using body plethysmography.

RESULTS: The mean FEV1, Rint, and Raw were 1.20 � 0.64L rangedfrom 0.57 to 2.13L (51 28%pred, 24-92%), 0.59 � 0.30 kPa/l/sec(0.28-1.12), and 0.30 � 0.14 kPa/l/sec (0.05-0.46), respectively. AlthoughRint was significantly correlated with Raw (r�0.86, p�0.05), the differ-ences tended to be bigger in patients with high Raw. Since airwaypressure curve after interruption was not linear, the oral pressuredetermination at the time point (t15) immediately after the valve inter-ruption, computed by back extrapolating a line drawn through two points(t30 and t70), was difficult to interprete.

CONCLUSION: These results suggest that Rint may be useful toestimate airway resistance even in patients with severe airflow limitation inthis system, although the value of the mesurements were higher than theconventionally measured Raw. The determination of the oral pressure atthe interruption established by Chowienczyk is needed to be physiologi-cally reexamined.

CLINICAL IMPLICATIONS: This technique would provide therough value of the airway resistance. It will be useful to study at thebedside where the body plethysmography can not work.

DISCLOSURE: Hajime Kurosawa, Employee One of the auther, KMaruta, is an employee of CHEST MI.

ASSOCIATION BETWEEN FEATURES OF VIBRATION RE-SPONSE IMAGING (VRI) OF THE LUNGS AND THE RESULTSOF METHACHOLINE INHALATION CHALLENGE TESTINGPayam Aghassi MD* J. Mark Madison MD Issahar Ben-Dov MDUniversity of Massachusetts Medical School, Worcester, MA

PURPOSE: Vibration Response Imaging (VRI) is a novel non-invasivetechnology that creates images of the lungs by recording vibrations fromthe chest wall during the respiratory cycle. It was hypothesized that somefeatures of VRI images at baseline might predict results of a subsequentlyperformed methacholine inhalation challenge (MIC) test.

METHODS: 14 patients underwent baseline VRI imaging immediatelyprior to a MIC test performed for evaluation of respiratory symptoms.Two readers that were blind to the MIC results independently scoredthese baseline VRI images, on a scale of 0-3, at different points of therespiratory cycle for shape and intensity, right-left symmetry, and maxi-mum vibration energy detected. Regression analysis was used to test theassociation between the 16 subcomponent scores describing the VRIimage and MIC test results.

RESULTS: VRI images were satisfactory for analysis in 13 patients andMIC test results were positive in 6. There was a correlation between thetotal VRI scores by the two readers (r�0.62, p�0.03). Average of the totalscores by the two readers had a poor association with MIC results (oddsratio�0.90, p�0.21). However, 3 subcomponent scores for specific imagefeatures (early inspiratory expansion, the direction of expansion duringinspiration, and maximum vibration energy) showed, in aggregate, apredictive trend (odds ratio�3.0, p�0.07). The 3 patients with the lowestsubcomponent scores had a positive MIC and the 2 patients with thehighest scores had a negative MIC.

CONCLUSION: Features of VRI images can be scored with interob-server correlation. Early inspiratory expansion, direction of image expan-sion during inspiration, and maximum vibration energy showed a trend forpredicting MIC test results. A larger, prospective clinical evaluation of ascoring system based on these image features needs to be performed.

CLINICAL IMPLICATIONS: A semi-quantitative scoring systembased on specific features of the baseline VRI image may be useful for thediagnosis of asthma. If such a scoring system can be validated prospec-tively, VRI would be a new and potentially sensitive method for evaluatingasthma.

DISCLOSURE: Payam Aghassi, Grant monies (from industry relatedsources) Supported by Deep Breeze, Ltd.; Product/procedure/techniquethat is considered research and is NOT yet approved for any purpose.

PULMONARY FUNCTION IN CHRONIC RENAL FAILURE: EF-FECTS OF PERITONEAL DIALYSIS AND HAEMODIALYSISAmela E. Matavulj MD* Pedja Kovacevic MD Slavimir Veljkovic MDZvezdana Rajkovaca MD Mirjana Djekic-Cadjo MD Nenad Ponorac MDMedical school, Department of Physiology, Banjaluka, Bosnia-Herze-govina

PURPOSE: In patients with chronic renal failure (CRF) there areincreased systemic complications induced by the kidney disorders. Everysystem in the body can be affected, including the lung. Pulmonary oedemaand pleural effusions are relatively common. Rarer complications includepulmonary fibrosis and calcification, pulmonary hypertension, haemo-siderosis, pleuritis and pleural fibrosis. Renal replacement therapy my alsoresult in complications. Haemodialysis causes recurrent episodes ofhypoxaemia due to partial blockage of the pulmonary capillary bed bywhite cells or silicone microemboli. We estimate effect of different formsof renal replacement therapy (peritoneal dialysis and haemodialysis) onventilator function improvement in patients with CRF [1, 2].

METHODS: We studied 43 patients (males, females) with CRF whowere clinically and radiologically free from known chronic lung and chestwall disease. Twenty one patients (group 1) were receiving continuousambulatory peritoneal dialysis (CAPD); we studied these patients with theabdomen containing dialysate. Twenty two patients (group 2) were beingtreated with regular haemodialysis. Forced vital capacity (FVC), forcedexpiratory volume in one second (FEV1), forced expiratory flow of vital




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capacity (FEF25, 50, 75) were recorded. The results were analyzed usingStudent t-test, and presented as mean � SD. All p values � 0,05 wereconsidered significant.

RESULTS: The values of ventilatory function (FEF25) were signifi-cantly lower in patients having continuous ambulatory peritoneal dialysis(table 1).

CONCLUSION: The values of ventilatory function (FEF25) weresignificantly lower in patients having continuous ambulatory peritonealdialysis.

CLINICAL IMPLICATIONS: Preliminary observations suggest re-versibility of airway obstruction with salbutamol.

DISCLOSURE: Amela Matavulj, None.

REGRESSION MODEL FOR THE ESTIMATION OF PRE-DICTED VALUES OF FORCED EXPIRATORY VOLUMES INFIRST SECOND (FEV1) BY PREDICTED VALUES OF PEAKEXPIRATORY FLOW RATE (PEFR) IN YOUNG MENAli Moghimi MD* Abbas Nemati MD Mahdi Rahmati MD Iran Univer-sity of Medical Sciences and Health Care Services, Tehran, Iran

PURPOSE: FEV1 is accepted as gold standard of the assessing airwaycaliber which needs spirometer. Despite of FEV1, PEFR could beevaluated by simple peak flow meter instruments, so it will be very helpfulto be able to estimate the amount of FEV1 in a patient by his or herPEFR. The aim of this study is to evaluate the correlation between thepredicted values of FEV1 and PEFR in patients underwent methacholinchallenge test (MCT) and design regression model of their correlation.

METHODS: This is a prospective cross-sectional study on 142 youngmen with respiratory symptoms suggesting asthma which were candidatesfor MCT. All the patients underwent MCT and spirometery according toAmerican Thorax Society guidelines. The measures of %FEV1 and%PEFR of patients were compared with each other. The normality ofdistributions was checked by Kolmogorov-Smirnov test. Pearson correla-tion coefficient was calculated and linear regression used for the statisticalanalysis.

RESULTS: Mean age of patients was 20.83 (SD, 1.92) years and allwere male. Although distribution of %FEV1 was not normal, that’s squarewas distributed normally. %PEFR and square of %FEV1 were signifi-cantly correlated (r�0.758;p�.000) and its regression model was (%FEV12 � 99.74 %PEFR – 381.05) with R�0.75. The model was not dependenton the %PEFR and the high and low measures did not affect model.

CONCLUSION: It is believed that assessment of airway caliberthrough PEFR monitoring may not be valid in some asthmatic subjects;yet, study of FEV1 and PEFR correlation looks like a different subject. Inaddition, it is first report of assessing correlation of PEFR with square ofFEV1 which seems to result in a fit model. Like any regression modelslack of plausibility is a major problem though further studies have to beconsidered.

CLINICAL IMPLICATIONS: By the mentioned model %FEV1 canbe predicted by %PEFR.

DISCLOSURE: Ali Moghimi, None.

DEEP BREATH MANEUVER ASSESSMENT ON GAS EX-CHANGE IN EISENMENGER SYNDROME PATIENTS WITHOBESITYMaria-Luisa Martınez-Guerra MD Luis-Efren Santos-Martinez MD*Edgar Bautista MD Tomas Pulido MD Gerardo Rojas MD DavidMendoza MD Sandoval Jose-Luis MD Silvio Namendys MD AliciaCastanon RN Julio Sandoval MD Instituto Nacional de CardiologıaIgnacio Chavez, Mexico City, Mexico

PURPOSE: Hypoxemia in Eisenmenger syndrome (ES) is a commonfeature of the disease. Improvement in PaO2 of severely obese patientswith hypoxemia through a deep breath maneuver (DBM) and improve-ment on the V/Q match has been described previously.Objetive: To assessthe impact of DBM on gas exchange (GE) on patients with both, ES andobesity.

METHODS: 30 patients with ES with obesity and obesity without ES,both with a body mass index (BMI) major than 35 were included. GE wasevaluated with ABG sampling at room air and 100% oxygen fraction. Theywent through routine evaluation including echocardiography and pulmo-nary function test. Values were expressed as mean � SD. Independentstudent t test were used to compare groups. p�0.05 was considered asstatistically significative.

RESULTS: 30 patients were included in two groups: 1) ES � obesityand 2) Obesity; Demographics variables as age, weight and height were:55 � 617; 11 years old, 87 � 17 kgs, and 153.1 � 9.5 respectively. The gasexchange values in the groups were:.

CONCLUSION: No changes were observed on GE with DBM in ESwith obesity patients.

CLINICAL IMPLICATIONS: DBM in severely obese patients isuseful to evaluate GE, but en ES with obesity patients, the DBM hasimportant limitations.

DISCLOSURE: Luis-Efren Santos-Martinez, None.

Tuberculosis: Diagnostic Evaluation12:30 PM - 2:00 PM

USEFULNESS OF QUANTIFERON-TB AS A DIAGNOSTICTOOL TO DETECT PLEURAL TUBERCULOSISYoujeong Sohn MD Dookyung Yang MD* Junghun Huh MD SookeolLee MD Choonhee Son MD Minki Lee MD Yunsung Kim MD EunjuSong Chulhun Chang MD Dong-A University Hospital, Busan, Korea

PURPOSE: Among several biological markers measured in pleuraleffusions, interferon (IFN)-gamma is the most sensitive and specific todiagnose pleural tuberculosis (TB). However the measurement of theIFN-gamma level in pleural fluid is not always available. The Quantif-eron-TB test (QFT) is a whole-blood IFN-gamma assay for the recogni-tion of cell-mediated immune response to Mycobacterium tuberculosis

Table 1

Replacement therapypredicted (� SD)

Function parametersPeritoneal dialysis

(CAPD) Haemodialysis

FVC 92(21) 100(17)FEV1 94(23) 98(20)FEF75�Tc�78 (24) 89(23)FEF50 64(31) 75(35)FEF25 57(20) 77(34)*

* p � 0,05




infection. We investigated whether QFT in whole-blood and pleuraleffusion is helpful to diagnose pleural TB.

METHODS: QFT was performed with the pleural fluid and wholeblood of patients with pleural effusion. We also measured pleural fluidadenosine deaminase (ADA) level and did pleural biopsy. Pleural TB wasdiagnosed if biopsy result shows chronic granulomatous inflammation.

RESULTS: Of the 28 patients with pleural effusion, 20 patients weredue to TB. The QFT of whole blood was positive in 12 out of 20 pleuralTB patients, and sensitivity was 60.0%. The QFT of pleural fluid waspositive in 8 out of 18 pleural TB patients. When we set cutoff value forADA level 40 IU/L, the sensitivity was 85% to detect pleural TB.

CONCLUSION: The sensitivity of the QFT in whole blood andpleural effusion was lower than the measurement of the pleural fluid ADAlevel.

CLINICAL IMPLICATIONS: Our result demonstrates that the QFTin whole blood and pleural fluid is not helpful to diagnose pleural TB inthe region where TB prevalence is high.

DISCLOSURE: Dookyung Yang, None.

USEFULNESS OF QUANTIFERON-TB AS A DIAGNOSTICTOOL FOR ACTIVE TUBERCULOSISYoujeong Sohn MD Dookyung Yang MD* Junghun Huh MD SookeolLee MD Choonhee Son MD Minki Lee MD Yunsung Kim MD EunjuSon Chulhun Chang MD Dong-A University Hospital, Busan, Korea

PURPOSE: The Quantiferon-TB test (QFT) is a whole-blood inter-feron (IFN)-gamma assay for the recognition of cell-mediated immuneresponse to Mycobacterium tuberculosis infection. It is already known asa useful diagnostic tool for the latent tuberculosis, but there is no studywhether it can be also used to detect active tuberculosis (TB). So weinvestigated usefulness of the QFT for the diagnosis of active TB.

METHODS: We prospectively studied in two tertiary care hospitalsfrom Aug. 2004 to Feb. 2005. 54 patients clinically suspected as active TBwere enrolled; 39 patients were AFB culture positive or histologicallyconfirmed and 15 patients were not. We measured IFN-gamma responseto PPD in whole blood assay.

RESULTS: The QFT of whole blood was positive in 25 out of 39 activeTB patients and negative in 7 out of 15 non-TB patients. So the sensitivity,specificity, positive predictive value and negative predictive value of theQFT were 64.1%, 46.6%, 75.7% and 33.3%, respectively.

CONCLUSION: Our result demonstrates that the QFT in wholeblood is not useful for the diagnosis of active TB in the region where TBincidence is high.

CLINICAL IMPLICATIONS: QFT in whole blood is not useful forthe diagnosis of active TB in the region where TB incidence is high.

DISCLOSURE: Dookyung Yang, None.

THE PREVALENCE OF LATENT PULMONARY TUBERCULO-SIS (LTB) IN A NORMAL AND A HIGH RISK POPULATIONGROUPS. Ali MBBS* N. Chew MBBS P. Manning PhD N. Noonan MD J. KeaneMD C. Bergin MD St. James’s Hospital, Dublin, Ireland

PURPOSE: To assess the efficacy of screening and compare theincidence of Latent Tuberculosis (LTB) and clinical Tuberculosis in twodifferent population groups.

METHODS: We evaluated the screening data of two different groupsin the country’s biggest Hospital. The normal population comprised theemployees joining the Hospital, while the high risk group comprised ofpatients suffering from HIV. The cases with positive Mantoux had beenoffered CXR and once found clear of TB were labelled as LTB.

RESULTS: The mean age of healthy group was 38 and HIV 51 years.1948 were men in the healthy and 207 in HIV group. The number ofnative Irish in these groups was 2001 and 99, while that of Non Irish was409 and 232. The number of Non Irish patients in HIV was 232(65.9%)from Sub Sahara, 33(9.3%) from Europe, 4(1.1%) from USA and1(0.28%) from Asia. The number of individual having LTB (positiveMontoux test and normal CXR) was 765(31.7%) in normal and 39(11.07)in HIV group.

CONCLUSION: The data in our study indicates that a significantproportion of normal healthy population and HIV group had LatentTuberculosis (LTB). While the incidence of LTB was higher in the normalhealthy population, the incidence of clinical TB was higher in HIV group.

CLINICAL IMPLICATIONS: This study strongly highlights thesignificance and need of screening for Tuberculosis.

DISCLOSURE: S. Ali, None.

OXIDANTS STRESS AND ANTIOXIDANTS IN PULMONARYTUBERCULOSISKiranjit Kaur MD Jai Kishan MD* Gurdeep K. Bedi MD Rajinderjit S.Ahi MBBS TB & Chest Dept/Hospital Govt. Medical College, Patiala,India

PURPOSE: Recent literature implicate free radicals in physiologic/pathophysiologic processes and in wide spectrum of diseases.Tuberculosisis an ancient disease but has stayed in modern times. Mycobacteria areintracellular pathogens who grow and replicate in the host macrophages.In an attempt to kill mycobacteria, host cells namely-macrophages,neutrophills and monocytes generate huge amounts of reactive oxygenspecies, which also contribute to inflammatory injury to host tissues. Manystudies are not avialable where oxidative stress and antioxidants have beenstudied in pulmonary tuberculosis (PTB). So present study was under-taken.

METHODS: In 50 patients of PTB and 30 normal controls,malonyl-dialdehyde(MDA)as marker of oxidative stressand glutathion-e(GSM),Vit.C,superoxide dismutase(SOD)fot antioxidants status werestudied.MDA,GSH,Vit. C and SOD were estimated by methods of Stocksand Dormandy(1971),Beutler et al (1963),varley (2004) and Marklundand Marklund (1974) respectively.Patients of PTB were classified accord-ing to radiological extant,sputum grading and cavity status.

RESULTS: Levels of MDA,GSM,Vit.C &SOD and there statisticalsignificance is as given in table below there was significant correlationbetween radiological extent,sputum grading and cavity status of PTB andthe levels of MDA, GSM,Vit. C and SOD.

CONCLUSION: There is oxidative stress and decreased antioxidantsactivity in patients of PTB which correlate with radiological extent,Sputumgrading and cavity status.

CLINICAL IMPLICATIONS: Antioxidants can have role in patientsof PTB for prevention and treatment of infammatory damage.

DISCLOSURE: Jai Kishan, None.

CHANGE OF IL-12 AND TNF-ALPHA PRODUCTIONS MEA-SURED BY WHOLE BLOOD CULTURE IN TUBERCULOSISPATIENTS AFTER TREATMENTYoung S. Kim MD* Jin W. Moon MD Chang H. Han MD Shin M. KangMD Moo S. Park MD Se K. Kim MD Joon Chang MD Sung K. Kim MDYonsei Univ College of Medicine, Seoul, South Korea

PURPOSE: Tuberculosis is one of the leading infectious diseases inadults, causing around 3 million deaths annually. Research on understand-ing the host defense and immunopathogenesis of tuberculosis is necessarybecause there is an urgent need for a new vaccine and adjunctiveimmunotherapy, particularly in patients with drug resistant Mycobacte-rium tuberculosis infection. Recently, many aspects of cytokine dynamicsin patients with active pulmonary tuberculosis have been investigatedthrough ex-vivo studies with specific or crude mycobacterial antigens, orM. tuberculosis.

METHODS: We used whole blood culture method in order to evaluateIL-12 and TNF-alpha productions in active TB patients, tuberculin skintest positive and negative healthy controls. We investigated the produc-tions of IL-12, TNF-alpha in response to nonspecific mitogens and M.tuberculosis specific antigens. We used many tuberculous antigens forstimulation. The tuberculous antigens are culture filtrate proteins (CFP),purified protein derivatives (PPD), antigen 85A M. tuberculosis proteins(Ag85A), early secretory antigen target-6 (ESAT-6), 38k Dalton antigen

InvestigationStudy GroupMean � SD

Control GroupMean � SD

Stat.Signi.

MDA 706.24 � 158.68 538.32 � 147.72 HSGSH 31.59 � 5.82 36.16 � 6.55 HSVit. C 0.68 � 0.11 1.14 � 0.22 HSSOD 18.83 � 5.10 24.04 � 6.87 HS


Tuberculosis: Diagnostic Evaluation,continued


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(38kDa), RNA polymerase � subunit B1 (rpoB1), RNA polymerase �subunits B2 (rpoB1), arabinofuranasyl lipoarabinomannan(araLAM),manosyl-capped lipoarabinomannan(manLAM), and non-specific mito-gens are concanavalinA(ConA), lipopolysaccaride(LPS), phytohaemagglu-tinin(PHA). In addition, we monitored the changes of each cytokineproduction in TB patients during the course of therapeutic treatment.

RESULTS: In our study, production of IL-12, TNF-alpha to non-mannose-capped lipoarabinomannan(araLAM) increased significantly inactive tuberculosis patients compared to healthy controls, After 2 month,production of IL-12, TNF-alpha to araLAM decreased significantlythroughout the therapeutic periods.

CONCLUSION: Our study suggest that productions of IL-12, TNF-alpha plays a important role in the pathogenesis and treatment oftuberculosis.

CLINICAL IMPLICATIONS: Whole blood culture method to IL-12,TNF-alpha may be used in the diagnosis of active pulmonary tuberculosis.

DISCLOSURE: Young Kim, None.

TUBERCULOUS LYMPHADENITIS: CLINICAL CHARACTER-ISTICS AND OUTCOME IN A COMMUNITY HOSPITALTapan K. Gayen MD* Ravindra Hanumaiah MD Vijay Rupanagudi MDKarthikeyan Kanagarajan MD Santi Dhar MD Coney Island Hospital,Brooklyn, NY

PURPOSE: Tuberculosis (TB) affecting the lymph nodes remain themost common extra pulmonary involvement by Mycobacterium Tubercu-losis (MTB). In United States, over the last 35 years, the proportion ofTuberculous lymphatic disease has risen substantially, whereas reductionshave been most pronounced in other forms of extra pulmonary TB. Theaim of our study is to identify characteristics associated with its presen-tation, diagnosis and treatment.

METHODS: Retrospective review of 50 cases of TB lymphadenitisseen between 1992 to 2005 in a community hospital. Diagnosis of TB

lymphadenitis was proven by lymph node biopsy based on the histologyand/or growth of MTB on culture.

RESULTS: The following results obtained.CONCLUSION: Foreign born particularly immigrants from Indian

subcontinent constituted the predominant patient subgroups with TBlymphadenitis. Cervical lymphadenopathy constituted predominantlymph node group involved. PPD was positive in only 60%, while only 8%had sputum growing MTB. 72% of patients had positive lymph nodeculture for MTB and in others pathology showing caseating granulomaswas needed to establish diagnosis. 6 months of treatment was adequate inmost of the patients. Major reasons for prolonged duration were adversereactions and non compliance. 8% of paradoxical reaction seen was similarto that described with TB involving other systems.

CLINICAL IMPLICATIONS: In patients with subacute to chroniclymphadenitis especially from Indian subcontinent, TB should be stronglyconsidered even if PPD is negative and sputum is negative for MTB.Lymph node pathology showing caseating granuloma establishes thediagnosis even if culture is negative.

DISCLOSURE: Tapan Gayen, None.

PULMONARY AND PLEURAL TUBERCULOSIS IN EXTREMEELDERLYEun A Eum MD* Yangjin Jegal MD Moo Cheol Shin MD Kwang WonSeo MD Woon-Jung Kwon MD Jong-Joon Ahn MD Department ofPulmonology and Critical Care Medicine, Ulsan University Hospital,Ulsan, Korea

PURPOSE: Several publications about tuberculosis in elderly patientshave suggested that their clinical presentation and clinical course might beatypical from those in elderly. This tendency may be more strengthenedwith advancing years in age. The aim of this study was to compare clinicalfeatures of pulmonary and pleural tuberculosis in extreme elderly (�80years old) with those in elderly (between 60 and 79).

METHODS: Thirty-seven extreme elderly with pulmonary and pleuraltuberculosis from Ulsan University hospital between January 2000 andDecember 2004 were compared with randomly selected fifty-six elderlypatients.

RESULTS: General weakness was the only symptom that was observedmore frequently in extreme elderly than in elderly (p�0.016). Othersymptoms such as cough, sputum, fever, weight loss, anorexia and chestpain were not different between two groups. Dyspnea tends to be morefrequent, and hemoptysis tends to be less common in extreme elderlyalthough they were not statistically significant (p�0.056, 0.053 respec-tively). Evolution time before diagnosis and laboratory findings at presen-tation were not different between two groups. The incidence of comorbidconditions such as chronic obstructive pulmonary disease, diabetes,gastrectomy and malignancies were not different between two groups.

Variable Value (%)

Median ageMale: Female

39 years1:1

DemographyIndian subcontinentUS bornOthers

32 (64%)8 (16%)10 (20%)

PPD positiveHIV positiveSputum culture � for MTB

30 (60%)7 (14%)4 (8%)

Lymph node Culture & SensitivityCulture � for MTBPansensitiveMulti drug resistant TB

36 (72%)35 (70%)

1 (2%)

Duration of treatment6 months9 months12 months18 months24 months*

35 (70%)6 (12%)4 (8%)3 (6%)2 (4%)

Adverse reactionsAbnormal Liver function testsSkin rashParadoxical reaction

11 (22%)4 (4%)4 (8%)

Reasons for prolonged treatmentAdverse reactionsNon complianceRelapseDrug resistance

6 (12%)6 (12%)2 (4%)1 (2%)

*One patient with multi drug resistance and another patient withrelapse received 24 months of treatment




Anorexia was more frequently observed in extreme elderly than elderlyafter initiation of antituberculous drugs. The incidences of hepatotoxicity,skin rash, optic neuritis and peripheral neuropathy were not different.Moreover, the mortality from tuberculosis was not different between twogroups. Three cases died from tuberculosis in extreme elderly. The causeof death for those three cases was mainly discontinuation of antitubercu-lous drug.

CONCLUSION: The clinical features and prognosis of pulmonary andpleural tuberculosis in extreme elderly were not significantly differentfrom those in elderly.

CLINICAL IMPLICATIONS: Tuberculosis even in extreme elderlyshould be treated with standard regimens because adverse effects ofantituberculous drugs and prognosis were not different from elderlypatients.

DISCLOSURE: Eun A Eum, None.

THORACIC COMPLICATIONS IN TUBERCULOSIS AND DIA-BETES PATIENTSMa Cecilia Garcia-Sancho MS* Enrique L. Segundo MD Rafael V.Vazquez MS Alfredo Torres MD Manuel Castillejos MS Miguel AngelSalazar Lezama MD National Institute of Respiratory Diseases, Mexico,Mexico

PURPOSE: To determine the prevalence of thoracic complicationsamong pulmonary tuberculosis and diabetes patients in comparison withpatients with tuberculosis alone.

METHODS: This study was a cross-sectional survey based on theretrospective analysis of data of tuberculosis subjects in diabetic and notdiabetic patients. The study was conducted at Clinic of Tuberculosis ofNational Institute of Respiratory Diseases (INER), Mexico.

RESULTS: One hundred and sixteen tuberculosis patients wereincluded from July to December of 2003. Fifty-two cases of diabetesmellitus were identified among 116 tuberculosis patients, prevalence:44.8%. Of116 patients, 56 (48.3%) were males, with a ratio male:female of0.93. Of 116 patients 91.4% have bacteriological confirmation. Of 116patients (92/116) 79.3% have from 0 to 5 years from diagnosis oftuberculosis. The tuberculosis and diabetes patients were older thantuberculosis patients (mean �SD 52.38�11.35 versus 40.70�16.55 p�.0001). Complications among diabetics or no diabetics patients were:bronchiectasis (96.2% versus 80.9%, p �.01); pneumonia (9.6% versus1.6%, p�.05); pneumonia by Mycobacterium tuberculosis (7.7% versus1.6%, p �.1) and hemoptysis (34.6% versus 29.7% p �.6). In multivariateanalysis diabetes mellitus was associated to older age (OR� 1.06 years[CI95% 1.02-1.10] p �.0001) and to the presence of bronchiectasis (OR�13.95 [CI95% 1.84-105] p �.01), controlling by crowding, pneumonia,empiema, hemoptysis and time since tuberculosis diagnosis.

CONCLUSION: The increased risk of bonchiectasies and pneumoniaamong patients with diabetes and tuberculosis suggest the difficulty of thehost in the infection control. One of two tuberculosis patients wasdiabetics at INER.

CLINICAL IMPLICATIONS: It is necessary to do bacteriologicaland clinical surveillance for pulmonary tuberculosis among diabeticpatients and clinical and metabolic surveillance for diabetes amongtuberculosis patients with the purpose to prevent sequels and deaths dueto tuberculosis.

DISCLOSURE: Ma Cecilia Garcia-Sancho, None.

CLINICO-RADIOLOGICAL PROFILE OF PLUMONARY TU-BERCULOSIS IN ALCOHOLICSRamakant Dixit MD Sidharth Sharma MBBS* J.L.N. Medical College,Ajmer, India

PURPOSE: Risk of tuberculosis is said to be higher in alcoholics dueto defect in host defence, whether this is associated with altered clinico-radiological presentation, we conducted this prospective study over last 2years.

METHODS: 64 consequtive patients having history of almost regularalcohol intake of more than 5 years, in whom pulmonary tuberculosis wasdiagnosed were included in this study. Their HIV seropositivity was ruledout by Elisa.

RESULTS: Most of the patients (70.3%) were above forty years of age.All were male and smoker. Cough (90.6%) and fever (65.6%) were chiefsymptoms followed by chest pain (45.3%) breathlessness (32.8%) andhaemoptysis (10.9%). On initial sputum examination, 42.1% were smear

positive. Radiologically bilateral lesions were seen in 60.9% cases andunilateral in 39% of which most were left sided. Disease was far advancedin 46.8%, moderately advanced in 43.7% and minimal in 9.3% cases.Patchy infiltration and nodular pattern was most common (75%) followedby cavitary (15.6%), Pleural effusion (7.8) and miliary pattern (1.5%).Lesions were almost equally distributed in upper, mid and tower zones.26.5% patients were having associated extrapulmonary tuberculosis.

CONCLUSION: In alcoholics due to decreased immunity due tovarious factors tubecrculosis is extensive and may take serious form.

CLINICAL IMPLICATIONS: In alcoholics, tuberculosis involve-ment is extensive and presents bilateral radiological shadows in majority ofcases. Non cavitary exudative lesions are more common along withextrapulmonary involvement in significant proportion of cases.

DISCLOSURE: Dr Sidharth Sharma, Product/procedure/techniquethat is considered research and is NOT yet approved for any purpose.

PULMONARY COMPLICATIONS IN PATIENTS WITH TUBER-CULOSISEnrique Lopez Segundo MD* Rafael Valdez MS Ma. Cecilia GarciaSancho MS Manuel Castillejos MS Alfredo Torres MD Miguel AngelSalazar MD National Institute of Respiratory Diseases, Mexico, Mexico

PURPOSE: To determine the prevalence of thoracic complications intuberculosis patients.

METHODS: This study was a cross-sectional survey based on theretrospective analysis of data of tuberculosis patients and was conductedat National Institute of Respiratory Diseases (INER), Mexico.

RESULTS: One hundred and twenty four tuberculosis patients wereincluded from July to December of 2003. Of124 patients, 58 (46.8%) weremales, with a ratio male:female of 0.88. Median age was 48 (range 16-80years). Of 124 patients (99/124) 80%% had 0-5 years since diagnosis.Complications were: bronchiectasis (107/124) 86.3%; pneumonia (7/124)5.7%; pneumonia due to Mycobacterium tuberculosis (5/124) 4.0%;empiema (4/124) 3.2%; fistula (3/124) 2.4%; aspergilloma (2/124) 1.6%;tracheal obstruction (1/124) 0.8%; fibrothorax (15/124) 12.1% and hemop-tysis (38/124) 30.2%. In multivariate analysis death was associated topleural effusion (OR� 15.07 [CI95% 1.12-201] p �.04) controlling bycrowding, pneumonia, empiema, hemoptysis, diabetes, time of diagnosisand age.

CONCLUSION: The increased risk of bonchiectasis, pneumonia andhemoptysis observed is due to delay in tuberculosis diagnosis andtreatment.

CLINICAL IMPLICATIONS: Delay in tuberculosis diagnosis couldbe determinant in the quality of life and survival of these patients.

DISCLOSURE: Enrique Lopez Segundo, None.

DIAGNOSTIC ROLES OF BRONCHOSCOPY IN PULMONARYTUBERCULOSISSang-Ha Kim MD* Won-Yeon Lee MD Tae-Won Hong MD Nak-WonLee MD Hoon Choi MD Suk-Joong Yong MD Kye-Chul Shin MDDepartment of Internal Medicine, Yonsei University Wonju College ofMedicine, Wonju, South Korea

PURPOSE: The fiberoptic bronchoscopy has been used widely indiagnosing pulmonary diseases. It is a useful procedure for evaluatingsuspected cases of pulmonary tuberculosis. The aim of the study was toclassify bronchoscopic findings of pulmonary tuberculosis and to evaluatethe diagnostic yield by bronchoscopic procedure.

METHODS: We have analyzed the clinical characteristics of 93patients who had visited our hospital and been performed bronchoscopicprocedure for the diagnosis of pulmonary tuberculosis from March 1,2003 to December 31, 2003, retrospectively. Pulmonary tuberculosis wasconfirmed by direct smear, culture, tissue biopsy and TB-PCR in allstudied subjects. Bronchoscopic findings of pulmonary tuberculosis wasclassified into three types (endobronchial tuberculosis, bronchial anthra-cosis and normal bronchus) and endobronchial tuberculosis classified intoseven subtypes as stenotic type with fibrosis, stenotic type without fibrosis,actively caseating type, tumorous type, ulcerative type, and granular type.

RESULTS: Only 24.7% (30/93 patients) had the positive results ofsputum smear and culture for AFB. For the bronchoscopic procedures,pulmonary tuberculosis was confirmed by direct smear and culture in59.1% (55/93), bronchoscopic biopsy in 66.7% (26/39), TB-PCR in 86.3%(63/73). The patient with normal bronchial finding was 31.2% (29/93patients) of the studied subjects. We observed that the prevalence of




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bronchial anthracosis was 18.3% (17/93) and endobronchial tuberculosiswas 50.5% (47/93). Out of the patients with endobronchial tuberculosis,actively caseating type and stenotic type without fibrosis were observed in34.0% (14/47), 25.5% (12/47), respectively. And we observed that thenonspecific bronchitic type, stenotic with fibrosis, tumorous type, ulcer-ative type and granular type were 19.1% (9/47), 6.4% (3/47), 6.4% (3/47),6.4% (3/47) and 2.1% (1/47), respectively.

CONCLUSION: The endobronchial tuberculosis was the most fre-quent finding of pulmonary tuberculosis except normal bronchial finding.It is important to find out the cases with endobronchial tuberculosis earlybecause it frequently combined with severe complications such as bron-chial stenosis.

CLINICAL IMPLICATIONS: We suggest that the bronchoscopyshould be considered when we evaluate the possibility of pulmonarytuberculosis in the countries with high prevalence of it.

DISCLOSURE: Sang-Ha Kim, None.

DIAGNOSIS OF PULMONARY TUBERCULOSIS IN PATIENTSWITH CLINICAL OR RADIOLOGICAL EVIDENCE OF DIS-EASE AND NEGATIVE SPUTUMViviane R. Figueiredo MD Francisco S. Vargas MD Marcia Seiscento MDJorge Kawakama MD Milena M. Acencio BS Cesar L. Moreira BS EvaldoMarchi MD Leila Antonangelo MD* Pulmonary Division-Heart Institute(InCor) and Department of Pathology, Sao Paul, Sao Paulo, Brazil

PURPOSE: To evaluate the performance of laboratorial tests indiagnosing tuberculosis in patients with clinical or radiological evidence ofdisease but with negative sputum.

METHODS: Thirty-four patients with clinical (cough, fever, weighloss) or radiological (micronodules, consolidation, cavitation, nodules)suspicion of pulmonary tuberculosis but having negative sputum weresubmmited to fiberoptic broncoscopy to obtain bronchoalveolar lavage(BAL). Sensitivity, Specificity, PPV and NPV of BAL smear, culture, PCRand ADA (cut-off 2.5 U/L); bronchial biopsy;smear and culture frominduced sputum (collected after the BAL)and PPD were evaluated.

RESULTS: From the 34 patients with tuberculosis suspicion, only 22(64.7%) had been confirmed the diagnosis. The performance of the testsis showed in the table bellow.

CONCLUSION: PPD and cultures (BAL and sputum) were the mostsensitive methods for the diagnosis of pulmonary tuberculosis. However,due to the low specificity of the PPD, this test may be judged with criteriain places where there is high prevalence of tuberculosis.

CLINICAL IMPLICATIONS: The diagnosis of tuberculosis in pa-tients with negative sputum is a clinical problem all over the world. Theassociation of multiple laboaratory tests can improve the diagnosis field.


CITOKYNES IN BRONCHOALVEOLAR LAVAGE FROM PA-TIENTS WITH PULMONARY TUBERCULOSIS AND NEGATIVESPUTUMLeila Antonangelo MD* Milena M. Acencio BS Francisco S. Vargas MDLisete R. Teixeira MD Marcia Seiscento MD Wilson L. Pedreira JuniorMD Gabriela G. Carnevale PharmD Viviane R. Figueiredo MD Pulmo-nary Division-Heart Institute (InCor) and Department of Pathology,Universi, Sao Paulo, Brazil

PURPOSE: To evaluate the IL-1�, TNF-� and TGF�1 profile insamples of brochoalveolar lavage obtained from patients with pulmonarytuberculosis and negative smear and culture sputum.

METHODS: Samples of bronchoalveolar lavage obtained from 19patients with pulmonary tuberculosis, 8 patients with others pulmonarydiseases and 4 patients without pulmonary disease (control) were evalu-ated for IL-1�, TNF� and TGF� by an ELISA assay. The Kruskal -Wallis

one way analysis of variance was used to compare the data between thegroups. Significant statistical differences were considered for p� 0.05.

RESULTS: The results are expressed in median (CI 25-75%) and aredemonstrated in the table below.

CONCLUSION: We do not observe significant differences for IL-1�,TNF� and TGF� among tuberculosis patients, patients with otherspulmonary diseases and control group.

CLINICAL IMPLICATIONS: This profile of cytokines do not con-tribute to differentiate tuberculosis from others pulmonary diseases andmust not be used for diagnosis in patients with clinical or radiologicalsuspicion of tuberculosis and negative smear.


INDUCED SPUTUM VERSUS FIBEROPTIC BRONCHOSCOPYIN DIAGNOSIS OF PULMONARY TUBERCULOSISAmr A. Darwish MD* Ahmed A. Abd el Rahman MD Wafaa A. ZahraanMD Nourane Y. Azab MD Mohammed A. Agha MD MenouffyiaUniversity, Menouffyia, Egypt

PURPOSE: Tuberculosis (TB) remains one of the deadliest diseases inthe world.Cases can’t expectorate sputum constitute a major problemespecially in developing countries. Therefore, the aim of this study was tocompare between sputum induction (SI) using nebulized hypertonicsaline and fiberoptic bronchoscopy (FOB) in the diagnosis of pulmonaryTB in clinically and radiologically suspected cases.

METHODS: This study included 30 patients(17 males and 13 females-)with clinical and radiological suspicion of pulmonary TB. They had eitherdry cough or negative repeated sputum examinations for AFB. Threesuccessive SI using nebulized hypertonic saline and FOB were done for allpatients. Ziehl-Neelson stain (Z.N.) and Lowenstein-Jensen media(L.J.)were be used for the diagnosis of tuberculosis.

RESULTS: The sensitivity, specificity and accuracy of SI comparedwith bronchial washing using Z.N. were 80%,100% and 90% respective-ly.While,using L.J. media the sensitivity, specificity and accuracy of SIcompared with bronchial washing were 88%, 100% and 90% respective-ly.The positive results of SI and post-bronchoscopic sputum were similar22 cases (66.7%). There was no significant difference (P�0.05) betweenSI, 20 cases (66.7)and bronchial brushing,23 case (76.7) in diagnisingpulmonary TB. The third SI sample is the most significant sample indetecting AFB (19 cases).

CONCLUSION: Sputum induction is an easy, effective, cheap andnon-invasive procedure for the diagnosis of pulmonary TB compared toFOB. Also, SI is very suitable diagnositic technique where FOB isnotavailable.

CLINICAL IMPLICATIONS: Sputum induction must be done toevery patient with clinical and radiological suspecion of pulmonary TBwho can’t expectorate sputum or their sputum were negative for AFB.Fiberoptic bronchoscopy should be postponed until three induced spu-tum samples proved to be negative for AFB.

DISCLOSURE: Amr Darwish, None.

EVALUATING THE DIAGNOSIS OF TUBERCULOSIS IN IN-DUCED SPUTUM COLLECTION AND BRONCHOALVEOLARLAVAGE SPECIMENSRogerio G. Xavier MD* Fabricio L. Savegnago Fernanda Damian NataliaFernandes Monica Rodrigues Patrıcia Passos Paulo Franciscatto PedroPiccinini Lucelia Henn MD Bronchology Unit, Hospital de Clınicas dePorto Alegre, Porto Alegre, Brazil

PURPOSE: Validation of induced sputum (IS) with aerosol hypertonicsaline solution followed by bronchoalveolar lavage (BAL) through flexiblebronchoscopy (FB) in patients without spontaneous sputum for thediagnosis of pulmonary tuberculosis (TB).

METHODS: Sputum was induced after 3 or more unsatisfactoryspontaneous collection for acid fast bacilli (AFB). FB was recommendedto collect BAL in a series of 99 patients with clinical suspicion of TB that

BALsmear

BALculture

BALPCR

BALADA

Bronchialbiopsy

Pos BALsmear

Pos BALculture PPD

Sensituvity (%) 13.6 66.7 35 35.7 31.8 21.1 53.3 90Specificity (%) 100 100 100 60 100 100 100 14.3PPV(%) 100 100 100 54.5 100 100 100 60.0NPV(%) 38.7 57.1 48.0 30.0 44.4 55.5 53.3 50

Control Tuberculosis Non-Tuberculosis p

IL-1� 7.8 (7.8-7.8) 7.8 (7.8-31.8) 7.8 (7.8-140.2) 0.515TNF-� 15.6 (15.6-15.6) 24.5 (15.6-41.8) 15.6 (15.6-52.7) 0.213TGF-�1 31.2 (31.2-31.2) 31.2 (31.2-31.2) 31.2 (31.2-65.2) 0.503




remained negative after AFB in IS specimens. It comprised 41 female and58 male individuals, 55 were HIV negative and 44 HIV positive. Micro-biology results were analysed from cultures in Middlebrook and Loewen-stein-Jensen media from IS and BAL specimens.

RESULTS: Diagnosis of TB was confirmed in 38 patients, 28 withpulmonary and 10 with extrapulmonary involvement; 48 patients hadother diagnosis confirmed but 13 other remained undiagnosed; 3 cases ofMOTT were identified in HIV negative individuals without TB. In the 28patients with pulmonary TB, 11 had a BAL procedure: AFB was positivein 8/28 at IS and 1/11 at BAL. M. tuberculosis was identified at culturesin IS specimens (22/28), BAL specimens (8/11) and both IS and BAL(7/28). Other diagnosis made at BAL in 5 HIV positive cases werepneumocystosis (n�2), cryptococcosis (n�2) and histoplasmosis (n�1).

CONCLUSION: Direct microbiology diagnosis of TB in IS and BALspecimens have not been well accomplished. Improvements for fasterresults are needed.

CLINICAL IMPLICATIONS: TB suspected patients without a pos-itive AFB result in either spontaneous or induced sputum and BALspecimens still must be treated empirically for TB until the culture resultsare obtained.

DISCLOSURE: Rogerio Xavier, None.

ACCURACY OF THE RADIOMETRIC BACTEC IN THE DIAG-NOSIS OF TUBERCULOUS PLEURAL EFFUSION COMPAREDTO PLEURAL BIOPSY AND CLINICAL COURSEBernardo D. Briones MD* Faculty of Medicine and Surgery, University ofSanto Tomas, Manila, Philippines

PURPOSE: To determine the accuracy of the Bactec system in thediagnosis of Tuberculous Pleural Effusion compared to histopathologyand clinical course.

METHODS: All patients in the Chest Clinic Registry with PleuralEffusion confirmed by x-ray and or ultrasound between January, 1995 toDecember, 2003 were studied. All subjects had clinical evaluation,Mantoux test, thoracentecis/pleural biopsy, effusion Kinyoun AFB smear,pleural tissue Bactec culture and histopathology. Laboratory and pathol-ogist had no prior knowledge of actual diagnosis. Patients were assessedindependently based on a modified ATS Classification for TB Diseasestatus and followed-up by same attending pulmonologist.

RESULTS: Data of 175 of 185 registered patients were available foranalysis. At 49.2% TB prevalence, Histopathology has 77.5% sensitivity,98.9% specificity, 69.8% positive predictive value, 81.7% negative predic-tive value, 9.8 Likelihood ratio (�), 0.23 likelihood ratio (-) and 88.2%overall accuracy while Bactec has 30.9% sensitivity, 93.6% specificity,83.3% positive predictive value, 55.6% negative predictive value, 4.8likelihood ratio (�), 0.74 likelihood ratio (-) and 61.6% overall accuracy.

CONCLUSION: Using a single pleural biopsy specimen, histopathol-ogy appears more accurate and faster than Bactec culture in the diagnosisof TBPE. There is no significant morbidity with the Cope Needle pleuralbiopsy.

CLINICAL IMPLICATIONS: The etiology of Pleural Effusion isalways a clinical dilema. Pleural biopsy with culture for M.TB oftenfacilitates the diagnosis and treatment in a high prevalece setting.

DISCLOSURE: Bernardo Briones, Grant monies (from sources otherthan industry) INCLEN Thesis grant on the original study of theserodiagnosis of PTB.

A COST-MINIMIZING DIAGNOSIS MODELS FOR DISCRIMI-NATION BETWEEN NEOPLASTIC AND TUBERCULOUSPLEURAL EFFUSIONS UTILIZING ROUTINE CLINICAL ANDLABORATORY VARIABLESRoberta K. Sales MD* Marcia Seiscento MD Francisco S. Vargas MDLisete R. Teixeira MD Vera L. Capelozzi MD Milena M. Acencio BSMarcelo A. Vaz MD Leila Antonangelo MD Pulmonary Division - HeartInstitute (InCor), University of Sao Paulo Medical Sc, Sao Paulo, Brazil

PURPOSE: To identify clinical and laboratory parameters capable todifferentiate between tuberculous and malignant pleural effusions withhigh efficiency and low-costs.

METHODS: Laboratory tests (glucose, protein, albumin, globulin,lactate dehydrogenase, cholesterol, apolipoprotein A, apolipoprotein B,adenosine deaminase (ADA), quantitative and oncotic cytology) wereanalysed from 403 cases of confirmed tuberculous (Tb�200) or malignant(Mal�203) pleural effusions. Clinical variables like age, pleural effusions

side of incidence (right or left) , size (� or � 75% of the compromisedhemithorax) and macroscopic appearance (hemorragic or not) were alsoanalysed. Statistical analysis: Firstly, we used univariate tests to detect thevariables that significantly differentiated the groups (Tb and Mal). After,we submit these selected variables to logistic regression. With the �coefficients associated to the variables that composed the best models wepurposed algorithms capable to do these diagnosis with the best efficien-cies and lower costs. After, we tested the classificatory power of themodels in 64 pleural exsudates whose diagnosis were unknown.

RESULTS: For pleural tuberculosis, the best model included: ADA,globulin and negative oncotic cytology given a 99.4% sensitivity;96.1%specifity;95.7% PPV and 99.5% of NPV. For neoplastic pleurisy, the bestmodel was composed by age, hemmorrhagic aspect, macrophage percen-tual and positive or suspicious cytology that given a 96.3% sensitivity;91.4% specifity;91.1% PPV and 96.6 of NPV. When these models wereapplied to the 64 exsudates, the sensitivity, specificity, PPV and NPV wererespectively: For tuberculosis diagnosis: 100%, 91.1%, 99.9% and100%.For malignancy: 82.1%, 100%, 100% and 87.8%.

CONCLUSION: These simplified models presented good efficiency indiagnosing pleural tuberculosis and malignancy and do this at the expenseof routine and low-cost variables.

CLINICAL IMPLICATIONS: The possibility of using these modelsin the clinical practice without to be necessary doing pleural biopsies.

DISCLOSURE: Roberta Sales, None.

A COMPARISON BETWEEN THE INCIDENCE OF TUBERCU-LOSIS (TBC) IN GREEK POPULATION AND THE POPULA-TION OF ECONOMICAL EMIGRANTS IN THE COUNTY OFEVIA GREECEGeorgios S. Vlachogeorgos MD* Helen Nicolopoulou MD StylianosPodaras MD General Hospital of Chalkis, Chalkida, Greece

PURPOSE: To compare the incidence of TBC between the Greekpopulation and the population of the economical emigrants in the countyof Evia Greece.

METHODS: All the new cases of TBC in the decade 1994-2003 in thecounty of Evia Greece were studied yearly. Greek population was studiedin contrast with the population of the economical emigrants. The numbersof the populations were considered after the National Statistic Service ofGreece.

RESULTS: There is a statistical significant difference between themean incidence in Greeks (3.57) and the economical emigrants (25.75)p�0.002.

CONCLUSION: a)For the last 3 studied years the incidence of theTBC in the Greek population has risen in parallel with the rising of theincidence of the disease in the population of economical emigrants b)Theeconomical emigrants may be one of the reasons of the reapperance of theTBC in the developed countries.

CLINICAL IMPLICATIONS: The economical emigrants must havefree admission to the public health services independent the legal statusthat they live in the respective country for the general benefit.

Scoring system to predict tuberculosis and malignancy

Tuberculosis - Score � 8.5 pointsCharacteristics Coefficient Score

ADA (�46.5) 6.288 4.0Negative Oncotic Cytology 6.456 4.5Globulin (�2.05 mg/dl) 1.897 1.5

Malignancy - Score � 8.5 points

Characteristics Coeficient Score

Age (�45.5 years) 2.511 6.0Hemorrhagic Aspect 1.048 2.5Macrophages Percentual 1.482 1.5Positive or Suspicious Oncotic Cytology 5.589 5.0




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DISCLOSURE: Georgios Vlachogeorgos, None.

POTT’S DISEASE “THE DILEMMA OF LOW BACK PAIN” HIGHRESOLUTION RADIODIAGNOSIS BY COMPUTERISRD SCAN(CT) & MAGNETIC RESONANCE (MRI) MADE POSSIBLE THEDIAGNOSISTIC ACUURACY IN INCONCLUSIVE CASESMohammad M. Ishaq Khan MD* Imran Khan MD Sameera M. I MDAl-Junaid Hospital, Nowshera, Pakistan

PURPOSE: Tuberculous spondylitis, i.e. Pott’s disease with relentlessprogress, shares the common clinical presentation with low back ache,seems to be of trivial nature may end in catastrophic complication i.e,“paraplegia”.

METHODS: A total of 45 patients(n�45),age 15-60 years both sexwith proven tuberculosis. The clinical and imaging details assessed in all45 cases.

RESULTS: Distribution of tuberculosis lesion in the order of fre-quency was cervical & cervicodorsal region(n�3,7%)dorsal/dorsolumberregion(n�17,37.8%),Lumber(n�19,42%),Lunbosacral & sacral re-gion(n�6,13%). The lamina were most commonly involved (24 patients,53.3%; 8 bilateral, 16 unilateral) followed by pedicles 10 patients,22.2%s%; 6 bilateral, 4 unilateral), articular processes (6 patients,13.3%; 3bilateral, 3 unilateral), spinous process (3Patients,6.7%), and transverseprocesses (2 cases,4.4%;1 bilateral, 1 unilateral). Bone destruction andmarrow changes were seen in all patients. Involvement of the entireposterior arch was seen in six patients. A total of 14 patients revealedextraspinal soft tissue collections.,Intraspinal extradural granulation tissue/abscess was seen in 11 patients. Spinal cord was either displaced orcompressed in 6 patients, and abnormal high signal intensity intrinsic cordchanges were seen in eight patients. Gait may be limping with variabledegree of muscle wasting. Off & on low grade fever was associated.Laboratory investigations had elevated ESR, relative lymphocytosis lowhemoglobin & few with tuberculin reaction conversion detected. Plainx-rays had irregular erosion of the end plate of adjacent vertebral bodies& narrowing of the intervening disk spaces. CT & MRI had revealed thenature of the lesion .With anti tubercular drugs on empirical ground,added diagnostic yield . with following outcome.1.Individuals diagnosedon empirical (ATD), 10-15%2.Diagnosis established on clinical manifes-tations only (Patients with poor economy could not afford expenses ofinvestigations), 5 - 10 % 3.Financially stable patients, diagnosis establishedon CT/MRI. 75 -85 %.

CONCLUSION: A large tubercular abscess compressing on spinalcord is a medical emergency, may result in irreversible paraphrases.

CLINICAL IMPLICATIONS: Patients with Pott’s disease has char-acteristic early insomnia from spasm of para spinal muscles, and lateinsomnia resulting from urinary bladder distension.

DISCLOSURE: Mohammad Ishaq Khan, None.

THE RISK OF TB INFECTION IN MEDICAL STUDENTS OFCHARLES UNIVERSITYJiri Homolka MD* Frantisek Krejbich MD Pavel Simecek MD 1st LungDepartment, Charles University, Prague, Czech Republic

PURPOSE: The aim of our study was to determine the risk of tbinfection in students of medical and non-medical faculties of CharlesUniversity during their studies.

METHODS: Students of Charles University were repeatedly testedwith tuberculin skin test (TST) at the beginning of their studies, in the 3rdyear and in the 5th or 6th year depending on the length of studies. Theincrease of TST for 10 mm or more was considered as the conversion ofTST. The annual risk of infection (ARI) was calculated according to Styblomethod.

RESULTS: 3116 students were tested with TST during the years1993-2003. 1224 were medical students, 1892 were students of otherfaculties. At the beginning of their studies no significant differencies wereobserved concerning the results of TST between these two groups. 35%were TST negative, 62% had TST between 6-15 mm and 3% had TST 16mm and more. Median of TST was 7 mm. In the 3rd year of studies themedical students showed a significant increase in TST results (14% TSTnegative, 74% TST 6-15 mm, 12% TST 16 mm and more, median TST 12mm). There was no significant change in TST results in students of otherfaculties. The conversion of TST in the 3rd year of medical studies wasdetected in 22% of medical students and in 6.5% of students of otherfaculties (p� 0.01).The annual risk of infection (ARI) was higher inmedical students during the first three years of their studies (ARI0.081)compared to the second three years (ARI 0.042). The ARI instudents of other faculties was 0.011.

CONCLUSION: Medical students are at significantly higher risk for tbinfection compared to the students of other faculties of Charles Univer-sity. The risk seems to be most prominent during the first three years ofmedical studies.

CLINICAL IMPLICATIONS: Study of medicine carries a significatrisk for acquiring tuberculosis even in countries with low prevalence oftuberculosis and functional system of tb control.

DISCLOSURE: Jiri Homolka, None.

Tuberculosis: Treatment12:30 PM - 2:00 PM

PULMONARY RESECTION FOR MULTI DRUG RESISTANTTUBERCULOSISAbulfazal Shirin Zadeh MD* Khalil Ansaarin MD Vahid Montazery MDSamad Mosaddeghi MD Mahmoodreza Miri MD Ashraf Fakhr Joo MDMohsen Sokooti MD Thoracic Department, Imam Hospital, Tabriz, Iran

PURPOSE: Tuberculosis was a scourge of early humans, as shown byits discovery in the lungs of Egyptian mummies. Nowadays mycobacte-rium tuberculosis(MTB) continues to be a major cause of morbidity andmortality throughout the world.The world health organization(WHO)declare MTB a global emergency.During MTB Therapy has been emer-gence of multi-drug resistant MTB(MDR-TB). MDR-TB is a strain ofmycobacterium tuberculosis that is resistant to current anti-tuberculosisagent.Multi-drug resistant MTB often requires surgical intervention.

METHODS: During 10 years period 50 patients (26 men and 24women)Had surgical intervention that underwent pulmonary resections.All patients had a minimum of 4 month of medical therapy beforeoperation.All patients had multi-drug resistant mycobacterium tuberculo-sis that were hospitalized at the thoracic surgery ward and underwentsurgical operation.

RESULTS: 50 patients underwent surgical operation. 19 patients (6women,13 men) had positive sputum at the time of surgery. Leftpulmonary involvement were 31 cases(62%) and right lung 19 cases(38%).37 patients (74%) had been taken 4 drug regimen and 13 patients(26%) 2drug regimen in the past. Emergence of MTB strains resistant to theprimary antibiotics has largely been due to physicians and patientcomplacency (irregular taking of drugs and early discontinuing).Hemop-tysis, total pulmonary destruction, hydropneumothorax, bronchopleuralfistula and positive sputum were the main causes of surgery. 30 patientsunderwent lobectomy, 12 patients segmentectomy and 8 patients pneu-

Table 1:

Year

Incidence inGreeks(Cases)

Incidence inEmigrants

(Cases)

1994 2.26 ( 5) 12.74 ( 1)1995 5.37 (12) 11.82 ( 1)1996 3.90 ( 9) - ( 0)1997 8.22 (19) - ( 0)1998 4.75 (11) 9.52 ( 1)1999 0.86 ( 2) 18.24 ( 2)2000 1.72 ( 4) 8.81 ( 1)2001 0.93 ( 2) 25.77 ( 3)2002 3.25 ( 7) 33.49 ( 4)2003 4.46 (10) 87.84 (11)




monectomy. Operative mortality was 4% (2 patients) ,significant morbid-ity was 14% (7 patients).After the operation, the sputum remained positivein 3 patients(6%). Mean length of follow-up was 3.5 years (4 to 80months).

CONCLUSION: Surgery remains as an important adjunct to medicaltherapy for patients with multi-drug resistant mycobacterium tuberculosis(MDR-MTB). In the setting of localized diseases, persistent cavitarydisease, lung or lobar destructions or patient intolerance to medicaltherapy, surgical resection of the lung should be undertaken. The surgicalcomplications and post surgical mortality and morbidity are acceptable.Postponing the surgical operation will worsen the results.

CLINICAL IMPLICATIONS: Timing of the operation and malnu-trition are major problems to be considered.

DISCLOSURE: Abulfazal Shirin Zadeh, None.

CYTOKINE CHANGES IN SEVERE PULMONARY TUBERCU-LOSIS AFTER INITIATION OF TREATMENT: A PILOT STUDYMariko S. Koh MBBS* E-Shyong Tai MBBS Constance Lo MBBSKenneth P. Chan MBBS Philip Eng MBBS Singapore General Hospital,Singapore, Singapore

PURPOSE: Sudden death occurs in a significant number of patientswith pulmonary tuberculosis after the initiation of anti-tuberculous ther-apy. We postulate that a Jarisch-Herxheimer (JH) –type response which ischaracterized by surge in Interleukin – 6 (IL-6), Interleukin- 8 (IL-8) andTumour necrosis factor alpha (TNF alpha) could be responsible for thisphenomenon.

METHODS: Five patients admitted to hospital for pulmonary tuber-culosis were enrolled in this pilot study. These patients had multi-lobarinvolvement, were sputum smear positive for acid-fast bacilli and had lowhaemoglobin and albumin, signifying severe disease. Vital signs, temper-ature and clinical responses were monitored. Venepuncture was carriedout 2, 4, 8, 12, 24, 48 and 72 hours after the first dose of anti-tuberculoustherapy. These samples were analyzed to determine the concentrations ofIL-6, IL-8 and TNF alpha at the various time points.

RESULTS: Several patterns of cytokine changes were noted. In twopatients, there was an increase in serum levels of IL-6 between 4 and 8hours and these returned to baseline levels within 24 hours. Neither ofthese patients experienced an adverse clinical event. Two patients hadrelatively high IL-8 levels to start with compared to the other patients andhad documented hypotensive episodes between 4 and 8 hours. Radiolog-ically, these patients had more severe disease.

CONCLUSION: An increase in IL-6 was observed in 2 patients whichmay be consistent with Jarisch-Herxheimer reaction. However, this wasnot accompanied by any clinical sequelae to support the occurrence ofsuch a reaction. In contrast, patients with high IL-8 at baseline did exhibitclinically significant deterioration consistent with previous studies whichhave found that increased concentration of IL-8 were found in patientswho died from tuberculosis compared to those who survived. Furtherstudies should be carried out to clearly document the prognostic signifi-cance of serum levels of cytokine at baseline and within the first 24 hoursfollowing commencement of anti-tuberculous therapy for pulmonarytuberculosis.

CLINICAL IMPLICATIONS: IL-6 and IL-8 levels may have prog-nostic significance in patients with pulmonary tuberculosis.

DISCLOSURE: Mariko Koh, None.

DOES UNIVERSAL DOT REALLY MAKES A DIFFERENCE INTUBERCULOSIS TREATMENT?Patricia Radilla MD Rafael Laniado-Laborin MPH* Universidad Au-tonoma de Baja California, Tijuana, Mexico

PURPOSE: Directly observed therapy (DOT) is frequently seen as theanswer to rising levels of tuberculosis. However, well conducted trialscomparing DOT with self treatment have showed that the effects of DOTon cure or treatment completion are similar to those of self-administeredtreatment. The objective of this study was to determine the effect of DOTon the outcome of antituberculosis treatment.

METHODS: Retrospective analysis covering the period 01/2000-09/2004; the information was retrieved from the files of the TuberculosisControl Program, ISESALUD, Ensenada, Mexico.

RESULTS: 524 patients were included in the analysis. 462 patients(88.16%) had never been treated before, 57 (10.8%) were relapses, and 5(0.95%) were failures from a previous regimen. DOT was administered to73.7% of the patients; in the rest (26.3%), treatment was self adminis-tered. Males defaulted treatment more frequently (25.5%) than females(16%; p�0.010). HIV/AIDS patients defaulted treatment more frequently(38.5%) than those not co-infected (20.3%), however due to the lownumber of coinfected patients (13), this difference was not statisticallysignificant (p�0.11). Patients addicted to illegal drugs and/or alcohol alsodefaulted treatment more frequently (31.6% vs. 19.3%, p�0.014). Inlogistic regression analysis only male gender (odds of abandoning treat-ment: 1.70, CI95% 1.03, 2.81; p�0.03) and the absence of addictions (OR0.55, CI95% 0.32, 0.97; p�0.04) were predictive of treatment completion.DOT was not predictive (1.33, CI95% 0.77, 2.30; p�0.30).

CONCLUSION: DOT did not improve in this group of patientstreatment completion, treatment failure and cure rates when comparedwith self-administered treatment.

CLINICAL IMPLICATIONS: Universal DOT is an expensive strat-egy; TB programs from developing countries might benefit from selectingfor DOT, patients with high risk for deafult.

DISCLOSURE: Rafael Laniado-Laborin, None.

TREATMENT OUTCOME OF TUBERCULOSIS UNDER DI-RECTLY OBSERVED TREATMENT SHORT COURSE ( DOTS )IN PATIENTS PRESENTING AT CHEST & TB HOSPITAL, AM-RITSARVishal Verma MBBS Jorawar Singh MBBS Nirmal Chand MS* J. S.Khalsa MBBS Dept. of Tuberculosis & Respiratory Diseases, Amritsar,India

PURPOSE: The present study was undertaken to determine thetreatment outcome of DOTS as prescribed under RNTCP. Side effectsand radiological improvement was also noted.

METHODS: A total of 150 cases of tuberculosis on the basis of history,sputum & radiological examination were selected. They were divided intothree categories under RNTCP. All the patients were administeredstandard regimens of antitubercular drugs as prescribed under DOTS.Sputum of all patients was examined before the start of treatment andthen at the end of intensive phase, 4or5or6 months and then at the end oftreatment. X-ray was taken before and at the end of treatment. Treatmentoutcome was determined.

RESULTS: 150 patients comprised of 91 males and 59 females. Coughwas the major complaint in 70% . Sputum conversion rate was 81% &85.71% for category I & II. Cure rate was 91% & 71.40% for category I& II. Treatment completion rate was 100% for category III. Overalldefault rate was 5.33%. Failure rate was 0.67%. Radiological improvementwas seen in 73.33%. 60.67% gained weight in the range of 6-10 Kg.Fatigue was major side effect under DOTS in 24% cases.

CONCLUSION: DOTS is an effective and economical treatment withsuccessful treatment outcome, sputum conversion and minimal sideeffects for tuberculosis.

Variable DOT Self-administered p

Addictions 16.6% 13.2% 0.37HIV/AIDS 2.7% 1.7% 0.53Cured 77.7% 79.8% 0.70Defaulted 22.3% 20.2% 0.70Failed 2.3% 1.6% 0.92


Tuberculosis: Treatment, continued


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CLINICAL IMPLICATIONS: DOTS in an effective therapy indeveloping countries like india whose almost 40% of the population ininfected with tuberculosis.

DISCLOSURE: Nirmal Chand, None.

RELAPSE AT 5 YEARS IN INDIAN REVISED NATIONAL TU-BERCULOSIS CONTROL PROGRAMME CAT I DOTS REGI-MENMukesh K. Tailor MBBS* J.L.N. Medical College, Ajmer, India

PURPOSE: To see the relapse rate and point of relapse in cat-I DOTStreated patients after 5 years of chemotherapy under Indian RevisedNational Control Programme.

METHODS: 128 patients of Pulmonary-tuberculosis registered undercat-I DOTS, between Oct-1999 and March-2000. Out of 128 cases, 22defaulted, 14 died, 5 failure and 2 transferred-out during treatment wereexcluded from analysis. Of remaining 85 cured cases, only 53 wereanalyzed because 32 could not be traced due to various reasons. Out ofthese 53, only 41 were alive at the time of assessment and 12 were founddead. Of the 53 patients, 12 were irregular during treatment. 7 alive-casesand 5 dead-cases were re-registered in DOTS cat-II (documentedrelapses). Verbal autopsy was carried out in all dead-cases and wasconclusive that they all died because of symptomatic PTB.

RESULTS: 19 (35.85%) patients relapsed during 5 years post treat-ment period. Of these 6 (31.6%) relapsed within 6 months of completionof DOTS, 4(21%) between 6 to 18 months, 3(15.8%) between 19 to 36months, 3 (15.8%) between 37 to 48 months and rest 3 during last 1 yearof follow-up.

CONCLUSION: Relapse rate following 5 years of cat-I treatment wasvery high (35.85%) and needs further studies to confirm these findings atlarge, because this has a significant bearing on eventual success of RNTCPin India.

CLINICAL IMPLICATIONS: Relapse rate following 5 years of cat-Itreatment was very high (35.85%) and needs further studies to confirmthese findings at large, because this has a significant bearing on eventualsuccess of RNTCP in India. We hypothesize high initial drug resistanceprevalent in community, teething problem of 1st year of implementationand occasional defaults during DOTS possibly responsible for this highrelapse rate.

DISCLOSURE: Mukesh Tailor, Product/procedure/technique that isconsidered research and is not yet approved for any purpose.

EVALUATION OF RISK FACTORS AND PREVALENCE OFDRUG RESISTANT TUBERCULOSIS IN NORTH INDIAJ.N. Pande MD U.B. Singh MD Sanjeev Sinha MD* R.C. Agarwal MBBSSPN Singh PhD Department of Medicine, All India Institute of MedicalSciences, New Delhi, Ind, New Delhi, India

PURPOSE: The prevalence of multi-drug resistant tuberculosis(MDR-TB) in different clinical settings [Primary health center (PHC),District tuberculosis center (DTC) and tertiary care center (Medicalcollege )] had not been systematically worked out. There is a need toestimate the magnitude of problem and to define the factors responsiblefor its emergence.

METHODS: A prospective study of risk factors of MDR-TB amongpatients seen at three sites during period of two years, 2000-2002. Patientsincluded from PHC, Ballabhgarh, DTC, Faridabad and tertiary carecenter, All India Institute of Medical Sciences, (AIIMS), New Delhi. Total1467 patients with pulmonary TB recruited from three sites and on whomthe drug susceptibility results were available after adequate qualitycontrol. Of these 678 patients were enrolled at AIIMS, 346 at PHC and443 at the DTC.

RESULTS: Overall, 123 (18.9, 95%CI: 11.9-25.8%) patients hadMDR-TB. Of the 329 patients without history of anti tuberculosistreatment (ATT) in the past, 28 (8.5,95%CI: 5.4-11.5%) patients hadMDR organisms. The corresponding proportion amongst those with pasthistory of ATT was 95 (29.7, 95%CI: 24.6-34.7%) out of 319. There wasconsiderable variation in the proportion of patients with MDR organisms(without past history of ATT) at three sites (6.9-11.8%). The prevalence ofMDR-TB in patients with past history of ATT at AIIMS hospital was 44.7,95%CI: 35.5-53.8%, PHC 23.1, 95%CI: 14.6-31.5% and DTC was 20.0,95%CI: 12.5-27.4%. Of the risk factors studied for MDR-TB, bacillaryload and previous treatment of TB were found significant (p�0.05).34 hadpauci-bacillary disease (smear negative but culture positive). The preva-

lence of HIV amongst these patients was 2.77%. HIV status, tobaccosmoking, excessive alcohol intake, age, sex, education and socio-economicstatus had no relation to infection with MDR organism.

CONCLUSION: This study highlights important differences in theprevalence of MDR-TB at three different clinical settings.

CLINICAL IMPLICATIONS: The findings of this study have majorimplications for the TB program in India.

DISCLOSURE: Sanjeev Sinha, None.

FREQUENCY OF VENOUS THROMBOEMBOLISM AMONG PA-TIENTS WITH TUBERCULOSIS DURING SHORT-COURSECHEMOTHERAPYMarco Ambrosetti MD* Maurizio Ferrarese MD Luigi R. Codecasa MDGiorgio Besozzi MD Antonio Sarassi MD Piero Viggiani MD Giovanni B.Migliori MD Division of Cardiology, IRCCS Fondazione S. Maugeri,Tradate, Italy

PURPOSE: The unexpected resurgence of tuberculosis (TB) in devel-oped countries, as far as the possibility of an hypercoagulable state givenby the infection “per se” and the use of anti-TB chemotherapy, providedthe rationale for evaluating venous thromboembolism (VTE) as a possiblecomplication of TB. Aim of the present study is to evaluate the incidenceof deep vein thrombosis (DVT) and pulmonary embolism (PE) in a largenational registry of actively treated TB patients in a low incidence country.

METHODS: The AIPO/SMIRA study is a prospective national mon-itoring activity on TB treatment results based on a network of 46 TB unitsnationwide, under the leadership of the Italian Association of HospitalPneumologists, the World Health Organization, and the Istituto Superioredi Sanita (technical branch of the Italian Ministry of Health). To date, theregistry enrolled 6,027 TB patients. An active survey for the appearance ofclinically evident DVT and PE was conducted on a subset of 1,237patients in the period 1998-2002.

RESULTS: Five (0.4%) patients developed proximal DVT within onemonth after initiation of anti-TB chemotherapy, complicated in 2 (0.2%)cases by PE. Two (0.2%) additional cases of PE without DVT occurred inthe first week of treatment. Overall, the prevalence rate of any VTE eventwas 0.6%, and all cases occurred among new pulmonary TB cases withrifampicin as part of the initial treatment.

CONCLUSION: TB, as other infectious conditions, is likely to in-crease the risk of VTE.

CLINICAL IMPLICATIONS: This evidence may support the use ofappropriate venous thromboprophylaxis in selected cases.

DISCLOSURE: Marco Ambrosetti, None.

SURGICAL TREATMENT FOR CHRONIC TUBERCULOUS EM-PYEMAMasanori Kaneda MD* Fumiaki Watanabe MD Tomohito Tarukawa MDToshiya Tokui MD Takashi Sakai MD NHO Mie Chuo Medical Center,Hisai City, Japan

PURPOSE: Despite advances in surgical techniques and supportivetherapy, chronic empyema is still associated with considerable morbidityand mortality. The purpose of this study was to evaluate the efficacy ofsurgical procedures.

METHODS: Thirty-seven patients with chronic tuberculous empyemawere studied. Twenty cases had bronchopleural fistula. All patients werestudied for more than three years. Mortality rates and recurrence rateswere evaluated.

RESULTS: Among 17 cases without bronchopleural fistula, 10 weretreated with decortication. Lung resection was necessary in two cases.Extrapleural pneumonectomy was performed in two cases, and thoraco-plasty in three cases. Other procedures included one muscle flap closure,and two open drainages. The mortality rate was 0% and the recurrencerate was 5.9%.Among the 20 cases with bronchopleural fistula, nine wereinitially treated with open drainage. In the second stage operation, onecase was treated with extrapleural pneumonectomy, but died fromcardio-respiratory failure. Extrapleural pneumonectomy combined withthoracoplasty (EPTP) was successfully performed in two cases, andthoracoplasty in four cases (two with omentopexy). One case was treatedwith a muscle flap closure. There was no recurrence, but the mortality ratewas 11.1%. The other 11 cases with fistula were treated with a single-stageoperation. Extrapleural pneumonectomy was performed in four cases,thoracoplasty in 5 cases, and a muscle flap closure with omentopexy wasperformed in one case. The result was two deaths and two recurrences.




Recently, EPTP by anterior approach was successfully performed in onecase with a severely damaged lung in spite of a poor general condition.The mortality rate of the single-stage operation was 18.2% and therecurrence rate was 18.2%. All the cases with recurrence were success-fully treated with additional surgical operations. Overall efficacy of thesurgical treatment was 86.5% (32/35).

CONCLUSION: Surgical treatment was a effective method for thetreatment of tuberculous empyema.

CLINICAL IMPLICATIONS: Chronic tuberculous empyema is adifficult disease to cure. The result of the surgical treatment was mucheffectibe than that of medical treatment.

DISCLOSURE: Masanori Kaneda, None.

Venous Thromboembolism12:30 PM - 2:00 PM

OBSERVED INCIDENCE OF VENOUS THROMBOEMBOLISMIN SOLDIERS FROM OPERATION IRAQI FREEDOM ANDOPERATION ENDURING FREEDOM ADMITTED TO A STATE-SIDE INTENSIVE CARE UNITWilliam L. Jackson, Jr. MD* Melanie Guerrero MD Kevin K. Chung MDBryan A. Fisk MD Andrew F. Shorr MD Walter Reed Army MedicalCenter, Washington, DC

PURPOSE: Venous thromboembolism (VTE) is a well-establishedcause of morbidity and mortality in the trauma patient. Soldiers injured inOperation Enduring Freedom (OEF) and Operation Iraqi Freedom(OIF) are often aeromedically evacuated shortly posttrauma, subjectingthem to lengthy transport and potential hypobaric hypoxia during theperiod of peak thrombogenesis. We sought to determine the observedincidence of VTE in soldiers injured in OEF and OIF who were admittedto the intensive care unit (ICU) of our military tertiary care facility.

METHODS: We retrospectively identified all patients injured in OEFand OIF admitted directly to the ICU at our institution for the 16-monthperiod between 28 March 2003 and 28 July 2004. Relevant variablesdetermined from chart review included mechanism of injury, location ofprimary and secondary injuries, Revised Trauma Score, type of VTEprophylaxis, and radiographic studies performed. All cases of VTE anddeath were recorded.

RESULTS: During the study period 231 trauma patients from OEFand OIF were admitted to the ICU. Forty patients (17.3%) developedVTE during hospitalization at our facility. Overall mortality was 2.2%. Oneof these five deaths was from pulmonary embolism. The most commonlyused form of prophylaxis was enoxaparin (30 mg SQ BID). Inferior venacava filters were placed infrequently. There was no observed difference indevelopment of VTE between patients who received pharmacologicprophylaxis and those who did not (22/130, 16.9% vs. 18/101, 17.8%;p�0.863).

CONCLUSION: VTE is common in the critically ill OEF/OIF popu-lation and incidence appears similar to that of civilian trauma populations.The VTE-related mortality appears to be low.

CLINICAL IMPLICATIONS: Despite the high severity of injury, therate of VTE in this population is no higher than that reported in othersettings. VTE infrequently results in mortality. Ideal means of prophylaxisin this trauma population should be reassessed.

DISCLOSURE: William Jackson, Jr., None.

DIABETES MELLITUS IS SIGNIFICANTLY ASSOCIATEDWITH PULMONARY EMBOLISM AND PULMONARY HYPER-TENSIONMohammad-Reza Movahed MD* Mehrtash Hashemzadeh MA M. Ma-zen Jamal MD University of California, Irvine Medical Center, Orange,CA

PURPOSE: Patients with diabetes mellitus (DM) suffer from hyper-coagulable state which may increase their risk for thromboembolism.However, the data about this association is contradictory in the literature.The goal of this study was to evaluate the occurrence of pulmonaryembolism and pulmonary hypertension (HTN) in patients with DM after

adjusting for coronary artery disease (CAD), congestive heart failure(CHF), hypertension and smoking using a large database.

METHODS: We used patient treatment files (PTF) to documentinpatients’ admissions containing discharge diagnoses (ICD-9 codes) fromall Veterans Health Administration Hospitals. The patients were dividedin two groups: ICD-9 code for DM (293,124) and a control group withICD-code for hypertension (HTN) but no DM (552,623). ICD-9 codesfor pulmonary embolism (415.19) and ICD-9 code for pulmonary hyper-tension (416.0) were used to study prevalence of these diseases in DMpatients vs the control. We performed uni- and multi-variant analysisadjusting for CAD, CHF and smoking. Continuous variables and binaryvariables were analyzed using X2 and Fisher’s Exact tests.

RESULTS: Pulmonary embolism was present in 2011 (0.7%) vs 2759(0.5% ) in the control group. Pulmonary hypertension was present in 3356(1.1%) vs 3357 (0.6%) in the control group. Using multivariate analysis,DM remained independently associated with pulmonary embolism (OR:1.27; CI: 1.19 to 1.35; p�0.000) and with pulmonary hypertension (OR:1.53; CI: 1.45 to 1.60; p�0.000).

CONCLUSION: Patients with DM have significantly higher preva-lence of pulmonary embolism and pulmonary hypertension independentof CAD, HTN, CHF or smoking.

CLINICAL IMPLICATIONS: This finding could partially explain thehigher risk of sudden death in diabetes patients in addition to othercardiovascular abnormalities. We suggest that the clinician should bemore aware of this risk that could be potentially treated and life saving.


CHARACTERISTICS AND PROGNOSTIC FACTORS OF PUL-MONARY SADDLE EMBOLUSLinda M. Lam DO* George Matuschak MD Stephen Trottier MD SaintLouis University, Saint Louis, MO

PURPOSE: Pulmonary saddle embolism is a radiographic descriptionof massive embolization implicitly assumed to confer increased mortality.However, supportive data are scant. This is a review of 19 patients with apulmonary saddle embolus over a 5 year period at a university medicalcenter, hypothesizing that: 1) such patients exhibit increased mortality;and 2) discrete prognostic factors stratify these and other adverseoutcomes.

METHODS: The medical records of patients between June 1999 andJune 2004 were retrieved to identify those with pulmonary saddle emboluson helical CT chest . Data collection included demographic data,APACHE II score, shock defined as requiring vasopressors and/orMAP � 60 mmHg, need for mechanical ventilation, PaO2/FIO2 ratio,presence of deep venous thrombosis, echocardiographic findings, andhospital morbidity and mortality. Data was summarized by mediancalculation, means � standard error and evaluated by X2 analysis, andbivariate correlation (SPSS v. 13 .0).

RESULTS: Saddle embolism was diagnosed in 6 females and 13 males(total n � 19), representing an incidence of 1.2%. Mean age was 58.2years old �/- SD 16.34 and median Apache II score of 9 (range 4-26). Fivepatients presented with hemodynamic instability, of which 2 patientsdemonstrated right ventricular systolic dysfunction. RV dilation found in7/10 patients. Co-existing deep vein thrombosis found in 10 patients andsuperficial thrombophebitis in 4 patients. Median Pa02/FIO2 ratio foundto be 233 (range 53-395). Four patients (22 %) required mechanicalventilation. No patients received thrombolytics. Seventeen (94 %) patientswere anticoagulated with heparin infusion. No significant correlationexisted among shock, occurrence or type of echocardiographic abnormal-ities, and degree of hypoxemia. All patients survived.

CONCLUSION: Saddle pulmonary embolism is not consistently asso-ciated with shock, echocardiographic abnormalities, or hypoxemia inpatients surviving the initial embolic event who were treated by standardanticoagulation regimens and/or caval interruption.

CLINICAL IMPLICATIONS: Saddle pulmonary embolism is notassociated with increase mortality based on shock, hypoxemia, or echcar-diographic abnormalities.

DISCLOSURE: Linda Lam, None.




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COMPARISON BETWEEN PERFUSION LUNG SCAN AND VEN-TILATION-PERFUSION LUNG SCAN IN PATIENTS WITH PUL-MONARY EMBOLISMG. Gandev MD* H. Rao MD S. Rashid BA K. Kanagarajan MD K. GuptaMD Coney Island Hospital, Brooklyn, NY

PURPOSE: Use of ventilation-perfusion (V/Q) scan to diagnose PE isa well established practice. However performing the ventilation part of thescan is technicaly demanding and associated with significant degree ofradiation exposure for both the technician and the patient. We conducteda retrospective study to compare the diagnostic abilities of perfusion lungscan and ventilation-perfusion (V/Q) scan for detecting pulmonary emboli.

METHODS: We reviewed the charts of all 283 patients who under-went nuclear lung imaging studies in 2004. Of these 283 patients, 46 hadboth nuclear lung imaging and pulmonary CT angiogram within 48 hoursof each other. Of these 46 patients, 16 had both ventilation and perfusionnuclear scan done and the remaining 30 had only perfusion scan done. Wecompared the sensitivity and specificity of nuclear lung imaging for bothgroups. We used pulmonary CT angiogram as a reference test fordiagnosis of pulmonary embolism.

RESULTS: There were 20 males and 26 females with age range: 18-88years, and mean age 53.6 years. For the group of patients who hadventilation-perfusion (V/Q) scan done the sensitivity was 100% and thespecificity 92%. For the group of patients who had only perfusion scandone the sensitivity was 100%, and the specificity was 80%.

CONCLUSION: Compared to perfusion scan alone ventilation-perfu-sion (V/Q) scan has similar sensitivity, but higher specificity for detectingPE.

CLINICAL IMPLICATIONS: Even though technically challengingand associated with higher degree of exposure to radiation performingventilation scan along with perfusion scan will increase the diagnosticaccuracy of nuclear lung imaging in the diagnosis of PE.

DISCLOSURE: G. Gandev, None.

CARDIOPULMONARY FINDINGS ON CT PULMONARY AN-GIOGRAPHY IN PATIENTS WITH SUSPECTED PULMONARYEMBOLISMShalin Amin MD* Tan-Lucien H. Mohammed MD Ruchi Yadav MBBSThe Cleveland Clinic Foundation, Cleveland, OH

PURPOSE: Multidetector CT pulmonary angiography (CTPA) hasbecome the standard technique utilized to diagnose pulmonary embolus(PE). Current literature has demonstrated that CTPA is excellent for theassessment of various cardiopulmonary pathologies as well. Our study wasperformed to identify, catalogue and determine the frequency of commoncardiopulmonary findings in a determined patient population.

METHODS: CTPA and corresponding medical records of nearly 750consecutive patients who underwent CTPA for PE at our institutionbetween January 2005 and September 2005 were retropectively reviewed.All studies were re-evaluated by a team of one thoracic radiologist and tworadiology residents. Correlative data, treatment outcome and short-termfollow-up were used to confirm these findings and diagnoses.

RESULTS: Cardiopulmonary pathologies were readily present in ourpatient population. Of these findings, pneumonia and emphysema werethe most common. Other common findings included congestive heartfailure, pulmonary fibrosis and coronary artery disease. Furthermore,cardiopulmonary findings which offered alternative and/or different diag-noses to explain the patients’ symptoms were present in nearly one thirdof cases.

CONCLUSION: Nearly all patients with suspected PE frequentlypresent with chest pain and/or dyspnea. However, these symptoms arenonspecific and can often signal cardiopulmonary pathology. CTPA, atechnique which has wide-gained acceptance in the evaluation of PE,offers the additional benefit of allowing excellent assesment of cardiopul-monary structures in this population. Abnormalities such as pneumonia,congestive heart failure and exacerbated emphysema are readily apparenton CTPA studies.

CLINICAL IMPLICATIONS: It is crucial for radiologists to includea systematic evaluation of the cardiopulmonary structures in their CTPAseach patterns.

DISCLOSURE: Shalin Amin, None.

SERUM ANGIOTENSIN CONVERTING ENZYME (ACE) IN PA-TIENTS WITH ACUTE PULMONARY THROMBOEMBOLISMZothanmawii Khiangte MD* Martin H. Bluth MD Rose Hardin MDEmad Kamel MD Cathy M. Mueller BS Sanjay Chawla MD Tamar S.Norowitz PhD Michael Zenilman MD Matthew Pincus MD SUNYDownstate Medical Center, Brooklyn, NY

PURPOSE: Angiotensin-converting enzyme (ACE) is produced byendothelial cells and is found in particularly high concentrations in thepulmonary vasculature. Circulating ACE levels are thought to representeither sloughing off of, or secretion from, endothelial cells. Pulmonaryendothelial injury likely occurs during pulmonary insult, such as an acutethromboembolism, and measurement of serum ACE levels may provide aclinically useful marker of pulmonary injury. We therefore investigatedthe utility of serum ACE levels in the evaluation of patients withpulmonary embolism (PE).

METHODS: Patients were evaluated for suspected PE either by catscan angiography (CTA) or ventilation perfusion (V/Q) scans, results ofwhich were interpreted by an independent radiologist. Serum sampleswere prospectively collected either at the time of admission or during aradiological procedure. ACE levels were measured by enzyme linkedimmunosorbant assay (ELISA) in a blinded manner. Patients receivingACE inhibitors were excluded from the study and serum from healthyvolunteers served as controls. ACE levels are expressed as ng/mL (mean�SE) with significance between groups set at p � 0.05 (student’s t-test).

RESULTS: Of the 45 patients evaluated, 19 were diagnosed with acutePE (15 CTA, 2 V/Q scan, 2 by both). Patients with PE tended to be older.At diagnosis, serum ACE levels for patients with pulmonary symptomswere as follows – PE: 312�30 ng/ml; non-PE: 299�24 ng/ml (p�NS). Incontrast, ACE levels differed significantly in pulmonary pathology groupsvs. normal controls (control ACE levels: 433�32 ng/ml; PE vs control,p�0.03; non-PE vs. control, p�0.006).

CONCLUSION: Although ACE levels did not significantly differbetween PE and non-PE patients, ACE levels were significantly de-creased in patients presenting with pulmonary symptoms when comparedwith controls.

CLINICAL IMPLICATIONS: Serum ACE levels can be useful indifferentiating patients with pulmonary symptoms from those with non-pulmonary causes. Furthermore, additional studies are needed to deter-mine if ACE can serve as a useful diagnostic marker in patients presentingin early vs. late stage PE and as a monitor of clinical course.

DISCLOSURE: Zothanmawii Khiangte, None.

Venous Thromboembolism: Treatment12:30 PM - 2:00 PM

OPTIMAL DOSING OF UNFRACTIONATED HEPARIN INOBESE PATIENTS WITH VENOUS THROMBOEMBOLISMSamar U. Khan DO* Maritza L. Groth MD Adam N. Hurewitz MDWinthrop University Hospital, Mineola, NY

PURPOSE: Failure to achieve therapeutic anticoagulation in the first24 hr after pulmonary embolism (PE) is associated with increased rate ofrecurrence in subsequent months. A weight-based nomogram is recom-mended for unfractionated heparin (UFH) to achieve the target PTT.However, for obese patients, the nomograms may not be accurate andwould necessitate very high doses if followed. Clinicians hesitate to useUFH nomograms in obese patients for fear of bleeding complications.

METHODS: We retrospectively reviewed the records of all obesepatients (BMI � 29) diagnosed with PE at our institution over a six monthinterval who were treated with UFH. Patient data obtained includedweight, age, height, and method of diagnosis of PE. We recorded theinitial bolus and infusion rate of UFH as well as the infusion rate thatultimately achieved a therapeutic PTT (60-90 sec).

RESULTS: Eight patients met all inclusion criteria. Their mean agewas 58 yr (range 25-80 y). Six were females. BMI (mean) was 36 kg/m2(range 29.3 - 44). Despite hospital guidelines, actual body weight (ABW)based nomogram was not used for either the bolus or the infusion rate.The average bolus was 55 units/kg (range 34-76). The average initialinfusion rate was 14 units/kg (range 11-16). With these initial doses, 50%were over-anticoagulated and 25% were under-anticoagulated. The aver-


Venous Thromboembolism, continued


age infusion rate to maintain therapeutic PTT was 12.8 units/kg (range8.4-15.8).

CONCLUSION: Weight based nomograms overestimate the dose ofUFH required to achieve therapeutic aPTT. By contrast, calculationsbased on ideal body weight (IBW) result in inadequate anticoagulation. Inthe majority of patients the dose that produced a therapeutic PTT was40% of the difference between the dose calculated based on IBW andABW.

CLINICAL IMPLICATIONS: The optimal dose of UFH to achievea therapeutic PTT in obese patients should not be based on either ABWor IBW but rather an estimated value around 40% above the IBW.However, our data are based on a small population and should beconfirmed with a larger sample.

DISCLOSURE: Samar Khan, None.

PLACEMENT OF FILTERS IN THE SUPERIOR VENA CAVAAND AZYGOS SYSTEM. PRELIMINARY EXPERIENCEJaime Tisnado MD* Malcolm K. Sydnor MD Uma R. Prasad MD MCVHospitals/VCU Medical Center, Richmond, VA

PURPOSE: Filter placement in the IVC is an established procedure toprevent PE from DVT of lower extremities and pelvis. The incidence ofPE from DVT of the upper extremities is increasing in this era ofaggressive medical therapy and widespread use of central catheters. Somepatients with IVC occlusion may develop large collaterals draining into theazygos veins. Therefore, in some of these patients the placement of a filterin the SVC and/or azygos is necessary to prevent PE from the SVC andupper extremities DVT. We understand that this topic is controversial andhas not received adequate attention in the literature. We, therefore,present our experience with 20 patients.

METHODS: We have placed filters in these very unusual locations in20 patients. Filters were placed in the SVC in 17 patients and in the azygosvein in 3 patients. Some of these patients also required placement of filtersin the IVC. Filters used were the “old” stainless steel Greenfield, theTitanium Greenfield, the “new” stainless steel Greenfield, the SimonNitinol, the Gunther tulip, and the Trap ease filters.

RESULTS: All procedures were successful. No complications relatedto the procedures were recorded. No SVC or azygos occlusions werefound. No migration or misplacement occurred.

CONCLUSION: Placement of filters in the SVC and/or azygos systemis a safe, easy, effective, albeit controversial, method to prevent PE incertain patients under specific circumstances.

CLINICAL IMPLICATIONS: Some patients with SVC and/or upperextremity DVT can benefit from placement of a filter in the SVC and/orazygos vein. It is safe to insert a filter in the SVC.

DISCLOSURE: Jaime Tisnado, None.

MASSIVE PULMONARY EMBOLISM: TRANSCATHETER LYSISWITH RETEPLASEJaime Tisnado MD* Muhammad S. Chaudhri MD Ferdinand K. Hui MDMCV Hospitals/VCU Medical Center, Richmond, VA

PURPOSE: Massive pulmonary embolism (PE) is a serious andrelatively common problem, sometimes very difficult to manage. Theconventional treatment (systemic anticoagulation and/or thrombolysis) isassociated with significant hemorrhagic and other complications. A newmethod of therapy is the selective, local, transcatheter infusion ofRetavase (Reteplase, recombinant) into the pulmonary arteries.

METHODS: Twelve patients (24-70 y.o.) with massive bilateral PE,hemodynamically unstable with severe respiratory compromise, weretreated with transcatheter directed thrombolysis with Reteplase infusionat 0.5-1 U/hr. Two catheters were simultaneously inserted into one or bothcommon femoral veins and placed in each one of the two pulmonaryarteries. The infusion time lasted from 20 to 48 hours.

RESULTS: All patients recovered well. All patients showed significantdrops in pulmonary artery systolic pressures ranging from 13-34 mm ofHg. Improvements in pulmonary perfusion with resolution of clot oc-curred at 24 hours (n � 6) and 48 hours (n � 6) of infusion. No significantcomplications occurred despite the severity of the clinical condition ofmost patients. Concomitant heparin (400-500 U/hr) was given to somepatients.

CONCLUSION: Bilateral selective pulmonary artery infusion of Re-tavase is safe, effective and well tolerated for the management of patientswith massive PE, especially those who are not candidates for theconventional means of therapy, and those patients being considered for amore aggressive management such as pulmonary embolectomy.

CLINICAL IMPLICATIONS: A very serious and potentially lethalcondition (massive PE) can be successfully managed with IR methods.Some of these patients would have needed, perhaps, open pulmonaryembolectomy, associated with high morbidity and mortality.

DISCLOSURE: Jaime Tisnado, None.


Venous Thromboembolism: Treatment,continued


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CHEST nov 2005