Sessions 16.2 to 18.4

152 1999 Cystic Fibrosis Conference

It has recently been shown that expression of the in-ducible form of nitric oxide synthase (NOS2) and NOproduction is reduced in airway epithelial cells from CFpatients and in lung and nasal epithelial cells frommouse models of CF (cftr -/-) (1,2). We have also shownthat NOS2 expression is lacking in epithelial cells of cftr-/- mouse ileal sections, where it is highly expressed inwild type mice, indicating that CFTR-mediated regula-tion of NOS2 expression is not restricted to airway ep-ithelium. These findings are likely to be biologically im-portant since NOS2 has been shown to be the dominantisoform of nitric oxide synthase in both of these tissues.

Reduced NO production in epithelial cells is an excel-lent candidate for a mechanism that may contribute to CFpathophysiology. A lack of epithelial NOS2 expressionand NO production likely contribute to the puzzling lackof exhaled NO observed from CF patients when com-pared to patients with other airway inflammatory diseasessuch as asthma. This well-established lack of NO produc-tion in CF airways becomes intriguing when consideredwith the secondary characteristics of CF airway diseasethat are difficult to directly attribute to CFTR activity. Wehave shown that NO-mediated increases in cGMP effec-tively inhibit amiloride-sensitive transepithelial sodiumabsorption in the nasal epithelium of cftr -/- mice, sug-gesting that a lack of epithelial NO production contributesto the abnormal regulation of sodium transport in CF air-ways through disrupted cGMP signaling. Similarly wehave demonstrated a NO-dependence on secondary chlo-ride secretory responses absent in CF (3). In addition to itsrole as a signaling molecule, NO is known to be an impor-tant component of the host immune system. NO is a po-tent antimicrobial agent and we have shown that airwaysof CF mice are less able to kill a small inoculum ofPseudomonas aeruginosa than airways of phenotypicallynormal mice. The addition of a NOS2 selective inhibitorto normal mice limited their ability to kill bacteria, impli-cating epithelial NO as an antibacterial innate defensemechanism that may be lacking in CF (1). A recent reportoffers a speculation that a lack of epithelial NO produc-tion may be responsible for the specificity of Pseudo-monas infection in CF, particularly the Burkholderiacepacia strain. The authors demonstrate that a combina-tion of NO and H2O2 was needed to effectively kill B.cepacia and that the influx of neutrophils into the CF air-ways may be insufficient to eliminate bacterial infectionin the absence of epithelial NO (4).

Given the inflammatory nature of CF disease, it is un-clear why NOS2 expression is reduced since its expres-

sion is usually increased under inflammatory conditions.In order to understand reduced NO production in CF ep-ithelium, we began analyzing factors responsible for theregulation of NOS2 expression. Our preliminary data in-dicate that alterations in the regulation of the signaltransducer and activator of transcription 1 (Stat1) are re-sponsible for the reduced expression of NOS2 in CF ep-ithelial cells. Our evidence shows that CF epithelial cellsoverexpress a specific inhibitor of Stat1, the protein in-hibitor of activated Stat1 (PIAS1). PIAS1 has previouslybeen shown to inhibit Stat1 signaling and to prevent theexpression of Stat1-dependent genes. These findingspredict that interferon-γ (IFN-γ) signaling would be sig-nificantly altered in CF cells, since Stat1 has been shownto be an integral part of the IFN-γ signaling cascade.This prediction is supported by our preliminary data thatshow the expression of the IFN-γ regulatory factor-1(IRF-1) is also diminished in CF cells after stimulationwith IFN-γ. Our data suggest that CFTR is somehowcontributing to the regulation of IFN-γ responsive genesthrough the regulation of Stat1 activity. We have alsoshown that the cytokine TGF-β1 is an effective negative-regulator of NOS2 expression in epithelial cells. We arecurrently exploring the relationship between TGF-β1and the expression of PIAS1 in CF epithelial cells.

References1. Kelley, T.J. and Drumm, M.L. (1998) Inducible nitric

oxide synthase expression is reduced in CF murineand human airway epithelial cells: possible involve-ment in CF-related sodium hyperabsorption and sus-ceptibility to bacterial infection. J. Clin. Invest. 102,1200-1207.

2. Meng, Q., Springall, D.R., Bishop, A.E., Morgan, K.,Evans, T.J., Habib, S., Gruenert, D.C., Gyi, K.M.,Hodson, M.E., Yacoub, M.H., and Polak, J.M. (1998)Lack of inducible nitric oxide synthase in bronchialepithelium: a possible mechanism of susceptibility toinfection in cystic fibrosis. J. Pathol. 184, 323-331.

3. Elmer, H.L., Brady, K.G., Drumm, M.L., and Kelley,T.J. (1999) Nitric oxide-mediated regulation oftransepithelial sodium and chloride transport inmurine nasal epithelium. Am. J. Physiol. 276, L466-L473.

4. Smith, A.W., Green, J., Charlotte, E.E., and Watson,M.L. (1999) Nitric oxide-induced potentiation of thekilling of Burkholderia cepacea by reactive oxygenspecies: implications for cystic fibrosis. J. Med. Mi-crobiol. 48, 419-423.

16.2NO-HIDING: REGULATION OF NOS2 EXPRESSION IN CF EPITHELIA

Thomas J. KelleyDepartment of Pediatrics, Case Western Reserve University, Cleveland, Ohio

138-164.Sess.3 8/18/99 2:46 PM Page 152 (Black plate)

Symposium Session Summaries 153

The infectious inflammatory-immune processes drivethe progressive pulmonary disease associated with cysticfibrosis (CF). This condition is thought to cause an im-balance in the lung’s antioxidant defense system leadingto severe oxidative stress. However, recent studies sug-gest that the CFTR gene defect itself may be an impor-tant component of the imbalance in the lung’s antioxi-dant defenses by modulating glutathione transport intothe epithelial lining fluid [1]. This together with malab-sorption of essential dietary antioxidants may make thecystic fibrosis patient less capable to defend against theinfectious inflammatory-immune processes that ulti-mately destroy the lung [2, 3]. This forms the rationalefor a therapeutic approach to use antioxidants, such asglutathione, in cystic fibrosis to correct this antioxidantimbalance and slow the progression of tissue destructionin the lung. There is ample evidence in the literature de-scribing oxidative stress in the CF patient [2, 4-6], butthere is some controversy whether it is due to the infec-tious process or is inherent to the gene deficit itself or acombination of both.

It is well recognized that infections can lead to theoverproduction of reactive oxygen and nitrogen species(ROS/RNS) that can damage tissue (Figure 1).ROS/RNS are integral parts of the host defense and arereleased by activated leukocytes such as macrophagesand neutrophils in response to bacterial and viral infec-tions. Tissue injury itself can increase free radical forma-tion by injury of mitochondria, release of redox activeiron and increased activity of calcium sensitive oxidases

such as xanthine oxidase. Overproduction of ROS/RNScan deplete tissue antioxidants and set up an imbalancethat can further contribute to tissue injury and impair-ment of repair mechanisms [8]. The role ROS/RNSspecies play in the pathophysiology of CF lung diseaseis not clear and there is still some controversy whetherthey cause or contribute significantly to tissue injury.

If an imbalance in the antioxidant defenses is inherentwith the gene defect itself as suggested by Linsdell andHanrahan [1], then the CF patient would be less able todefend against oxidative stress. This concept is difficultto test in humans due to the elevated antioxidant defensesduring early development and the early onset of chronicinfections. However, data from CFTR mutant mice sup-ports the concept in those mice that lack functionalCFTR have exaggerated inflammatory responses topseudomonas infections and increased mortality [9].Also, it has been reported that CF patients have muchlower concentrations of glutathione in their lung surfacelining fluid than normal individual [10]. However, it isnot clear whether this deficit in lung glutathione is due tochronic oxidative stress or the CFTR gene defect or both.

It is becoming clear that the use of antioxidants maybe beneficial in CF patients, regardless on whether thegene defect or the infectious inflammatory-immuneprocesses or a combination of both processes producesthe antioxidant imbalance in the lungs of CF patients.There are a few concerns about the use of antioxidantssuch as glutathione in CF and include: 1) its effect onhost defense in a patient population that is chronically

16.3MECHANISMS OF OXIDANT INJURY IN THE CYSTIC FIBROSIS AIRWAY

Brian J. Day, Ph.D.Departments of Medicine and Pharmaceutical Sciences, National Jewish Medical & Research Center and the

University of Colorado Heath Sciences Center, Denver, CO USA

Figure 1. ROS/RNS that are formed during infection and may be involved in tissue injury (modified from [7]).



infected; and 2) the purity of the glutathione, since onlythe reduced form will be of benefit and the oxidizedform may actually be harmful due the body’s attempt toconvert to the reduced form that requires energy andmay not be able to secrete it. In summary, the presentdata forms the rationale for a therapeutic approach to useantioxidants, such as glutathione, in cystic fibrosis tocorrect an antioxidant imbalance and slow the progres-sion of tissue destruction in the lung.

References:1. Linsdell, P. & Hanrahan, J.W. (1998) Am J Physiol

275, C323-326.2. Portal, B.C., Richard, M.J., Faure, H.S., Hadjian,

A.J., & Favier, A.E. (1995) Am J Clin Nutr 61, 843-847.

3. Homnick, D.N., Cox, J.H., DeLoof, M.J., & Ringer,

T.V. (1993) J Pediatr 122, 703-707.4. Brown, R.K., McBurney, A., Lunec, J., & Kelly, F.J.

(1995) Free Radic Biol Med 18, 801-806.5. Hull, J., Vervaart, P., Grimwood, K., & Phelan, P.

(1997) Thorax 52, 557-560.6. Langley, S.C., Brown, R.K., & Kelly, F.J. (1993) Pe-

diatr Res 33, 247-250.7. van der Vliet, A., Eiserich, J.P., Marelich, G.P., Halli-

well, B., & Cross, C.E. (1997) Adv Pharmacol 38,491-513.

8. Crystal, R.G. (1991) Am J Med 91, 39S-44S.9. Heeckeren, A., Walenga, R., Konstan, M.W., Bon-

field, T., Davis, P.B., & Ferkol, T. (1997) J Clin In-vest 100, 2810-2815.

10.Roum, J.H., Buhl, R., McElvaney, N.G., Borok, Z.,& Crystal, R.G. (1993) J Appl Physiol 75, 2419-2424.

The collectins are a family of polypeptides that in-clude surfactant proteins A, D (SP-A and SP-D), conglu-tinin and mannose binding proteins, all of which are in-volved in various aspects of host defense in mammals.Surfactant proteins A and D are expressed selectively incells lining the respiratory tract, being synthesized byepithelial cells of the tracheal-bronchial glands, con-ducting airways and alveolar Type II cells. Gene targetedablation of both SP-A and SP-D in transgenic mice, hasprovided insight into their unique and distinct roles inlung host defense and inflammation.

SP-A knockout mice (SP-A -/-) are highly susceptibleto pulmonary infections caused by various pathogenicorganisms, including Pseudomonas aeruginosa, H. in-fluenza, group B streptococcus, respiratory syncytialvirus, and adenovirus. Phagocytosis and killing of thesepathogens by alveolar macrophages from SP-A (-/-)mice are markedly impaired and readily restored by in-tratracheal administration of SP-A. Pulmonary inflam-mation, neutrophilic infiltrates, and cytokine productionare increased in SP-A (-/-) mice following exposure torespiratory pathogens. Furthermore, oxygen radical pro-duction is impaired in alveolar macrophages from SP-A(-/-) mice. Thus, SP-A is an important host defense mol-ecule, with anti-inflammatory and host defense proper-ties, that likely plays a critical role in innate defense ofthe lung.

In contrast to findings in SP-A (-/-) mice, SP-D (-/-)mice develop severe pulmonary emphysema and pul-monary fibrosis during the postnatal period. Analysis ofalveolar macrophages from SP-D (-/-) mice demonstrateda marked increase in basal hydrogen peroxide production,establishing a previously unrecognized role for SP-D inthe modulation of oxidant balance in the lung. Thus, SP-Dis required for maintenance of alveolar structures and in-hibition of pulmonary fibrosis even in the normal, unchal-lenged lung. Reintroduction of SP-A or SP-D to the SP-A(-/-) and SP-D (-/-) mice, respectively, corrects lungpathology. Thus, SP-A and SP-D play important and dis-tinct roles in host defense and regulate both oxidant bal-ance and inflammatory responses in pulmonary cells.Since concentrations of SP-A, and particularly of SP-D,are markedly reduced in bronchoalveolar lavage materialfrom patients with cystic fibrosis (Postle et al., 1999), thecollectins may serve as potential therapeutic moleculesfor cystic fibrosis lung disease.

ReferencePostle, A. D., Mander, A., Reid, K. B., Wang, J. Y,

Wright, S. M., Moustaki, M., and Warner, J. O.(1999) Deficient hydrophilic lung surfactant proteinsA and D with normal surfactant phospholipid molec-ular species in cystic fibrosis. Am. J. Respir. CellMol. Biol. 20:90-98.

16.4ROLE OF COLLECTINS IN THE MODULATION OF PULMONARY HOST

DEFENSE AND INFLAMMATIONJeffrey A. Whitsett, M.D.

Children’s Hospital Medical Center, Cincinnati, OH 45229-3039



Malnutrition and progressive lung disease are hall-marks of cystic fibrosis (CF). Poor nutritional statuslikely affects lung growth, host defense, and ability torepair lung injury, while lung disease likely affectsweight and height through appetite suppression and in-creased energy expenditure. Thus, the two are inextrica-bly woven together. Although this may be obvious inolder CF patients with advanced disease, the relationshipbetween nutritional status and severity of lung disease inyounger patients has not been determined. Understand-ing this relationship has important therapeutic implica-tions. If poor nutritional status early in life is shown tobe an independent risk factor for severity of lung dis-ease, then early nutritional intervention might slow itsprogression. Alternatively, if severity of lung diseaseearly in life is shown to be a risk factor for poor nutri-tional status, then early aggressive pulmonary interven-tion might lead to better nutritional status and overallwell-being. Currently, our ability to study this relation-ship is limited because the severity of lung disease (e.g.by FEV1) cannot be objectively measured in most pa-tients < 6 years of age, although nutritional status(weight and height) is easily assessed. Therefore, in this

study, our approach is to determine whether nutritionalstatus at age 3 predicts pulmonary function at age 6. Wealso consider some of the pulmonary signs and symp-toms that can be assessed at age 3, such as cough, spu-tum production and respiratory tract infection byPseudomonas.

Data from patients participating in the EpidemiologicStudy of Cystic Fibrosis (ESCF) were used for thisanalysis. To be included, patients must a) have enrolledin ESCF before age 3 years, b) have been followed inESCF until at least age 6 years, c) have weight andheight measurements during this time period, and d)have at least one valid spirometry test between age 5.5and 7.5 years, obtained at a time of clinical stability. 862patients met this criteria. Patients were categorized intoquartiles based on their best FEV1 (percent of predicted)obtained between age 5.5 and 7.5. Weight and heightpercentiles for age and percentage of ideal body weightwere examined at the clinic visits closest to ages 3 (±0.5)and 6 (±0.5) years, for each FEV1 quartile. Hypothesistesting was done using one way analysis of variance pro-cedures to compare nutritional indices across FEV1 cate-gories. Presented are means (±S.D.).

17.2THE RELATIONSHIP BETWEEN NUTRITIONAL STATUS IN EARLY LIFE

AND PULMONARY FUNCTION IN CYSTIC FIBROSISM.W. Konstan1, S.M. Butler2, C.A. Johnson2, J.S. Wagener3, H.C. Lai4, W.J. Morgan5

for the Investigators and Coordinators of the Epidemiologic Study of Cystic Fibrosis1Case Western Reserve University, Cleveland, OH, 2Genentech, South San Francisco, CA, 3University of Colorado,

Denver, CO, 4University of Wisconsin, Madison, WI, and 5 University of Arizona, Tucson, AZ

FEV1 (% pred) Weight Percentile Height Percentile % Ideal Weight

Age 5.5- 7.5 yrs 3 yrs 6 yrs 3 yrs 6 yrs 3 yrs 6 yrs

Q1 ≥110 (n=215) 41 ± 25 45 ± 26 35 ± 26 33 ± 26 103 ± 9 107 ± 9Q2 <110 - 97 (n=216) 39 ± 28 42 ± 28 35 ± 28 34 ± 28 102 ± 9 105 ± 9Q3 < 97 - 84 (n=215) 33 ± 26 36 ± 25 32 ± 26 31 ± 27 101 ± 9 103 ± 10Q4 < 84 (n=216) 27 ± 25 27 ± 24 29 ± 26 25 ± 25 100 ± 9 102 ± 9

p<0.001 p<0.001 p=0.12 p=0.02 p<0.001 p<0.001

FEV1 (% pred) Cough Sputum Clubbing Crackles Pseudomonas

Age 5.5- 7.5 yrs 3yrs 6yrs 3yrs 6yrs 3yrs 6yrs 3yrs 6yrs 3yrs 6yrs

Q1 ≥110 62% 72% 20% 35% 16% 32% 5% 6% 31% 52%Q2 <110 - 97 69% 75% 24% 34% 14% 34% 5% 5% 38% 56%Q3 < 97 - 84 75% 80% 33% 44% 22% 36% 5% 9% 39% 64%Q4 < 84 80% 85% 39% 53% 25% 53% 14% 21% 58% 77%

All p-values < 0.001 except for: cough at age 6 (p< 0.01), clubbing at age 3 (p=0.01)



These data reveal that nutritional indices at age 3 and6 correlate with FEV1 at about age 6 in similar ways,suggesting that lower nutritional status at age 3 is a riskfactor for lower pulmonary function at age 6. However,it is possible that patients with lower weight, height andpercent of ideal body weight at age 3 already have lowerpulmonary function at that age. We assessed the degreeof lung disease in these patients by recording pulmonarysigns and symptoms known to correlate with FEV1 inolder patients (clubbing, crackles, cough, sputum pro-duction, and Pseudomonas status). The percentage ofpatients at each age with these indicators of lung diseaseare presented. Hypothesis testing was done using chi-squared tests of independence to compare signs andsymptoms across FEV1 categories.

We found that patients with low FEV1, compared tohigher FEV1, at age 5.5-7.5 years had more signs andsymptoms of pulmonary disease and a higher incidenceof Pseudomonas at age 3 (and at age 6). Further analysissuggests that, at age 3 (and at age 6), lower values of thenutritional indices were associated with more symptomsof lung disease.

Finally, we assessed the use of pancreatic enzymesand nutritional supplements (oral and enteral) in thesepatients. There was no difference in the use of pancreaticenzymes by age or FEV1 status (used by 96-98% of allpatients). Nutritional intervention was greater at ages 3and 6 in those with lower pulmonary function (and, as

expected, in those with worse nutritional status). Thefollowing table shows the percentage of patients usingnutritional therapies:

FEV1(% pred) Oral Enteral

Age 5.5-7.5 yrs 3 yrs 6 yrs 3 yrs 6 yrs

Q1 ≥110 19% 27% 3% 5%Q2 <110 - 97 24% 36% 4% 5%Q3 < 97 - 84 27% 38% 5% 3%Q4 < 84 39% 46% 7% 13%

p<0.001 p<0.001 p=0.374 p<0.001

Although these results demonstrate a relationship be-tween nutritional status at age 3 and pulmonary functionat age 6, they also suggest a relationship with pulmonarydisease at age 3. Thus, we cannot demonstrate that re-duced nutritional status precedes reduced lung function.As ESCF continues, we will be able to consider patientsbelow age 3. Eventually, we hope that assessing these re-lationships beginning with newly diagnosed infants willprovide better insights into the relationship of nutritionalstatus early in life with the progression of pulmonarydisease in patients with cystic fibrosis.

Supported by Genentech, Inc., South San Francisco,CA

Despite the correspondence of gene mutation to func-tional abnormalities of the CFTR protein, genotype ap-pears to be a poor predictor of severity of lung diseaseand overall clinical course of CF except in a small mi-nority of patients with very mild mutations. It is possiblethat other currently unidentified modifier genes mighteventually explain some of the variability seen in the CFpopulation at large, but at this time the marked hetero-geneity in disease progression is largely unexplained bygenotype.

Socioeconomic status (SES) is an important determi-nant of health in the general population, and low SESleads to increased prevalence and severity of many dis-eases. Asthma is a well studied example. CF is unique inthat it is a genetic disease cared for by a dedicated net-work of subspecialty clinics, so some of the hypothe-sized etiologies of the adverse effect of poverty on healthmay not apply. Nevertheless, it is plausible that low SESmight be associated with poorer CF outcomes. Previousstudies in the U.K. have shown that CF patients from

lower social classes have a lower median age at death(1), and that CF children of single or teenage mothershave higher morbidity (2).

In order to investigate this phenomenon in the U.S.,we initially performed a cross-sectional study of 282 CFpatients attending the large pediatric CF clinic at UNC-Chapel Hill, using Medicaid status as a marker of lowSES (3). This analysis found that patients receivingMedicaid had a decline in pulmonary function that wasparallel to those who were not Medicaid eligible, but thepercent predicted FEV1 averaged 11.6 less throughoutthe entire age range. These patients received more in-tense CF treatment, as measured by number of outpa-tient clinic visits as well as hospital utilization, evenwhen adjusting for their greater severity of lung disease,so (in contrast to asthma) poor access to medical carecould not be invoked as a contributing cause.

Older patients were excluded from this study becauseit is more likely in adults than in children that severe dis-ease would lead to low SES. Similarly, Medicaid eligi-

17.3POVERTY AND DISEASE SEVERITY IN CF: SOCIAL AND BIOLOGICAL

IMPLICATIONSMichael S. Schechter, MD, MPH

Department of Pediatrics, Wake Forest University School of Medicine, Winston-Salem, North Carolina



bility is a reasonable proxy measure of low SES, butonly if it can be shown that it is not the result of in-creased medical expenditures secondary to greater dis-ease severity. This preliminary study required confirma-tion primarily because as a cross-sectional structure itcould not discern whether Medicaid status preceded orfollowed the development of worsening disease.

We subsequently performed a historical cohort analy-sis of untransplanted CF patients under 20 years of ageusing US National Cystic Fibrosis Patient Registry datafor 1986-1994 (4,5). Medicaid status was again used as asurrogate for low SES. In this study, patients on Medic-aid every year they were listed in the registry were com-pared to those never on Medicaid, using regressionanalysis to control for age, gender, race, and genotype.The adjusted risk of death during the period studied was2.1 times higher for Medicaid patients than those not re-ceiving Medicaid. The mean percent predicted FEV1 ofsurviving Medicaid patients was 9.2 less than that of thenon-Medicaid patients. Medicaid patients were 2.3 timesmore likely to be below the 5th percentile for weight and2.2 times more likely to be below the 5th percentile forheight. Medicaid patients were 1.6 more likely to requireIV antibiotic treatment of a pulmonary exacerbation.There was no difference in the number of outpatientclinic visits. The adjusted median age at diagnosis was35 days older for Medicaid patients, but it is unclearwhether the magnitude of that difference is meaningful.

The literature suggests that in general, the mediators ofthe relationship between low SES and adverse health out-comes include barriers in accessing care, poor nutrition,exposure to pollutants (including tobacco smoke), in-creased incidence of viral respiratory infections, stress,and lower adherence to medical regimens. We have col-lected preliminary questionnaire data to begin to identifywhich of these are important in CF patients (6). The fol-lowing factors were associated with decreased pul-monary function: history of RSV infection; low utiliza-tion of a primary care physician; residence >1 hour fromthe center; cigarette smoke exposure in the home; ruralresidence (if low-income families were excluded); andlow family income in urban dwellers. The following fac-tors were associated with decreased height or weight:prenatal tobacco exposure; early childhood tobaccosmoke exposure; parental misunderstanding of dietaryrecommendations; low maternal education; and rural res-idence. Parental smoking, which was also associatedwith earlier median age at diagnosis and increased needfor IV antibiotics, was much more likely in low SES fam-ilies. Dietary recommendations were much more likely

to be misunderstood when maternal educational statuswas low. Problems with affordability of medical care,medications, or food, perceived barriers in access to care,reported adherence to therapy, missed patient visits, daycare exposures, and crowding were evaluated and werenot associated with either low SES or adverse outcomes.

The reason that low SES patients suffer more severeconsequences of CF is presumably because poverty isassociated with a clustering of detrimental environmen-tal influences. These findings have three important im-plications. First, we can readily identify in the poor agroup of patients at risk for adverse outcomes. As a pub-lic health measure, it might be appropriate to offer thisgroup more intense standard treatment (more antibiotics,more anti-inflammatory therapy, etc.) than a lower riskgroup, though this approach is unproven. Certainly, ifthe specific cause or causes of the link between povertyand more severe lung disease is identified, then morespecific effective therapies could be offered to these pa-tients. This knowledge would also lead to improvementsin outcome for others who are not low SES but may stillbe exposed to any of these risk factors. Secondly, be-cause of its association with adverse health outcomes,low SES must be considered as a potential confounder inall clinical research trials, and appropriately adjusted for.Finally, a better understanding of environmental riskfactors and how they mediate adverse outcomes wouldprovide insight into the basic biology and pathogenesisof CF lung disease.

References:1. Britton J. Effects of social class, sex, and region of

residence on age at death from cystic fibrosis. BrMed J. 1989;298:483-7.

2. Macpherson C, Redmond AO, Leavy A, McMullanM. A review of cystic fibrosis children born to singlemothers. Acta Paediatrica. 1998;87:397-400.

3. Schechter, MS, and Margolis, PA. Relationship be-tween socioeconomic status and disease severity incystic fibrosis. J. Pediatr. 1998;132:260-64.

4. Schechter MS, Margolis PA, Shafer MD. Relation-ship between poverty and disease severity in cystic fi-brosis patients. Pediatr Pulmonol 1996; Suppl13:489

5. Schechter MS, Shelton BJ, Margolis PA. Mortality inMedicaid and Uninsured Patients with CF – AnAnalysis of CFF National Registry Data. Pediatr Pul-monol 1998; Suppl15:483.

6. Schechter MS, Anderson RT. Environmental and so-cial determinants of outcome in CF. Pediatr Pul-monol 1998; Suppl15:482.



Pseudomonas aeruginosa (PA) in the respiratory tractof patients with cystic fibrosis (CF) is related to de-creased survival, a more rapid decline in pulmonaryfunction, greater abnormalities on chest radiographs, in-creased probability of hospitalization, and increasedmortality.1-5 Early therapy may reduce the chance of thePA persisting in the airway.6 However, there is no con-sensus on how often patients should be cultured,whether or not patients should be treated at the time offirst detection, or what therapy should be used. We pre-viously reported risk factors for new detection of PA inCF patients.7 This study is a continuation of the previousstudy and is designed to: 1) compare the prognoses ofpatients with and without new detection of PA and 2)evaluate the outcomes associated with antibiotic treat-ment following new detection.

The Epidemiologic Study of Cystic Fibrosis (ESCF)includes serial data from over 20,000 CF patients. ESCFsubjects were included in this study if: 1) they had atleast 3 years of active follow-up, 2) they had culturesnegative for PA in both the year prior to and year follow-ing ESCF study enrollment 3) they had at least one cul-ture during the second year after enrollment (observa-tion year), and 4) they were followed for at least twoyears following this culture during the observation year.Patients with cultures positive for B. cepacia and S. mal-tophilia were excluded.

Methods: Patients were divided into PA negative andPA positive groups based on whether any culture duringthe observation year was positive for PA. Patients whowere prescribed anti-Pseudomonas antibiotics during thesix months following the culture were defined as treatedcases. Baseline data included: age, gender, genotype,pulmonary function (FEV1), disease severity, nutritionalstate, and frequency of clinic visits and bacteria cultures.Outcome measures included change in nutritional para-meters, change in pulmonary function, and the fre-quency of clinic visits and re-culture during the twoyears following new detection.

Results: 1701 patients had at least two negative PAcultures during enrollment and the first study year. 308(18%) of these patients had their first recorded positivePA culture during the observation year. The risk of a newpositive culture was unrelated to gender (female 18%,male 18%), genotype, or pancreatic insufficiency. Newdetection was similar for all age groups (p=0.09, Table1) Predictors of new detection included: lower pul-monary function (p=0.031), lower ideal body weight(p=0.012), the number of pulmonary exacerbations(p<0.005), and the number of cultures obtained duringthe observation year (<0.001).

During the two years following new detection, PApositive patients were more likely to have a pulmonaryexacerbation (81% vs. 53%, p<0.001), be hospitalized(52% vs. 25%, p<0.001), and have a subsequent culturepositive for PA (52% vs 11%, p<0.001).

Following a positive culture, 151 (49%) patients re-ceived PA specific antibiotic therapy within six months.Compared with non-treated PA positive patients, treatedpatients had lower pulmonary function (p<0.001) orlower weight for age (p=0.048) (Table 2). Treatment re-sulted in a slight increase in FEV1 over one year(p=0.08), but over two years did not alter the rate of pul-monary function decline (Figure), nutritional state, orlikelihood of having a subsequent PA positive culture(51% in treated and 53% in non-treated patients over 2years).

These results suggest that the risk of PA new detectionis related to the number of respiratory exacerbations andthe number of cultures obtained during a 12 month pe-riod as well as the patient’s baseline pulmonary functionand percent of ideal body weight. Compared with PAnegative patients, PA positive patients have greater med-ical problems following new detection. Treatment at thetime of new detection may result in acute pulmonaryfunction benefit, however, treatment may not alter thepatient’s pulmonary function decline or nutritional statusover a two year follow-up period.

17.4NEW CASES OF PSEUDOMONAS AERUGINOSA:

TREATMENT AND OUTCOMESJ.S. Wagener1, S.M. Butler2, H. Rabin3, W. Regelmann4, C. Johnson2 for the Investigators and Coordinators of the

Epidemiologic Study of Cystic Fibrosis1University of Colorado, Denver, CO, 2Genentec, S. San Francisco, CA, 3University of Calgary, Calgary, Canada,

4University of Minnesota, Minneapolis, MN.

Table 1. New Pseudomonas aeruginosa cases separated by age. (number in cell and % of age group)

0-5 years 6-12 years 13-17 years 18-24 years ≥25 years

PA Negative 450 (83%) 617 (83%) 184 (77%) 81 (76%) 61 (86%)PA Positive 90 (17%) 128 (17%) 54 (23%) 26 (24%) 10 (14%)



1. Kerem E, et.al. Pulmonary function and clinicalcourse in patients with cystic fibrosis after pul-monary colonization with Pseudomonas aeruginosa.J Pediatr 1990; 116:714-9.

2. Kulczycki LL, et.al. Pseudomonas colonization incystic fibrosis. A study of 160 patients. JAMA 1978;240:30-4.

3. Hudson VL, et.al. Prognostic implications of initial

oropharyngeal bacterial flora in patients with cysticfibrosis diagnosed before the age of two years. J Pe-diatr 1993; 122:854-60.

4. Pamukcu A, et.al. Effects of pseudomonas aerugi-nosa colonization on lung function and anthropomet-ric variables in children with CF. Pediatr Pulmonol1995; 19:10-5.

5. Henry RL, et.al. Mucoid Pseudomonas aeruginosa isa marker of poor survival in cystic fibrosis. PediatrPulmonol 1992; 12:158-61.

6. Valerius NH, et.al. Prevention of chronic Pseudo-monas aeruginosa colonization in cystic fibrosis byearly treatment. Lancet 1991; 338:725-6.

7. Wagener J, Butler S, Rabin H, Regelmann W, John-son C. New cases of Pseudomonas aeruginosa: Riskfactors and outcomes. Pediatr Pulmonol 1998; Suppl17:147-8.

Supported by Genentech, Inc., South San Francisco, CA

Table 2. Treated vs. non-treated patients at the time ofnew PA detection. (mean ± SD)

% pred FEV1 Weight for Age

Treated 76.9 ± 21.3 29.3 ± 26.2%Not Treated 89.6 ± 18.1 35.2 ± 26.0%

Figure. Pulmonary function (FEV1 percent predicted) change over time. (mean ± SE)

Cystic Fibrosis centres must assess and assist the fam-ilies of CF patients because high levels of family supporthave been associated with good psychological adjust-ment in patients [1]. Chronic illness in childhood hasmassive physical, social and psychological effects onfamilies who, in addition to fulfilling their usual familyduties, roles and obligations, are expected to meet theneeds arising from their child’s CF disease [2]. Adultswith CF continue to need the physical, mental, emo-tional and spiritual support of their families throughtimes of chronic or acute illness.

What constitutes a family? Families of CF patients areas varied as the patients themselves. Pediatric CF centrescannot expect to interact with married heterosexual cou-ples parenting one or more children with CF. Instead, CFcentres often interact with single parent families,blended families or foster families when patients areunder the guardianship of child welfare organizations.Social workers for adult CF clinics often do not meet thebirth families of adult patients because patients have ge-ographically moved away from home, patients no longerwish parental involvement in their medical care deci-

18.1CF FAMILIES: FUNCTION AND FRICTION

D.F. Ellergodt and H.R. RabinAdult Cystic Fibrosis Clinic, University of Calgary Medical Clinic of the Foothills Medical Centre, Calgary,

Alberta, Canada



sions or patients are estranged from their birth families.In adult centres, families are frequently represented byspouses, partners, siblings or children.

Often CF patients are supported not only by rela-tives but also by social support networks which mayinclude friends, co-workers, neighbors, church mem-bers or service organizations. For example, CanadianHutterite CF patients are usually supported by theirnuclear family and the entire religious colony. Hospi-tal and clinic staff can become the social support net-work for both pediatric and adult hospitalized CF pa-tients who live out-of-town or have few visitors. CFcentres will interact with whomever is providing phys-ical, mental, emotional and spiritual support to CF pa-tients. Attributes of affection, strong emotional ties, asense of belonging and durability of relationships de-termine family composition [11].

Patients and their families can either be coping withdisease through family functional behavior or familyfrictional behavior. Just as the composition of family isunpredictable, so is family behavior. Family behavior isinfluenced by many factors such as parental and maritalrelationships, finances, individual coping skills, CF dis-ease status and the ability to share the caregiving burden.Assessing how families of patients with CF adapt to theillness provides indicators as to the care and supportneeded by patients and their families [8].

To assess the family life of the adult CF patients newto the Calgary Adult CF Clinic, the patients are inter-viewed by the clinic social worker using the CalgaryFamily Assessment Model authored by Lorraine Wrightand Maureen Leahey of the Faculty of Nursing, TheUniversity of Calgary [11]. An understanding of familydynamics is essential for determining the support systemavailable to the adult CF patient in times of crisis. Thisassessment process identifies family functional behaviorand family frictional behavior from the adult patient’spoint of view. The model has three assessment cate-gories: Family Structure, Family Development and Fam-ily Functioning.

The Family Structure assessment category records thefamily genogram, patient attachment diagram includingsocial support networks and the internal family structuresuch as rank order and subsystems that socialize to-gether. The external family structure and context includeethnicity, race, religion, social class status and mobility,environment and extended family. This review of the CFpatient’s family structure helps conceptualize the pa-tient’s family situation. The Family Development assess-ment category records the patient’s current family lifestage such as patient still living at home, launched fromhome, married or patient as a parent. Major alterations infamily life such as death, separation, divorce and remar-riage are summarized. The Family Functioning assess-ment category records patient and family tasks includingCF routine, strengths and difficulties in expressive func-tioning such as emotional and circular communication,

established family roles and methods of influence or -control.

Families display functional behavior when they areable to provide for the physical, emotional, mental andspiritual needs of the family members. Well functioningfamilies are also able to communicate thoughts and feel-ings effectively and are able to cope with a crisis experi-ence such as an acute illness. Areas of family frictioncan vary from sparring with family over CF routine in-cluding diet, physiotherapy, medication and exercise tototal estrangement from the birth or marital family. As-sessment of family functional behavior and family fric-tional behavior prepares the CF team for probable familyreaction if the patient’s health deteriorates.

The assessment provides a metaperspective on the CFpatient’s family situation, which is recorded on the pa-tient’s medical chart. The assessment process continuesinformally by the social worker at each visit to the CFclinic, as family behavior is influenced by on-going lifeevents. The disease has a ripple effect on the family andsocial support network. Treatment requirements affectthe family’s daily routine, diet, finances and holidays.Nuclear and extended family may have genetic testingthat identifies the disease in other family members. Ifpartners are identified as carriers, reproduction decisionsare affected. Family members may become actively in-volved with CF foundations and fund-raising or choosecareers as CF professionals. Married patients will inter-act with their in-laws who may or may not understandthe disease and required daily CF routine. The adult pa-tient’s ability to have children, continue working or per-form household functions influences family and socialsupport relationships. Patients may choose to relocatecloser to extended family and social support networks asthe disease advances. Family and friends may volunteerto be donors for living donor lung transplantation [7].

Patients and families may experience the trauma ofdeath from CF of other family members. Surviving fam-ily members are forced to examine their own mortality.Some family members reconcile with their loss as wellas can be expected and feel strengthened by coping withthe death experience. Other family members may re-spond with feelings of unresolved grief, hopelessnessand distancing or over-protectiveness towards remainingfamily members with CF.

Early or late diagnosis means patients or families haveeither grown with the disease or have had to adjust laterin life to all the implications of CF. In addition, theseverity of patient illness and different parenting or mar-ital styles result in drastically different patient and fam-ily experiences. Family reactions can range from denial,discontent and disintegration to coping, cooperation andcommitment. CF centre responses to family reactionsmay include offering information, supportive coun-selling, adjustment to illness counselling, marital orfamily therapy, resource education and crisis coun-selling. CF centres must continually assess family func-



tional behavior and family frictional behavior in order tooffer appropriate assistance and support for patients andfamilies coping with CF disease.

References:1. Ievers, C.E. and Drotar, D. Family and parental func-

tioning in cystic fibrosis. J. Dev Behav Pediatr1996;17: 48-55.

2. Wiseman, H. The effects of chronic childhood illnesson families. Nurs Times 1996;92:44-46.

3. Derouin, D. and Jessee, P.O. Impact of a chronic ill-ness in childhood: siblings’ perceptions. IssuesCompr Pediatr Nurs 1996; 19:135-147.

4. Quittner, A.L., Tolbert, V.E., Regoli, M.J., Orenstein,D.M., Hollingsworth, J.L. and Eigen, H. Develop-ment of the role-play inventory of situations and cop-ing strategies for parents of children with cystic fi-brosis. J Pediatr Psychol 1996; 21:209-235.

5. Matloff, E.T. and Zimmerman, S.J. Framework for aproactive parent support group; The syracuse cystic fi-brosis model. J Pediatr Health Care 1996; 10:264-271.

6. Chafe, J., Parmer, J. and Boyack, J. A family systemsapproach to intervention with the adult CF patient.(Abstract 330). Pediatr Pulmonol 1993:Supplement9:292.

7. Mallory, G.B. Jr. and Cohen, A.H. Donor considera-tions in living-related donor lung transplantation.Clin Chest Med 1997; 18:239-244.

8. Coyne, I.T. Chronic illness: the importance of sup-port for families caring for a child with cystic fibro-sis. J Clin Nurs 1997; 6:121-129.

9. Hodson, M.E. Psychosocial aspects for the manage-ment of adults with cystic fibrosis. Pediatr PulmonolSuppl 1997; 16:113-114.

10.Quittner, A.L., Opipari, L.C., Espelage, D.L., Carter,B., Eid, N. and Eigen, H. Role strain in couples withand without a child with a chronic illness; Associa-tions with marital satisfaction, intimacy, and dailymood. Health Psychol 1998; 17:112-124.

11.Wright, L.M. and Leahey, M . Nurses and families: Aguide to family assessment and intervention. F.A.Davis Company, Philadelphia1994 (2nd edition).

The improved medical treatments currently availablefor people with cystic fibrosis (CF) has increased life-expectancy but possibly has some features that could beconstrued by patients and their families as disadvanta-geous, these treatments are complex, time-consuming,visible and life-long. There is a tendency for all treat-ment to be home rather than hospital based. This has po-tential impact on the home life of children with CF andfor the burden of responsibility placed on major carers.Potentially, the daily experiences and relationships ofthese children are greatly affected by CF treatment in thehome. The sibling relationship is an important childhoodrelationship and so it is valid to question the impact CFhas upon it.

The relationship between siblings in childhood has aunique quality, being unlike any other childhood rela-tionship or influence. Young siblings share experiences,environment and many aspects of their genetic makeup,which potentially affect their emotional and cognitivedevelopment. The childhood sibling relationship allowsthe freedom and, in most cases, the security for testingextremes of behaviour. The sibling relationship, there-fore, suggests a fruitful ground for exploring the influ-ences of children on each other and, in particular, the de-velopment of socio-emotional behaviour and a sense ofself (1). The qualities expressed by individual siblingsand the pattern of expression within the sibling relation-

ship appear to remain relatively stable across the span ofchildhood. It is possible, therefore, that sibling relation-ships, distinctive in their high frequency of interaction,have a formative influence on childhood developmentand CF may interfere with this.

When one sibling has a chronic illness or disability itseems appropriate to assume there will be developmen-tal effects on the children concerned. Attempts to iden-tify the presence or absence of effects of the chronic ill-ness on siblings found parent report of psychosocialsymptoms in their well siblings was usually the methodof choice. There have been reports of enuresis,headaches, depression, and abdominal pain in the sib-lings of children with leukaemia (2) as well as behaviourproblems (3) poor school performance (2, 4, 5) socialisolation and decreased social confidence (5, 6) and jeal-ousy (7) in the siblings of children with a range ofchronic disease.

There are methodological problems with the abovestudies, firstly, the findings are likely to be biased by thepsychiatric measures employed to elicit information.Secondly, information is provided by parents who willbe giving their perception of difficulties in the sibling.This may be confounded by their own personal difficul-ties in being part of a family with a sick or disabledchild. Thirdly, few of these studies used control groups.The reports of dysfunction are mean rates of symptom or

18.2SIBLINGS AND CF: WHEN SHOULD WE BE WORRIED?

Mandy BryonDepartment Psychological Medicine, Great Ormond Street Hospital for Children, London, U.K.



questionnaire scores of the group of well siblings sam-pled. Often, the only comparison is with the sick child.Rarely is normative data used (3).

The aims of this study were firstly, that the subjects ofthe study were the siblings themselves and not their par-ents. Both the well and sick children to be included. Sec-ondly, to measure the qualities of the sibling relationshiprather than looking for dysfunction in the well sibling.Thirdly, to assess the impact of CF on the sibling rela-tionship by measuring the well sibling’s current impres-sion of the effects of the disease. Fourthly, to include acomparison group of healthy siblings.

The measures chosen are the Sibling Inventory of Be-haviour (SIB) (8) with subscales for aggression, avoid-ance, companionship and teaching, the Sibling Inventoryof Disagreements (SID) (9), and the Sibling PerceptionQuestionnaire (SPQ) (10). The sample comprised, 44well siblings, mean age 13.07 (sd 2.99); 45 CF siblings,mean age 12.84 (sd 2.58) and 137 comparison siblings,mean age 13.15 (sd 1.39).

Results: The reports of the sibling relationship usingthe SIB and SID for the well siblings and comparisongroup were compared using independent t-tests. Therewere no differences on any of the subscales. Comparisonof the measures for the well and CF siblings indicatedthat there were differences, with the well siblings signif-icantly more likely to report aggression (t=-2.320,p<0.05) and disagreements (t=-2.230, p<0.05) in theirCF siblings, and the CF siblings significantly morelikely to report teaching from their well sibling (t=2.389,p<0.05). A correlation of well sibling’s perceptions ofCF using the SPQ on the SIB and SID relationship mea-sures was made. A step-wise multiple regression re-vealed that aggression and disagreements between thewell and CF siblings were predicted by the well sibling’sagreement with the interpersonal items (those indicatinglack of appreciation of differential parental attention)(t=2.833, t=3.738, p<0.01). Additionally, companion-ship and teaching between the well and CF siblings werepredicted by the well sibling’s agreement with the com-munication items (those indicating that the well siblingfelt informed about the disease and treatments) (t=3.818,t=3.630, p<0.001).

Conclusions: The qualities of the sibling relationshipsreported by well and CF siblings did not differ fromthose reported by normal siblings. That is, the well sib-lings experience and report similar “sibling behaviours”for their sibling with CF as those reported betweenhealthy sibling pairs. Sibling relationships when onechild has CF, as reported by the well sibling, are notnecessarily different from those between healthy chil-dren. When controlling for natural differential effects inthe childhood sibling relationship of age differences,birth order and gender, the siblings with CF were morelikely to report positive behaviours in their well sib-lings. It could be suggested therefore, that an effect ofCF is to produce more companionable and empathic be-

haviours in well siblings. There are differences in theindividual qualities of well-CF sibling dyads dependingon the perceived effect of the illness by the well sibling.It was found that the sibling relationship will be nega-tive when the well sibling perceives a greater number ofproblems associated with the disease. Communicationgenerally and information about the illness specificallypredicts positive sibling relationships. Personal dissatis-faction by the well sibling with the differential attentionpaid to the sick sibling by others is predictive of nega-tive sibling relationships marked by aggression and dis-agreements.

Rather than identifying the dysfunction of well sib-lings of children with CF, this study instead finds, on thewhole, normality. Negative qualities in the well and CFsibling relationship are identified and these relate to thewell sibling’s impression of CF. Thus, it is possible todiscover when we should be worried about the siblingrelationship: Risk factors for negative sibling relation-ships, were identified as, the differential treatment ofwell and sick siblings by parents and others, the exclu-sion of the well child from information about the illness,limitations of family activity without due explanationand poor communication about the illness to all familymembers.

References:(1) Dunn, J. (1988). Sibling influences on childhood de-

velopment, Journal of Child Psychology and Psychi-atry, 29(2), 119-127.

(2) Binger, C.M., Ablin, A.R., Feuerstein, M.D., Kush-ner, J.H., Zoger, S., and Mikkelsen, C. (1969). Child-hood leukaemia: Emotional impact on patient andfamily. New England Journal of Medicine, 280, 414-418.

(3) Trieber, F., Mabe, P.A.I., and Wilson, G. (1987). Psy-chosocial adjustment of sickle cell children and theirsiblings. Children’s Health Care, 16, 82-88.

(4) Lavigne, J.V., Traisman, H.S., Marr, T.J., and Chas-noff, I.J. (1982). Parental perceptions of the psycho-logical adjustment of children with diabetes and theirsiblings. Diabetes Care, 5, 420-426.

(5) Vance, J.C., Fazan, L.E., Satterwhite, B., and Pless,I.B. (1980). Effects of nephrotic syndrome on thefamily: A controlled study. Pediatrics, 65, 948-955.

(6) Cairns, N., Clark, G.M., Smith, S.D., and Lansky,S.B. (1979). Adaptation of siblings to childhood ma-lignancy. Journal of Pediatrics, 95, 42-48.

(7) Koocher, G.P., and O’Malley, J.F. (1981). The Damo-cles Syndrome. Psychological consequences of sur-viving childhood cancer. New York: McGraw-Hill.

(8) Schaeffer, E., and Edgerton, M. (1981). The SiblingInventory of behaviour. Chapel Hill: University ofNorth Carolina Press.

(9) Plomin R., Reiss, D., Hetherington, E.M., and Howe,G.W. (1994). Nature and Nurture: Genetic contribu-tions to measures of the family environment. Devel-



opmental Psychology, 30(1), 32-43.(10) Carpenter, P.J., and Sahler, O.J.Z. (1991). Sibling

perceptions and adaptation to childhood cancer. In

J.H. Johnson and S. Bennett Johnson (Eds.) Ad-vances in Child Psychology. J. Hillis Miller HealthCenter, Gainsville: University of Florida Press.

CF is a multi-system disease and professionals univer-sally acknowledge that the care offered to patients andtheir families should be holistically based. Althoughthere is growing recognition of the problems associatedwith the day to day management of treatment regimens,as clinicians we may need to take into account the over-whelming psychological burden parents and carers en-counter when living with this life threatening disease.Much of the research examining the impact of caring fora sick relative has been focused in the field of adult men-tal health. Such research has mostly been concernedwith the coping mechanisms of relatives caring forsomeone with a psychiatric illness. The concept of thetreatment related burden of care for the relatives or par-ents is considered to be an important concern for theprofessionals looking after patients with CF. Expecta-tions of responsibility placed on carers should be ac-cordingly modified. To appropriately tailor the amountof treatment responsibility assigned to parents lookingafter children with CF and additionally provide adequatesupport, ‘burden’ must be measured in some way.Hoenig and Hamilton (1966)1 describe burden as any-thing that occurs as a disruption factor in family lifeowing to the patient’s illness. The effects of the burdenof care on the carer and the result of stress and time mayalso be identified in other aspects of life, for example;work, leisure activities, finances and interactions withinand beyond the family.

There are many aspects of care that must be carried outat home on a daily basis to allow the child with CF to livea ‘normal’ life. Studies show that parental coping appearsto correlate strongly with the health of the child with CF.Reed (1990)2 found that children of families that are notcoping tend to be hospitalised more than those of familiesthat are coping well. A longer study by Patterson et al(1993)3 found that when both parents coped well the chil-dren were healthier (seen as an improvement in lungfunction trend) and compliance with treatment was betterthan the group who were identified as non copers.

Not only is clinical status implicated in caring for achronically ill child but studies looking at the effect ofthe burden of caring for CF directly on parents haveshown problems with marital relationships, difficultiesin accepting the illness, and inattention to other childrenin the family4. Depression, strain in the care-giving role,

and global parenting stress5 have also been describedand in all of the studies it is the main care giver, motheror father, who report as having the major problems.

CF has profound influences on every aspect of familylife, both practically in the day to day management ofthe disease, and psycho-socially as the burden of caringfor a child with a chronic, life threatening disease in-creases. People with CF are now seeing the majority oftheir treatment regimes being carried out at home, fami-lies are unanimous in their acceptance of home manage-ment and the perceived benefit that it brings. However,treatment in the home means that the illness is more vis-ible, the differences between the child with CF and thehealthy peers or siblings are more apparent and the re-sponsibility of the parent as doctor or nurse increases.These changes beg the question - what effect does hometreatment have on normal family functioning?

Previous work from this centre has shown that fami-lies do not appear to differ greatly from control familieswhen the usual psychological measures of adjustmentare used. However, more detailed assessment indicatesthat although having a child with CF does not automati-cally lead to psycho-pathology, parents identify moresituation specific problems than parents who do not carefor a child with chronic illness6. Further work is cur-rently being carried out with the same population toidentify whether time increases or decreases parents per-ceptions of these problems.

Using validated questionnaires - Beck’s HopelessnessScore, General Health Questionnaire 28, and Impact ofIllness Scale, parents were asked about their lives withCF at the begining and end of a two year period. A con-trol goup were used to compare the scores at the beginingof the study and the paired differences of each parent’squestionnaire scores over the two year period wereanalysed. To date, results indicate that over time parentsreport that nothing has changed in their lives and identifythe same situation specific problems regarding the intru-sion of CF. It is interesting to note however, that althoughthere were no changes to the burden of care identified byparents, two years later they have highlighted the finan-cial implications of bringing up a child with CF. Manymothers in this study were in work before the birth oftheir child with CF and gave up completely or returned topart time or lower paid work following diagnosis (due to

18.4COPING WITH CF—ARE WE EXPECTING TOO MUCH OF THE FAMILIES?

Susan Madge MSc RN RSCNGreat Ormond Street Hospital for Children, London, UK



the rigorous demands of treatment). The implications ofthis change in circumstance are perhaps now being feltby the parents and being identified as a problem.

As clinicians we must not be led astray by the moreobvious markers of coping in our families, such as treat-ment regimens reported to be carried out successfully.When offering an holistic package of care we should beaware that the knowledge of CF may be having an over-whelming effect on parents not identified on a more dayto day level. We should therefore ensure that our supportreflects an acknowledgement of the increasingly longterm psychological burden that these parents carry.

References1 Hoenig J, Hamilton MW: The schizophrenic patient

in the community and his effect on the household. Int

J Soc Psych 1966; 12:165-176.2 Reed SB: Potential for alterations in family process:

when a family has a child with cystic fibrosis. IssueCompre Paed Nurs 1990; 13:15-23.

3 Patterson JM, BuddJ, Goettz D, et al: Family corre-lates of a 10 year pulmonary health trend in cystic fi-brosis. Pediatrics 1993; 91:383-389.

4 Goldberg S, Morris P, Symonds RJ, et al: Chronic ill-ness in infancy and parenting stress: a comparison ofthree groups of parents. J Ped Psychol 1990; 15:347-358.

5 Holroyd J, Guthrie D: Family stress with chronicchildhood illness. J Clin Psychol 1986; 42:552-561.

6 Madge S: Parental quality of life when their child hascystic fibrosis. Abstract. Paediatric Pulmonology,Supp 17. 1998.


Documents

Sessions 16.2 to 18.4