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8/8/2019 Lecture 4 Chronic Obstructive Pulmonary Disease
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CHRONIC OBSTRUCTIVE PULMONARY DISEASE
Definition of COPD
ATS/ERS
y A preventable and treatable disease state characterized by airflow limitation that isnot fully reversible.
y The airflow limitation is usually progressive and is associated with an abnormalinflammatory response of the lungs to no xious particles or gases, primarily caused by
cigarette smoking.
y Although COPD affects the lungs, it also produces significant systemic consequences.Smoking causes 80-90% of COPD.50% of smokers develop chronic bronchitis15-20% of smokers develop clinical airflow obstructionObstructive Pulmonary Diseases
Any disease affecting the upper or lower airways can be associated with obstruction
of airflow from the lungs.
This presentation will focus on those pathological processes primarily affecting the
lower airways, including:
Emphysema Chronic Bronchitis Asthma Bronchiectasis Bronchiolitis obliterans (constrictive bronchiolitis) Tracheobronchomalacia*
*A deficiency in the cartilaginous wall of the trachea and/or bronchus, can also lead to to
airway obstruction, but will not be addressed further in this presentation.
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Aetiology: Other Risk factors
British hypothesis: frequent lung infections (esp. in childhood)
Dutch hypothesis: atopy and AHR
Occupational/chemicals: coal, cotton, cement dust, cadmium
Environmental pollution: particulate air pollutionDiet low in fish, fruit and antioxidants
Low birth weight
Genetic factors: FH of COPD, E1-antitrypsin
COPD is a growing burden to society and the patient
COPD is a growing cause of morbidity and mortality worldwide
In 2005, COPD caused 5% of all deaths worldwide
More than 3 million people died from COPD in 2005: this is greater than that of lung and
breast cancer combined
COPD is projected to be the third biggest killer by 2020
1990 2020
Ischemic heart disease
CVD disease
Lower respiratory infection
Diarrhoeal disease
Perinatal disorders
COPD
Tuberculosis
Measles
Road traffic accident
Lung cancer
Stomach cancer
HIV
Suicide
3rd
6th
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Clinical Features of COPD
Typically smokers - mean 20 cigs/day for 20 years
Usually present in 5th decade of life with productive cough or acute chest illness
when the disease is far advanced
DOE not usual until 6th or 7th decade Patients who are dyspneic give up activitiesHx of wheezing accompanying dyspnea may lead to erroneous dx of asthma
Sputum production initially only in AM
daily volume rarely exceeds 60 ml usually mucoidAcute exacerbations characterized by increased cough, purulent sputum, wheezing,
dyspnea, sometimes fever
Interval between exacerbations grows shorter with disease progression
Differential Diagnosis: COPD and Asthma
COPD ASTHMA
Onset in mid-life Symptoms slowly progressive Long smoking history Dyspnea during exercise Largely irreversible airflow
limitation
Onset early in life (oftenchildhood)
Symptoms vary from day to day Symptoms at night/early morning Allergy, rhinitis, and/or eczema
also present
Family history of asthma Largely reversible airflow
limitation
Emphysema (The Pink Puffer Phenotype)
A condition of the lung characterized by abnormal, permanent enlargement of airspaces
distal to the terminal bronchiole, accompanied by the destruction of their walls, and
withoutobvious fibrosis
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Three principle types:
A. Centriacinar(centrilobular) y Predominantly in upper lung zones.y Associated with smoking & pneumoconiosis.
B. Panacinar(panlobular) y More progressive, and with more severe symptoms because it involves the lower
lung zones (areas of greater gas exchange).
y Associated with alpha-1-antitrypsin deficiency.C. Distalacinar(paraseptal)
y Focal or multifocal disease.y Involves distal alveolar sacs and ducts, resulting in subpleural blebs and bullae.y More likely to cause spontaneous pneumothorax.
Protease-Anti-protease Theory:
Emphysema results from the destructive effect of high protease activity in subjects
with low anti-protease activity
Chronic Bronchitis (The Blue Bloater Phenotype)
Cough productive of sputum on most days during at least three consecutive monthsfor more than two successive years
More profound hypoxemia at rest
Elevated PaCO2 with chronic respiratory acidosis
Cor pulmonale with right heart failure
ANTIELASTASE
1 - antitrypsin
PMN
ELASTASE
MAC
ELASTIC
DAMAGE
EMPHYSEMA
1 ANTITRYPSIN
DEFICIENCY
SMOKING
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Di
nosis of C
D
Spi o
t
SYMPTOMS
COUGH
S
UTUM
DYS
EXPOSURE TO RISK FA
TORS
TOB CCO
OCCUPATIONS
INDOOR/OUTDOOR POLLUTION
SPIROMETERY
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Spirometry: Normal and Patients with COPD
Classification of COPDS
everity byS
pirometry
Stage I: Mild FEV1/FVC < 0.70
FEV1 > 80% predicted
Stage II: Moderate FEV1/FVC < 0.70
50% < FEV1 < 80% predicted
Stage III: Severe FEV1/FVC < 0.70
30% < FEV1 < 50% predicted
Stage IV: Very Severe FEV1/FVC < 0.70
FEV1 < 30% predicted or
FEV1 < 50% predictedplus chronic
respiratory failure
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Chest radiographic findings:
Poor in evaluating very early disease due to limitations in small airway visualization.
As the disease progresses, CXR can directly demonstrate disease pathology, as well
as indirect signs of increased lung compliance and air -trapping.
Identification of emphysema on CXR:
Signs of hyperinflation
Irregular, asymmetric areas of decreased lung density
Vascular deficiency:
Rapidly attenuating peripheral pulmonary arteries, may be absent peripherally Increased branching angles Smaller-than-expected caliber Signs of pulmonary artery hypertensionBullaeSaber-sheath trachea
CT findings
Relatively well-defined, low attenuation areas with very thin (invisible) walls,
surrounded by normal lung parenchyma.
As disease progresses:
Amount of intervening normal lung decreases. Number and size of the pulmonary vessels decrease. +/- Abnormal vessel branching angles (>90o), with vessel bowing around the
bullae.
Chest radiographic findings
It is difficult to know which radiographic findings are attributable to chronic
bronchitis, rather than to emphysema, because they commonly coexist.
CXR is poor at detecting or excluding chronic bronchitis.
CXR is helpful in excluding diseases that can clinically mimic chronic bronchitis(TB, tumor, bronchiectasis, and abscess).
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Principle CXR abnormalities
Thickening of bronchial walls
Overinflation*
Oligemia*
Signs of pulmonary artery hypertension
*Many argue that the overinflation and oligemia seen in chronic bronchitis may be due to
superimposed emphysema
ChronicBronchitis
CT findings
Limited literature on CT features of chronic bronchitis.
Bronchial wall thickening has been documented in patients with chronic bronchitis,
but has also been observed in patients without respiratory symptoms.
Quantitative CT
Spirometically triggered images at 10% and 90% vital capacity (VC) have been
reported to be able to distinguish patients with chronic bronchitis from those
with emphysema.
Patients with emphysema had significantly lower mean lung attenuation at90% VC than normal subjects or patients with chronic bronchitis.
Attenuation was the same for normal subjects and those with chronicbronchitis.
Manage Stable COPD
Manage Stable COPD: Bronchodilators
Bronchodilator medications are central to the symptomatic management of COPD.
They are given on an as-needed basis or on a regular basis to prevent or reduce
symptoms.
y Alleviate symptomsy Improve exercise tolerancey Improve quality of lifey Decrease the incidence of exacerbationsy Decrease hyperinflation
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Inhaledtherapyis preferred
Beta2-agonists: increase cyclic adenosine monophosphate levels and promote
airway smooth-muscle relaxation
y Short acting: Albuteroly Long acting: Salmeterol (Serevent) and Formoterol fumarate (Foradil)
Anticholinergics : block muscarinic receptors
y Short acting: Ipratropium bromide (Atrovent)y Long acting: Tiotropium bromide (Spiriva)Combination: (Combivent)
Phosphodiesterase Inhibitors: increase intracellular cyclic adenosine
monophosphate levels within airway smooth muscle
y 3rd line agenty Improves respiratory muscle function, stimulates the respiratory center,
decreases dyspnea, and enhances activities of daily living
y
Toxic side effects: tachyarrhythmias, nausea, vomiting, seizuresy Monitoring should include intermittent serum level measurements: target range
8-12mcg/mL
Inhaled Steroids (ICS)
Inhaled Steroids (ICS) in Stable COPD
Glucocorticoids act at multiple points within the inflammatory cascade.
Regular treatment with ICS does notmodifythe long-termdecline in FEV1.
Appropriate for symptomatic COPD patients with an FEV1 < 50% and repeated
exacerbations (Stage IIIandIV).
ICS reduce frequencyof exacerbationsandimprove healthstatus (Evidence A).
ICS combined with long-acting b2-agonist more effective than individual components
Steroids in Stable COPD
GOLD guidelines recommend a trial of 6 weeks to 3 months of ICS to identify subset
of patients who may benefit.
Short course oforalsteroidsisa poor predictor of long-term response to ICS.Long-termtreatmentwithoralsteroidsis NOTrecommended(Evidence A ):
No evidence of long-term benefit Major side effects: skin damage, cataracts, diabetes, osteoporosis, secondary
infection, psychosis, fluid retention.
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Other pharmacologic treatments
Vaccines: Influenza vaccine reduces serious illness and death in COPD patients by
50%. Pneumococcal vaccine is recommended every 5 years although data in COPD
patients is lacking.
Otheranti-inflammatoryagents: Cromolyn, nedocromil, and leukotriene inhibitors
have not been adequately tested in patients with COPD
Alpha-1 Antitrypsin Augmentation Therapy: young patients with severe deficiency
and established emphysema
Antibiotics are not recommended other than in treating infectious exacerbations
(Doxycycline, amoxicillin, macrolide, fluoroquinolones)
Mucolyticagents: not recommended
Antioxidants (N-acetylcysteine)mayreduce the frequencyof exacerbations
Antitussives: contraindicatedin stable COPD because cough is protective
Pulmonary Rehabilitation in Stable COPD
All COPD-patients benefit from exercise training programs, improving with respect to
both exercise tolerance and symptoms of dyspnea and fatigue (Evidence A).
The minimum length of an effective rehab program is 2 months; the longer the
better (Evidence B).
Comprehensive pulmonary rehabilitation program includes exercise training,
nutrition counseling, and education.
Manage Stable COPD: Oxygen
The long-term administration of oxygen (> 15 hours per day) to patients with chronicrespiratory failure (Stage IV) has been shown to increase survival (Evidence A).
Oxygen administration reduces hematocrit, pulmonary artery pressures, dyspnea,and rapid eye movement related hypoxemia during sleep.
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Oxygen therapy
The goal is to prevent tissue hypoxia by maintaining arterial oxygen saturation
(Sa,O2) at >90%.
Main delivery devices include nasal cannula and venturi mask.
Arterial blood gases should be monitored for arterial oxygen tension (Pa,O2),
arterial carbon dioxide tension ( Pa,CO2) and pH.
Arterial oxygen saturation as measured by pulse oximetry (Sp,O2) should be
monitored for trending and adjusting oxygen settings.
If CO2 retention occurs, monitor for acidemia.
If acidaemia occurs, consider mechanical ventilation.
Therapy at Each Stage of COPD
FEV1/FVC 80%
predicted
FEV1/FVC < 70%
50% < FEV1< 80%predicted
FEV1/FVC < 70%
30% < FEV1< 50%
predicted
FEV1/FVC < 70%
FEV1< 30%
predicted Or FEV1< 50% predicted
plus chronic
respiratory failure
I: Mild IV: Very SevereIII: SevereII: Moderate
Active reduction of risk factor(s); influenza vaccination
Addshort-acting bronchodilator (when needed)
Addregular treatment with one or more long-acting bronchodilators (when needed);
Addrehabilitation
Addinhaled glucocorticosteroids if repeated exacerbations
Addlong term oxygenif chronic respiratory failure.
Considersurgical treatments
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Pharmacotherapy in COPD
Surgical Treatments
Bullectomy: In carefully selected patients, this procedure is effective in reducing
dyspnea and improving lung function (Evidence C)
Lung Volume Reduction Surgery
Lung Transplantation: In appropriately selected patients, improves quality of life and
functional capacity (Evidence C). Criteria for referral: FEV1
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COPD Exacerbation
Definition Elements
Worsening dyspnea
Increased sputum purulence
Increase in sputum volume
Severity
Severe - all 3 elements
Moderate - 2 elements
Mild - 1 element plus:
URI in past 5 days
Fever without apparent cause
Increased wheezing or cough
Increase (+20%) of respiratory rate or heart rate
Assessment of severity of exacerbation
Peak flow
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Pathoph
siolo
-Cu
nt Hypoth
sis
Effect
on Lung Function Decline
ChronicInfl
mm
tion
Exacer
ation
Acute
Inflammation
Unknown20
Air
Pollution
5%
B ! cterial
Infection
50%
ViralInfection
25%
109 pt"
(mean FEV1 = 1# 0L over4 year"
Fre$
uentexacer%
ator&
:
faster decline in PEFR and FEV1 more c ' ronic symptoms (dyspnea,
whee(
e)
no differences in PaO2 or PaCO2Conclusion:
Fre0
uentexacer1
ationsaccelerate declinein
lungfunction
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The Clinical Course Of COPD: Consequences ofExacerbatio n
Therapy of COPD Exacerbation (Guidelines)
Variable ACCP-ACP GOLD
Steroids Yes, for up to two weeks Yes, oral or IV for 10-14 days
Oxygen Yes Yes - target PaO2 60 torr or
Sat of 90% with ABG check
ChestPT No Maybe - for atelectasis or
sputum control
Mucokinetics No Not discussed
Exacerbation
2e
3 4ce
3
5ealt
5-
relate3
6 4ality of
life
Increase3
mortality wit
5
exacerbation
5ospitalizations
Accelerate7 7 eclinein FEV1
Increase3
5
ealt5
reso
4
rce
4
tilization an3
3irect costs
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Manage 8 xacerbations: Key Points
RoleofInfectioninC9
PD 8 xacerbation
Up to 60% o@
exa A erbationB
are due to respiratory in@
ections.
Bacteria C In@ ections: H. in@ C eunza, M. catarrha C is, S.pneu D oniae.AcE uisition of new strainsvs.colonization
Viral InF
ections: InF
Guenza,
Harain
F
Guenza,Coronavirus, Rhinovirus.
Coinfection iscommon
Antibiotic Therapy forCI
PD P xacerbation
Place Q o-controlled studies demonstrated that antibioticsimproveclinical outcomein manypatients with COPD e R acerbation.
A recent meta-analysis demonstrated improved Survival in moderate -to-severeCOPD treated with antibioticscompared to placebo (Puhaneta
S
.2007T
Inhaled bronchodilators (Beta2-agonists
and/or anticholinergicsU, and systemic,
preferably oral, glucocortico-steroids are
effective for the treatment of COPD
eV
acerbations (Evidence A).
80% of AECB are infectious. Environmental
factors and medication nonadherence are
20%.
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Indications for Antibiotics in COPD Exacerbation
Increased sputum purulence with increased SOB of sputum volume. Need for hospitalization. Need for mechanical ventilation.
Risk factors for poor outcome:a) Comorbiditiesb) Severe underlying COPD (FEV-1 3/year)d) Recentantibioticuse (within the past3 months)
Antibiotic Treatment for Exacerbation of COPD
Mild
Only 1 of the 3 cardinal
symptoms: Increased dyspnea Increased sputum volume Increased sputum purulence
No antibiotic Increased bronchodilators Symptomatic therapy Instruct patient to report
additional cardinal symptoms
Moderate orSever
At least 2 of the 3 cardial
symptoms:Increased dyspnea
Increased sputum volume
Increased sputum purulence
UncomplicatedCOPD
Noriskfactors
Age 50 percent
< 3 exacerbations / year
No cardiac disease
ComplicatedCOPD
1 ormore riskfactors
Age > 65 years
FEV1 < 50 percent predicted
3 exacerbation / year
Cardiac disease
Advanced macrolide (azithromycin,
clarithromycin)
Cephalosporin (cefuroxime,
cefpodoxime, cefdinir)
Doxycycline
Trimethoprim/sulfamethoxazole
If recent (
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Manage Exacerbations: NIV
y Noninvasive intermittent positive pressure ventilation (NIPPV) in acuteexacerbations improves blood gases and pH, reduces in -hospital mortality, decreases
the need for invasive mechanical ventilation and intubation, and decreases the
length of hospital stay (Evidence A).
Noninvasive intermittent positive pressure ventilation (NIPPV)
y Selection criteria: Moderate to severe dyspnea with use of accessory muscles and paradoxical
abdominal motion
Moderate to severe acidosis and hypercapnia Respiratory frequency >25/min
Aims of NPPV
y Improve gas exchange (decrease CO2 and increase O2)y Rest or improve respiratory musclesy Stabilize the upper airwayy Improve quality of life/exercise tolerancey Prevent cardiovascular consequences of nocturnal hypercapnia and hypoxia
Assisted ventilation
1. Noninvasive positive pressure ventilation (NPPV) should be offered to patients withexacerbations when, after optimal medical therapy and oxygenation, respiratory
acidosis (pH
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NIPPV
Exclusion criteria:
Respiratory arrest
Cardiovascular instability
Somnolence, impaired mental status, uncooperativepatient High aspiration riskViscous or copioussecretions
Recent facial or gastroesophageal surgery
Craniofacial traumaExtreme obesity
Assisted ventilation
Patientsmeeting exclusion criteria should be considered for immediate intubation
and ICU admission.
Auto-PEEP (IntrinsicPEEP)
Example:ifPEEPi = +8W thepatienteffortmustbe>-8tocreateairfloX
y In patients with COPD Rate of lung emptying becomes impaired because of increased expiratory
resistance and expiratory airflow limitation
Therefore, apositive pressure ispresent at end expiration (PEEP)y Patient must overcome a positivepressure before inspiration can begin
Inspiration reY uires negativepressure
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Indications for ICU Admission in COPD Exacerbation
1. Severe dyspnea that responds inadequately to initial emergency therapy2. Confusion lethargy or respiratory muscle fatigue (the last characterized by
paradoxical diaphragmatic motion
3.
Persistent or worsening hypoxemia despite supplemental oxygen or severe /worsening respiratory acidosis (pH < 7.30)
4. Assisted mechanical ventilation is required, whether by means of endotracheal tubeor noninvasive teachnique
Bronchiectasis
A chronic, necrotizing infection of the bronchi & bronchioles, leading to abnormal,
permanent dilatation of the involved airways.
May develop in association with:
Bronchial obstruction: localized (tumor, foreign body) or diffuse (asthma, chronicbronchitis)
Congenital/Hereditary: CF, Kartageners syndrome Necrotizing pneumoniaIncidence markedly decreased, due to the advent of antibiotics and immunizations.
Pathology:
Obstruction and infection are the major influences associated with bronchiectasis.
Bronchial obstruction leads to atelectasis of airways distal to the obstruction.
Bronchial wall inflammation & intraluminal secretions cause dila tation of the patentairways proximal to the obstruction.
Process becomes irreversible if the obstruction persists or if there is added infection.
Vicious cycle of recurrent/chronic infections perpetuates the airway inflammation &
dilatation, leading to extensive endobronchial destruction.
FYI: There are different types of bronchiectasis:
Cylindrical
Airway wall is regularly/uniformly dilated.
Varicose
Greater dilatation with alternating areas of constriction and dilatation.Cystic
Progressive, distal enlargement resulting in sac-like terminations of the airways. Cystic spaces can be several centimeters in diameter and contain air-fluid levels.
Most Severe
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COPD vs. Bronchiectasis
Variable ChronicObstructive
PulmonaryDisease
Bronchiectasis
Cause Cigarette smoking Infection or genetic or
immune defect
Role of infection Secondary Primary
Predominant organism in
sputum
Streptococcus pneumoniae,
Haemophilus influenzae
H.influenzae, pseudomonas
aeruginosa
Airflow obstruction and
hyperresponsiveness
Present Present
Findings on chest imaging Hyperlucency,
hyperinflation, airways
dilatations
Airway dilatation and
thickening, mucous plugs
Quality of sputum
(in the steady state)
Mucoid, clear Purulent, three layered
Pathophysiology
Permanent abnormal dilation and destruction of bronchial walls
Two factors
Infection Impairment of drainage, airway obstruction, and/or defect in host defense
Biomarkers: inflammatory cells or 8-iso-prostaglandin F(2) in sputum
Etiology
Pulmonary infections
viral, mycoplasma, TB, MAC
Airway obstruction
Defective host defenses
ABPA (allergic bronchopulmonary aspergillosis)
Rheumatic and other systemic dz
RA, Sjogrens syndrome
Ulcerative colitisDyskinetic cilia
Cystic fibrosis rare in TW
Cigarette smoking?
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Clinical Manifestations:
Chronic cough and expectoration of copious, purulent sputum.
+/- dyspnea
+/- hemoptysis
+/- fever, weight loss, anemia, clubbing
Chest radiographic findings:
Earliest finding is bronchial wall thickening Curvilinear/reticular opacities With further dilatation & wall thickening, see tram lines & ring shadows Variable areas of atelectasis Generalized hyperinflation of involved lobe Signs of pulmonary artery hypertension
Most frequent CT findings:
Lack of tapering of the bronchial lumen Bronchial wall thickening Bronchial dilatation Visualized peripheral bronchi Mucus plugging
Management
Infection control
bronchial hygiene
Surgical resection in selected patient
Infection Control
Acute exacerbation
viscous, dark sputum, lassitude, SOB, pleurisy Fevers and chills generally absent CXR rarely show new infiltrates H. influen ae and P. aeruginosa FQ is reasonable (eg. ciprofloxacin) for 7~10 days
Less frequent
Mostfrequent
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Prevention
Daily ciprofloxacin (500~1500mg) in 2~3 doses
Macrolide daily or three times weekly
Daily use of a high dose oral antibiotic, such as amoxicillin 3 g/day
Aerosolization of an antibioticIntermittent intravenous antibiotics
Problematic Pathogen
Pseudomonas aeruginosa
Almost impossible to irradicate
Wilson CB et al.
Reduced QoL More extensive bronchiectasis on CT Increased number of hospitalizationsCiprofloxacin quickly develops resistance
Bronchial Hygiene
Oral hydration
Nebulization
Normal saline
Acetylcyteine
Recombinant DNAase
Hypertonic saline, mannitol, dextran, lactose
PhysiotherapyChest percussion
Prone position
Bronchodilator? Steroid? NSAID?
Surgical Intervention
Removal of the most involved segments Most common: middle and lower lobe resecton Hemoptysis: Bronchial a. embolization
Lung transplantation
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Lung Transplantation
Overall 1-year survival : 68% (54-91%)
Overall 5-year survival : 62% (41-83%)
Subgroup
SLTX : 1 yr survival 57% (20%-94%) n=4 Mean FEV1 : 50% predicted (34%-61%), Mean FVC : 53% predicted (46 -63%)2 lungs : 1 yr survival 73% (51 -96%) n = 10
Mean FEV1 : 73% predicted (58%-97%), Mean FVC : 68% predicted (53%-94%)
What is cystic fibrosis (CF)?
A multisystem disease
Autosomal recessive inheritance
Cause: mutations in the cystic fibrosis transmembrane conductance regulator (CFTR)
chromosome 7 codes for a c-AMP regulated chloride channel
Clinical features of Cystic Fibrosis
Chronic Sino-Pulmonary Disease Nutritional deficiency/GI abnormality Obstructive Azoospermia Electrolyte abnormality CF in a first degree relative
Burden of CF
Most common life-shortening recessive genetic disease in Caucasians
1:3,500 newborns in the US 1 in 10,500 Native Americans 1 in 11,500 Hispanics 1 in 14,000 to 17,000 African Americans 1 in 25,500 AsiansAbout 30,000 people affected in United States
>10,000,000 people carriers of mutant CFTR
80% cases diagnosed by age 3
Almost 10% diagnosed 18 years
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Ca Survival
Overall trend is improved survival
Femalesurvival worse than malebetween 2-20years of age1
35% ofpatients are older than 18years of age2
Median survival 36.8years
3
compared to 1930s when life expectancy was about 6months
2
TypesofmutationsinC b TR
Airway surfaceliquidlow volumehypothesisandCbTR
Normal CFTR inhibits a sodiumchannel (ENaC)
Mutant CFTR----ENaC not inhibited Sodium absorption is increased Water followssodium ASL volume decreases
Normal CFTR will cause Cl- ions to besecreted if the ASL fluid is low
Mutant CFTR Cl- ions not secretedAirway surfaceliquidlow volumehypothesisandconsequences
Cilia do not beat well when PCL volume is depleted
Mucins are not diluted and cannot beeasilyswept up the airway
Mucus becomesconcentrated
Results in increased adhesion to airwaysurface
Promoteschronic infection
Class I Defectiveprotein production
Class II Defects in processing
F508
Class III CFTR reaches cell surface but
regulation is defective (channel
not activated)
Class IV CFTR in membrane with
defectiveconduction
Class V Decreased synthesis of CFTR
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Chronic Sino-Pulmonary Disease
Chronic infection with CF pathogens Endobronchial disease
Cough/sputum production
Air obstruction---wheezing; evidence of obstruction on PFTs Chest x-ray anomalies Digital Clubbing
Sinus disease Nasal Polyps CT or x-ray findings of sinus disease
Nasal Polyps
Benign lesions in nasal airway
If large enough, can be associated with significant nasal obstruction, drainage,
headaches, snoring
Likely associated with chronic inflammation
May need surgical intervention
High recurrence rate
Digital Clubbing
Bulbous swelling at end of fingers
Normal angle between nail and nail bed lost ---Schamroth sign
Can be associated with pulmonary disease, cardiac disease, ulcerative colitis, and
malignancies
Nutritional deficiency
Pancreatic insufficiency
Autopsy of malnourished infants--1938--- cystic fibrosis of the pancreas---mucus plugging of glandular ducts
1
Chloride impermeability affects HCO3- secretion and fluid secretion inpancreatic ducts
2
Pancreatic enzymes stay in ducts and are activated intraductallyAutolysis of pancreas
Inflammation, calcification, plugging of ducts, fibrosis
Malabsorption Failure to thrive Fat soluble vitamin deficiency
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Infertility
Men
Abnormal embryologic development of the epididymal duct and vas deferens---
may be incomplete of absent
Congential bilateral absence of the vas deferens97-98% of men with CFWomen
Lower fertility rate than non-CF women
Viscid mucoid cervical secretions of low volume in women with CF
Pregnancy and CF:
Goss et al, 2003---no significant difference in survival in women who became
pregnant with CF compared to women who did not become pregnant (after
adjusting for disease severity)
Electrolyte abnormality---history
Dr. Paul di Sant Agnese
y 1949 NYC heat wave ----noted CF infants to have a higher rate of heat prostrationthan non-CF
Showed that sodium and chloride concentration in CF patients sweat was
5 times higher than in non-CF
Became basis for sweat chloride testElectrolyte abnormality
Clinically---hypochloremic metabolic alkalosis CFTR on luminal side of sweat duct
Chloride goes in from lumen via CFTR and out to blood by other transporters
Sodium goes in via ENaC
Defective CFTR---Na and Cl- movement and reabsoprtion into lumen impeded
Diagnosis---Sweat chloride
Technique first described by Gibson and Cooke in 1950s
Chemical that stimulates sweating placed under electrode pad; saline underother electrode pad on arm
Mild electric current is passed between electrodes Sweat collected
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Sweat chloride
Positive Sweat chloride: 60-165 meq/L Borderine sweat chloride: 40-60 meq/L Normal sweat chloride: 0-40
False positives:
Hypothyroidism Addison disease Ectodermal dysplasia Glycogen storage disease Edema Malnutrition Lab error (evaporation or contamination of sample)False negatives:
Edema Malnutrition Some CF mutations Sample diluted
Genetic testing
Mutation analysis available Varies from screening for most common mutations to sequencing entire CFTR
gene
Treatment: Nutrition
Follow nutrition parameters closely
Pancreatic enzymes
Vitamin supplementation
Other nutritional supplementation
Tube feedings High calorie supplemental shakes, formulas
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Nutrition parameters
Percent ideal body weight (IBW%)
90-110%: Normal 85-89%: Underweight
80-84%: Mild malnutrition 75-79%: Moderate malnutrition