Genetic Lung Disease

Question 1

Alpha 1 Antitrypsin Deficiency

Answer 1

• Autosomal codominant; ~1:2500 European ancestry
• DOE age 20-50, wt loss, resp infections, fatigue
• Emphysema (some of your COPD pts actually have this!)
• Cirrhosis of the liver (~15%) and hepatocellular carcinoma

Question 2

Primary Spontaneous Pneumothorax

Answer 2

• Autosomal dominant gene mutation (rare)
• All with mutation get blebs -> 40% get pneumo
• Ruptured Blebs; 13-60% chance of recurrence

Question 3

Idiopathic Pulmonary Fibrosis

Answer 3

• Most sporadic; familial autosomal dominant with reduced penetrance
• 13-20 per 100,000 worldwide, 100,000 in US, 30-40,000 new US diag/yr
• Age 50-70; SOB, persistent dry cough, wt loss, clubbing
• Scarring of lungs -> reduced O2 delivery; lung cancer, PE, pulmonary htn possible

Question 4

Cystic Fibrosis

Answer 4

-Epithelial tissue malfunction causes the organ damage
-caused by mutations in the(CFTR) protein, a complex chloride channel and regulatory protein found in all exocrine tissues
-Deranged transport of chloride and/or other CFTR-affected ions, such as sodium and bicarbonate, leads to : Thick, viscous secretions in the lungs, pancreas, liver, intestine, and reproductive tract, Increased salt content in sweat gland secretions
-1 in 20 Americans are carriers, 30,000 Americans affected, 2500 babies per year in the US, Mostly Northern European ancestry whites
-Loss of excessive amounts of salt in sweat
-Upsets balance of electrolytes -> abnormal heart rhythms
-Propensity toward dehydration and shock
-Thick accumulations of mucous in pancreas and lungs
-Malnutrition, poor growth
-Frequent respiratory infections, breathing difficulty, permanent lung damage (usual cause of death)
-Also may get liver disease, diabetes, pancreatitis, gallstones, osteoporosis, infertility
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Question 5

Cystic fibrosis: clinical features

Answer 5

Upper respiratory
-Chronic Sinusitis
-Nasal Polyps
Pulmonary
-Cough, productive, occ hemoptysis
-Chronic infections with multiple organisms
-Pseudomonas Colonization
-Gradual decline in pulmonary function
-Acute exacerbations
Gastrointestinal
-Infants: Meconium ileus
-Older: Distal intestinal obstruction syndrome (RLQ pain, mass)
-Pancreatic Insufficiency (almost all) – frequent, bulky, foul-smelling stools; fat and fat -soluble vitamin malabsorption
-Diabetes (later in life) - hyperglycemia
Genitourinary
-Late onset of puberty
-Males: azoospermic (obliteration of vas deferens)
-Females: 20% infertile; if conceive, normal pregnancy and breast feed normally
Other
-Clubbing

Question 6

CF: diagnostic criteria

Answer 6

• Clinical symptoms consistent with CF in at least one organ system
• Evidence of cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction (any of the following):
• Elevated sweat chloride >60 mmol/L (on two occasions)
• Presence of two disease-causing mutations in CFTR
• Abnormal nasal potential difference

Question 7

CF: tests

Answer 7

-Sweat chloride test
-Nasal potential difference (NPD)
CXR
-Early: hyperinflation (small airway obstruction)
-Later: bronchial cuffing
-Finally: Brochiectasis
PFTs
-Early: increased ratio of RV to TLC (small airways disease
-Later: Reversible (secretions and reactive airways) and irreversible (chronic destruction of the airway) changes to FVC and FEV1

Question 8

CF: management

Answer 8

• Best managed in a CF center
• Treat pulmonary infections appropriately
• Rapid acting bronchodilator (e.g. Albuterol) prior to -Chest PT or other inhaled treatments
• Inhaled DNase I – decreases viscosity of secretions
• Inhaled hypertonic saline – hydrate mucous
• Chest Physiotherapy
• Azithromycin – slows pulmonary decline, likely due to anti-inflammatory and/or antibiotic
• High-dose ibuprofen for those with good lung function
• Avoid steroids (likely to increase infection)
• Oxygen as necessary
• Lung transplant