83. Obstructive lung diseases (cystic fibrosis, bronchiectasis) - etiology, pathogenesis, clinical manifestations.

Obstructive lung diseases (cystic fibrosis, bronchiectasis) - etiology, pathogenesis, and clinical manifestations.

I. Cystic fibrosis (CF)

Etiology

• Autosomal recessive genetic disorder.
• Mutation in CFTR gene (cystic fibrosis transmembrane conductance regulator) —most commonly ΔF508 mutation.
• Leads to defective chloride (Cl ) channel function.

Pathogenesis

1. Defective CFTR → impaired Cl and water transport across epithelial cells.
2. Dehydrated, thick mucus in airways → impaired mucociliary clearance.
3. Mucus plugging → chronic bacterial infections (especially Staphylococcus aureus, Pseudomonas aeruginosa ).
4. Persistent inflammation → bronchial wall damage and bronchiectasis.
5. Similar thick secretions in pancreas, GI tract → exocrine pancreatic insufficiency, malabsorption, meconium ileus (in newborns).

Clinical manifestations

Respiratory

• Chronic productive cough.
• Recurrent pulmonary infections.
• Wheezing, dyspnea.
• Nasal polyps.
• Digital clubbing.
• Progressive respiratory failure.

Gastrointestinal

• Steatorrhea (fatty stools) due to pancreatic insufficiency.
• Failure to thrive in children.
• Vitamin deficiencies (A, D, E, K).

Other

• Male infertility (absence or atresia of vas deferens).
• Salty sweat (due to abnormal sweat gland function).

II. Bronchiectasis - Bronchiectasis is a chronic lung condition where the walls of your airways (bronchi) widen and are thickened from inflammation and infection

Etiology

• Severe or recurrent infections (pneumonia, TB).
• CF (most common inherited cause).
• Primary ciliary dyskinesia (Kartagener syndrome).
• Bronchial obstruction ( tumor, foreign body).
• Hypogammaglobulinemia (immune deficiency).

Pathogenesis

1. Chronic infection and inflammation → destruction of bronchial wall components (elastic and muscular layers).
2. Bronchial dilation and permanent abnormal widening.
3. Impaired mucociliary clearance → retention of secretions → further infections → vicious cycle.

Clinical manifestations

Respiratory

• Chronic productive cough with large volumes of purulent, foul-smelling sputum.
• Hemoptysis (due to bronchial wall damage).
• Dyspnea, wheezing.
• Recurrent infections.

Other

• Digital clubbing.

Weight loss, fatigue.