Tutorial 08: Obstructive Lung Diseases

Obstructive lung diseases share the feature of increased resistance to airflow, primarily during expiration. The major conditions are emphysema, chronic bronchitis (which together constitute COPD), asthma, and bronchiectasis.

Emphysema is defined pathologically as irreversible enlargement of airspaces distal to the terminal bronchiole, accompanied by destruction of alveolar walls without fibrosis. The key mechanism is an imbalance between proteases (elastase and other MMPs released by neutrophils and macrophages) and antiproteases (primarily α1-antitrypsin). Smoking recruits neutrophils to the lung and impairs AAT function by oxidising its active site. Loss of alveolar walls destroys the elastic recoil of the lung; during expiration, increased intrathoracic pressure collapses small airways, trapping air (dynamic airway collapse → air trapping → hyperinflation). FEV₁/FVC ratio is reduced (<70%); TLC is increased. Centriacinar emphysema (most common, smoking-related) destroys respiratory bronchioles in the upper lobes, sparing distal alveoli. Panacinar emphysema (AAT deficiency) destroys the entire acinus from respiratory bronchiole to alveolar sac, predominantly in the lower lobes.

Chronic bronchitis is defined clinically, not pathologically: productive cough with sputum for at least three months in two consecutive years. It results from chronic airway irritation (predominantly smoking) causing mucous gland hyperplasia (Reid index — the ratio of mucous gland thickness to total bronchial wall thickness — is increased to >0.5 in chronic bronchitis), goblet cell metaplasia of the surface epithelium, and chronic mucosal inflammation. Airways narrow from mucus, oedema, and smooth muscle hypertrophy.

COPD patients classically are classified into two phenotypes. "Pink puffers" (predominantly emphysema): maintain normoxia by increasing respiratory rate (pursed-lip breathing to create positive end-expiratory pressure); barrel-chested; thin. "Blue bloaters" (predominantly chronic bronchitis): retain CO₂, become chronically hypoxic and hypercapnic; cor pulmonale (right heart failure from chronic hypoxic pulmonary vasoconstriction) is common.

Bronchiectasis is permanent, abnormal dilation of bronchi resulting from destruction of the bronchial wall by repeated or severe infection and inflammation. The dilated airways pool secretions, predisposing to further infection (a vicious cycle). Causes include cystic fibrosis, primary ciliary dyskinesia, post-infectious (childhood measles, pertussis, TB), immunodeficiency, and allergic bronchopulmonary aspergillosis.

Cystic fibrosis (CF) is the most common lethal autosomal recessive disorder in people of Northern European descent, caused by mutations in the CFTR gene on chromosome 7q31. CFTR encodes a chloride channel on the apical surface of epithelial cells. The most common mutation is ΔF508 (deletion of phenylalanine at position 508), causing misfolding and premature degradation of CFTR. Loss of CFTR function in airways impairs chloride secretion and sodium hyperabsorption, producing dehydrated, viscous mucus. This chronically impairs mucociliary clearance, leading to bacterial colonisation (initially Staphylococcus aureus, later Pseudomonas aeruginosa), progressive bronchiectasis, and respiratory failure. CF also causes exocrine pancreatic insufficiency (blocked ducts → autodigestion), infertility in males (absent vas deferens), and meconium ileus in newborns.

Cor pulmonale is right ventricular hypertrophy and failure caused by pulmonary hypertension from primary lung disease. In COPD, chronic hypoxaemia causes hypoxic pulmonary vasoconstriction (HPV) → pulmonary arterial hypertension → right ventricular pressure overload → RV hypertrophy and eventual failure (cor pulmonale). Clinical features: raised JVP, peripheral oedema, hepatomegaly.