Obstructive Lung Disease
COPD, asthma, and bronchiectasis behind a low FEV1/FVC
The obstructive pattern
Low FEV1/FVC. Obstructive diseases narrow the airways or let them collapse during expiration, so air gets in more easily than it gets out. Spirometry shows FEV1/FVC < 0.7, with FEV1 reduced more than FVC. Trapped air raises RV, FRC, and TLC (hyperinflation, flattened diaphragms on chest x-ray), and the expiratory limb of the flow-volume loop is scooped out.
Why air is trapped. In emphysema, lost elastic recoil removes the radial traction that holds small airways open, so they collapse early in expiration (dynamic airway compression). In chronic bronchitis and asthma, mucus, wall thickening, and smooth muscle contraction narrow the lumen directly. Pursed-lip breathing adds back-pressure that splints airways open.
DLCO sorts them. DLCO falls in emphysema, where the alveolar-capillary bed is destroyed, but is normal in chronic bronchitis and normal or even high in asthma.
COPD: chronic bronchitis and emphysema
Chronic bronchitis. A clinical diagnosis: productive cough for ≥3 months per year in ≥2 consecutive years. Smoke-driven hypertrophy and hyperplasia of submucosal mucous glands raise the Reid index (gland layer ÷ wall thickness between epithelium and cartilage) above 50%. Mucus plugging and V/Q mismatch cause early hypoxemia and CO₂ retention, so the "blue bloater" is cyanotic and prone to pulmonary hypertension, cor pulmonale, and peripheral edema.
Emphysema. A pathologic diagnosis: permanent enlargement of airspaces distal to the terminal bronchiole, with destruction of alveolar walls and loss of elastic recoil (compliance rises). The "pink puffer" is thin, with a barrel chest, pursed-lip breathing, decreased breath sounds, and hyperresonance; hyperventilation keeps PaO₂ up until late. DLCO is low because the capillary bed is destroyed, the key PFT difference from chronic bronchitis, where DLCO is preserved.
| Feature | Chronic bronchitis | Emphysema |
|---|---|---|
| Definition | Clinical: productive cough ≥3 mo/yr for ≥2 years | Pathologic: enlarged airspaces, destroyed alveolar walls |
| Key lesion | Mucous gland hyperplasia (Reid index >50%) | Lost elastic recoil, ↑ compliance |
| Nickname | Blue bloater | Pink puffer |
| Hypoxemia | Early; cyanosis, CO₂ retention | Late; hyperventilation maintains PaO₂ |
| Exam | Productive cough, edema from cor pulmonale | Barrel chest, pursed lips, ↓ breath sounds |
| DLCO | Normal | ↓ |
Emphysema: pathogenesis, patterns, and α1-antitrypsin
Protease-antiprotease imbalance. Smoke recruits neutrophils and macrophages that release elastase, while oxidants in smoke inactivate α1-antitrypsin (A1AT), the main antielastase. Unopposed elastase digests elastin in alveolar walls, and airspaces merge as recoil is lost.
- SmokingRecruits neutrophils and macrophages
- Elastase releasedPlus oxidant inactivation of A1AT
- Unopposed proteaseDigests elastin
- Alveolar wall destructionLoss of elastic recoil
Distribution predicts the cause. Which part of the acinus (respiratory bronchiole → alveolar ducts → alveoli) is destroyed points to the mechanism.
| Type | Part of acinus | Location | Association |
|---|---|---|---|
| Centriacinar (centrilobular) | Respiratory bronchioles; distal alveoli spared | Upper lobes | Smoking (most common type) |
| Panacinar | Entire acinus, uniformly | Lower lobes | α1-antitrypsin deficiency |
| Paraseptal (distal acinar) | Distal acinus along pleura and septa | Subpleural | Bullae → spontaneous pneumothorax in young adults |
α1-Antitrypsin deficiency. SERPINA1 (chromosome 14) alleles show codominant inheritance, and PiZZ causes severe deficiency. The mutant protein misfolds and is trapped in the hepatocyte endoplasmic reticulum, forming PAS-positive, diastase-resistant globules that injure the liver (neonatal cholestasis through cirrhosis). Too little A1AT reaches the lung, so elastase acts unopposed, producing panacinar, lower-lobe emphysema that appears early and is greatly accelerated by smoking. Suspect it in a young or nonsmoking patient with emphysema and abnormal liver tests.
Two hits from one mutation: the lung is starved of A1AT (too little secreted) while the liver is poisoned by the retained protein.
Asthma
Reversible, Th2-driven bronchoconstriction. Asthma is reversible airway obstruction from bronchial hyperresponsiveness and inflammation, classically a type I (IgE-mediated) hypersensitivity in atopic patients. Th2 cytokines orchestrate it: IL-4 drives IgE class switching, IL-5 recruits and activates eosinophils, and IL-13 stimulates mucus. Triggers include allergens, cold air, exercise, viral infection, and aspirin.
Early and late phases. Allergen cross-links IgE on sensitized mast cells, which release histamine and leukotrienes within minutes (bronchospasm, edema, mucus). Hours later, a late phase recruits eosinophils whose products (e.g., major basic protein) damage epithelium and sustain hyperreactivity.
Pathology. Bronchial smooth muscle hypertrophy, goblet cell hyperplasia with mucus plugging, a thickened basement membrane, and eosinophil-rich infiltrates. Sputum shows Curschmann spirals (spiral mucus casts of shed epithelium) and Charcot-Leyden crystals (crystallized eosinophil protein, galectin-10).
Aspirin-exacerbated respiratory disease (Samter triad). Asthma + nasal polyps + aspirin/NSAID sensitivity. COX inhibition shunts arachidonic acid into the lipoxygenase pathway, raising leukotrienes (C4, D4, E4) that constrict bronchi.
Confirming asthma. Reversibility: FEV1 rises ≥12% and ≥200 mL after a bronchodilator. If baseline spirometry is normal, a methacholine (muscarinic agonist) challenge unmasks hyperreactivity when FEV1 falls ≥20%. IL-5 is the target of mepolizumab in severe eosinophilic asthma.
Bronchiectasis and ABPA
Permanent airway dilation. Bronchiectasis is permanent bronchial dilation from chronic necrotizing infection: poor clearance lets bacteria persist, inflammation destroys the muscle and elastic tissue of the wall, and the widened airways pool more secretions. Expect copious foul-smelling sputum, recurrent infections, hemoptysis, and often clubbing. CT shows "tram-track" parallel airway walls and the signet-ring sign (a dilated bronchus larger than its companion artery). Causes:
- Cystic fibrosis: thick, dehydrated secretions from CFTR dysfunction.
- Kartagener syndrome: primary ciliary dyskinesia (dynein arm defect) with situs inversus, chronic sinusitis, bronchiectasis, and infertility.
- ABPA, airway obstruction (tumor, foreign body), and chronic infection.
Allergic bronchopulmonary aspergillosis (ABPA). A hypersensitivity reaction to Aspergillus colonizing the airways of patients with asthma or CF, not an invasive infection. Features: very high IgE, eosinophilia, central (proximal) bronchiectasis, and migratory infiltrates. Treat with corticosteroids ± itraconazole.
A poorly controlled asthmatic or CF patient with rising IgE, eosinophilia, and central bronchiectasis has ABPA until proven otherwise.