How obstructive lung disease is tested on Step 1
Expect PFT numbers, a histology finding, a child with exercise-induced wheeze, or a young nonsmoker with lower-lobe emphysema and liver disease, with questions on mechanism or drug choice.
In obstructive disease, airways narrow or collapse during expiration. FEV1 falls more than FVC, so the FEV1/FVC ratio drops, and trapped air raises residual volume and total lung capacity.
Asthma vs COPD
The two can overlap, but their typical features differ.
Pathology of COPD
COPD combines destruction of alveolar walls (emphysema) and mucus hypersecretion in the airways (chronic bronchitis).
| Feature | Emphysema-predominant ("pink puffer") | Bronchitis-predominant ("blue bloater") |
|---|---|---|
| Mechanism | Protease–antiprotease imbalance destroys alveoli | Mucous gland hypertrophy, airway inflammation |
| Gas exchange | Relatively preserved O₂ until late | Hypoxemia, hypercapnia early |
| Exam | Barrel chest, pursed lips, thin | Cyanosis, edema, overweight |
| Complications | Pneumothorax (bullae) | Cor pulmonale, polycythemia |
| DLCO | ↓ | Normal or mildly ↓ |
α1-antitrypsin deficiency also causes liver disease: misfolded protein accumulates as PAS-positive globules in hepatocytes.
Drug therapy
Bronchodilators relax airway smooth muscle; anti-inflammatory drugs reduce the underlying inflammation.
| Class | Example | Mechanism | Key use or toxicity |
|---|---|---|---|
| SABA | Albuterol | β2 agonist → ↑ cAMP → relaxation | Rescue; tremor, tachycardia, ↓ K⁺ |
| LABA | Salmeterol, formoterol | Long-acting β2 agonist | Never alone in asthma (always with ICS) |
| ICS | Budesonide, fluticasone | Glucocorticoid — ↓ cytokine transcription | Asthma controller; thrush (rinse mouth) |
| LAMA / SAMA | Tiotropium / ipratropium | Muscarinic M3 antagonist | COPD maintenance; dry mouth |
| Leukotriene antagonists | Montelukast, zafirlukast; zileuton | Block CysLT1 receptor; zileuton blocks 5-lipoxygenase | Aspirin-exacerbated disease; zileuton hepatotoxic |
| Biologics | Omalizumab, mepolizumab, dupilumab | Anti-IgE; anti-IL-5; anti-IL-4Rα | Severe eosinophilic or allergic asthma |
| Methylxanthine | Theophylline | PDE inhibition, adenosine antagonism | Narrow window; seizures, arrhythmias; CYP interactions |
| Roflumilast | — | PDE-4 inhibitor | Severe COPD with chronic bronchitis |
Acute severe asthma: oxygen, nebulized SABA + ipratropium, systemic steroids, IV magnesium; a normal or rising PaCO₂ signals fatigue and impending respiratory failure. Current GINA guidance prefers as-needed low-dose ICS-formoterol over a SABA alone as the reliever.
Clinical application
Young emphysema should raise suspicion for an inherited cause.
A 38-year-old who never smoked has progressive dyspnea. PFTs show FEV1/FVC 0.55 with ↑ TLC and ↓ DLCO; imaging shows lower-lobe predominant emphysema. Liver enzymes are mildly elevated. What is the diagnosis and mechanism?
- Obstruction with low DLCO indicates emphysema.
- Lower-lobe panacinar emphysema in a young nonsmoker suggests α1-antitrypsin deficiency.
- Without α1-antitrypsin, neutrophil elastase destroys alveolar walls unopposed.
- The PiZZ protein misfolds and accumulates in hepatocytes, causing liver injury.
Answer. α1-Antitrypsin deficiency (PiZZ). Check serum α1-antitrypsin level and genotype; treatment includes avoiding smoke and, in some patients, augmentation therapy.