Obstructive lung diseases — COPD

COPD overview

• Obstructive airway diseases: limitation of airflow due to ↑ resistance from partial/complete obstruction
• Hallmark: ↓ FEV₁ (forced expiratory volume in 1 sec); FVC normal or ↑ → FEV₁/FVC ratio is decreased
• Major symptom: dyspnea (shortness of breath)

Disease	Site	Pathological changes	Etiology	Symptoms
Asthma	Bronchus	Smooth muscle hypertrophy, hyperplasia, excessive mucus, inflammation	Immunologic or undefined	Episodic wheezing, cough, dyspnea
Emphysema	Acinus/alveoli	Airspace enlargement, wall destruction	Tobacco smoke	Dyspnea
Chronic bronchitis	Bronchus	Mucus gland hypertrophy and hyperplasia, hypersecretion	Tobacco smoke, air pollutants	Cough, sputum production, dyspnea
Bronchiectasis	Bronchus	Airway dilation and scarring	Persistent or severe infections	Cough, purulent sputum, fever, dyspnea

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Bronchial Asthma

Definition

• Chronic inflammatory disorder of the airways → recurrent episodes of wheezing, breathlessness, chest tightness, coughing
• Key feature: increased airway responsiveness (bronchospasm) to various stimuli

Symptoms

• Intermittent and reversible airway obstruction
• Chronic bronchial inflammation with eosinophils
• Bronchial smooth muscle hypertrophy and hyperreactivity
• Increased mucus secretion

Types

1. Atopic asthma (extrinsic) — most common; childhood onset; family history; Type I hypersensitivity (IgE-mediated, Th2); triggered by environmental antigens (dust, pollen, dander, food)
2. Non-atopic asthma (intrinsic) — no family history; no allergies; triggered by viral infections and air pollutants

Pathogenesis (atopic)

• Excessive Th2 response → cytokines:
  • IL-4 → stimulates IgE production
  • IL-5 → activates eosinophils
  • IL-13 → stimulates mucus production
  • IgE → coats mast cells → granule release upon allergen re-exposure
• Two-phase allergen response:
  • Acute phase: bronchoconstriction, edema, mucus secretion
  • Late phase (4–8 hrs later): eosinophil influx → major basic protein release → tissue damage
• Recurring inflammation → airway remodeling: smooth muscle hypertrophy + collagen deposition

Morphology

• Overdistended lungs due to overinflation (air trapping)
• Bronchi and bronchioles occluded by mucus plugs
• Histology:
  • Curschmann’s spirals: whorls of shed epithelium
  • Charcot-Leyden crystals + many eosinophils
• Airway remodeling: thickened basement membrane, SM hypertrophy, enlarged submucosal glands

Clinical

• Severe dyspnea and wheezing; difficulty with exhalation (air trapping → hyperinflation)
• Attacks last 1 to many hours; resolve spontaneously or with bronchodilators + corticosteroids
• More disabling than lethal

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Emphysema

Definition

• COPD restricted to the acini
• Permanent enlargement of airspaces distal to the terminal bronchioles with wall (alveolar) destruction, but without fibrosis
• Patients: breathless but able to maintain adequate oxygenation → avoid cyanosis

Types (by anatomical distribution)

1. Centroacinar (centrilobular) — respiratory bronchioles affected, distal alveoli spared; upper lobes (esp. apex); most common in cigarette smokers
2. Panacinar (panlobular) — entire acinus enlarged; lower lobes; associated with α₁-antitrypsin deficiency
3. Distal acinar (paraseptal) — proximal acinus spared, distal affected; near pleura; cyst-like bullae; associated with spontaneous pneumothorax in young adults
4. Irregular — acinus irregularly involved; associated with scarring; most common form, usually asymptomatic

Pathogenesis: 2 imbalances

1. Protease-antiprotease imbalance:
   • α₁-antitrypsin (antiprotease) deficiency → unopposed neutrophil protease activity → elastic destruction
   • Smoking: attracts/activates neutrophils → enhances elastase activity in macrophages
2. Oxidant-antioxidant imbalance:
   • Tobacco smoke → ROS → depletes anti-oxidants → tissue damage + inactivation of native anti-proteases → functional α₁-antitrypsin deficiency

Morphology

• Panacinar: pale, voluminous lungs
• Centroacinar: deeper pink, less volume; upper 2/3rds most affected
• Histology: alveolar wall destruction without fibrosis → enlarged air spaces; loss of elastic tissue → collapse on expiration; fewer alveolar capillaries

Clinical

• Without chronic bronchitis (“pink puffer”): barrel chest, dyspnea with prolonged expiration, hyperventilation; adequate oxygenation; severe weight loss
• With chronic bronchitis (“blue bloater”): less prominent dyspnea; CO₂ retained → hypoxia + cyanosis; obesity; secondary pulmonary hypertension
• Death: pulmonary failure (respiratory acidosis, hypoxia, coma) or cor pulmonale (right-sided heart failure)

💡 High-yield: Asthma = IgE/Th2; eosinophils; Curschmann’s spirals + Charcot-Leyden crystals; reversible bronchospasm. Emphysema = alveolar destruction without fibrosis; α₁-AT deficiency → panacinar; smoking → centroacinar. Pink puffer (emphysema) vs. blue bloater (emphysema + bronchitis). FEV₁/FVC ↓ in all COPD.