Pathophysiology of Asthma — Summary

Two Main Types

Key Steps

1. Sensitization — Antigen-presenting cells (dendritic cells) activate Th2 lymphocytes, which release:
   • IL-4 → stimulates B cells to switch to IgE production
   • IL-5 → recruits and activates eosinophils
   • IL-13 → goblet cell metaplasia and mucus hypersecretion
2. Early Phase (0–30 min) — Re-exposure to allergen cross-links IgE on mast cells → degranulation → release of histamine, leukotrienes (LTC4/D4/E4), prostaglandins, and PAF → rapid bronchoconstriction, vasodilation, edema
3. Late Phase (4–12 hrs) — Chemokines recruit eosinophils, neutrophils, and T cells → sustained cytokine-driven inflammation → prolonged airflow limitation
4. Triple Mechanism of Airflow Obstruction
   • Bronchial smooth muscle contraction
   • Inflammation and edema of the bronchial wall
   • Mucus hypersecretion plugging the lumen
5. Airway Hyperresponsiveness — Heightened bronchoconstrictor response to stimuli; eosinophil-derived major basic protein damages the epithelium, lowering the threshold for further responses
6. Airway Remodeling (if untreated):
   • Sub-basement membrane fibrosis
   • Smooth muscle hyperplasia
   • Bronchial gland hypertrophy
   • Goblet cell metaplasia → Adds an irreversible component to obstruction