Asthma Pathophysiology — Summary

1. Sensitization Phase (First Exposure)

• Trigger (allergen, e.g., pollen, dust mite) enters the airway
• Dendritic cells process and present antigen to naïve T-cells
• T-cells differentiate into Th2 cells, secreting:
  • IL-4 → stimulates B-cells to produce IgE
  • IL-5 → activates eosinophils
  • IL-13 → mucus secretion + IgE production
• IgE binds to Fc receptors on mast cells (sensitization complete)

2. Immediate Phase (0–30 min on re-exposure)

• Antigen cross-links IgE on mast cells → mast cell degranulation
• Released mediators:
  • Leukotrienes (LTC4, LTD4, LTE4) — prolonged bronchoconstriction + mucus
  • Histamine — bronchospasm + vasodilation
  • Prostaglandin D2 — bronchoconstriction
  • Acetylcholine (via vagal reflex) — smooth muscle contraction
• Result: bronchospasm, increased vascular permeability, mucus hypersecretion

3. Late-Phase Reaction (2–8 hours)

• IL-5 + eotaxin recruit eosinophils, neutrophils, basophils, and more T-cells
• Eosinophils release:
  • Major basic protein (MBP) and eosinophil cationic protein (ECP) → epithelial damage
  • ROS → oxidative injury
  • Galectin-10 → forms Charcot-Leyden crystals → amplifies inflammation
• Sustained bronchoconstriction and airway wall inflammation

4. Chronic Changes — Airway Remodeling

• Subepithelial fibrosis (thickened basement membrane)
• Smooth muscle hypertrophy and hyperplasia
• Goblet cell proliferation → excess mucus
• Angiogenesis and submucosal gland enlargement
• Result: irreversible airflow limitation and increased exacerbation severity

Final Outcome

Airway hyperresponsiveness → Recurrent episodes of wheeze, chest tightness, dyspnea, and cough

• Robbins, Cotran & Kumar — Pathologic Basis of Disease, Ch. 15 (Pathogenesis of Asthma, Fig. 15.10)
• Lippincott Illustrated Reviews: Pharmacology, Ch. 41 (Pathophysiology of Asthma)
• Fishman's Pulmonary Diseases and Disorders (Lymphocytes and T-cell subsets in asthma)