Expansion
Histamine and leukotrienes early, cellular infiltration late
Expansion
Early phase (minutes, peaking at 15 to 30 minutes)
- IgE cross-linking on mast cells causes degranulation
- Histamine, tryptase, prostaglandin D2 and leukotrienes C4, D4 and E4
- Effect: bronchoconstriction, mucosal oedema, mucus secretion
- Reversed by beta-2 agonists
Late phase (4 to 8 hours)
- Cytokine-driven recruitment of eosinophils, T helper 2 lymphocytes, basophils and neutrophils
- Eosinophil products such as major basic protein damage the epithelium
- Effect: sustained inflammation and bronchial hyperresponsiveness
- Prevented by corticosteroids, not by bronchodilators
Chronic exposure causes airway remodelling: smooth muscle hypertrophy, basement membrane thickening, goblet cell hyperplasia and angiogenesis, which contributes to the fixed component of airflow obstruction.
This sequence explains the therapeutic hierarchy: relievers for the early phase, inhaled corticosteroids as preventers for the late phase, and leukotriene receptor antagonists or biologics targeting IgE and interleukin-5 for specific pathways.