Pathophysiology
Clinical meaning
Asthma is a chronic inflammatory disorder of the airways characterized by reversible bronchoconstriction, airway inflammation, and airway hyperresponsiveness (AHR). The inflammatory process involves two phases: (1) Early-phase response (minutes): Allergen cross-links IgE on mast cell surfaces, triggering immediate degranulation and release of preformed mediators - histamine (bronchoconstriction, vasodilation), tryptase, and newly synthesized leukotrienes (LTC4, LTD4, LTE4 - potent bronchoconstrictors 1000x more potent than histamine) and prostaglandins. This produces acute bronchospasm. (2) Late-phase response (4-8 hours): Chemotactic factors attract eosinophils, neutrophils, T-helper 2 (Th2) lymphocytes, and basophils to the airways. Eosinophils release major basic protein (MBP) and eosinophil cationic protein, which are directly toxic to airway epithelium, causing epithelial shedding and exposure of sensory nerve endings (contributing to AHR). Chronic inflammation leads to structural airway remodeling: subepithelial fibrosis, smooth muscle hypertrophy, mucous gland hyperplasia, angiogenesis, and irreversible airway narrowing. Status asthmaticus is a severe, prolonged asthma attack unresponsive to standard bronchodilator therapy, representing a medical emergency with risk of respiratory arrest.