Clinical meaning
Asthma is a chronic inflammatory disorder of the airways characterized by reversible airflow obstruction, bronchial hyperresponsiveness, and airway remodeling. The pathophysiology involves a Th2-mediated immune response with eosinophilic inflammation. Allergen exposure triggers dendritic cell presentation to naive T cells, driving Th2 differentiation and release of IL-4, IL-5, and IL-13. IL-4 promotes IgE class switching in B cells, IL-5 recruits and activates eosinophils, and IL-13 stimulates goblet cell hyperplasia and mucus hypersecretion. Mast cell degranulation releases histamine, prostaglandins, and leukotrienes (especially LTC4, LTD4, LTE4) causing bronchoconstriction. Chronic inflammation leads to airway remodeling: subepithelial fibrosis, smooth muscle hypertrophy, angiogenesis, and mucous gland hyperplasia, resulting in fixed airflow limitation over time.
Diagnosis & workup
Diagnostics & workup: - Spirometry with bronchodilator reversibility (FEV1 increase >= 12% and >= 200 mL) - Peak expiratory flow (PEF) variability > 20% over 2 weeks - Fractional exhaled nitric oxide (FeNO) > 25 ppb suggests eosinophilic inflammation - Methacholine or exercise challenge test for suspected asthma with normal spirometry - Serum total IgE and specific IgE or skin prick testing for allergen sensitization - CBC with differential (eosinophilia > 0.3 x 10^9/L)