Pathophysiology
Allergen exposure activates dendritic cells and Th2 lymphocytes to release IL-4, IL-5 and IL-13. This drives IgE production, eosinophil recruitment, mast cell degranulation and smooth muscle hyperplasia. The result is bronchoconstriction, airway wall oedema, mucus hypersecretion and, over time, airway remodelling with subepithelial fibrosis.
Sources: GINA 2025 Global Strategy for Asthma Management; NEJM 2023;389:2321 - Biologics in severe asthma; NICE NG80 Asthma diagnosis and management
Clinical presentation
Episodic wheeze, cough (often nocturnal), chest tightness and dyspnoea triggered by allergens, exercise, cold air, viral URIs, NSAIDs (aspirin-exacerbated respiratory disease) or beta-blockers. Between attacks the exam may be normal. Severe attacks: silent chest, accessory muscle use, tripod position, pulsus paradoxus, inability to speak in full sentences.
Sources: GINA 2025 Global Strategy for Asthma Management; NEJM 2023;389:2321 - Biologics in severe asthma; NICE NG80 Asthma diagnosis and management
Diagnosis
Spirometry shows obstructive pattern (FEV1/FVC <0.70) with ≥12% and ≥200 mL improvement in FEV1 after bronchodilator. If baseline is normal, methacholine challenge (≥20% drop in FEV1) or peak-flow variability supports the diagnosis. FeNO >25 ppb suggests eosinophilic airway inflammation. Chest X-ray is often normal and mainly rules out alternative causes.
Sources: GINA 2025 Global Strategy for Asthma Management; NEJM 2023;389:2321 - Biologics in severe asthma; NICE NG80 Asthma diagnosis and management
Stepwise therapy (GINA)
Track 1 (preferred, ≥12 y): as-needed low-dose ICS-formoterol at all steps, escalating from as-needed only (Step 1-2) to maintenance ICS-formoterol (Step 3) to medium/high-dose (Step 4-5). Add LAMA (tiotropium) and biologics (omalizumab, mepolizumab, benralizumab, dupilumab) for severe uncontrolled disease. Avoid SABA-only therapy - it is associated with excess exacerbations and death.
Sources: GINA 2025 Global Strategy for Asthma Management; NEJM 2023;389:2321 - Biologics in severe asthma; NICE NG80 Asthma diagnosis and management
Acute exacerbation
Oxygen to SpO2 93-95% (94-98% in pregnancy/children), nebulised SABA + ipratropium, systemic corticosteroids within 1 hour, magnesium sulphate IV for severe attacks, and ICU care if PaCO2 rises or the chest becomes silent. Discharge on tapering steroids and reinforce inhaler technique and written action plan.
Sources: GINA 2025 Global Strategy for Asthma Management; NEJM 2023;389:2321 - Biologics in severe asthma; NICE NG80 Asthma diagnosis and management
