L07: Asthma

Asthma is a chronic inflammatory disorder of the airways characterised by reversible airflow obstruction, bronchial hyper-responsiveness, and airway remodelling. It affects approximately 10–15% of children and 5–10% of adults in developed countries and is increasing in prevalence.

The hygiene hypothesis proposes that reduced childhood exposure to infections and microbial products — a consequence of improved sanitation and antibiotic use — shifts the immune balance from Th1 (cell-mediated) toward Th2 (humoral) responses. Th2-skewed immunity predisposes to atopic disease including asthma, allergic rhinitis, and eczema. The epigenetic mechanism underlying this shift includes DNA methylation changes in T-cell differentiation genes that can be influenced by environmental exposures.

The pathophysiology of asthma has two phases. The early (immediate) phase occurs within minutes of allergen exposure: IgE antibodies (produced by B cells under Th2 cytokine stimulation, particularly IL-4 and IL-13) are bound to high-affinity IgE receptors (FcεRI) on mast cells and basophils in the airway mucosa. Allergen cross-links IgE on mast cell surfaces, triggering degranulation: histamine, leukotrienes (LTC4, LTD4, LTE4), prostaglandins (PGD2), and tryptase are released. This is a Type I (IgE-mediated) hypersensitivity reaction. The effects are bronchoconstriction, mucosal oedema, and mucus hypersecretion — producing the acute attack.

The late phase occurs 4–8 hours later: Th2 cytokines (IL-4, IL-5, IL-13) recruit eosinophils into the airway mucosa. Eosinophils release major basic protein and eosinophil cationic protein, causing epithelial damage and perpetuating inflammation. This phase is characterised by Type IV (cell-mediated/delayed) hypersensitivity. Repeated episodes of late-phase inflammation drive airway remodelling: smooth muscle hypertrophy and hyperplasia (increasing bronchoconstriction), subepithelial basement membrane thickening (collagen deposition beneath the epithelium — a distinctive histological feature of asthma), mucous gland hyperplasia, and angiogenesis.

Macroscopic examination of lungs in a fatal asthma attack shows over-inflated lungs that fail to collapse, with airways plugged by thick, tenacious mucus. Microscopically, the mucus plugs contain Curschmann's spirals (inspissated mucus casts of small airways) and Charcot-Leyden crystals (eosinophil granule proteins). The epithelium shows patchy shedding (desquamation) with exposed basement membrane.

Triggers of asthma include allergens (house dust mite, pollen, animal dander), respiratory viral infections (rhinovirus, RSV), cold air, exercise, irritants (cigarette smoke, fumes), and aspirin (in aspirin-exacerbated respiratory disease, COX-1 inhibition redirects arachidonic acid toward leukotriene synthesis).

Treatment targets the pathophysiology: inhaled corticosteroids (ICS) suppress eosinophilic inflammation and are the cornerstone of maintenance therapy; short-acting beta-2 agonists (SABA, e.g., salbutamol) cause rapid bronchodilation via airway smooth muscle relaxation; long-acting beta-2 agonists (LABA) provide sustained bronchodilation; leukotriene receptor antagonists (montelukast) block LTD4; monoclonal antibodies targeting IgE (omalizumab) or IL-5 (mepolizumab) are used in severe eosinophilic asthma.