Expansion
Inflammation, bronchoconstriction and airway remodelling
Expansion
Three components
- Inflammation: eosinophils, mast cells, Th2 lymphocytes, driven by IL-4, IL-5 and IL-13, with IgE mediated mast cell degranulation
- Bronchoconstriction: smooth muscle contraction, mucosal oedema and mucus plugging
- Remodelling: basement membrane thickening, smooth muscle hypertrophy and hyperplasia, goblet cell hyperplasia, subepithelial fibrosis and angiogenesis
“Inflammation and constriction are reversible; remodelling is not.” That is the argument for early anti-inflammatory treatment rather than symptomatic bronchodilation.
Histological findings, classically in fatal asthma:
- Curschmann spirals: whorled mucus casts of small airways
- Charcot-Leyden crystals: from eosinophil membrane protein
- Creola bodies: shed epithelial cell clusters
- Thickened basement membrane and mucus plugging of the airways
The type 2 (T2 high) phenotype is characterised by eosinophilia, raised FeNO and atopy, and it is the one that responds to corticosteroids and to biologics targeting IgE (omalizumab), IL-5 (mepolizumab) and IL-4/13 (dupilumab).
Non-T2 asthma is neutrophilic or paucigranulocytic, commoner in obesity, smoking and late onset disease, and responds poorly to steroids.