Abstract
Asthma is characterised clinically by intermittent bronchoconstriction and pathologically by structural airway changes termed airway remodelling. Remodelling is associated with adverse long term outcomes and has been attributed to eosinophilic inflammation. In vitro studies suggest that mechanical forces occurring during bronchoconstriction may induce remodelling independent of inflammation. This hypothesis was examined in human volunteers with asthma.
Methods: 48 asthmatics were randomised to 1 of 4 inhalation challenges involving 3 challenges at 48hr intervals: Challenge substances were; allergen (house dust mite), methacholine, saline or salbutamol followed by methacholine. Bronchoalveolar lavage (BAL) and bronchial biopsies were obtained before and 4 days after the challenges.
Results: Allergen and methacholine challenges induced similar immediate bronchoconstriction. Eosinophilic inflammation increased only in the allergen group (BAL eosinophils (p=0.01), BAL eosinophil cationic protein (p=0.002) and tissue eosinophils (p=0.05)). Markers of remodelling increased in both the allergen and methacholine groups, with no increase in saline or salbutamol/methacholine groups. Sub-basement membrane collagen thickness (p<0.001), epithelial mucus staining (p=0.003) and cell division in the epithelium (p=0.001) and the submucosa (p<0.001) all increased as did epithelial TGF-β immunoreactivity (p<0.01). There were no differences between the allergen and methacholine groups.
Conclusions: Experimentally induced bronchoconstriction without additional airway inflammation is sufficient to induce airway remodelling in asthma.
- © 2011 ERS