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ASTHMA |
Airway Disease Section, National Heart and Lung Institute, Imperial College and Royal Brompton and Harefield NHS Trust, London, UK
Correspondence to:
Correspondence to:
Professor Kian Fan Chung
National Heart and Lung Institute, Imperial College, Dovehouse Street, London SW3 6LY, UK; f.chung{at}imperial.ac.uk
Background: Airway wall remodelling and inflammation are features of chronic asthma. Transforming growth factor ß (TGF-ß) has been implicated in these processes.
Aim: To determine the effect of allergen challenge on airway inflammation and remodelling and whether TGF-ß isoforms and the Smad signalling pathways are involved.
Methods: Thirteen patients with atopic asthma underwent inhalational challenge with 0.9% saline, followed by allergen 3–4 weeks later. After both challenges, fibreoptic bronchoscopy was undertaken to obtain bronchial biopsies and tissue samples were processed for immunohistochemistry and examined by microscopy.
Results: Forced expiratory volume in 1 s (FEV1) fell after allergen challenge (mean (SE) –28.1 (0.9)% at 30 min with a late response at 7 hours (–23.0 (1.2)%). Allergen challenge caused an increase in neutrophils and eosinophils in the bronchial mucosa compared with saline. Sub-basement membrane (SBM) thickness did not change after allergen, but tenascin deposition in SBM was increased. Intranuclear (activated) Smad 2/3 and Smad 4 detected by immunohistochemistry were increased after allergen challenge in epithelial and subepithelial cells of bronchial biopsies. No inhibitory Smad (Smad 7) protein was detected. TGF-ß isoforms 1, 2 and 3 were expressed predominantly in bronchial epithelium after saline and allergen challenges, but only TGF-ß2 expression was increased after allergen. Double immunostaining showed an increase in TGF-ß2 positive eosinophils and neutrophils but not in TGF-ß1 positive eosinophils and neutrophils after allergen challenge.
Conclusions: TGF-ß2 may contribute to the remodelling changes in allergic asthma following single allergen exposure.
Abbreviations: FEV1, forced expiratory volume in 1 s; MBP, major basic protein; NE, neutrophil elastase; SBM, sub-basement membrane; TGF-ß, transforming growth factor-ß
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