Abstract
The alteration of the mesenchymal layer underlying the bronchial epithelium, triggered by epithelial dysfunction, is a topic of emerging interest in asthma. Whether this dysfunction is already present in asthmatic children, and therefore in the early stages of the disease, has been scarcely investigated. We evaluated the degree of epithelial damage, E-cadherin (E-cad) and TGFβ1 expression, and their relation with basement membrane (BM) thickness in asthmatic children. Bronchial biopsies were obtained from 27 children undergoing bronchoscopy for appropriate indications: 16 asthmatics (age2-10yrs) and 11 nonasthmatic controls (4-9yrs). Epithelial damage and BM thickness were quantified by histochemistry and E-cad and TGFβ1 by immunohistochemistry. Asthmatic children had evidence of epithelial damage compared to controls (median;range:52;20-91 vs 33;0-83% p<0.05), and E-cad, evaluated by a semiquantitative score was increased in areas of damaged epithelium, but not in those of intact epithelium (61;33-100 vs 39;28-52% p<0.05). Furthermore, asthmatic children had increased epithelial expression of TGFβ1 (10;0-70 vs 1;0-13cell/mm p=0.01) and a thickened BM compared to controls (5;4-12 vs 4;2-5μm p=0.003). Of interest the expression of E-cad in damaged epithelium was related to both TGFβ1 expression (r=0.56,p=0.003) and BM thickening (r=0.42,p=0.04). In conclusion this study shows that, in children with asthma, damaged epithelial cells may promote a fibrotic reaction and thickening of the underlying mesenchymal layer through the expression of stress signals (E-cadherin), and growth factors (TGFβ). Epithelial damage is therefore an early event in the natural history of the disease which may profoundly affect airway remodeling.
- © 2011 ERS