Epithelial stress and structural remodelling in childhood asthma

Abstract

Background: In adult asthma the bronchial epithelium shows high expression of the epidermal growth factor receptor (EGFR) and the cyclin dependent kinase inhibitor, p21waf, linked to ongoing stress and injury. Methods: To determine if these are early markers of disease, sections of bronchial specimens obtained post mortem or by bronchoscopy from non-asthmatic (n = 7), moderate (n = 7), or severe (n = 9) asthmatic children aged 5-15 years were examined immunohistochemically. All severe and one moderately asthmatic children were receiving inhaled corticosteroids. Results: The lamina reticularis of the asthmatic biopsy sections was found to be thicker (p = 0.01) than normal with increased deposition of collagen III (p = 0.007); submucosal eosinophil numbers did not differ between groups. As in adults, there was an asthma-related increase in epithelial EGFR (p<0.002) but there was no evidence of proliferation, with Ki67 being reduced (p = 0.001) and p21 increased (p<0.004). The thickness of the lamina reticularis was significantly correlated with epithelial EGFR (rho = 0.77, p<0.001). Conclusions: These data provide evidence that, in asthmatic children, the epithelium is stressed or injured without significant eosinophilic inflammation. This change in the epithelial phenotype is associated with collagen deposition in the lamina reticularis, suggesting that the epithelial mesenchymal trophic unit is active early in, and may contribute to, the pathogenesis of asthma.