Intrinsic Biochemical and Functional Differences in Bronchial Epithelial Cells of Asthmatic Children

Rationale: Convincing evidence of epithelial damage and aberrant repair exists in adult asthmatic airways even in the absence of inflammation. However, comparable studies in children have been limited by access and availability of clinical samples. Objectives: To determine whether bronchial epithelial cells from asthmatic children are inherently distinct from those obtained from non-asthmatic children. Methods: Epithelial cells were obtained by non-bronchoscopic bronchial brushing of mild asthmatic (7), atopic non-asthmatic (9) and healthy children (12). Cells were subject to morphological, biochemical, molecular and functional assessment. Responses were also compared to commercially available epithelial cultures and the transformed cell line 16HBE140. Results: All epithelial cells exhibited a “cobblestone” morphology that was maintained throughout culture and repeated passage. Expression of cytokeratin-19 varied with disease phenotype being greatest in healthy non-atopics and lowest in asthmatics. In contrast, expression of cytokeratin 5/14 was greatest in asthmatics and least in healthy non-atopics samples. Asthmatic epithelial cells also spontaneous produced significantly greater amounts of IL-6, PGE2 and EGF, equivalent amounts of IL-1ß, sICAM-1, but significantly lower amounts of TGFß-1. This profile was maintained through successive passage. Asthmatic epithelial cells also exhibited greater rates of proliferation than non-asthmatic cells. Conclusions: This study has shown that epithelial cells from mildly asthmatic children are intrinsically different both biochemically and functionally to epithelial cells from non-asthmatics. Importantly, these differences are maintained over successive passage, suggesting that they are not dependent on an in vivo environment. WORD COUNT: 234.