The role of epithelial injury and repair in the origins of asthma

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Abstract
We currently understand little about the mechanisms that lead to asthma. The bronchial epithelium is the first cell layer of contact with the environment and as such is an especially attractive target in which to identify novel mechanisms and new therapeutic strategies in disease development. We discuss the role of epithelial injury and wound repair in the origins of asthma. The presence of inflammation, thickening of the basement membrane and angiogenesis have been described in bronchial biopsies from asthmatic children. We and others have demonstrated the utility of bronchial brushings from children for the isolation, characterization and culture of primary epithelial cells. The results of these experiments suggest that intrinsic differences exist between asthmatic and nonasthmatic epithelial cells. It is becoming increasingly clear from studies involving adults and, more recently, children, that the epithelium orchestrates inflammatory and remodeling responses of the airway. Equally clear is that the asthmatic epithelium responds inappropriately to challenge and displays signs of dysregulated repair. Understanding the regulatory mechanisms involved in these processes, including the role of resident/recruited progenitor cells, is crucial if we are to halt the progression of asthma when the disease first manifests in childhood.