The bronchial epithelium as a key regulator of airway inflammation and remodelling in asthma

While asthma is an inflammatory disorder of the airways involving mediator release from mast cells and eosinophils and orchestrated by T cells, inflam mation alone is insufficient to explain the chronic nature of the disease a nd its progression. Evidence is presented that the epithelium is fundamenta lly disordered in chronic asthma manifest by increased fragility, and an al tered phenotype to one that secretes mucus, mediators, cytokines, chemokine s and growth factors. Epithelial injury is mediated by exogenous factors su ch as air pollutants, viruses and allergens as well as by endogenous factor s including the release of proteolytic enzymes from mast cells (tryptase, c hymase) and eosinophils (MMP-9). Following injury, the normal epithelium sh ould respond with increased proliferation driven by ligands acting on epide rmal growth factor (EGF) receptors or through transactivation of the recept or. The epithelial response to these stimuli in asthma appears to be impair ed despite upregulation of CD44 capable of enhancing presentation of EGF li gands to epidermal growth factor receptors (EGFR). Because the epithelium i s 'held' in this repair phenotype, it becomes a continuous source of proinf lammatory products as well as growth factors that drive airway wall remodel ling.