The bronchial epithelium in chronic and severe asthma.
Although patients with severe, steroid-refractory asthma represent a minor proportion of the asthmatic population, they consume a disproportionate amount of healthcare costs and have a greatly impaired quality of life. They respond poorly to conventional anti-inflammatory therapy and frequently exhibit a component of fixed airflow obstruction that has been linked to airway wall remodeling. In addition to its classic barrier function, the bronchial epithelium responds to changes in the external environment by secreting cytoprotective molecules and mediators that signal to cells of the immune system. In asthma, the bronchial epithelium is stressed and damaged, with shedding of the columnar cells into the airway lumen. This damage and ensuing repair responses are proposed to orchestrate airway inflammation and remodeling via activation of myofibroblasts in the underlying lamina reticularis. This allows the two cell types to work as a trophic unit, propagating and amplifying the response at the cell surface into the submucosa. Because wound healing involves inflammation, repair, and remodeling processes, this review considers the evidence that exaggerated inflammation and remodeling of the airways arise as a consequence of abnormal injury and repair responses coordinated by the bronchial epithelium, highlighting, where possible, steroid-insensitive components.
Davies
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Respiratory, Cell & Molecular Biology Division, School of Medicine, University of Southampton, Level D Centre Block, Southampton General Hospital, Tremona Rd, Southampton, SO16 6YD, UK. donnad@soton.ac.uk
D001249:Asthma / Q000473:pathology*; D001980:Bronchi / Q000473:pathology*; D002908:Chronic Disease; D002986:Clinical Trials as Topic; D006801:Humans; D020545:Respiratory Mucosa / Q000473:pathology*; D012720:Severity of Illness Index