Inflammation of the airway wall and airway hyperresponsiveness are consistent features of chronic asthma. We investigated how damage of the bronchial epithelium is related to airy hyperresponsiveness and how bronchial Infiltration of eosinophils and lymphocytes is related to bronchial epithelial damage. We examined the biopsy specimens of bronchial mucosa taken from 19 patients with chronic asthma by electron microscopy. We also measured the incidence of opening of epithelial tight junctions, the widening of intercellular spaces in the epithelium, and the density of infiltrated eosinophils and lymphocytes in bronchial mucosa. Airway responsiveness was accessed by measuring PC20-acetylcholine (PC20-ACh). The inflammatory cells in the airway mucosa were counted by electron microscopy. Lymphocytes were most abundant, being 54.5% of the cells counted; eosinophils were 22.1%, neutrophils were 4.9%, and mast cells were 4.6%. A significant correlation was noted between the density of eosinophils and that of lymphocytes infiltrated in the airway mucosa (r = 0.80, p<0.01), suggesting that T cells may potentiate eosinophil infiltration. With increased density of eosinophils infiltrated in bronchial mucosa, both the incidence of opening of tight junctions of epithelial ciliary cells and the degree of widening of intercellular spaces in epithelium increased significantly (r = 0.51, p<0.05; r = 0.52, p<0.05), suggesting that eosinophils are related to damage of the bronchial epithelium. No correlation was observed between the density of lymphocyte infiltration and the degree of epithelial damage. Airway responsiveness expressed by PC20-ACh showed significant correlations between the incidence of openings of epithelial tight junctions and that of the widening of bronchial intercellular spaces (r = -0.59, p<0.002; r = -0.65, p<0.01). From these findings, we conclude that the epithelial changes seen at the ultrastructural level correlate directly with eosinophil infiltration and airway hyperresponsiveness In our population of asthmatic patients and that this did not change if the subjects were atopic. There was no direct correlation between the presence of lymphocytes and epithelial damage, but the strong correlation between the presence of lymphocytes and eosinophils suggests that lymphocytes are linked to the development of eosinophilic infiltration into the bronchial mucosa, with resultant epithelial damage and airways hyperresponsiveness.
