[Relationship between bronchial reactivity to inhaled acetylcholine, eosinophil infiltration and a widening of the intercellular space in patients with asthma].

: The hypothesis that epithelial damage is related to the development of bronchial hyperreactivity has been supported by many studies. Therefore, we further examined whether or not subjects with bronchial epithelium damage showed increased bronchial responsiveness. We took biopsy specimens of the airway mucosa from 20 asthmatic patients with various degrees of disease severity and bronchial hyperreactivity by using a bronchofiber scope. The morphology of the biopsy specimens was studied by electron microscopy. Bronchoscopy was carried out after local anesthesia. Specimens of bronchial mucosa were obtained from 20 asthmatic patients (14 males, 6 females) in remission. The electronmicroscopic studies showed widening of the intercellular space between the epithelial cells and openings of the tight junctions, as well as infiltrations of eosinophils and their granules beneath and between epithelial cells. The tight junction refers to the space between epithelial cells exposed to the airway surface, leading down to the intercellular space. The intercellular space refers to the space between epithelial cells, below the tight junction. Interestingly, eosinophils and their granules were found mainly in the widened intercellular space. The incidence of a widening of the intercellular space was higher in specimens showing eosinophil infiltration than in those not showing eosinophil infiltration. A significant correlation was found between the respiratory threshold to acetylcholine and the percentage of opened tight junctions (r = -0.47, p less than 0.05) and/or the widening of the space between epithelial cells (r = -0.65, p less than 0.01). These results suggest that widening of the intercellular space may be caused by infiltrations of eosinophils and that this widening increases bronchial reactivity.