Bronchial Biopsies in Asthma: An Ultrastructural, Quantitative Study and Correlation with Hyperreactivity

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Abstract
Little is known of the structural changes in mild asthma. We have studied the light and electron microscopic structure of lobar bronchial biopsies taken at fiberoptic bronchoscopy from 11 atopic asthmatics, four of whom were symptomatic and seven of whom were asymptomatic. The former and three of the latter had bronchial hyperresponsiveness to methacholine (PC20 < 4 mg/ml). Quantitative comparisons were made with biopsies from ten control subjects with normal airway reactivity; five had hay fever and five were nonatopic healthy volunteers. Complete absence of surface epithelium was found in three cases of symptomatic asthma, and stratified squamous epithelium was present in the fourth. A biopsy from one of the healthy control subjects had also lost its surface epithelium. The degree of epithelial loss in all subjects correlated with the degree of airway reactivity (rs = 0.67, p < 0.001). The reticular lamina of the epithelial basement membrane showed a trend toward thickening in the seven hyperreactive asthmatics (p < 0.001; median test). There was a tendency to high numbers of inflammatory cells in the lamina propria, but not in the submucosa, of asthmatics, but the differences between groups did not achieve statistical significance. There were significant alterations (px2 < 0.001) in the proportions of each type of inflammatory cell found in the lamina propria and submucosa of symptomatic asthmatics; an increase in irregularly shaped lymphocytes contributed most to the observed alteration. Where surface epithelium was present, intraepithelial lymphocytes formed the major proportion of intraepithelial "migratory" cells: 64% in normal control subjects, 78% in subjects with hay fever, and 87% in asymptomatic asthmatics. There were no obvious differences in the frequency of ciliary abnormalities or the presence of epithelial or subepithelial edema, mast cells, nerve fibers, vascular congestion, extravasation of erythrocytes, or platelets. However, platelets were found aggregated together with electron-dense fibrous material at the airway lumenal edge in biopsies of the symptomatic asthma group. Mucous cell hyperplasia was not a feature of either the asymptomatic asthma or the hay fever group. The results support the hypothesis that epithelial fragility is closely linked to airway hyperreactivity and demonstrate that thickening of the reticular lamina begins early in the condition. The appearance of irregularly shaped lymphocytes in symptomatic asthmatics requires further study to characterize their phenotype and involvement in the pathogenesis of asthma.