Intraepithelial Mast Cells in Allergic and Nonallergic Asthma: Assessment Using Bronchial Brushings

Abstract Mast cell mediators are known to contribute to the pathogenesis of asthma. There is some disagreement concerning the numbers of mast cells in asthmatic mucosa. In this study a standardized bronchial brush technique was developed and used to assess intraepithelial mast cells and other inflammatory cells in allergic and nonallergic asthmatic and nonasthmatic subjects. A total of 10 nonasthmatic (5 allergic) and 13 asthmatic (8 allergic) subjects with stable controlled asthma treated with β-agonist only were assessed by history, spirometry, allergy prick tests, and methacholine airway responsiveness. During fiberoptic bronchoscopy, bronchoalveolar lavage (BAL) was performed from the middle lobe and standardized bronchial brushings were taken from the lingula and left lower lobe bronchi. Quantitative cell counts were performed blind to the clinical characteristics of the subjects. The average total cell recovery from the brushings was 1.04 (SEM 0.09) × 106 ml, with a cell viability of 64% (5.3%). Reproducible total cell and mast cell counts were obtained from brushings taken from two lobar bronchi (ICC 0.86). Mast cells were significantly elevated in asthmatic compared with nonasthmatic subjects (1.5 ± 0.34 versus 0.15 ± 0.06%). Allergic asthmatic subjects had the greatest numbers of mast cells (1.86 ± 0.48%); however, the numbers present in brushings from nonallergic asthmatic subjects were also increased (1.03 ± 0.45%). The mast cells had the staining characteristics of mucosal mast cells, with formalin-blockable metachromatic staining and positive staining for tryptase. Both asthmatic groups also had elevated BAL eosinophils, and neutrophils were elevated in nonallergic asthmatic subjects. We conclude that bronchial brushings are a useful technique for sampling intraepithelial mast cells and that there is an accumulation of mast cells within the airway epithelium in asthma that is independent of allergy. The microenvironment within the bronchial epithelium may favor mast cell accumulation and the acquisition of a particular mast cell phenotype, which in turn may contribute to persisting airway inflammation and hyperresponsiveness in asthma.