Myofibroblast involvement in the allergen-induced late response in mild atopic asthma

We undertook a detailed cellular and ultrastructural examination of branchial biopsies from seven allergic asthmatic patients and 10 nonasthmatic control subjects (five atopic and five nonatopic) to determine the nature of the inflammation that occurs during allergen-induced late-phase responses (LPRs). The asthmatic subjects had mild asthma (FEV1 = 94 +/- 9% predicted; mean +/- SEM) and required only intermittent use of beta(2)-agonists. Airway mucosal biopsy specimens were obtained on a single occasion from the nonasthmatic controls and on two occasions from the asthmatic subjects, at 24 h after diluent challenge and 24 h after challenge with allergen 3 wk later. The mean maximal decrease in FEV1 during the late response after allergen challenge was 30%, and that after administration of diluent was 4%. In coded plastic sections, subepithelial cells were counted with both light and electron microscopy, and the numbers present were expressed per 0.1 mm(2) of tissue. Light microscopy revealed statistically significant increases in the total number of inflammatory cells (P < 0.02) and in ''activated fibroblasts'' after allergen challenge (P < 0.05). Electron microscopy showed significant increases after allergen challenge in the total number of eosinophils (P < 0.05) and cells with the ultrastructural features of myofibroblasts. The latter cells constituted 1.5% of cells after administration of diluent, and this increased to 15.5% after allergen challenge (P < 0.05). Mast cells were significantly more abundant in the atopic nonasthmatic controls than in the asthmatic subjects after allergen challenge. The study demonstrates that the profile of inflammatory cells in asthma at 24 h after allergen challenge is distinct from that in stable asthma and in nonasthmatic controls, and that migratory cells with a contractile phenotype appear in greater numbers in the late response. We propose that subjects who repeatedly develop a late response have increased numbers of migrating, contractile cells that may contribute to formation of the increased branchial smooth-muscle mass observed in fatal asthma.