AIRWAY WALL REMODELING AFTER CESSATION OF EXPOSURE TO ISOCYANATES IN SENSITIZED ASTHMATIC SUBJECTS

To determine whether the cessation of exposure to isocyanates is assoc iated with structural changes of the airway wall in sensitized subject s, we studied bronchial biopsies from 10 subjects with occupational as thma induced by toluene diisocyanate (TDI). Bronchial challenges with TDI and methacholine were performed and biopsies were taken on two occ asions, at diagnosis and 6 to 21 mo after cessation of exposure to TDI . After bronchoscopy, biopsies were forma[in-fixed or snap-frozen in l iquid nitrogen and then processed for a quantitative histochemical and immunohistochemical analysis. After cessation of exposure, we observe d a significant decrease of the sensitivity to TDI (p < 0.05), of the thickness of subepithelial fibrosis (p < 0.007), and of the numbers of subepithelial fibroblasts (p < 0.05), mast cells (p < 0.02), and lymp hocytes (p < 0.03) as compared with values at diagnosis. By contrast, the nonspecific bronchia[ hyperresponsiveness and the numbers of macro phages and eosinophils did not change. In conclusion, in patients with occupational asthma induced by TDI, the cessation of exposure to the sensitizing agent is associated with a reduced thickness of subepithel ial fibrosis and with a reduced number of subepithelial fibroblasts, m ast cells, and lymphocytes in the bronchial mucosa, suggesting a remod eling of the airway wall with the avoidance of the specific stimulus.