AIRWAY INFLAMMATION AFTER REMOVAL FROM THE CAUSAL AGENT IN OCCUPATIONAL ASTHMA DUE TO HIGH AND LOW-MOLECULAR-WEIGHT AGENTS

In order to determine 1) the features of airway inflammation after removal from exposure to high (HMW) and low (LMW) molecular weight agents 2) if there are any differences in the pattern of inflammation induced by these two types of agents, we studied 18 subjects with a recently confirmed diagnosis of occupational asthma (OA) due to HMW (n=11) and LMW (n=7) agents. The duration of asthma symptoms varied from 2 to 108 months (mean 33 months), and withdrawal from exposure to the sensitizing agent from 3 to 24 weeks (mean 10 weeks). All subjects underwent measurements of expiratory flow rates, methacholine inhalation tests, and a flexible bronchoscopy with bronchoalveolar lavage (BAL) and bronchial biopsies. Endoscopic findings were compared with a group of 10 normal subjects. At the time of the bronchoscopy, asthma symptoms were minimal in most subjects. Although 15/18 subjects had normal forced expiratory volume in one second (FEV(1)>80% pred), all subjects had increased airway responsiveness to methacholine (provocation concentration producing a 20% fall in FEV(1)=0.2-10.0 mg.ml(-1)). BAL analysis showed similar median percentages of the total number of cells and differentials in control subjects and those exposed to HMW and LMW agents. Bronchial biopsies showed that mean inflammatory cell count, both epithelial and sub-epithelial, was similarity raised in OA subjects exposed to either HMW or LMW agents, compared to controls, except for epithelial lymphocyte count. In contrast to the controls, bronchial biopsy of both groups with OA also showed other changes such as extensive epithelial desquamation, ciliary abnormalities of the epithelial cells, smooth muscle hyperplasia and subepithelial fibrosis. Bronchial biopsies from subjects with occupational asthma showed similar significant inflammatory changes after withdrawal from exposure to either high or low molecular weight sensitizing agent, even when symptoms were minimal.