INCREASED LEVELS OF GLUTATHIONE IN BRONCHOALVEOLAR LAVAGE FLUID FROM PATIENTS WITH ASTHMA

Patients with asthma generate increased amounts of reactive oxygen spe cies (ROS) from peripheral blood cells and cells recovered by bronchoa lveolar lavage (BAL). ROS produce many of the pathophysiologic changes associated with asthma and may contribute to its pathogenesis. Althou gh antioxidant defenses inhibit the changes produced by ROS, no data a re available on local antioxidant defenses in asthma. The present stud y was designed to begin to explore these defenses by measuring superox ide dismutase (SOD) and catalase activities and total glutathione (GSH ) levels in BAL fluid from normal subjects and patients with mild asth ma. Baseline pulmonary function and methacholine bronchoprovocation te sts were performed on all subjects. BAL was achieved by instilling fiv e 20-ml aliquots of phosphate-buffered saline in each of three lung se gments. The fluids recovered from the first 20-ml aliquot and that fro m the next four aliquots were labeled bronchial and alveolar fluid, re spectively. Patients with asthma had a lower FEV1 (p < 0.005), less BA L fluid recovered (p < 0.05), and an increased percentage of bronchial eosinophils (p < 0.05). There were no differences in BAL total cell c ount or protein concentration. Catalase activity was not consistently detected in the unconcentrated BAL fluid from either group. SOD activi ty was found in both bronchial and alveolar samples, but it was simila r in the two groups of subjects. The GSH concentration in bronchial fl uid was higher in the patients with asthma (23.9 +/- 6.2 vs 13.0 +/- 1 .8 muM/mg protein; p < 0.05); a similar trend was seen in the alveolar fluid (36.5 +/- 9.4 vs 23.3 +/- 3.0 muM/mg protein). Further, patient s with the higher alveolar fluid GSH levels had lower methacholine air way reactivity (p < 0.025). These data suggest that patients with mild asthma have increased antioxidant defenses, which may balance an incr ease in oxidant generation and contribute to their relatively mild dis ease.