Increased levels of glutathione in bronchoalveolar lavage fluid from patients with asthma

Patients with asthma generate increased amounts of reactive oxygen species (ROS) from peripheral blood cells and cells recovered by bronchoalveolar lavage (BAL). ROS produce many of the pathophysiologic changes associated with asthma and may contribute to its pathogenesis. Although antioxidant defenses inhibit the changes produced by ROS, no data are available on local antioxidant defenses in asthma. The present study was designed to begin to explore these defenses by measuring superoxide dismutase (SOD) and catalase activities and total glutathione (GSH) levels in BAL fluid from normal subjects and patients with mild asthma. Baseline pulmonary function and methacholine bronchoprovocation tests were performed on all subjects. BAL was achieved by instilling five 20-ml aliquots of phosphate-buffered saline in each of three lung segments. The fluids recovered from the first 20-ml aliquot and that from the next four aliquots were labeled bronchial and alveolar fluid, respectively. Patients with asthma had a lower FEV₁ (p < 0.005), less BAL fluid recovered (p < 0.05), and an increased percentage of bronchial eosinophils (p < 0.05). There were no differences in BAL total cell count or protein concentration. Catalase activity was not consistently detected in the unconcentrated BAL fluid from either group. SOD activity was found in both bronchial and alveolar samples, but it was similar in the two groups of subjects. The GSH concentration in bronchial fluid was higher in the patients with asthma (23.9 ± 6.2 vs 13.0 ± 1.8 μM/mg protein; p < 0.05); a similar trend was seen in the alveolar fluid (36.5 ± 9.4 vs 23.3 ± 3.0 μM/mg protein). Further, patients with the higher alveolar fluid GSH levels had lower methacholine airway reactivity (p < 0.025). These data suggest that patients with mild asthma have increased antioxidant defenses, which may balance an increase in oxidant generation and contribute to their relatively mild disease.