Pulmonary glutathione levels in acute episodes of farmer's lung

Acute episodes of farmer's lung (FL) are associated with activation and migration of neutrophils into the lungs, causing oxidative stress. We conducted a study to evaluate the effect of episodes of FL on antioxidant defense of the lung by glutathione (GSH). A total of 15 patients with symptomatic FL (one female and 14 males, age 42 +/- 1 yr [mean +/- SEM]) underwent a standardized hay exposure test for 1 h and were then monitored through lung function measurements for 6 h, after which bronchoalveolar lavage (BAL) was performed. As a control, 10 asymptomatic farmers (AF) (two males and eight females, age 43 +/- 1 yr) underwent the same diagnostic procedures. At 3 to 6 h after antigen exposure, the lung function of FL patients was significantly impaired (VC: -31 +/- 4%; single-breath diffusing capacity of carbon monoxide [DLCO]: -17 +/- 3%; and PaO2: -14 +/- 2%, all versus baseline, whereas in AF, only minor changes occurred VC: -4 +/- 5%; DLCO: -9 +/- 3%, and PaO2: -5 +/- 2%, all versus baseline). The number of neutrophils in bronchoalveolar ravage fluid was increased in FL patients as compared with AF (29 +/- 7 x 104/ml versus 10 +/- 7 x 10(4)/ml, p < 0.05). The concentrations of total and reduced glutathione (GSH, and GSH, respectively) in epithelial lining fluid were decreased in FL patients and increased in AF (GSHT: 292.5 +/- 27.5 mu M versus 1,185.0 +/- 189.9 mu M, respectively, p < 0.001; GSH: 256.8 +/- 22.1 mu M versus 1,054.5 +/- 172.9 mu M, respectively, p < 0.001). These findings suggest that the individual ability to upregulate GSH in the alveolar space in response to an inflammatory stimulus may have implications for the development of symptomatic FL. We conclude that intrapulmonary GSH levels are distinctly different in patients with FL and AF, and that the regulation of GSH may play an important role in the pathogenesis of FL.