Increased glutathione disulfide and nitrosothiols in sputum supernatant of patients with stable COPD

Study objectives: Increased oxidant burden is involved in the pathogenesis of COPD. Glutathione (GSH) is a major antioxidant scavenging reactive oxygen and nitrogen species. We studied the concentrations of total and reduced GSH, glutathione disulfide (GSSG), and nitrosothiols in sputum supernatant of patients with COPD. Design: Twenty-five patients with moderate-to-severe COPD (FEV1 61 +/- 12% of predicted) and 25 healthy nonsmoking control subjects underwent sputum induction. Sputum total GSH and GSSG were measured spectrophotometrically, and nitrosothiols were quantified by enzyme assay. Exhaled nitric oxide (eNO) was also measured to correlate eNO with nitrosothiols in induced sputum. Measurements and results: Compared with healthy subjects, patients with COPD had increased sputum neutrophils (geometric mean, 65%; 95% confidence interval [CI], 57.5 to 71; vs 21%; 95% CI, 13.2 to 31.6; p < 0.001); total GSH (geometric mean, 7.1 mumol/L; 95% CI, 2.95 to 17; vs 5.1 mumol/L; 95% CI, 3.2 to 83.1; p = 0.024); GSSG (geometric mean, 4.1 mumol/L; 95% CI, 1.7 to 10; vs 0.84 mumol/L; 95% CI, 0.35 to 1.99; p = 0.002); and nitrosothiols (geometric mean, 60.4 mumol/L; 95% CI, 40 to 95.5; vs 38 mumol/L; 95% CI, 31.6 to 43.6; p = 0.04). Sputum GSSG was positively correlated with neutrophils (rho = 0.47, p = 0.016) and nitrosothiols (rho = 0.49, p = 0.024) in patients with COPD, whereas there was no correlation of eNO with nitrosothiols (rho = 0.38, p = 0.1). Conclusions: Sputum concentrations of GSSG and nitrosothiols are increased in patients with COPD and associated with neutrophilic inflammation. These data underline the role of oxidative stress in the pathogenesis of COPD, and suggest that GSH is important to scavenge both reactive oxygen and nitrogen species.