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Background Oxidative stress is involved in the pathogenesis of allergic inflammatory diseases, such as rhinitis and asthma. Glutathione is a vital intracellular and extracellular protective pulmonary antioxidant. It plays a key role in regulating oxidant-induced lung epithelial cell function and also in the control of proinflammatory processes. Objective To quantify oxidative stress in sputum of asthmatic patients compared with healthy subjects. Methods We quantified induced sputum supernatant concentrations of total and oxidized glutathione in 20 patients with mild asthma without inhaled corticosteroid treatment, 19 patients with moderate-persistent asthma treated with inhaled corticosteroids (median dose, 900 μg/d of beclomethasone equivalent), and 15 healthy, nonatopic, nonsmoking subjects. Results Total glutathione levels were significantly increased in mild and persistent asthma compared with healthy subjects [geometric mean (95% confidence interval), 9.2 μm (7.1-12 μm) and 8.7 μm (5.9-12.5 μm) vs 4 μm (2.7-6 μm); P = .039 and .042, respectively]. In contrast, there were no differences in total and oxidized glutathione levels between steroid-naive and steroid-treated asthmatic patients ( P > .20 for all comparisons). Persistent, steroid-treated asthmatic patients had higher sputum counts of neutrophils than steroid-naive asthmatic patients [geometric mean (95% confidence interval), 35.6% (28.2%-42.7%) vs 17.7% (11.7%-27.1%), P = .04]. There was a positive correlation of total glutathione with sputum total cells (ρ = 0.32, P = .02). Conclusions Total glutathione is increased in induced sputum of patients with mild and moderate asthma. These data underline the contribution of oxidative stress to the pathogenesis of allergic asthmatic inflammation.

Background: The pathogenesis of late asthmatic reactions after allergen challenge in contrast to isolated early responses is incompletely understood. Recently, the antioxidant glutathione and endogenous nitrosothiols were shown to protect against bronchoconstriction. We compared reduced (GSH) and oxidized glutathione (GSSG) and nitrosothiols in induced sputum following allergen challenge in mild asthmatics with isolated early (EAR) and dual early and late (LAR) asthmatic responses. Methods: Exhaled nitric oxide, sputum cells and sputum supernatant concentrations of GSH, GSSG and nitrosothiols were quantified 2–5 days prior to and 24 h after allergen challenge in 24 mild asthmatics (12 EAR, 12 LAR, only beta-agonists prn). Results: There were no differences at baseline between EAR and LAR asthmatics for any of the parameters (p > 0.1, all comparisons). Mean ± SD fall in forced expiratory volume in 1 s, expressed as the percentage decrease compared to the baseline value, between 3 and 8 h after allergen challenge was 1 ± 5% in the group of patients without LAR vs. 24.9 ± 8.7% in the group of patients with LAR (p < 0.001). Sputum eosinophils increased in both groups (p < 0.05, both comparisons), whereas neutrophils only increased in LAR subjects (p = 0.06 vs. EAR). In contrast, GSH was significantly increased 24 h after challenge only in EAR asthmatics [geometric mean with 95% confidence intervals: before: 3.3 µM (1.25–7.9 µM), after: 5.9 µM (2.7–12.9 µM), p = 0.05; mean difference vs. LAR subjects: 6 µM (0.1–12 µM), p = 0.048], and the proportion of GSSG was positively correlated with postallergen eosinophils in all patients (rho = 0.4, p = 0.05). There was no change in nitrosothiols after 24 h in either EAR or LAR subjects (p > 0.23, all comparisons). Conclusions: GSH increases 24 h after allergen challenge in isolated early responders. These data suggest that different adoptive responses to allergen may result in different physiologic phenotypes. Further studies on the role of glutathione in allergen-induced bronchoconstriction are clearly warranted.