Sputum Levels of Reduced Glutathione Increase 24 Hours after Allergen Challenge in Isolated Early, but Not Dual Asthmatic Responders

Abstract

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.