NEBULIZED GLUTATHIONE INDUCES BRONCHOCONSTRICTION IN PATIENTS WITH MILD ASTHMA

To assess the effects on bronchial responsiveness of nebulized glutath ione (GSH), one of the most efficient scavengers of oxidant substances in the airways, we studied eight patients with mild asthma (FEV1, 88 +/- 11% predicted [SD]) in a randomized, double-blind, cross-over, pla cebo-controlled fashion. Bronchial challenge was measured using both F EV1 and total pulmonary resistance (Rrs) by the forced oscillation tec hnique. Patients received nebulized GSH (600 mg with 4 ml of 0.9% sodi um chloride) or placebo (identical saline solution) over a period of 2 5 min, 1 wk apart. Placebo provoked subclinical mild bronchoconstricti on (changes from baseline: FEV1, -1%; Rrs, +17%); by contrast, GSH cau sed major airway narrowing (changes from baseline: FEV1, -19%; Rrs, +6 1%) and induced cough (four patients) or breathlessness (three patient s). Differences between placebo and GSH after challenge were also noti ceable in both FEV1 (p = 0.03) and Rrs (p = 0.02). Neither osmolarity (660 mosm . kg(-1)) nor pH (3.0) of the GSH solution accounted for the se effects. Nebulized salbutamol (5.0 mg) given before the GSH challen ge blocked GSH-induced bronchoconstriction. Furthermore, GSH-induced F EV1 falls were inversely correlated with metabisulfite bronchoprovocat ion (provocative dose [PD20], 1.49 +/- 1.83 mu mol) but not with metha choline challenge. The detrimental effects of nebulized GSH on the air way bronchial tone in patients with mild asthma strongly suggests bron choconstriction provoked by sulfite formation.