Am. J. Respir. Crit. Care Med., Volume 156, Number 2, August 1997, 425-430

Nebulized Glutathione Induces Bronchoconstriction in Patients with Mild Asthma

RAMON M. MARRADES, JOSEP ROCA, JOAN ALBERT BARBERÁ, LLUÍS de JOVER, WILLIAM MACNEE, and ROBERT RODRIGUEZ-ROISIN

Servei de Pneumologia i Al.lèrgia Respiratòria, Departament de Medicina, Hospital Clínic and Unitat de Bioestadística, Departament de Salut Pública i Legislació Sanitària, Universitat de Barcelona, Barcelona, Catalunya, Spain; and Respiratory Medicine Unit, Department of Medicine, Royal Infirmary, Edinburgh, Scotland, United Kingdom

To assess the effects on bronchial responsiveness of nebulized glutathione (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, placebo-controlled fashion. Bronchial challenge was measured using both FEV₁ and total pulmonary resistance (Rrs) by the forced oscillation technique. Patients received nebulized GSH (600 mg with 4 ml of 0.9% sodium chloride) or placebo (identical saline solution) over a period of 25 min, 1 wk apart. Placebo provoked subclinical mild bronchoconstriction (changes from baseline: FEV₁, 1%; Rrs, +17%); by contrast, GSH caused major airway narrowing (changes from baseline: FEV₁, 19%; Rrs, +61%) and induced cough (four patients) or breathlessness (three patients). Differences between placebo and GSH after challenge were also noticeable in both FEV₁ (p = 0.03) and Rrs (p = 0.02). Neither osmolarity (660 mosm · kg¹) nor pH (3.0) of the GSH solution accounted for these effects. Nebulized salbutamol (5.0 mg) given before the GSH challenge blocked GSH-induced bronchoconstriction. Furthermore, GSH-induced FEV₁ falls were inversely correlated with metabisulfite bronchoprovocation (provocative dose [PD₂₀], 1.49 ± 1.83 µmol) but not with methacholine challenge. The detrimental effects of nebulized GSH on the airway bronchial tone in patients with mild asthma strongly suggests bronchoconstriction provoked by sulfite formation.

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