Abstract:Background: Oxidative stress is presumed to impair -adenoceptor function and airway patency. Erdosteine (E), a mucomodulatory compound, has shown important antioxidant properties. Methods:The objective was to assess the effect of antioxidant interventions on short-term airway response to salbutamol in non-reversible mild-to-moderate COPD patients. Thirty COPD patients (GOLD class 1-2), current smoker (!10 pack/year), randomly received E 300 mg, N-acetylcysteine (NAC) 600 mg, or placebo, twice daily for ten days. Reversibility to salbutamol 200 mg was tested in baseline, after four and ten days of each treatment. ROS and 8-isoprostane blood levels were measured on the same days. Between-treatment comparison was performed by ANOVA and t-test or Wilcoxon test, and p50.05 assumed. E enhanced FEV1 reversibility after four and ten days significantly (þ5.1% and þ5.0%; both p50.01 vs. placebo), while NAC only showed a transient effect at day 4 (þ3.0%, p50.05), but not at day 10 (þ1.3%, p ¼ ns).Results: E and NAC caused significant drops in ROS blood levels after four and ten days (p50.001 and p50.0001 vs. placebo). In contrast to NAC, E lowered 8-isoprostane levels substantially for ten days (p ¼ 0.017 and p ¼ 0.0004 vs. placebo, respectively). Only E restored significantly short-term reversibility in COPD patients previously unresponsive to 2 -adrenergics. Conclusions: This effect seems more related to the peculiar protection against lipid peroxidation rather than to the scavenging activity, which proves equal to that of NAC. E provides a sort of indirect bronchodilation through 're-sensitisation' of 2 -adrenoceptors. Once confirmed in further controlled studies, it may be useful in long-term treatment of COPD.