Erdosteine enhances airway response to salbutamol in patients with mild-to-moderate COPD

• Published in: Therapeutic advances in respiratory disease Vol. 2; no. 5; p. 271
• Main Authors: Dal Negro, Roberto, Visconti, Maria, Trevisan, Fiorenza, Bertacco, Stefano, Micheletto, Claudio, Tognella, Silvia
• Format: Journal Article
• Language: English
• Published: England SAGE Publishing 01-10-2008
• Subjects: Adrenergic beta-Agonists - therapeutic use; Aged; Albuterol - therapeutic use; Bronchi - drug effects; Drug Synergism; Expectorants - pharmacology; Female; Forced Expiratory Volume; Humans; Lipid Peroxidation - drug effects; Male; Middle Aged; Oxidative Stress - drug effects; Pulmonary Disease, Chronic Obstructive - drug therapy; Reactive Oxygen Species - analysis; Thioglycolates - pharmacology; Thiophenes - pharmacology
• ISSN: 1753-4658
• DOI: 10.1177/1753465808096109

Oxidative stress is presumed to impair beta-adenoceptor function and airway patency. Erdosteine (E), a mucomodulatory compound, has shown important antioxidant properties.
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 (>or=10 pack/year), randomly received E 300 mg, N-acetylcysteine (NAC) 600 mg, or placebo, twice daily for ten days. Reversibility to salbutamol 200 microg 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 p<0.05 assumed. E enhanced FEV1 reversibility after four and ten days significantly (+5.1% and +5.0%; both p<0.01 vs. placebo), while NAC only showed a transient effect at day 4 (+3.0%, p<0.05), but not at day 10 (+1.3%, p = ns).
E and NAC caused significant drops in ROS blood levels after four and ten days (p<0.001 and p<0.0001 vs. placebo). In contrast to NAC, E lowered 8-isoprostane levels substantially for ten days (p = 0.017 and p = 0.0004 vs. placebo, respectively). Only E restored significantly short-term reversibility in COPD patients previously unresponsive to beta(2)-adrenergics.
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 beta( 2)-adrenoceptors. Once confirmed in further controlled studies, it may be useful in long-term treatment of COPD.