Erdosteine enhances airway response to salbutamol in patients with mild-to-moderate COPD.
BACKGROUND
Oxidative stress is presumed to impair beta-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 (>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).


RESULTS
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.


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 beta( 2)-adrenoceptors. Once confirmed in further controlled studies, it may be useful in long-term treatment of COPD.
Dal Negro
Roberto
R
Lung Department, Orlandi General Hospital, Bussolengo, Verona, Italy. rdalnegro@ulss22.ven.it
Visconti
Maria
M
Trevisan
Fiorenza
F
Bertacco
Stefano
S
Micheletto
Claudio
C
Tognella
Silvia
S
D000318:Adrenergic beta-Agonists / Q000627:therapeutic use*; D000368:Aged; D000420:Albuterol / Q000627:therapeutic use*; D001980:Bronchi / Q000187:drug effects; D004357:Drug Synergism; D005100:Expectorants / Q000494:pharmacology*; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects*; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy*; D017382:Reactive Oxygen Species / Q000032:analysis; D013864:Thioglycolates / Q000494:pharmacology*; D013876:Thiophenes / Q000494:pharmacology*
D000318:Adrenergic beta-Agonists; D005100:Expectorants; D017382:Reactive Oxygen Species; D013864:Thioglycolates; D013876:Thiophenes; C048498:erdosteine; D000420:Albuterol