title: Efficacy of erdosteine 900 versus 600 mg/day in reducing oxidative stress in patients with COPD exacerbations: Results of a double blind, placebo-controlled trial.
abstract: BACKGROUND
  Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are associated with increased airway and systemic inflammation. There is evidence that erdosteine accelerates recovery from AECOPD by reducing airway inflammation.
  
  
  OBJECTIVE
  To investigate the dose-dependent antioxidant/anti-inflammatory activity of erdosteine in COPD patients.
  
  
  METHODS
  In this single-centre, double blind, double dummy study, patients with mild-to-moderate COPD (GOLD stage II-III), were randomised to receive either placebo or two dosages of oral erdosteine (300 mg tid or 300 mg bid + 1 capsule of indistinguishable placebo) for 28 days in addition to their standard treatment. Primary variables were plasma reactive oxygen species (ROS) and 8-isoprostane levels, while secondary variable was lung function (FEV1; FEV1/FVC; FEV1 short-term reversibility), all assessed in baseline; every two weeks during the study, and one week after the end of the study.
  
  
  RESULTS
  Baseline demographic characteristics, plasma ROS and 8-isoprostane levels and lung function were not significantly different in the 24 eligible patients (14 males, aged 38-75 years). At 2 weeks, there was a dose-dependent decrease in ROS in the erdosteine groups. By week 4 there were significant differences in ROS levels compared to baseline between patients receiving 900 mg/day (p < 0.003) and those receiving 600 mg/day (p < 0.04). This effect continued in the follow-up week (p < 0.021). Erdosteine also lowered 8-isoprostane plasma levels after 4 weeks (p < 0.01), and this effect lasted over the post-treatment week. Moreover, % FEV1 reversibility after salbutamol 400 mcg obtained after a 4 -week treatment of erdosteine 900 mg/day was significantly higher than that obtained after 600 mg/day (p < 0.01). Erdosteine was well tolerated and no treatment-related adverse event was reported.
  
  
  CONCLUSIONS
  Results confirm the antioxidant dose- and time-dependent activity of erdosteine, and support the utility of including erdosteine it in the therapeutic strategy for the prevention and treatment of oxidative stress-induced inflammation, which frequently leads to AECOPD occurrence.
authors.affiliation: National Centre for Respiratory Pharmacoeconomics and Pharmacoepidemiology (CESFAR), Verona, Italy. Electronic address: robertodalnegro@gmail.com.
authors.forename: R W
authors.initials: RW
authors.lastname: Dal Negro
authors.affiliation: BioLab, Bussolengo General Hospital, ULSS22 Regione Veneto, Italy. Electronic address: mvisconti@ulss22.ven.it.
authors.forename: M
authors.initials: M
authors.lastname: Visconti
authors.affiliation: Research & Clinical Governance (R&CG), Verona, Italy. Electronic address: turcop@libero.it.
authors.forename: P
authors.initials: P
authors.lastname: Turco
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000420:Albuterol / Q000494:pharmacology; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology; D001993:Bronchodilator Agents / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005100:Expectorants / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects*; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000503:physiopathology; D017382:Reactive Oxygen Species / Q000378:metabolism; D013864:Thioglycolates / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D013876:Thiophenes / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000975:Antioxidants; D001993:Bronchodilator Agents; D005100:Expectorants; D017382:Reactive Oxygen Species; D013864:Thioglycolates; D013876:Thiophenes; C048498:erdosteine; D000420:Albuterol
keywords: Airway inflammation; Antioxidants; COPD exacerbations; Chronic obstructive pulmonary disease; Erdosteine; Oxidative stress