Benefits of high-dose N-acetylcysteine to exacerbation-prone patients with COPD

Chest. 2014 Sep;146(3):611-623. doi: 10.1378/chest.13-2784.

Abstract

Background: Although high-dose N-acetylcysteine (NAC) has been suggested to reduce COPD exacerbations, it is unclear which category of patients with COPD would benefit most from NAC treatment. The objective of this study was to compare the effect of high-dose NAC (600 mg bid) between high-risk and low-risk Chinese patients with COPD.

Methods: Patients with spirometry-confirmed stable COPD were randomized to treatment with either NAC 600 mg bid or placebo in addition to their usual treatments. Patients were followed up every 16 weeks for a total of 1 year. Further analysis was performed according to each patient's exacerbation risk at baseline as defined by the current GOLD (Global Initiative for Chronic Obstructive Lung Disease) strategy to analyze the effect of high-dose NAC in high-risk and low-risk patients.

Results: Of the 120 patients with COPD randomized (men, 93.2%; mean age, 70.8 ± 0.74 years; prebronchodilator FEV₁, 53.9 ± 2.0%; baseline characteristics comparable between treatment groups), 108 (NAC, 52; placebo, 56) completed the 1-year study. For high-risk patients (n = 89), high-dose NAC compared with placebo significantly reduced exacerbation frequency (0.85 vs 1.59 [P = .019] and 1.08 vs 2.22 [P = .04] at 8 and 12 months, respectively), prolonged time to first exacerbation (P = .02), and increased the probability of being exacerbation free at 1 year (51.3% vs 24.4%, P = .013). This beneficial effect of high-dose NAC vs placebo was not significant in low-risk patients.

Conclusions: High-dose NAC (600 mg bid) for 1 year reduces exacerbations and prolongs time to first exacerbation in high-risk but not in low-risk Chinese patients with COPD.

Trial registry: ClinicalTrials.gov; No.: NCT01136239; URL: www.clinicaltrials.gov.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcysteine / therapeutic use*
  • Aged
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Female
  • Forced Expiratory Volume / physiology
  • Free Radical Scavengers / therapeutic use*
  • Hong Kong
  • Humans
  • Male
  • Physical Endurance / physiology
  • Pulmonary Disease, Chronic Obstructive / drug therapy*
  • Pulmonary Disease, Chronic Obstructive / epidemiology*
  • Pulmonary Disease, Chronic Obstructive / physiopathology
  • Risk Factors
  • Severity of Illness Index*
  • Surveys and Questionnaires
  • Treatment Outcome

Substances

  • Free Radical Scavengers
  • Acetylcysteine

Associated data

  • ClinicalTrials.gov/NCT01136239