Efficacy of oral long-term N-acetylcysteine in chronic bronchopulmonary disease: a meta-analysis of published double-blind, placebo-controlled clinical trials

Clin Ther. 2000 Feb;22(2):209-21. doi: 10.1016/S0149-2918(00)88479-9.


Objective: This meta-analysis was performed to assess the possible prophylactic benefit of prolonged treatment with oral N-acetylcysteine (NAC) in chronic bronchitis (CB) based on qualifying clinical trials. Treatment of acute exacerbations with NAC was not investigated.

Background: Prolonged treatment with oral NAC has been investigated in a number of studies of patients with CB. NAC prevented acute exacerbations and symptoms of CB in some but not all trials.

Methods: The trials included in this analysis were selected from a MEDLINE search of the period from January 1, 1980, through June 30, 1995; references in the articles retrieved in the initial search; and consultation with 2 experts. Selection was based on the following criteria: published, double-blind, placebo-controlled, chronic bronchopulmonary disease, duration of therapy > or =2 months, and data sufficient to calculate an outcome variable permitting direct comparison of studies (effect size) for both NAC and placebo groups. The primary end point was the incidence of acute exacerbations in 7 of 8 trials and clinical assessment in the other. In 7 studies, inclusion criteria were based on Medical Research Council criteria for CB, with an additional criterion in some trials. For the meta-analysis, the end points of individual trials were transformed into an effect size as a common outcome.

Results: Of 21 trials initially identified, 8 qualified for inclusion. References from the 8 papers and consultation with the experts produced 8 additional publications, 1 of which qualified for inclusion. NAC was administered orally at a daily dose of 400 mg (1 study), 600 mg (5 studies), or 1200 mg (1 study). One other trial used a dose of 600 mg 3 times per week. The duration of treatment was 3 months (1 study), > or =5 months (2 studies), or 6 months (7 studies). The results of this meta-analysis showed a statistically significant effect size for NAC compared with placebo. The overall value of effect size was -1.37 (95% CI, -1.5 to -1.25). Sensitivity analyses did not significantly alter these results. In a subset analysis of trials with the number of acute exacerbations as a clinical end point, a mean difference of -0.32 clinical event (95% CI, -0.50 to -0.18) was found (ie, a 23% decrease in the number of acute exacerbations compared with placebo).

Conclusion: These findings suggest that a prolonged course of oral NAC prevents acute exacerbations of CB, thus possibly decreasing morbidity and health care costs.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcysteine / administration & dosage
  • Acetylcysteine / adverse effects
  • Acetylcysteine / therapeutic use*
  • Administration, Oral
  • Antiviral Agents / administration & dosage
  • Antiviral Agents / adverse effects
  • Antiviral Agents / therapeutic use*
  • Bronchial Diseases / drug therapy*
  • Controlled Clinical Trials as Topic
  • Double-Blind Method
  • Drug Administration Schedule
  • Humans
  • Lung Diseases, Obstructive / drug therapy


  • Antiviral Agents
  • Acetylcysteine