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

Objective: This meta-analysis was performed to assess the possible prophyla ctic benefit of prolonged treatment with oral N-acetylcysteine (NAC) in chr onic bronchitis (CB) based on qualifying clinical trials. Treatment of acut e exacerbations with NAC was not investigated. Background: Prolonged treatment with oral NAC has been investigated in a nu mber 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( R) search of the period from January 1, 1980, through June 30, 1995; refere nces in the articles retrieved in the initial search; and consultation with 2 experts. Selection was based on the following criteria: published, doubl e-blind, placebo-controlled, chronic bronchopulmonary disease, duration of therapy greater than or equal to 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 cr iteria for CB, with an additional criterion in some trials. For the mete-an alysis, 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. Refe rences from the 8 papers and consultation with the experts produced 8 addit ional publications, 1 of which qualified for inclusion. NAC was administere d orally at a daily dose of 400 mg (1 study), 600 mg (5 studies), or 1200 m g (1 study). One other trial used a dose of 600 mg 3 times per week. The du ration of treatment was 3 months (1 study), 25 months (2 studies), or 6 mon ths (7 studies). The results of this meta-analysis showed a statistically s ignificant 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 o f -0.32 clinical event (95% CI, -0.50 to -0.18) was found (ie, a 23% decrea se in the number of acute exacerbations compared with placebo). Conclusion: These findings suggest that a prolonged course of oral NAC prev ents acute exacerbations of CB, thus possibly decreasing morbidity and heal th care costs.