Eight RCTs were included (2,214 randomised; 1,819 included in the meta-analysis).
N-acetylcysteine was associated with a significant reduction in the odds of experiencing one or more exacerbations over 6 months compared to placebo (OR 0.49, 95% CI: 0.32, 0.74, p=0.001); the NNT was 7. Statistically significant heterogeneity was detected (p=0.001). After excluding patients in one study who were taking concurrent inhaled corticosteroids, there was no evidence of statistical heterogeneity (p=0.41).
No significant correlation was found between baseline FEV1% predicted and the effect of N-acetylcysteine (p=0.6).
In studies in which more than 50% of patients were current smokers, N-acetylcysteine was associated with a significant reduction in the odds of experiencing one or more exacerbations compared with placebo (OR 0.36, 95% CI: 0.24, 0.55, p<0.001; 3 studies).
Among patients not using inhaled corticosteroids, N-acetylcysteine was associated with a significant reduction in the odds of experiencing one or more exacerbations compared with placebo (OR 0.42, 95% CI: 0.32, 0.54, p<0.0001).
There was no evidence of publication bias: the funnel plot was symmetrical and Begg’s test was not statistically significant (p=0.62).