Background: Chronic Bronchitis (CB) is a common trait in COPD and may precede the development of airflow limitation, characterising a 'pre-COPD' population.

Aims and objectives: To determine whether treatment with N-acetylcysteine (NAC) improves respiratory symptoms and quality of life or reduces the number of exacerbations in patients with or without a clear evidence of airflow obstruction or of CB.

Methods: A systematic review yielded a total of 20 RCTs and 4044 patients treated with oral NAC (doses varying from 400 mg to 3600 mg daily) or placebo for at least two months up to three years. Analyses were performed on studies that included patients with a CB diagnosis and no reported spirometric abnormalities (CB/pre-COPD group), as well as on studies that included patients with COPD and/or CB and a clear evidence of airflow obstruction (COPD group). A random-effects model was used to pool effect sizes and, and Knapp-Hartung adjustments were used to calculate the confidence interval around the pooled effect.

Results: NAC was more likely to improve symptoms and quality of life in the CB/pre-COPD group of patients (OR 3.47; 95% CI 1.92 to 6.26) and to reduce the total number of exacerbations (IRR 0.81; 95% CI 0.69 to 0.95). Results for the COPD group confirmed NAC effect on reducing the incidence of exacerbations (IRR 0.76; 95% CI 0.59 to 0.99).

Conclusions: The results of the meta-analysis suggest that oral treatment with NAC may improve respiratory symptoms and reduce exacerbations in CB/preCOPD patients.