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Vol. 60. Issue 5.
Pages 269-278 (May 2024)
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Vol. 60. Issue 5.
Pages 269-278 (May 2024)
Original Article
N-acetylcysteine Treatment in Chronic Obstructive Pulmonary Disease (COPD) and Chronic Bronchitis/Pre-COPD: Distinct Meta-analyses
Alberto Papia,
Corresponding author

Corresponding author.
, Franco Alfanoa, Tommaso Bigonia, Lorenzo Mancinib, Amal Mawassb, Federico Baraldia, Cristina Aljamac, Marco Contolia, Marc Miravitllesc
a Department of Translational Medicine, University of Ferrara Medical School, University of Ferrara, Sant’Anna University Hospital, Ferrara, Italy
b Alira Health S.r.l., 20121 Milan, Italy
c Pneumology Department, Hospital Universitari Vall d’Hebron, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain

  • Treatment effects on PROs in chronic bronchitis (CB) with/out COPD are scarcely known.

  • N-acetylcysteine (NAC) improve symptoms and/or QoL in studies conducted in CB.

  • NAC reduce exacerbations in studies conducted in subjects with CB.

  • Similarly, NAC reduce exacerbations and improve symptoms and/or QoL in COPD studies.

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N-acetylcysteine (NAC) is a mucolytic agent with antioxidant properties. Oxidative stress is a key pathogenic mechanism in chronic respiratory conditions such as COPD and chronic bronchitis (CB). In these meta-analyses we investigated the efficacy of NAC in subjects with COPD or CB, the latter being a potential pre-COPD condition (CB/pre-COPD).


The meta-analyses were conducted according to PRISMA guidelines. Exacerbations were assessed using total number of exacerbations. Improvement in patients’ respiratory symptoms and/or patients quality of life (QoL) were measured by validated tools or assessed at the end of the study.


Twenty studies were included, of which seven evaluated NAC in patients with symptoms of CB/pre-COPD as entry criterion.

NAC treated patients showed a significant reduction of the incidence of exacerbations as compared to placebo both in COPD (IRR=0.76; 95% confidence interval (CI) 0.59–0.99) and CB/pre-COPD (IRR=0.81; 95% CI 0.69–0.95). Sensitivity analyses in studies with duration higher than 5 months, confirmed the overall results.

CB/pre-COPD patients treated with NAC were significantly more likely to experience an improvement in symptoms and/or QoL compared to placebo (odds ratio (OR)=3.47; 95% CI 1.92–6.26). A similar trend was observed in the few COPD studies evaluable.

Sensitivity analyses showed a significant association of NAC with improvement in symptoms and/or QoL both in CB/pre-COPD and COPD patients.


These findings provide novel data of NAC on the improvement in symptoms and QoL in addition to prevention of exacerbations in COPD and CB/pre-COPD.

PROSPERO registry no. CRD42023468154.

Chronic bronchitis


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