Meta-Analysis Confirms Cough Medicine Can Improve Symptoms, Lung Function in AECOPD

A meta-analysis of published literature confirmed that N-aceteylcysteine, a cough medication, was effective at improving symptoms and lung function of patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD).

Therapy that incorporates N-aceteylcysteine (NAC), a cough medication sometimes used as a remedy for acetaminophen overdose, was found to improve symptoms and lung function in patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD), according to a meta-analysis.

The analysis, published in Annals of Palliative Medicine, provides insight into the limited number of studies that have evaluated the effects of NAC therapy in patients with AECOPD, which has not been extensively explored and has only been conducted with small sample sizes.

“All in all, the results of this study can provide a reliable theoretical basis for the clinical treatment of AECOPD, so that patients can benefit from NAC treatment,” wrote the investigators from Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, and Chinese Academy of Sciences Sichuan Translational Medicine Research Hospital.

Patients with COPD develop acute exacerbations 0.5 to 3.5 times annually. AECOPD is generally caused by oxidative stress; however, treating the condition with antioxidant therapy could lead to decreased lung function in patients with AECOPD.

Past research has shown that NAC, an antioxidant with mucus-dissolving properties, is effective at treating respiratory interstitial pulmonary disease. Guidelines from China in 2007 for AECOPD treatment claimed that NAC can both reduce AECOPD incidence and severity. Long-term multicenter randomized controlled trials are still needed to determine the efficacy of NAC in improving lung function in AECOPD.

The investigators performed a database search of PubMed, Medline, Cochrane Library, Chinese Biomedical Literature Database, China National Knowledge Infrastructure, Wanfang, Weipu, Google Scholar, and others for literature that pertained to NAC treatment of AECOPD, published from their initiation through November 25, 2020. The studies had to be randomized controlled experiments written in Chinese or English that included an AECOPD diagnosis in line with Chinese guidelines and a pathological control analysis with an index comparison.

After identifying 1281 potential studies and excluding ineligible papers and duplicates, 15 articles were included in the final analysis. Nine studies were considered good quality and had a low risk of bias, and the remaining 6 studies were determined to be of low quality and had a high risk of bias. Twelve studies were retrospective analyses, and 3 were randomized controlled trials. Overall, data on 1605 patients were analyzed, and the study sample sizes ranged from 72 to 146 patients.

The improvement rate was examined for 8 experiments, comprising 905 cases, 451 of which were in the experimental group and 454 in the control group. The results of the meta-analysis demonstrated a risk rate of 1.09 (95% CI, 1.04-1.14; P < .0001). Additionally, the investigators determined that the research accuracy was high and that the risk of publication bias was low.

Ten experiments analyzed forced expiratory volume in 1 second (FEV1), totaling 1049 cases, with 525 in the experimental group and 524 in the control group. The meta-analysis revealed that FEV1 was significantly higher in the experimental group compared with the control group, producing a mean difference of 30.63 (95% CI, 25.48-35.78; P < .0001). The research accuracy was determined to be high, and there was no risk of publication bias.

FEV1 and forced vital capacity (FEV1/FVC) were analyzed in 6 experiments that consisted of 697 cases, of which 347 were in the experimental group and 350 were in the control group. The meta-analysis showed that the experimental group had a much higher FEV1/FVC than the control group, demonstrating a mean difference of 30.42 (95% CI, 24.00-36.85; P < .0001). The accuracy of the research was high, and no publication bias was detected.

Glutathione sulfur transferase (GSH-ST) was examined in 6 experiments, involving 645 cases, with 323 in the experimental group and 322 in the control group. The meta-analysis results found that GSH-ST activity was significantly greater in the experimental group than the control group. The mean different was 3.10 (95% CI, 1.38-4.82; P = .0004).

In addition to the small sample sizes across the publications, the investigators said that a key limitation of their analysis was that the patients’ conditions, infection control, and nutritional support may have impacted the improvement rate of lung function.


Jiang C, Zou J, Lv Q, Yang Y. Systematic review and meta-analysis of the efficacy of N-acetylcysteine in the treatment of acute exacerbation of chronic obstructive pulmonary disease. Ann Palliat Med. June 2021.10(6):6564-6576. doi: 10.21037/apm-21-1138