Effect of high-dose N-acetylcysteine on exacerbations and lung function in patients with mild-to-moderate COPD: a double-blind, parallel group, multicentre randomised clinical trial

Evidence for the treatment of patients with mild-to-moderate chronic obstructive pulmonary disease (COPD) is limited. The efficacy of N-acetylcysteine (an antioxidant and mucolytic agent) for patients with mild-to-moderate COPD is uncertain. In this multicentre, randomised, double-blind, placebo-controlled trial, we randomly assigned 968 patients with mild-to-moderate COPD to treatment with N-acetylcysteine (600 mg, twice daily) or matched placebo for two years. Eligible participants were 40-80 years of age and had mild-to-moderate COPD (forced expiratory volume in 1 second [FEV<sub>1</sub>] to forced vital capacity ratio <0.70 and an FEV<sub>1</sub> ≥ 50% predicted value after bronchodilator use). The coprimary outcomes were the annual rate of total exacerbations and the between-group difference in the change from baseline to 24 months in FEV<sub>1</sub> before bronchodilator use. COPD exacerbation was defined as the appearance or worsening of at least two major symptoms (cough, expectoration, purulent sputum, wheezing, or dyspnoea) persisting for at least 48 hours. Assessment of exacerbations was conducted every three months, and lung function was performed annually after enrolment. The difference between the N-acetylcysteine group and the placebo group in the annual rate of total exacerbation were not significant (0.65 vs. 0.72 per patient-year; relative risk [RR], 0.90; 95% confidence interval [CI], 0.80-1.02; P = 0.10). There was no significant difference in FEV<sub>1</sub> before bronchodilator use at 24 months. Long-term treatment with high-dose N-acetylcysteine neither significantly reduced the annual rate of total exacerbations nor improved lung function in patients with mild-to-moderate COPD. Chinese Clinical Trial Registration: ChiCTR-IIR-17012604.

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Journal
Nature Communications
Published
2024-09-30
DOI
https://doi.org/10.1038/s41467-024-51079-1
Citations
32
Primary Topic
Chronic Obstructive Pulmonary Disease (COPD) Research
Type
article
Field-Weighted Citation Impact
13.41
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article

Effect of high-dose N-acetylcysteine on exacerbations and lung function in patients with mild-to-moderate COPD: a double-blind, parallel group, multicentre randomised clinical trial

Yumin Zhou, Zanfeng Wang, Dongxing Zhao, Yinghua Ying et al.
32 citations
Nature Communications
Chronic Obstructive Pulmonary Disease (COPD) Research
13.41
article

Effect of high-dose N-acetylcysteine on exacerbations and lung function in patients with mild-to-moderate COPD: a double-blind, parallel group, multicentre randomised clinical trial

Yumin Zhou, Zanfeng Wang, Dongxing Zhao, Yinghua Ying, Weimin Yao, Zhiyi He, Ling Su, Peiyu Huang, Zhou Yong, Liping Wei, Heshen Tian, Huilan Zhang, Yanfan Chen, Yongshui Fu, Weiguang Lai, Zhishan Deng, Jianping Gui, Changli Yang, Xiangwen Luo, Jia Tian, Pixin Ran, Guoping Hu, Fan Wu, Cong Liu, Jianhui Huang, Jie Cao, Shan Cai, Nanshan Zhong, Shen Yao, Ziwen Zhao, Shengming Liu, Haiyan Zhao, Zhe Shi, Chun Chang, Fenglei Li, Yongliang Jiang, Yunzhen Zhang, Zhiguang Liu, Qijian Cheng, Shuqing Yu, Shujing Chen
article en
32 citations

Abstract

Evidence for the treatment of patients with mild-to-moderate chronic obstructive pulmonary disease (COPD) is limited. The efficacy of N-acetylcysteine (an antioxidant and mucolytic agent) for patients with mild-to-moderate COPD is uncertain. In this multicentre, randomised, double-blind, placebo-controlled trial, we randomly assigned 968 patients with mild-to-moderate COPD to treatment with N-acetylcysteine (600 mg, twice daily) or matched placebo for two years. Eligible participants were 40-80 years of age and had mild-to-moderate COPD (forced expiratory volume in 1 second [FEV<sub>1</sub>] to forced vital capacity ratio <0.70 and an FEV<sub>1</sub> ≥ 50% predicted value after bronchodilator use). The coprimary outcomes were the annual rate of total exacerbations and the between-group difference in the change from baseline to 24 months in FEV<sub>1</sub> before bronchodilator use. COPD exacerbation was defined as the appearance or worsening of at least two major symptoms (cough, expectoration, purulent sputum, wheezing, or dyspnoea) persisting for at least 48 hours. Assessment of exacerbations was conducted every three months, and lung function was performed annually after enrolment. The difference between the N-acetylcysteine group and the placebo group in the annual rate of total exacerbation were not significant (0.65 vs. 0.72 per patient-year; relative risk [RR], 0.90; 95% confidence interval [CI], 0.80-1.02; P = 0.10). There was no significant difference in FEV<sub>1</sub> before bronchodilator use at 24 months. Long-term treatment with high-dose N-acetylcysteine neither significantly reduced the annual rate of total exacerbations nor improved lung function in patients with mild-to-moderate COPD. Chinese Clinical Trial Registration: ChiCTR-IIR-17012604.

Nature CommunicationsVol. 15(1)
Central South University (CN), Guangdong Medical College (CN), Shanghai Jiao Tong University (CN), Peking University (CN), Fudan University (CN), Wenzhou Medical University (CN), Ruijin Hospital (CN), First Affiliated Hospital of Wenzhou Medical University (CN), Sir Run Run Shaw Hospital (CN), Tianjin Medical University General Hospital (CN), Second Affiliated Hospital of Guangzhou Medical University (CN), Third Affiliated Hospital of Guangzhou Medical University (CN), First Affiliated Hospital of Guangzhou Medical University (CN), Guangzhou Liwan District Traditional Chinese Medicine Hospital (CN), Second People Hospital of Hunan (CN), ShenZhen People’s Hospital (CN), Guangzhou Regenerative Medicine and Health Guangdong Laboratory (CN), Guangzhou First People's Hospital (CN), First Affiliated Hospital of GuangXi Medical University (CN), Zhongshan Hospital (CN), Pudong Medical Center (CN), County Hospital (GB), Huizhou Central People's Hospital (CN), First Hospital of China Medical University (CN), Peking University Third Hospital (CN), Hunan Provincial People's Hospital (CN), Second Xiangya Hospital of Central South University (CN), Second Affiliated Hospital of Zhejiang University (CN), Tongji Hospital (CN), First Affiliated Hospital of Jinan University (CN), Huazhong University of Science and Technology (CN), Zhejiang University (CN), China Medical University (CN), Guangzhou Medical University (CN)
Good health and well-being
Openalex Percentile: Top 1%
Chronic Obstructive Pulmonary Disease (COPD) Research
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