碳半胱氨酸对轻中度慢性阻塞性肺病患者病情加重和肺功能的影响：一项多中心、双盲、随机、安慰剂对照试验。

IF 9.2 3区医学 Q1 RESPIRATORY SYSTEM

Archivos De Bronconeumologia Pub Date : 2025-09-01 DOI:10.1016/j.arbres.2025.01.004

Yumin Zhou , Fan Wu , Haiqing Li , Zhishan Deng , Li Lin , Hong Huang , Haiyan Zhao , Yiran Wang , Lingwei Wang , Qijian Cheng , Shan Cai , Zhiyi He , Yinghua Ying , Peiyu Huang , Heshen Tian , Jieqi Peng , Shan Xiao , Xiang Wen , Huajing Yang , Youlan Zhen , Pixin Ran

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引用次数: 0

摘要

目的：在重度至极重度慢性阻塞性肺疾病（COPD）患者中，碳半胱氨酸可在一定程度上减少急性发作频率，改善呼吸道症状。该研究的目的是评估碳半胱氨酸对轻中度COPD患者急性加重率和肺功能的疗效。方法：在这项4期多中心、双盲、随机、安慰剂对照、平行组试验中，我们以2:1的比例随机分配轻度至中度COPD患者接受碳半胱氨酸（500mg，每日3次）或匹配的安慰剂治疗，为期12个月。符合条件的参与者年龄在40-80岁之间。主要结局是12个月试验期间COPD（轻度、中度或重度）加重的年发生率，或使用支气管扩张剂前12个月FEV1与基线的差异。结果：由于COVID-19大流行导致招募慢于预期，估计样本量为732例的招募在539例患者后停止。确实达到了年加重率的样本量，但没有达到肺功能的样本量。在539例患者中，362例随机接受半胱氨酸治疗，177例接受相应的安慰剂治疗。碳半胱氨酸组和安慰剂组COPD加重的年发生率无显著差异(0.39 vs 0.46 /患者/年；相对危险度[RR]， 0.85；95%置信区间[CI]， 0.64-1.13；P = 0.273)。根据现有的样本量，尚未观察到碳半胱氨酸组和安慰剂组在使用支气管扩张剂前12个月FEV1变化的差异(46±12 vs 50±17ml；平均差值6 ml；95% CI, -24 ~ 36；调整P = 0.700)。结论：我们的研究结果表明，碳半胱氨酸可能不会显著降低轻中度COPD患者的年总加重率。研究结果可能被高估了碳半胱氨酸在减少轻中度COPD恶化方面的疗效，以及基线不平衡的潜在混淆。对肺功能的影响尚不能充分评价。临床试验已在chictr.org注册（ChiCTR1800016712）。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

Effect of Carbocysteine on Exacerbations and Lung Function in Patients With Mild-to-Moderate Chronic Obstructive Pulmonary Disease: A Multicentre, Double-Blind, Randomized, Placebo-Controlled Trial

查看原文本刊更多论文

Effect of Carbocysteine on Exacerbations and Lung Function in Patients With Mild-to-Moderate Chronic Obstructive Pulmonary Disease: A Multicentre, Double-Blind, Randomized, Placebo-Controlled Trial

Objectives

Carbocysteine can reduce the frequency of acute exacerbations and improve respiratory symptoms to a certain extent in severe to very severe chronic obstructive pulmonary disease (COPD) patients. The objective of the study was to evaluate the efficacy of carbocysteine on the rate of exacerbations and pulmonary function for mild-to-moderate COPD patients.

Methods

In this phase 4, multicenter, double-blind, randomized, placebo-controlled, parallel-group trial, we randomly assigned mild-to-moderate COPD patients in a 2:1 ratio to treatment with carbocysteine (500 mg, thrice daily) or matched placebo for 12 months. Eligible participants were 40–80 years of age. The coprimary outcomes were the annual rate of exacerbations of COPD (mild, moderate or severe) during the 12-month trial period or the difference in the FEV₁ before bronchodilator use at 12-month from baseline.

Results

Owing to slower-than-anticipated recruitment caused by the COVID-19 pandemic, recruitment of an estimated sample size of 732 patients stopped after 539 patients. The sample size was indeed reached for the annual rate of exacerbations but not for pulmonary function. Among 539 patients, 362 were randomized to receive carbocysteine and 177 to receive matched placebo. There was no significant difference in the annual rate of exacerbations of COPD between carbocysteine group and placebo group (0.39 vs. 0.46 per patient year; relative risk [RR], 0.85; 95% confidence interval [CI], 0.64–1.13; P = 0.273). Based on the available sample size, the difference in the change of FEV₁ before bronchodilator use at 12 months between carbocysteine group and placebo group has not been observed (46 ± 12 vs. 50 ± 17 ml; mean difference, 6 ml; 95% CI, −24 to 36; adjusted P = 0.700).

Conclusions

Our findings suggested that carbocysteine might not significantly reduce the annual rate of total exacerbations in patients with mild-to-moderate COPD. The findings may have been compromised by an overestimation of the efficacy of carbocysteine on reducing exacerbations in mild-to-moderate COPD and potential confounding by baseline imbalances. The efficacy on lung function could not be adequately evaluated.

Clinical trial registered with Chictr.org.cn (ChiCTR1800016712).

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来源期刊

Archivos De Bronconeumologia Medicine-Pulmonary and Respiratory Medicine

CiteScore

3.50

自引率

17.50%

发文量

330

审稿时长

14 days

期刊介绍： Archivos de Bronconeumologia is a scientific journal that specializes in publishing prospective original research articles focusing on various aspects of respiratory diseases, including epidemiology, pathophysiology, clinical practice, surgery, and basic investigation. Additionally, the journal features other types of articles such as reviews, editorials, special articles of interest to the society and editorial board, scientific letters, letters to the editor, and clinical images. Published monthly, the journal comprises 12 regular issues along with occasional supplements containing articles from different sections. All manuscripts submitted to the journal undergo rigorous evaluation by the editors and are subjected to expert peer review. The editorial team, led by the Editor and/or an Associate Editor, manages the peer-review process. Archivos de Bronconeumologia is published monthly in English, facilitating broad dissemination of the latest research findings in the field.