高剂量 N-乙酰半胱氨酸治疗稳定期 COPD：为期 1 年的双盲、随机、安慰剂对照 HIACE 研究。
High-dose N-acetylcysteine in stable COPD: the 1-year, double-blind, randomized, placebo-controlled HIACE study.
机构信息
Kwong Wah Hospital, Hong Kong, China.
Medical Department, Innovation & Medical Sciences, Zambon Company SpA, Bresso, Italy.
出版信息
Chest. 2013 Jul;144(1):106-118. doi: 10.1378/chest.12-2357.
BACKGROUND
The mucolytic and antioxidant effects of N-acetylcysteine (NAC) may have great value in COPD treatment. However, beneficial effects have not been confirmed in clinical studies, possibly due to insufficient NAC doses and/or inadequate outcome parameters used. The objective of this study was to investigate high-dose NAC plus usual therapy in Chinese patients with stable COPD.
METHODS
The 1-year HIACE (The Effect of High Dose N-acetylcysteine on Air Trapping and Airway Resistance of Chronic Obstructive Pulmonary Disease-a Double-blinded, Randomized, Placebo-controlled Trial) double-blind trial conducted in Kwong Wah Hospital, Hong Kong, randomized eligible patients aged 50 to 80 years with stable COPD to NAC 600 mg bid or placebo after 4-week run-in. Lung function parameters, symptoms, modified Medical Research Council (mMRC) dyspnea and St. George's Respiratory Questionnaire (SGRQ) scores, 6-min walking distance (6MWD), and exacerbation and admission rates were measured at baseline and every 16 weeks for 1 year.
RESULTS
Of 133 patients screened, 120 were eligible (93.2% men; mean age, 70.8±0.74 years; %FEV1 53.9±2.0%). Baseline characteristics were similar in the two groups. At 1 year, there was a significant improvement in forced expiratory flow 25% to 75% (P=.037) and forced oscillation technique, a significant reduction in exacerbation frequency (0.96 times/y vs 1.71 times/y, P=.019), and a tendency toward reduction in admission rate (0.5 times/y vs 0.8 times/y, P=.196) with NAC vs placebo. There were no significant between-group differences in mMRC dypsnea score, SGRQ score, and 6MWD. No major adverse effects were reported.
CONCLUSION
In this study, 1-year treatment with high-dose NAC resulted in significantly improved small airways function and decreased exacerbation frequency in patients with stable COPD.
TRIAL REGISTRY
ClinicalTrials.gov; No.: NCT01136239; URL: www.clinicaltrials.gov.
背景
N-乙酰半胱氨酸（NAC）的黏液溶解和抗氧化作用在 COPD 治疗中可能具有重要价值。然而，临床研究并未证实其有益效果，这可能是由于 NAC 剂量不足和/或使用的疗效参数不充分所致。本研究旨在探讨高剂量 NAC 联合常规治疗对中国稳定期 COPD 患者的疗效。
方法
这项在香港广华医院进行的为期 1 年的 HIACE（高剂量 N-乙酰半胱氨酸对慢性阻塞性肺疾病空气潴留和气道阻力的影响-一项双盲、随机、安慰剂对照试验）双盲试验，纳入了年龄在 50 至 80 岁之间、稳定期 COPD 患者，经过 4 周的导入期后，将患者随机分为 NAC 600mg，每日 2 次（bid）组或安慰剂组。在基线时和此后的每 16 周，测量肺功能参数、症状、改良的医学研究理事会呼吸困难量表（mMRC）评分和圣乔治呼吸问卷（SGRQ）评分、6 分钟步行距离（6MWD）以及急性加重和住院率。
结果
在筛选的 133 例患者中，有 120 例符合条件（93.2%为男性；平均年龄为 70.8±0.74 岁；FEV1%为 53.9±2.0%）。两组的基线特征相似。在 1 年时，NAC 组用力呼气流量 25%至 75%（P=.037）和强迫振荡技术显著改善，急性加重频率显著降低（0.96 次/年比 1.71 次/年，P=.019），住院率有降低趋势（0.5 次/年比 0.8 次/年，P=.196）。NAC 组与安慰剂组之间在 mMRC 呼吸困难评分、SGRQ 评分和 6MWD 方面无显著差异。两组均未报告重大不良事件。
结论
在这项研究中，稳定期 COPD 患者接受 1 年高剂量 NAC 治疗，可显著改善小气道功能，并降低急性加重频率。
试验注册
ClinicalTrials.gov；编号：NCT01136239；网址：www.clinicaltrials.gov。
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