Evaluation of high dose N- Acetylcysteine on airway inflammation and quality of life outcomes in adults with bronchiectasis: A randomised placebo-controlled pilot study

IF 3.3 3区 医学 Q2 PHARMACOLOGY & PHARMACY
L. Jayaram, P.T. King, J. Hunt, M. Lim, C. Park, E. Hu, L. Dousha, P. Ha, J.B. Bartlett, Southcott Am, S. Muruganandan, S. Vogrin, M.A. Rees, O.M. Dean, C.A. Wong
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引用次数: 0

Abstract

Background

High dose N acetylcysteine (NAC), a mucolytic, anti-inflammatory and antioxidant agent has been shown to significantly reduce exacerbations, and improve quality of life in placebo controlled, double blind randomised (RCT) studies in patients with COPD, and in an open, randomised study in bronchiectasis. In this pilot, randomised, double-blind, placebo-controlled study, we wished to investigate the feasibility of a larger clinical trial, and the anti-inflammatory and clinical benefits of high dose NAC in bronchiectasis.

Aims

Primary outcome: to assess the efficacy of NAC 2400 mg/day at 6 weeks on sputum neutrophil elastase (NE), a surrogate marker for exacerbations. Secondary aims included assessing the efficacy of NAC on sputum MUC5B, IL-8, lung function, quality of life, and adverse effects.

Methods

Participants were randomised to receive 2400 mg or placebo for 6 weeks. They underwent 3 visits: at baseline, week 3 and week 6 where clinical and sputum measurements were assessed.

Results

The study was stopped early due to the COVID pandemic. In total 24/30 patients were recruited, of which 17 completed all aspects of the study. Given this, a per protocol analysis was undertaken: NAC (n = 9) vs placebo (n = 8): mean age 72 vs 62 years; male gender: 44% vs 50%; baseline median FEV11.56 L (mean 71.5 % predicted) vs 2.29L (mean 82.2% predicted). At 6 weeks, sputum NE fell by 47% in the NAC group relative to placebo (mean fold difference (95%CI: 0.53 (0.12,2.42); MUC5B increased by 48% with NAC compared with placebo. Lung function, FVC improved significantly with NAC compared with placebo at 6 weeks (mean fold difference (95%CI): 1.10 (1.00, 1.20), p = 0.045. Bronchiectasis Quality of life measures within the respiratory and social functioning domains demonstrated clinically meaningful improvements, with social functioning reaching statistical significance. Adverse effects were similar in both groups.

Conclusion

High dose NAC exhibits anti-inflammatory benefits, and improvements in aspects of quality of life and lung function measures. It is safe and well tolerated. Further larger placebo controlled RCT's are now warranted examining its role in reducing exacerbations.

评估大剂量 N-乙酰半胱氨酸对成人支气管扩张症患者气道炎症和生活质量的影响:随机安慰剂对照试验研究
背景高剂量N乙酰半胱氨酸(NAC)是一种粘液溶解剂、抗炎剂和抗氧化剂,在慢性阻塞性肺疾病患者的安慰剂对照、双盲随机(RCT)研究和支气管扩张症的开放随机研究中,NAC已被证明可显著减少病情恶化和改善生活质量。在这项试验性、随机、双盲、安慰剂对照研究中,我们希望调查更大规模临床试验的可行性,以及大剂量 NAC 对支气管扩张症的抗炎和临床疗效。次要目标包括评估 NAC 对痰 MUC5B、IL-8、肺功能、生活质量和不良反应的疗效。结果由于 COVID 大流行,研究提前结束。共招募了 24/30 名患者,其中 17 人完成了所有研究内容。有鉴于此,我们按方案进行了分析:NAC(n = 9)与安慰剂(n = 8):平均年龄 72 岁 vs 62 岁;性别为男性:44%对50%;基线中位 FEV11.56 升(平均预测值为 71.5%)对 2.29 升(平均预测值为 82.2%)。6周时,NAC组的痰NE相对于安慰剂下降了47%(平均倍差(95%CI:0.53 (0.12,2.42));与安慰剂相比,NAC组的MUC5B增加了48%。肺功能方面,与安慰剂相比,NAC治疗6周后FVC明显改善(平均折叠差异(95%CI):1.10(1.00,1.20),P = 0.045)。支气管扩张症患者在呼吸和社会功能领域的生活质量测量结果显示出有临床意义的改善,其中社会功能达到统计学意义。结论高剂量 NAC 具有抗炎、改善生活质量和肺功能指标的作用。该疗法安全且耐受性良好。现在有必要进一步开展更大规模的安慰剂对照 RCT 研究,探讨其在减少病情恶化方面的作用。
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来源期刊
CiteScore
6.20
自引率
0.00%
发文量
41
审稿时长
42 days
期刊介绍: Pulmonary Pharmacology and Therapeutics (formerly Pulmonary Pharmacology) is concerned with lung pharmacology from molecular to clinical aspects. The subject matter encompasses the major diseases of the lung including asthma, cystic fibrosis, pulmonary circulation, ARDS, carcinoma, bronchitis, emphysema and drug delivery. Laboratory and clinical research on man and animals will be considered including studies related to chemotherapy of cancer, tuberculosis and infection. In addition to original research papers the journal will include review articles and book reviews. Research Areas Include: • All major diseases of the lung • Physiology • Pathology • Drug delivery • Metabolism • Pulmonary Toxicology.
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