【翻译】尝试翻译钟南山最近发表在柳叶刀呼吸疾病杂志的文章

原文： http://d.dxy.cn/detail/6304214
摘要： http://chest.dxy.cn/article/72971
【Introduction】
COPD is characterised by persistent air? ow limitation and frequent recurrent acute exacerbations that contribute to disease severity in individual patients.COPD with acute exacerbations results in a faster decline in lung function,
impairment of health status,reduction in exercise tolerance, and high economic burden, leading to substantial rates of hospital admission, readmission and mortality. Therefore, e?ective prevention and treatment of exacerbations has
been strongly recommended by the Global Initiative for Chronic Obstructive Lung Disease (GOLD).Many factors are involved in the pathophysiology of COPD, such as mucus hypersecretion, oxidative stress, and in? ammation of the airways and lungs. Thus, drugs that have antioxidative and anti-in? ammatory properties, and mucolytic activity, might be e? ective for treatment of COPD.
N-acetylcysteine is a well-known, e? ective mucolyticdrug that reduces sputum viscosity and elasticity improves mucociliary clearance and modulates the in?ammatory response. Furthermore, N-acetylcysteine has both direct and indirect antioxidant properties, which have been extensively assessed in in-vitro and in-vivo studies, and might be important for the long-term management of patients with COPD. Previous studies showed that treatment with
N-acetylcysteine (400–1200 mg per day) reduced rates of acute COPD exacerbations and hospital readmissions.
Nevertheless, these studies were not recognised as strong evidence because of limitations in their design, such as
small sample sizes, absence of double-blinding and placebo controls, or a short study duration. Moreover
inconsistent results have been reported. In the BRONCUS study, 523 patients with moderate-to-severe
COPD were treated with N-acetylcysteine (600 mg per day) for 3 years; compared with placebo, active
treatment did not signi? cantly reduce the exacerbation rate, apart from in patients not concomitantly treated
with inhaled corticosteroids. Schermer and colleagues reported that exacerbation rates did not reduce signi? cantly in a trial of 286 patients with COPD or chronic bronchitis who were treated with twice daily inhaled ? uticasone propionate 500 μg, once daily oral N-acetylcysteine 600 mg, or placebo for 3 years. For these reasons, N-acetylcysteine is not widely used in patients with COPD.
Because a dose-e? ect association of N-acetylcysteine has been shown, we postulated that an increased dose of N-acetylcysteine might achieve improved outcomes. We aimed to assess whether long-term treatment with
high-dose N-acetylcysteine could reduce COPD exacerbation rates, and whether the bene? ts of treatment
would be apparent with and without concomitant treatment with inhaled corticosteroids.
【介绍】
COPD是一种以气流持续受限且频发急性加重的疾病，而后者有助于区分病情严重程度。COPD患者发生急性加重，可导致肺功能下降地更快，健康状况受损，运动耐受能力下降，还需要更高的医药费，导致住院率、再住院率、死亡率增加。所以GOLD强烈推荐有效的预防和治疗COPD急性加重的措施。
很多因素与COPD的病理生理有关，比如黏液分泌增多、氧化应激、气道和肺部炎症。因此，有抗氧化和抗炎特性，且有黏液溶解活性的药物或许对COPD的治疗有效。
N-乙酰半胱氨酸是一个广为人知的、有效的黏液溶解剂，能够减少痰液的粘稠性和破坏其弹性，从而增强黏膜纤毛清除力和调节炎症反应。此外，大量体外、体内试验已经评估证明了N-乙酰半胱氨酸具有直接和间接的抗氧化能力，这可能对于COPD的长期治疗管理是很有帮助的。
既往研究显示，N-乙酰半胱氨酸（400-1200mg/天）能够减少COPD的急性加重率和再入院率。然而，人们认为这些研究结果不能作为强证据，因为这些研究设计不够完善，比如样本量小、没有双盲、没有对照安慰剂组，或者研究时程短。此外，这些研究结果并不一致。在BRONCUS研究里，523名中-重度的COPD患者接受N-乙酰半胱氨酸治疗3年（600mg/天）；与安慰剂组相比，除了那些没有同时吸入激素治疗的患者，试验组并没有显著降低COPD急性加重率。Schermer及其同事报道，在一项长达3年、含有286名COPD或慢性支气管炎患者的试验中，两组均给予吸入氟替卡松（500μg/次，2次/天）治疗，其中一组额外口服N-乙酰半胱胺酸（600mg/天），另一组用安慰剂，试验组的急性加重率下降并不明显。基于这些研究结果，N-乙酰半胱胺酸在COPD患者上用的并不广泛。
由于发现了N-乙酰半胱胺酸的剂量-效应关系，我们设想增大N-乙酰半胱胺酸的剂量或许会提高治疗效应。我们旨在评估高剂量N-乙酰半胱胺酸是否能够减少COPD急性加重率，在联合（或不联合）吸入激素治疗的前提下从N-乙酰半胱胺酸治疗中获益是否明显。