University of Edinburgh/MRC Centre for Inflammation Research, Queen's Medical Research Institute, Edinburgh, UK.
Tayside Respiratory Research Group, Ninewells Hospital and Medical School, Dundee, UK.
Lancet Respir Med. 2014 Jun;2(6):455-63. doi: 10.1016/S2213-2600(14)70050-5. Epub 2014 Mar 24.
Bronchiectasis is characterised by chronic cough, sputum production, and recurrent chest infections. Pathogenesis is poorly understood, but excess neutrophilic airway inflammation is seen. Accumulating evidence suggests that statins have pleiotropic effects; therefore, these drugs could be a potential anti-inflammatory treatment for patients with bronchiectasis. We did a proof-of-concept randomised controlled trial to establish if atorvastatin could reduce cough in patients with bronchiectasis.
Patients aged 18-79 years were recruited from a secondary-care clinic in Edinburgh, UK. Participants had clinically significant bronchiectasis (ie, cough and sputum production when clinically stable) confirmed by chest CT and two or more chest infections in the preceding year. Individuals were randomly allocated to receive either high-dose atorvastatin (80 mg) or a placebo, given orally once a day for 6 months. Sequence generation was done with a block randomisation of four. Random allocation was masked to study investigators and patients. The primary endpoint was reduction in cough from baseline to 6 months, measured by the Leicester Cough Questionnaire (LCQ) score, with a lower score indicating a more severe cough (minimum clinically important difference, 1·3 units). Analysis was done by intention-to-treat. The trial is registered with ClinicalTrials.gov, number NCT01299181.
Between June 23, 2011, and Jan 30, 2011, 82 patients were screened for inclusion in the study and 22 were excluded before randomisation. 30 individuals were assigned atorvastatin and 30 were allocated placebo. The change from baseline to 6 months in LCQ score differed between groups, with a mean change of 1·5 units in patients allocated atorvastatin versus -0·7 units in those assigned placebo (mean difference 2·2, 95% CI 0·5-3·9; p=0·01). 12 (40%) of 30 patients in the atorvastatin group improved by 1·3 units or more on the LCQ compared with five (17%) of 30 in the placebo group (difference 23%, 95% CI 1-45; p=0·04). Ten (33%) patients assigned atorvastatin had an adverse event versus three (10%) allocated placebo (difference 23%, 95% CI 3-43; p=0·02). No serious adverse events were recorded.
6 months of atorvastatin improved cough on a quality-of-life scale in patients with bronchiectasis. Multicentre studies are now needed to assess whether long-term statin treatment can reduce exacerbations.
Chief Scientist's Office.
支气管扩张症的特征是慢性咳嗽、咳痰和反复的胸部感染。发病机制尚不清楚，但可见过度的中性粒细胞气道炎症。越来越多的证据表明他汀类药物具有多效性作用；因此，这些药物可能是支气管扩张症患者潜在的抗炎治疗方法。我们进行了一项概念验证随机对照试验，以确定阿托伐他汀是否可以减少支气管扩张症患者的咳嗽。
从英国爱丁堡的一家二级保健诊所招募了年龄在 18-79 岁之间的患者。参与者有临床意义的支气管扩张症（即，临床稳定时咳嗽和咳痰），通过胸部 CT 证实，并且在前一年中有两次或两次以上的胸部感染。个体被随机分配接受高剂量阿托伐他汀（80mg）或安慰剂，每天口服一次，持续 6 个月。序列生成采用 4 个块随机化。随机分配对研究调查人员和患者进行了屏蔽。主要终点是通过莱斯特咳嗽问卷（LCQ）评分从基线到 6 个月的咳嗽减少，得分越低表示咳嗽越严重（最小临床重要差异，1.3 单位）。分析采用意向治疗。该试验在 ClinicalTrials.gov 上注册，编号为 NCT01299181。
在 2011 年 6 月 23 日至 2011 年 1 月 30 日之间，对 82 名患者进行了筛查以纳入研究，其中 22 名患者在随机分组前被排除在外。30 名患者接受了阿托伐他汀治疗，30 名患者接受了安慰剂治疗。接受阿托伐他汀治疗的患者与接受安慰剂治疗的患者相比，从基线到 6 个月时 LCQ 评分的变化不同，阿托伐他汀组的平均变化为 1.5 个单位，而安慰剂组的平均变化为 0.7 个单位（平均差异 2.2，95%CI 0.5-3.9；p=0.01）。在 LCQ 上改善 1.3 个单位或更多的阿托伐他汀组患者有 12 名（40%），而安慰剂组患者有 5 名（17%）（差异 23%，95%CI 1-45；p=0.04）。接受阿托伐他汀治疗的 10 名（33%）患者发生不良事件，而接受安慰剂治疗的 3 名（10%）患者发生不良事件（差异 23%，95%CI 3-43；p=0.02）。没有记录到严重不良事件。
6 个月的阿托伐他汀治疗改善了支气管扩张症患者的生活质量咳嗽。现在需要进行多中心研究，以评估长期他汀类药物治疗是否可以减少恶化。
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