McGarvey Lorcan, Morice Alyn H, Smith Jaclyn A, Birring Surinder S, Chuecos Ferran, Seoane Beatriz, Jarreta Diana
Centre for Infection and Immunity, Queen's University Belfast , Belfast , UK.
Hull York Medical School, University of Hull, Castle Hill Hospital , Cottingham , UK.
BMJ Open Respir Res. 2016 Dec 8;3(1):e000148. doi: 10.1136/bmjresp-2016-000148. eCollection 2016.
Cough and sputum are troublesome symptoms in chronic obstructive pulmonary disease (COPD) and are associated with adverse outcomes. The efficacy of aclidinium bromide 400 µg twice daily in patients with stable COPD has been established in two phase III studies (ACCORD COPD I and ATTAIN) and a phase IIIb active-comparator study. This analysis evaluated cough-related symptoms across these studies.
Patients were randomised to placebo, aclidinium 200 µg or 400 µg twice daily in ACCORD (12 weeks) and ATTAIN (24 weeks), or to placebo, aclidinium 400 µg twice daily or tiotropium 18 µg once daily (6-week active-comparator study). Analysed end points included changes from baseline in Evaluating Respiratory Symptoms (E-RS; formerly known as EXAcerbations of Chronic pulmonary disease Tool), total and cough/sputum scores and frequency/severity of morning and night-time cough and sputum symptoms.
Data for 1792 patients were evaluated. E-RS cough/sputum domain scores were significantly reduced with aclidinium 400 µg versus placebo in ATTAIN (-0.7 vs -0.3, respectively; p<0.01) and the active-comparator study (-0.6 vs -0.2, respectively; p<0.01). In the active-comparator study, significantly greater improvements were observed with aclidinium versus placebo for severity of morning cough (-0.19 vs -0.02; p<0.01) and phlegm (-0.19 vs -0.02; p<0.05). In ACCORD, aclidinium reduced night-time cough frequency (-0.36 vs 0.1 for placebo; p<0.001) and severity (-0.24 vs -0.1 for placebo; p<0.05), and frequency of night-time sputum production (-0.37 vs 0.05 for placebo; p<0.001).
Aclidinium 400 µg twice daily improves cough and sputum expectoration versus placebo in stable COPD.
NCT00891462; NCT01001494; NCT01462929.
咳嗽和咳痰是慢性阻塞性肺疾病（COPD）中令人困扰的症状，且与不良预后相关。在两项III期研究（ACCORD COPD I和ATTAIN）以及一项IIIb期活性药物对照研究中，已证实每日两次吸入400μg阿地溴铵对稳定期COPD患者的疗效。本分析评估了这些研究中与咳嗽相关的症状。
在ACCORD研究（12周）和ATTAIN研究（24周）中，患者被随机分配至安慰剂组、每日两次吸入200μg或400μg阿地溴铵组；在一项为期6周的活性药物对照研究中，患者被随机分配至安慰剂组、每日两次吸入400μg阿地溴铵组或每日一次吸入18μg噻托溴铵组。分析的终点包括评估呼吸症状（E-RS，前身为慢性肺病急性加重工具）自基线的变化、总分以及咳嗽/咳痰评分，以及早晚咳嗽和咳痰症状的频率/严重程度。
对1792例患者的数据进行了评估。在ATTAIN研究中，与安慰剂相比，每日两次吸入400μg阿地溴铵可显著降低E-RS咳嗽/咳痰领域评分（分别为-0.7和-0.3；p<0.01），在活性药物对照研究中也是如此（分别为-0.6和-0.2；p<0.01）。在活性药物对照研究中，与安慰剂相比，阿地溴铵在改善晨咳严重程度（-0.19比-0.02；p<0.01）和痰液（-0.19比-0.02；p<0.05）方面有更显著的改善。在ACCORD研究中，阿地溴铵降低了夜间咳嗽频率（安慰剂组为0.1，阿地溴铵组为-0.36；p<0.001）和严重程度（安慰剂组为-0.1，阿地溴铵组为-0.24；p<0.05），以及夜间咳痰频率（安慰剂组为0.05，阿地溴铵组为-0.37；p<0.001）。
对于稳定期COPD患者，每日两次吸入400μg阿地溴铵较安慰剂可改善咳嗽和痰液咳出情况。
NCT00891462；NCT01001494；NCT01462929。
