Make Barry, Hanania Nicola A, ZuWallack Richard, Kalberg Christopher, Emmett Amanda, Brown Christy P, Knobil Katharine
National Jewish Medical and Research Center, Denver, Colorado 80206, USA.
Clin Ther. 2005 May;27(5):531-42. doi: 10.1016/j.clinthera.2005.05.009.
The pathology of chronic obstructive pulmonary disease (COPD) includes both obstructive and inflammatory components.
The aim of this study was to confirm the findings of a previous study that compared the efficacy of a combination of 2 short-acting bronchodilators with the use of an inhaled corticosteroid and a long-acting beta-agonist in the treatment of COPD.
We conducted an 8-week, multicenter, randomized, double-blind, double-dummy, parallel-group study of subjects with moderate to severe COPD to compare fluticasone propionate/salmeterol 250/50 microg BID (FSC) with ipratropium/albuterol 36/206 microg QID (IB/ALB). The primary efficacy measure was morning preadministration forced expiratory volume in 1 second (FEV(1)). Secondary measures were morning peak expiratory flow (PEF), 6-hour FEV(1) AUC, percentage of symptom-free nights, Transition Dyspnea Index (TDI) score, and overall daytime symptom score. Additional measures included sleep symptoms, supplemental albuterol use, and nighttime awakenings due to respiratory symptoms. Safety evaluations were based on clinical adverse events and COPD exacerbations.
Baseline characteristics were similar between the FSC (n = 180) and IB/ALB (n = 181) groups, including mean age (63.7 and 65.4 years, respectively), mean body weight (81 and 79 kg, respectively), screening pulmonary function (mean [SD], 43.7% [14.2%] and 41.6% [13.4%] of predicted FEV(1)), race (82% and 91% white), and sex (64% and 62% male). FSC resulted in greater improvements in morning preadministration FEV(1), morning PEF, and 6-hour FEV(1) AUC (all, P < 0.001), TDI score (P = 0.026), overall daytime symptom score (P = 0.024), percentage of symptom-free nights (P = 0.010), nighttime awakenings due to respiratory symptoms (P = 0.002), sleep symptom score (P = 0.003), and percentage of days and nights without rescue albuterol use compared with IB/ALB (P = 0.021 and P < 0.001, respectively). Compared with day 1, the FEV(1) AUC at week 8 increased by 0.38 L-h with FSC and decreased by 0.18 L-h with IB/ALB (P < 0.001 between groups). The type and incidence of adverse events were similar between the 2 groups. One or more adverse event was reported for 81 (45%) and 85 (47%) subjects in the FSC and IB/ALB groups, respectively.
In this 8-week study, subjects with moderate to severe COPD experienced greater improvements in lung function and symptom measures with FSC than with IB/ALB.
慢性阻塞性肺疾病（COPD）的病理包括阻塞性和炎症性成分。
本研究旨在证实先前一项研究的结果，该研究比较了两种短效支气管扩张剂联合使用与吸入性糖皮质激素和长效β受体激动剂治疗COPD的疗效。
我们对中重度COPD患者进行了一项为期8周的多中心、随机、双盲、双模拟、平行组研究，比较丙酸氟替卡松/沙美特罗250/50微克每日两次（FSC）与异丙托溴铵/沙丁胺醇36/206微克每日四次（IB/ALB）。主要疗效指标是晨起给药前1秒用力呼气容积（FEV₁）。次要指标包括晨起呼气峰值流速（PEF）、6小时FEV₁曲线下面积（AUC）、无症状夜晚的百分比、过渡性呼吸困难指数（TDI）评分和总体日间症状评分。其他指标包括睡眠症状、沙丁胺醇补充使用情况以及因呼吸道症状导致的夜间觉醒。安全性评估基于临床不良事件和COPD急性加重情况。
FSC组（n = 180）和IB/ALB组（n = 181）的基线特征相似，包括平均年龄（分别为63.7岁和65.4岁）、平均体重（分别为81千克和79千克）、筛查时的肺功能（预测FEV₁的均值[标准差]，分别为43.7%[14.2%]和41.6%[13.4%]）、种族（82%和91%为白人）以及性别（64%和62%为男性）。与IB/ALB相比，FSC在晨起给药前FEV₁、晨起PEF和6小时FEV₁ AUC方面有更大改善（均P < 0.001），TDI评分（P = 0.026）、总体日间症状评分（P = 0.024）、无症状夜晚的百分比（P = 0.010）、因呼吸道症状导致的夜间觉醒（P = 0.002）、睡眠症状评分（P = 0.003）以及未使用急救沙丁胺醇的日夜百分比（分别为P = 0.021和P < 0.001）。与第1天相比，第8周时FSC组的FEV₁ AUC增加了0.38升·小时，而IB/ALB组减少了0.18升·小时（两组间P < 0.001）。两组不良事件的类型和发生率相似。FSC组和IB/ALB组分别有81名（45%）和85名（47%）受试者报告了一项或多项不良事件。
在这项为期8周的研究中，中重度COPD患者使用FSC比使用IB/ALB在肺功能和症状指标方面有更大改善。
