David Geffen School of Medicine at UCLA, 37-131 Center for Health Sciences, 10833 Le Conte Avenue, Los Angeles, CA 90095, USA.
Pulm Pharmacol Ther. 2011 Feb;24(1):147-52. doi: 10.1016/j.pupt.2010.07.003. Epub 2010 Jul 24.
A recent randomized, double-blind, parallel-group, active-controlled, multicenter study of 255 patients ≥ 40 years of age with chronic obstructive pulmonary disease (COPD) showed that combined formoterol (FOR) and tiotropium (TIO) treatment in patients with COPD significantly improved lung function as well as symptoms and other patient-reported outcomes compared with TIO alone. FOR and TIO are long-acting bronchodilators that represent the β₂-adrenergic agonist and anticholinergic classes, respectively. However, the possible influence of smoking status, inhaled corticosteroid (ICS) use, baseline disease severity, and gender differences on bronchodilator efficacy requires further investigation. Using data from the previously published study mentioned above, a post hoc analysis was performed to examine the efficacy of combined FOR + TIO treatment compared with TIO monotherapy in subgroup analyses of men and women, current and ex-smokers, ICS users and non-ICS users, and patients with moderate and severe/very severe COPD. Efficacy comparisons were based on the changes in forced expiratory volume in 1 s measured 0-4 h after the morning dose (FEV₁ AUC₀₋₄h). After a run-in period, patients were treated for 12 weeks with either FOR 12 μg twice daily (BID) plus TIO 18 μg once daily (QD) in the morning (AM, n = 124) or with FOR placebo BID plus TIO 18 μg QD AM (n = 131). The least squares mean change from baseline in the normalized FEV₁ AUC₀₋₄h was assessed using analysis of covariance. With the exception of treatment differences at week 4 in smokers and subjects with "very severe" COPD, and at weeks 4, 8, and 12 for ICS users and non-ICS users (p values not determined), FOR + TIO was significantly superior (P < 0.05) to TIO alone at all time points (weeks 4, 8, 12, and endpoint), regardless of gender, smoking status, ICS use, or COPD severity. We conclude that coadministered FOR + TIO significantly improves lung function compared with TIO treatment alone in COPD patients regardless of differences in patient subgroups.
一项最近的、随机的、双盲的、平行组、阳性对照、多中心研究纳入了 255 例年龄≥40 岁的慢性阻塞性肺疾病（COPD）患者，结果显示，与单独应用噻托溴铵（TIO）相比，COPD 患者中联合应用福莫特罗（FOR）和噻托溴铵（TIO）治疗可显著改善肺功能以及症状和其他患者报告的结局。FOR 和 TIO 分别是长效支气管扩张剂，代表β₂-肾上腺素能激动剂和抗胆碱能药物类别。然而，吸烟状态、吸入性皮质类固醇（ICS）的使用、基线疾病严重程度以及性别差异对支气管扩张剂疗效的可能影响仍需要进一步研究。本研究使用了先前发表的研究数据，进行了一项事后分析，以检查与 TIO 单药治疗相比，FOR + TIO 联合治疗在男性和女性、当前吸烟者和既往吸烟者、ICS 使用者和非 ICS 使用者以及中重度/极重度 COPD 患者亚组分析中的疗效。疗效比较基于清晨剂量后 0-4 小时测量的用力呼气量 1 秒（FEV₁ AUC₀₋₄h）的变化。在导入期后，患者接受为期 12 周的治疗，其中 124 例患者接受每日两次 12 μg 福莫特罗（BID）加每日一次 18 μg 噻托溴铵（QD）（早晨，n = 124），131 例患者接受每日两次 12 μg 福莫特罗安慰剂（BID）加每日一次 18 μg 噻托溴铵 QD（早晨，n = 131）。使用协方差分析评估从基线正常化的 FEV₁ AUC₀₋₄h 的最小二乘均值变化。除了吸烟者和“极重度”COPD 患者在第 4 周以及 ICS 使用者和非 ICS 使用者在第 4、8 和 12 周时的治疗差异（未确定 P 值）外，FOR + TIO 在所有时间点（第 4、8、12 周和终点）均显著优于 TIO 单药（P < 0.05），无论性别、吸烟状态、ICS 使用或 COPD 严重程度如何。我们的结论是，无论患者亚组存在差异，与单独应用 TIO 相比，COPD 患者中联合应用 FOR + TIO 可显著改善肺功能。
