David Geffen School of Medicine at UCLA, Los Angeles, California 90095, USA.
Adv Ther. 2009 Nov;26(11):1024-34. doi: 10.1007/s12325-009-0080-z. Epub 2009 Dec 2.
The use of one or more long-acting bronchodilators is key in the maintenance therapy of chronic obstructive pulmonary disease (COPD). This analysis pooled the results of two double-blind studies evaluating the efficacy and safety of adding nebulized formoterol fumarate inhalation solution (FFIS) to maintenance tiotropium (TIO) treatment.
Following a run-in period of 7-14 days with once-daily TIO 18 microg, COPD subjects (> or =25% to <65% predicted forced expiratory volume in 1 second [FEV(1)]) were randomized to twice-daily FFIS 20 microg (n=145) or nebulized placebo (PLA, n=140) while continuing on maintenance TIO for 6 weeks. Efficacy was measured using serial spirometry, transition dyspnea index (TDI), rescue albuterol use, and St. George's Respiratory Questionnaire (SGRQ).
The mean standardized area under the curve for FEV(1) over 3 hours (FEV(1)AUC(0-3)), the primary efficacy variable, was significantly higher in the FFIS/TIO group than the PLA/TIO group on day 1 (140 mL difference, P<0.0001) and week 6 (192 mL difference, P<0.0001). Mean TDI scores in the FFIS/TIO and PLA/TIO groups were 1.97 and 0.67, respectively (P=0.0001). Mean albuterol use declined in the FFIS/TIO group from 2.6 to 1.5 puffs/day compared with little change in the PLA/TIO group (P<0.0001). SGRQ scores were similar between treatment groups with the exception of the symptoms score, which improved in the FFIS/TIO group (-5.8) compared with PLA/TIO (-1.0), and more FFIS/TIO-treated subjects experienced a clinically significant improvement in total SGRQ score. More PLA/TIO-treated subjects than FFIS/TIO-treated subjects experienced adverse events (AEs) (45.7% vs. 31.0%) and COPD exacerbations (7.9% vs. 3.4%).
The addition of FFIS to maintenance TIO treatment for moderate to severe COPD results in significantly improved FEV(1) and dyspnea, decreased rescue medication use, and a lower incidence of AEs and COPD exacerbations. The addition of FFIS to TIO yields clinically and statistically significant benefits for COPD patients and might be of long-term benefit.
长效支气管扩张剂的使用是慢性阻塞性肺疾病（COPD）维持治疗的关键。这一分析汇总了两项双盲研究的结果，评估了在维持治疗中添加福莫特罗富马酸盐雾化吸入溶液（FFIS）对噻托溴铵（TIO）的疗效和安全性。
在每日一次 TIO 18 mcg 的预治疗期（7-14 天）后，中重度 COPD 患者（FEV（1）占预计值的>或=25%至<65%）随机分为每日两次 FFIS 20 mcg（n=145）或雾化安慰剂（PLA，n=140），同时继续接受 TIO 维持治疗 6 周。通过连续肺活量测定、过渡性呼吸困难指数（TDI）、沙丁胺醇救急使用和圣乔治呼吸问卷（SGRQ）来评估疗效。
主要疗效变量（FEV（1）AUC（0-3））在 3 小时内的平均标准化曲线下面积（FEV（1）AUC（0-3）），在 FFIS/TIO 组显著高于 PLA/TIO 组，第 1 天为 140 mL（差异，P<0.0001），第 6 周为 192 mL（差异，P<0.0001）。FFIS/TIO 组和 PLA/TIO 组的平均 TDI 评分分别为 1.97 和 0.67（P=0.0001）。FFIS/TIO 组沙丁胺醇救急使用从 2.6 减至 1.5 喷/天，而 PLA/TIO 组变化不大（P<0.0001）。SGRQ 评分在两组之间相似，除了症状评分，FFIS/TIO 组（-5.8）改善优于 PLA/TIO 组（-1.0），且更多的 FFIS/TIO 治疗患者总 SGRQ 评分有临床意义的改善。与 FFIS/TIO 组（31.0%）相比，更多的 PLA/TIO 组（45.7%）患者出现不良反应（AE）和 COPD 加重。
在中重度 COPD 的维持治疗中，FFIS 的加入可显著改善 FEV（1）和呼吸困难，减少救急药物的使用，AE 和 COPD 加重的发生率降低。FFIS 联合 TIO 治疗 COPD 患者具有显著的临床和统计学益处，可能具有长期益处。
