University of Groningen and the Department of Pulmonary Medicine and Tuberculosis, University Medical Center Groningen, and Groningen Research Institute for Asthma and COPD, Groningen, The Netherlands.
N Engl J Med. 2012 Sep 27;367(13):1198-207. doi: 10.1056/NEJMoa1208606. Epub 2012 Sep 2.
Some patients with asthma have frequent exacerbations and persistent airflow obstruction despite treatment with inhaled glucocorticoids and long-acting beta-agonists (LABAs).
In two replicate, randomized, controlled trials involving 912 patients with asthma who were receiving inhaled glucocorticoids and LABAs, we compared the effect on lung function and exacerbations of adding tiotropium (a total dose of 5 μg) or placebo, both delivered by a soft-mist inhaler once daily for 48 weeks. All the patients were symptomatic, had a post-bronchodilator forced expiratory volume in 1 second (FEV(1)) of 80% or less of the predicted value, and had a history of at least one severe exacerbation in the previous year.
The patients had a mean baseline FEV(1) of 62% of the predicted value; the mean age was 53 years. At 24 weeks, the mean (±SE) change in the peak FEV(1) from baseline was greater with tiotropium than with placebo in the two trials: a difference of 86±34 ml in trial 1 (P=0.01) and 154±32 ml in trial 2 (P<0.001). The predose (trough) FEV(1) also improved in trials 1 and 2 with tiotropium, as compared with placebo: a difference of 88±31 ml (P=0.01) and 111±30 ml (P<0.001), respectively. The addition of tiotropium increased the time to the first severe exacerbation (282 days vs. 226 days), with an overall reduction of 21% in the risk of a severe exacerbation (hazard ratio, 0.79; P=0.03). No deaths occurred; adverse events were similar in the two groups.
In patients with poorly controlled asthma despite the use of inhaled glucocorticoids and LABAs, the addition of tiotropium significantly increased the time to the first severe exacerbation and provided modest sustained bronchodilation. (Funded by Boehringer Ingelheim and Pfizer; ClinicalTrials.gov numbers, NCT00772538 and NCT00776984.).
一些哮喘患者尽管接受了吸入性糖皮质激素和长效β-激动剂（LABAs）治疗，但仍频繁发生哮喘加重和持续性气流阻塞。
在两项涉及 912 例接受吸入性糖皮质激素和 LABA 治疗的哮喘患者的复制随机对照试验中，我们比较了加用噻托溴铵（总剂量为 5μg）或安慰剂对肺功能和哮喘加重的影响，两者均通过软雾吸入器每日一次给药，共 48 周。所有患者均有症状，支气管扩张剂后一秒用力呼气量（FEV1）占预计值的 80%以下，并且在过去一年中至少有一次严重加重史。
患者的基线 FEV1 平均为预计值的 62%；平均年龄为 53 岁。在 24 周时，两项试验中，与安慰剂相比，噻托溴铵治疗的患者的峰值 FEV1 自基线的平均（±SE）变化更大：试验 1 中差异为 86±34ml（P=0.01），试验 2 中差异为 154±32ml（P<0.001）。与安慰剂相比，噻托溴铵治疗在试验 1 和试验 2 中也改善了预剂量（谷值）FEV1：差异分别为 88±31ml（P=0.01）和 111±30ml（P<0.001）。噻托溴铵的加入增加了首次严重加重的时间（282 天 vs. 226 天），严重加重的风险总体降低了 21%（风险比，0.79；P=0.03）。没有死亡发生；两组的不良事件相似。
在接受吸入性糖皮质激素和 LABAs 治疗但控制不佳的哮喘患者中，加用噻托溴铵可显著延长首次严重加重的时间，并提供适度持续的支气管扩张作用。（由勃林格殷格翰和辉瑞公司资助；ClinicalTrials.gov 编号，NCT00772538 和 NCT00776984。）
