Dept of Medicine, David Geffen School of Medicine, UCLA, 10833 Le Conte Avenue, Los Angeles, CA 90095-1690, USA.
Eur Respir J. 2010 Feb;35(2):287-94. doi: 10.1183/09031936.00082909. Epub 2009 Aug 28.
UPLIFT (Understanding Potential Long-Term Improvements in Function with Tiotropium), a 4-yr trial of tiotropium in chronic obstructive pulmonary disease, allowed for assessment of smoking status on long-term responses to maintenance bronchodilator therapy. 5,993 patients were randomised (tiotropium/placebo). Lung function, St George's Respiratory Questionnaire, exacerbations and adverse events were followed. Patients were characterised as continuing smokers (CS), continuing ex-smokers (CE), or intermittent smokers (IS) based on self-reporting smoking behaviour. 60%, 14% and 26% of patients were CE, CS and IS, respectively. The rate of forced expiratory volume in 1 s (FEV(1)) decline for placebo patients was most rapid in CS (-52+/-4, -37+/2 and -23+/2 mL.yr(-1) in CS, IS, and CE, respectively). Tiotropium did not alter FEV(1) decline, but was associated with significant improvements in pre- and post-bronchodilator FEV(1) over placebo that persisted throughout the 4-yr trial for each smoking status (pre-bronchodilator: 127, 55 and 97 mL at 48 months in CS, IS and CE, respectively; p< or =0.0003). Tiotropium reduced exacerbation risk in CS (HR (95% CI) 0.80 (0.67-0.95)), in CE (0.85 (0.79-0.92)) and trended towards significance in IS (0.89 (0.79-1.00)). At 4 yrs, St George's Respiratory Questionnaire for tiotropium patients improved the most in CS (-4.63 units, p = 0.0006) and the least in IS (-0.60 units, p = 0.51), [corrected] compared with control. Tiotropium provided long-term benefits irrespective of smoking status, although differences among categories were observed.
UPLIFT（噻托溴铵对慢性阻塞性肺疾病长期功能改善的理解）是一项为期 4 年的噻托溴铵治疗慢性阻塞性肺疾病的试验，允许评估吸烟状态对维持性支气管扩张剂治疗的长期反应。5993 名患者被随机分组（噻托溴铵/安慰剂）。观察肺功能、圣乔治呼吸问卷、加重情况和不良事件。根据自我报告的吸烟行为，患者被分为继续吸烟者（CS）、持续戒烟者（CE）或间歇性吸烟者（IS）。60%、14%和 26%的患者分别为 CE、CS 和 IS。安慰剂组患者的 1 秒用力呼气量（FEV1）下降率在 CS 中最快（-52+/-4、-37+/2 和-23+/2 mL.yr-1，CS、IS 和 CE 分别）。噻托溴铵没有改变 FEV1 的下降，但与安慰剂相比，预支气管扩张剂和后支气管扩张剂 FEV1 的显著改善相关，这种改善在整个 4 年试验中持续存在，适用于每种吸烟状态（预支气管扩张剂：48 个月时 CS、IS 和 CE 分别为 127、55 和 97 mL；p<或=0.0003）。噻托溴铵降低了 CS（HR（95%CI）0.80（0.67-0.95））、CE（0.85（0.79-0.92））和 IS（0.89（0.79-1.00））的加重风险。在 4 年时，噻托溴铵患者的圣乔治呼吸问卷改善最大的是 CS（-4.63 单位，p = 0.0006），改善最小的是 IS（-0.60 单位，p = 0.51），与对照组相比。噻托溴铵提供了长期获益，无论吸烟状态如何，尽管在不同类别之间观察到差异。
