Respiratory Division and Pulmonary Rehabilitation, UZ Gasthuisberg, Herestraat 49, B3000 Leuven, Belgium.
Eur Respir J. 2010 Jul;36(1):65-73. doi: 10.1183/09031936.00127809. Epub 2010 Feb 25.
The aim of the present study was investigate the long-term effect of tiotropium as first maintenance respiratory medication in chronic obstructive pulmonary disease (COPD). A 4-yr, randomised, multicentre, double-blind, parallel-group, placebo-controlled trial (Understanding Potential Long-term Impacts on Function with Tiotropium (UPLIFT) was conducted. Analysis focused on the effect of tiotropium versus matching placebo in the 810 (13.5%) COPD patients not on other maintenance treatment (long-acting beta-agonists, inhaled corticosteroids, theophyllines or anticholinergics) at randomisation. Spirometry, health-related quality of life (St George's Respiratory Questionnaire (SGRQ) score), exacerbations of COPD and mortality were also analysed. 403 patients (mean+/-sd age 63+/-8 yrs, post-bronchodilator forced expiratory volume in 1 s (FEV(1)) 53+/-12% predicted) received tiotropium and 407 (64+/-8 yrs of age, post-bronchodilator FEV(1) 51+/-12% pred) received placebo. Post-bronchodilator FEV(1) decline was 42+/-4 mL.yr(-1) in the tiotropium group and 53+/-4 mL.yr(-1) in the placebo group (p = 0.026). At 48 months, the morning pre-dose FEV(1) was 134 mL higher in the tiotropium group compared to the placebo group (p<0.001). SGRQ total score declined more slowly in the tiotropium group (difference of 1.05+/-0.34 units.yr(-1); p = 0.002). This was particularly significant for the impact (difference of 1.08+/-0.37 units.yr(-1); p = 0.004) and activity (1.44+/-0.40 units.yr(-1); p<0.001) domains, but not for symptoms (0.26+/-0.50 units.yr(-1); p = 0.6). At 48 months, the difference in total score was 4.6 units (p<0.001) with tiotropium compared to placebo. In patients with COPD who are not on maintenance therapy, tiotropium is associated with significant benefits in disease progression.
本研究旨在探讨噻托溴铵作为慢性阻塞性肺疾病（COPD）的一线维持治疗药物的长期疗效。进行了一项为期 4 年、随机、多中心、双盲、平行分组、安慰剂对照试验（Understanding Potential Long-term Impacts on Function with Tiotropium（UPLIFT））。分析重点是噻托溴铵与随机分组时未接受其他维持治疗（长效β激动剂、吸入皮质激素、茶碱或抗胆碱能药物）的 810 例（13.5%）COPD 患者的安慰剂相比的疗效。还分析了肺量测定、与健康相关的生活质量（圣乔治呼吸问卷（SGRQ）评分）、COPD 恶化和死亡率。403 例患者（平均+/-标准差年龄 63+/-8 岁，支气管扩张后用力呼气量 1 秒（FEV1）占预计值的 53+/-12%）接受噻托溴铵治疗，407 例（64+/-8 岁，支气管扩张后 FEV1 占预计值的 51+/-12%）接受安慰剂治疗。噻托溴铵组支气管扩张后 FEV1 下降 42+/-4 mL.yr(-1)，安慰剂组下降 53+/-4 mL.yr(-1)（p=0.026）。48 个月时，噻托溴铵组清晨预给药前 FEV1 比安慰剂组高 134 mL（p<0.001）。噻托溴铵组 SGRQ 总分下降更缓慢（差异为 1.05+/-0.34 单位.yr(-1)；p=0.002）。这在影响（差异为 1.08+/-0.37 单位.yr(-1)；p=0.004）和活动（1.44+/-0.40 单位.yr(-1)；p<0.001）领域尤为显著，但在症状（0.26+/-0.50 单位.yr(-1)；p=0.6）领域则不显著。48 个月时，噻托溴铵组总评分比安慰剂组高 4.6 分（p<0.001）。在未接受维持治疗的 COPD 患者中，噻托溴铵可显著改善疾病进展。
