Decramer Marc, Celli Bartolome, Tashkin Donald P, Pauwels Romain A, Burkhart Deborah, Cassino Cara, Kesten Steven
Respiratory Division, University Hospitals, Leuven, Belgium.
COPD. 2004;1(2):303-12. doi: 10.1081/copd-200026934.
An accelerated loss of lung function is one of the defining characteristics of chronic obstructive pulmonary disease (COPD). To date, the only successful intervention shown to conclusively attenuate the loss of lung function over time is smoking cessation. Pharmacological interventions including inhaled corticosteroids and ipratropium bromide have not altered the rate of decline of lung function. Tiotropium is an inhaled anticholinergic that provides 24-hour bronchodilation with once-daily dosing due to prolonged muscarinic M3 receptor blockade. Controlled clinical trials have suggested sustained efficacy for periods of up to one year. We therefore initiated a four-year, controlled clinical trial (UPLIFT, Understanding the Potential Long-Term Impacts on Function with Tiotropium) in patients with COPD to evaluate the long-term effects of tiotropium on the rate of decline in lung function and health status as well as the frequency of exacerbations. The design of such large, long-term clinical trials presents unique methodological challenges including the definition of endpoints, the quality and variability of spirometric measurements and premature patient discontinuations from the trial. The present manuscript outlines the rationale for the UPLIFT study, and reviews the study design and the steps taken to address methodological challenges experienced in other long term studies. Careful design and implementation of the UPLIFT trial is anticipated to yield high quality results that will help in increasing our understanding of the long term natural history of COPD in a global population as well as to elucidate the role that tiotropium can play in affecting the course of this debilitating disease.
肺功能加速丧失是慢性阻塞性肺疾病（COPD）的主要特征之一。迄今为止，唯一被证实能最终减缓肺功能随时间丧失的成功干预措施是戒烟。包括吸入性糖皮质激素和异丙托溴铵在内的药物干预并未改变肺功能下降的速率。噻托溴铵是一种吸入性抗胆碱能药物，由于其对毒蕈碱M3受体的长效阻滞作用，每日一次给药即可提供24小时支气管扩张作用。对照临床试验表明其疗效可持续长达一年。因此，我们启动了一项针对COPD患者的为期四年的对照临床试验（UPLIFT，了解噻托溴铵对功能的潜在长期影响），以评估噻托溴铵对肺功能下降速率、健康状况以及急性加重频率的长期影响。如此大规模、长期的临床试验设计带来了独特的方法学挑战，包括终点的定义、肺量计测量的质量和变异性以及患者提前退出试验等问题。本手稿概述了UPLIFT研究的基本原理，并回顾了研究设计以及为应对其他长期研究中遇到的方法学挑战所采取的措施。预计UPLIFT试验的精心设计和实施将产生高质量的结果，这将有助于增进我们对全球人群中COPD长期自然史的了解，并阐明噻托溴铵在影响这种使人衰弱疾病进程中所能发挥的作用。
