Fragoso Carlos A Vaz, Gill Thomas M, Leo-Summers Linda S, Van Ness Peter H
a Department of Internal Medicine , Veterans Affairs (VA) Connecticut Healthcare System , West Haven , Connecticut , USA.
b Department of Internal Medicine , Yale University School of Medicine , New Haven , Connecticut , USA.
COPD. 2018 Feb;15(1):17-20. doi: 10.1080/15412555.2018.1424815.
Clinical trials of pharmacotherapy in chronic obstructive pulmonary disease (COPD) often include older persons with moderate-to-severe airflow-obstruction, as defined by the Global Initiative for chronic Obstructive Lung Disease (GOLD). In this context, spirometric airflow-obstruction establishes COPD. Because GOLD misidentifies COPD and its severity in older persons, we set out to apply more age-appropriate spirometric criteria from the Global Lung function Initiative (GLI) in a prior clinical trial of COPD pharmacotherapy, specifically the Towards a Revolution in COPD Health (TORCH) trial - N = 6,112, mean age 65 years. In the TORCH trial, which enrolled GOLD-defined moderate COPD (26.2%, n = 1,200) and GOLD-defined severe COPD (73.8%, n = 4,511), the GLI reclassification yielded a higher frequency of severe COPD (89.6%, n = 5,474), the inclusion of restrictive-pattern (6.9%, n = 420) and, in turn, a very low frequency of moderate COPD (3.5%, n = 212). These GLI reclassification results suggest that GOLD-based enrollment criteria for the TORCH trial may have assembled a cohort that was: 1) less likely to respond to COPD pharmacotherapy, given the greater representation of severe COPD, very minor representation of moderate COPD, and inclusion of a non-obstructive spirometric impairment (restrictive-pattern); and 2) more likely to have medication-related adverse events, given the inappropriate use of COPD pharmacotherapy in misidentified COPD (restrictive-pattern). We therefore propose that future clinical trials of COPD pharmacotherapy should consider GLI criteria for defining COPD, including a greater representation of GLI-defined moderate COPD.
慢性阻塞性肺疾病（COPD）药物治疗的临床试验通常纳入慢性阻塞性肺疾病全球倡议组织（GOLD）所定义的中重度气流阻塞的老年人。在此背景下，肺量计测定的气流阻塞可确诊COPD。由于GOLD错误地识别了老年人中的COPD及其严重程度，我们在之前一项COPD药物治疗的临床试验中，即迈向COPD健康革命（TORCH）试验（N = 6112，平均年龄65岁），着手应用全球肺功能倡议组织（GLI）制定的更适合老年人的肺量计标准。在TORCH试验中，纳入了GOLD定义的中度COPD（26.2%，n = 1200）和GOLD定义的重度COPD（73.8%，n = 4511），根据GLI重新分类后，重度COPD的比例更高（89.6%，n = 5474），纳入了限制性模式（6.9%，n = 420），相应地，中度COPD的比例非常低（3.5%，n = 212）。这些GLI重新分类的结果表明，TORCH试验基于GOLD的纳入标准可能聚集了这样一组人群：1）对COPD药物治疗反应的可能性较小，因为重度COPD的比例更高，中度COPD的比例非常小，且纳入了非阻塞性肺量计损害（限制性模式）；2）发生药物相关不良事件的可能性更大，因为在错误识别的COPD（限制性模式）中不恰当地使用了COPD药物治疗。因此，我们建议未来COPD药物治疗的临床试验应考虑采用GLI标准来定义COPD，包括纳入更多GLI定义的中度COPD患者。
