The 6-Minute-Walk Distance Test as a Chronic Obstructive Pulmonary Disease Stratification Tool Insights from the COPD Biomarker Qualification Consortium
The 6-Minute-Walk Distance Test as a Chronic Obstructive Pulmonary Disease Stratification Tool Insights from the COPD Biomarker Qualification Consortium
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DOI：
10.1164/rccm.201508-1653oc
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发表时间：
2016-12-15
影响因子：
24.7
通讯作者：
Rennard, Stephen
中科院分区：
文献类型：
--
作者：
Celli, Bartolome;Tetzlaff, Kay;Rennard, Stephen
原理：6分钟步行距离（6MWD）测试可预测慢性阻塞性肺疾病（COPD）的死亡率。是否研究类型的可变性（观察性）。介入性或区域性试验限制了该试验作为分层工具或治疗试验结果测量的使用，目前尚不清楚。目的：分析来自几项大型观察性研究和支气管扩张剂随机临床试验的原始数据，以支持6MWD试验作为COPD药物开发工具的资格。方法：纳入了来自6项观察性研究（n = 9641）和5项介入性研究（n = 4856）的14497例COPD患者的原始数据，这些研究的患者人数超过100人，持续时间超过6个月。测量地理、人体测量、FEV1、呼吸困难、合并症和健康状况评分。通过研究类型、年龄和性别调整，评估6MWD与死亡率、住院率和病情加重之间的关系。使用受试者工作曲线计算结果预测的阈值。分析吸入支气管扩张剂治疗和手术肺减容后6MWD的变化，以评估该试验作为结局指标的反应性。测量结果和主要结果：6个月、12个月和超过12个月时，非幸存者、住院患者或病情加重患者的6MWD明显低于无事件患者。在这些时间点，用于预测死亡率的6MWD受试者工作特征曲线下面积分别为0.71、0.70和0.68，用于预测住院的6MWD受试者工作特征曲线下面积分别为0.61、0.60和0.59。治疗后，6MWD在安慰剂和支气管扩张剂之间没有差异，但在手术肺减容后与药物治疗相比增加。研究类型（观察性或治疗性）或地区之间的差异并未影响6MWD预测结果的能力。结论：6MWD测试可用于对COPD患者进行临床试验和干预，旨在改善病情恶化、住院或死亡。
Rationale: The 6-minute-walk distance (6MWD) test predicts mortality in chronic obstructive pulmonary disease (COPD). Whether variability in study type (observationalvs. interventional) or region performed limits use of the test as a stratification tool or outcome measure for therapeutic trials is unclear.Objectives: To analyze the original data from several large observational studies and from randomized clinical trials with bronchodilators to support the qualification of the 6MWD test as a drug development tool in COPD.Methods: Original data from 14,497 patients with COPD from six observational (n = 9,641) and five interventional (n = 4,856) studies larger than 100 patients and longer than 6 months in duration were included. The geographical, anthropometrics, FEV1, dyspnea, comorbidities, and health status scores were measured. Associations between 6MWD and mortality, hospitalizations, and exacerbations adjusted by study type, age, and sex were evaluated. Thresholds for outcome prediction were calculated using receiver operating curves. The change in 6MWD after inhaled bronchodilator treatment and surgical lung volume reduction were analyzed to evaluate the responsiveness of the test as an outcome measure.Measurements and Main Results: The 6MWD was significantly lower in nonsurvivors, those hospitalized, or who exacerbated compared with those without events at 6, 12, and greater than 12 months. At these time points, the 6MWD receiver operating characteristic curve-area under the curve to predict mortality was 0.71, 0.70, and 0.68 and for hospitalizations was 0.61, 0.60, and 0.59, respectively. After treatment, the 6MWD was not different between placebo and bronchodilators but increased after surgical lung volume reduction compared with medical therapy. Variation across study types (observational or therapeutic) or regions did not confound the ability of 6MWD to predict outcome.Conclusions: The 6MWD test can be used to stratify patients with COPD for clinical trials and interventions aimed at modifying exacerbations, hospitalizations, or death.