六分钟步行距离测试作为慢性阻塞性肺疾病分层工具。慢性阻塞性肺疾病生物标志物鉴定联盟的见解。
The 6-Minute-Walk Distance Test as a Chronic Obstructive Pulmonary Disease Stratification Tool. Insights from the COPD Biomarker Qualification Consortium.
作者信息
Celli Bartolome, Tetzlaff Kay, Criner Gerard, Polkey Michael I, Sciurba Frank, Casaburi Richard, Tal-Singer Ruth, Kawata Ariane, Merrill Debora, Rennard Stephen
机构信息
1 Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
2 Boehringer Ingelheim, Ingelheim, Germany.
出版信息
Am J Respir Crit Care Med. 2016 Dec 15;194(12):1483-1493. doi: 10.1164/rccm.201508-1653OC.
RATIONALE
The 6-minute-walk distance (6MWD) test predicts mortality in chronic obstructive pulmonary disease (COPD). Whether variability in study type (observational vs. 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, FEV, 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.
理论依据
6分钟步行距离（6MWD）测试可预测慢性阻塞性肺疾病（COPD）患者的死亡率。目前尚不清楚研究类型（观察性研究与干预性研究）或研究开展地区的差异是否会限制该测试作为分层工具或治疗试验结局指标的应用。
目的
分析来自多项大型观察性研究以及支气管扩张剂随机临床试验的原始数据，以支持将6MWD测试作为COPD药物研发工具的合理性。
方法
纳入来自6项观察性研究（n = 9641）和5项干预性研究（n = 4856）的14497例COPD患者的原始数据，这些研究纳入患者超过100例，持续时间超过6个月。测量地理信息、人体测量学指标、第一秒用力呼气容积（FEV）、呼吸困难程度、合并症及健康状况评分。评估经研究类型、年龄和性别校正后的6MWD与死亡率、住院率及急性加重发生率之间的关联。使用受试者工作特征曲线计算结局预测阈值。分析吸入支气管扩张剂治疗及手术肺减容术后6MWD的变化，以评估该测试作为结局指标的反应性。
测量指标及主要结果
在6个月、12个月及超过12个月时，与未发生不良事件的患者相比，死亡患者、住院患者或急性加重患者的6MWD显著降低。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，用于预测住院率的曲线下面积分别为0.61、0.60和0.59。治疗后，安慰剂组和支气管扩张剂组的6MWD无差异，但与药物治疗相比，手术肺减容术后6MWD增加。研究类型（观察性或治疗性）或地区的差异并未混淆6MWD预测结局的能力。
结论
6MWD测试可用于对COPD患者进行分层，以开展旨在改善急性加重、住院或死亡情况的临床试验及干预措施。
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