Rennard Stephen I, Locantore Nicholas, Delafont Bruno, Tal-Singer Ruth, Silverman Edwin K, Vestbo Jørgen, Miller Bruce E, Bakke Per, Celli Bartolomé, Calverley Peter M A, Coxson Harvey, Crim Courtney, Edwards Lisa D, Lomas David A, MacNee William, Wouters Emiel F M, Yates Julie C, Coca Ignacio, Agustí Alvar
1 Pulmonary and Critical Care Medicine, University of Nebraska Medical Center, Omaha, Nebraska.
Ann Am Thorac Soc. 2015 Mar;12(3):303-12. doi: 10.1513/AnnalsATS.201403-125OC.
Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease that likely includes clinically relevant subgroups.
To identify subgroups of COPD in ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints) subjects using cluster analysis and to assess clinically meaningful outcomes of the clusters during 3 years of longitudinal follow-up.
Factor analysis was used to reduce 41 variables determined at recruitment in 2,164 patients with COPD to 13 main factors, and the variables with the highest loading were used for cluster analysis. Clusters were evaluated for their relationship with clinically meaningful outcomes during 3 years of follow-up. The relationships among clinical parameters were evaluated within clusters.
Five subgroups were distinguished using cross-sectional clinical features. These groups differed regarding outcomes. Cluster A included patients with milder disease and had fewer deaths and hospitalizations. Cluster B had less systemic inflammation at baseline but had notable changes in health status and emphysema extent. Cluster C had many comorbidities, evidence of systemic inflammation, and the highest mortality. Cluster D had low FEV1, severe emphysema, and the highest exacerbation and COPD hospitalization rate. Cluster E was intermediate for most variables and may represent a mixed group that includes further clusters. The relationships among clinical variables within clusters differed from that in the entire COPD population.
Cluster analysis using baseline data in ECLIPSE identified five COPD subgroups that differ in outcomes and inflammatory biomarkers and show different relationships between clinical parameters, suggesting the clusters represent clinically and biologically different subtypes of COPD.
慢性阻塞性肺疾病(COPD)是一种异质性疾病,可能包括具有临床相关性的亚组。
在ECLIPSE(纵向评估COPD以识别预测性替代终点)研究对象中,使用聚类分析确定COPD的亚组,并评估这些聚类在3年纵向随访期间具有临床意义的结局。
采用因子分析将2164例COPD患者入组时测定的41个变量缩减为13个主要因子,并将载荷最高的变量用于聚类分析。评估聚类与3年随访期间具有临床意义的结局之间的关系。在聚类内部评估临床参数之间的关系。
利用横断面临床特征区分出五个亚组。这些组在结局方面存在差异。A组包括病情较轻的患者,死亡和住院人数较少。B组在基线时全身炎症较轻,但健康状况和肺气肿程度有显著变化。C组有许多合并症、全身炎症证据且死亡率最高。D组第一秒用力呼气容积(FEV1)较低、肺气肿严重,急性加重和COPD住院率最高。E组在大多数变量方面处于中间水平,可能代表一个包含进一步聚类的混合组。聚类内部临床变量之间的关系与整个COPD人群不同。
利用ECLIPSE研究中的基线数据进行聚类分析,确定了五个COPD亚组,它们在结局和炎症生物标志物方面存在差异,并且临床参数之间呈现不同关系,这表明这些聚类代表了临床上和生物学上不同的COPD亚型。