Annual FEV1 changes and numbers of circulating endothelial microparticles in patients with COPD: a prospective study

Toru Takahashi, Seiichi Kobayashi, Naoya Fujino, Takaya Suzuki, Chiharu Ota, Yukiko Tando, Mitsuhiro Yamada, Masaru Yanai, Mutsuo Yamaya, Shin Kurosawa, Masanori Yamauchi, Hiroshi Kubo, Toru Takahashi, Seiichi Kobayashi, Naoya Fujino, Takaya Suzuki, Chiharu Ota, Yukiko Tando, Mitsuhiro Yamada, Masaru Yanai, Mutsuo Yamaya, Shin Kurosawa, Masanori Yamauchi, Hiroshi Kubo

Abstract

Objective: Growing evidence suggests that endothelial injury is involved in the pathophysiology of chronic obstructive pulmonary disease (COPD). Circulating endothelial microparticles (EMPs) increase in patients with COPD because of the presence of endothelial injury. We examined the relationship between EMP number and changes in forced expiratory volume in 1 s (FEV1) in patients with COPD.

Design: Prospective study.

Setting: One hospital in Japan.

Participants: A total 48 outpatients with stable COPD coming to the hospital from September 2010 to September 2011.

Primary and secondary outcomes measured: Blood samples were collected and vascular endothelial (VE)-cadherin EMPs (CD144+ EMPs), E-selectin EMPs (CD62E+ EMPs) and platelet endothelial cell adhesion molecule EMPs (CD31+/CD41- EMPs) were measured using fluorescence-activated cell sorting. Annual FEV1 changes were evaluated using FEV1 data acquired a year before and a year after sample collection.

Results: The number of E-selectin and VE-cadherin EMPs showed significant negative correlations with annual FEV1 changes (rs=-0.65, p<0.001, rs=-0.43, p=0.003, respectively). Leucocyte counts tended to be correlated with annual FEV1 changes, but this correlation was not significant (rs=-0.28, p=0.057). There were significant differences in annual FEV1 changes between with and without history of frequent exacerbation (p=0.006), and among Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages (p=0.009). Multiple linear regression analysis revealed E-selectin EMP to be the only significant parameter associated with annual FEV1 changes, independent of VE-cadherin EMP, GOLD stages, leucocyte counts, and history of frequent exacerbation. Receiver operating characteristic curves showed the optimum E-selectin EMP cut-off level for prediction of rapid FEV1 decline (>66 mL/year) to be 153.0/µL (areas under curve 0.78 (95% CI 0.60 to 0.89); sensitivity, 67%; specificity, 81%).

Conclusions: The high E-selectin EMP levels in stable patients with COPD are predictive of rapid FEV1 decline.

Trial registration number: UMIN000005168.

Figures

Figure 1
Figure 1
Flowchart of patient enrolment and reasons for exclusion. COPD, chronic obstructive pulmonary disease; EMP, circulating endothelial microparticle; FACS; fluorescence-activated cell sorting; FEV1, forced expiratory volume in 1 s.
Figure 2
Figure 2
Comparisons of annual forced expiratory volume in 1 s (FEV1) changes (A) among Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages and (B) between patients with and without a history of frequent exacerbation.
Figure 3
Figure 3
Correlations between annual FEV1 changes and (A) VE-cadherin EMPs, (B) E-selectin EMPs and (C) PECAM EMPs. Filled circles indicate patients with a history of frequent exacerbation and open circles indicate patients without a history of frequent exacerbation. EMPs, circulating endothelial microparticles; FEV1, forced expiratory volume in 1 s; PECAM, platelet endothelial cell adhesion molecule; PFP, platelet-free plasma; VE-cadherin, vascular endothelial-cadherin.
Figure 4
Figure 4
Receiver operating characteristic (ROC) curve of E-selectin endothelial microparticle number for prediction of rapid forced expiratory volume in 1 s decline.

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