Endothelial microparticles in mild chronic obstructive pulmonary disease and emphysema. The Multi-Ethnic Study of Atherosclerosis Chronic Obstructive Pulmonary Disease study

Abstract

Rationale: Basic research implicates alveolar endothelial cell apoptosis in the pathogenesis of chronic obstructive pulmonary disease (COPD) and emphysema. However, information on endothelial microparticles (EMPs) in mild COPD and emphysema is lacking.

Objectives: We hypothesized that levels of CD31(+) EMPs phenotypic for endothelial cell apoptosis would be elevated in COPD and associated with percent emphysema on computed tomography (CT). Associations with pulmonary microvascular blood flow (PMBF), diffusing capacity, and hyperinflation were also examined.

Methods: The Multi-Ethnic Study of Atherosclerosis COPD Study recruited participants with COPD and control subjects age 50-79 years with greater than or equal to 10 pack-years without clinical cardiovascular disease. CD31(+) EMPs were measured using flow cytometry in 180 participants who also underwent CTs and spirometry. CD62E(+) EMPs phenotypic for endothelial cell activation were also measured. COPD was defined by standard criteria. Percent emphysema was defined as regions less than -950 Hounsfield units on full-lung scans. PMBF was assessed on gadolinium-enhanced magnetic resonance imaging. Hyperinflation was defined as residual volume/total lung capacity. Linear regression was used to adjust for potential confounding factors.

Measurements and main results: CD31(+) EMPs were elevated in COPD compared with control subjects (P = 0.03) and were notably increased in mild COPD (P = 0.03). CD31(+) EMPs were positively related to percent emphysema (P = 0.045) and were inversely associated with PMBF (P = 0.047) and diffusing capacity (P = 0.01). In contrast, CD62E(+) EMPs were elevated in severe COPD (P = 0.003) and hyperinflation (P = 0.001).

Conclusions: CD31(+) EMPs, suggestive of endothelial cell apoptosis, were elevated in mild COPD and emphysema. In contrast, CD62E(+) EMPs indicative of endothelial activation were elevated in severe COPD and hyperinflation.

Figures

Figure 1.

Flowchart of study participants. COPD = chronic obstructive pulmonary disease; CT = computed tomography; EMP = endothelial microparticle; MESA = Multi-Ethnic Study of Atherosclerosis.

Figure 2.

Endothelial microparticles and severity of chronic obstructive pulmonary disease. Smoothed regression plots of the relationship of counts of CD31+ (dark line) and CD62E+ (dashed line) endothelial microparticles to the percent predicted FEV1. The plots were obtained from regression models adjusted for age, sex, race and ethnicity, cohort, smoking status, pack-years, educational attainment, body mass index, height, weight, diabetes mellitus, hypertension, oxygen saturation, white blood cell count, sleep apnea, high-density lipoprotein, and statin use. The hash marks denote data points. EMP = endothelial microparticle.

Figure 3.

CD31+ endothelial microparticle count and percent emphysema on computed tomography. Smoothed regression plot of the relationship of counts of CD31+ endothelial microparticles to the percentage of emphysema-like lung on computed tomography (dark line). The lighter lines are 95% confidence intervals. The plot was obtained from a regression model adjusted for age, sex, race and ethnicity, cohort, smoking status, pack-years, educational attainment, body mass index, height, weight, diabetes mellitus, hypertension, oxygen saturation, white blood cell count, sleep apnea, high-density lipoprotein, statin use, and high milliamperes. The hash marks denote data points. EMP = endothelial microparticle; HU = Hounsfield unit.

Figure 4.

CD31+ and CD62+ endothelial microparticles and chronic obstructive pulmonary disease (COPD) subphenotypes of pulmonary diffusing capacity and hyperinflation. (a) Smoothed regression plot of the relationship of counts of CD31+ endothelial microparticles to diffusing capacity. (b) Smoothed regression plot of the relationship of counts of CD62E+ endothelial microparticles to the ratio of residual volume to total lung capacity. The plots were obtained from regression models adjusted for age, sex, race and ethnicity, cohort, smoking status, pack-years, educational attainment, body mass index, height, weight, diabetes mellitus, hypertension, oxygen saturation, white blood cell count, sleep apnea, high-density lipoprotein, and statin use. The dark lines are the regression lines; the lighter lines are 95% confidence intervals. The hash marks denote data points. DlCO = diffusing capacity of the lung for carbon monoxide; EMP = endothelial microparticle; RV/TLC = residual volume/total lung capacity.