Endothelial Microparticles in Mild Chronic Obstructive Pulmonary Disease and Emphysema. The Multi-Ethnic Study of Atherosclerosis Chronic Obstructive Pulmonary Disease Study

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

Chronic Obstructive Pulmonary Disease (COPD) is associated with pulmonary artery stiffness - the MESA COPD study

This study seeks to evaluate indices of pulmonary artery (PA) stiffness in patients with COPD and compare with normal controls. We hypothesize that patients with COPD would have increased pulmonary artery stiffness. To test this we determine the pulmonary artery area change (distensibility in %) by cardiac MRI and relate the distensibility to a wide range of severity of COPD. The MESA COPD Study recruited 290 patients (135 patients of various COPD severity and 155 controls) from four field centers in the US, age 50-79 years with ≥10 pack-years of smoking, all free of clinical cardiovascular disease. COPD was defined on post-bronchodilator spirometry by GOLD criteria (FEV1/FVC 80% = mild, 50-80%=moderate, <50%=severe). All participants underwent full-lung CTs. Percent emphysema was defined as the percentage of total voxels within the lung field that fell below -910 Hounsfield units. MRI studies were performed using 1.5T scanners. To measure ventricular function, the entire heart was imaged in short-axis orientation using a retrospectively gated steady-state free precession sequence. Phase-contrast images of the pulmonary arteries were obtained using a segmented fast gradient echo sequence with free breathing and analyzed quantitatively using dedicated software (FLOW, Medis). Distensibility of the pulmonary vessels (in %) are measured by the following formula, 100×(maximum PA area-minimum PA area)/minimum PA area. The base model (model 1) was adjusted for age, gender, height, weight, race/ethnicity and cohort of selection, given relationships of COPD severity to the pulmonary distensibility. We then additionally adjusted for smoking status, pack-years, diabetes mellitus, hypertension, oxygen saturation, LDL, HDL and statin use (model 2). Table 1 summarizes the clinical characteristics of 290 participants stratified by COPD severity. Distensibility of the main, right and left PA was reduced in COPD compared to controls in both models (Table 2). Main and right pulmonary distensibilities were inversely related to percent emphysema after minimal adjustment (model 1, P=0.21 and 0.07, respectively) and similar trends with statistical significance in the full model (model 2, P=0.049 and 0.01, respectively). Pulmonary distensibilities was positively associated with the percent predicted FEV1 but only left PA attain statistical significance after base adjustment (model 1, P=0.047). We conclude that in COPD patients without overt cardiovascular disease, pulmonary artery distensibility is reduced. Higher pulmonary arterial stiffness also correlated with the percent emphysema on CT scan and FEV1

ROSE:radiology, obstruction, symptoms and exposure - a Delphi consensus definition of the association of COPD and bronchiectasis by the EMBARC Airways Working Group

Introduction: The coexistence of chronic obstructive pulmonary disease (COPD) and bronchiectasis (BE) seems to be common and associated with a worse prognosis than for either disease individually. However, no definition of this association exists to guide researchers and clinicians. // Methods: We conducted a Delphi survey involving expert pulmonologists and radiologists from Europe, Turkey and Israel in order to define the “COPD-BE association”. A panel of 16 experts from EMBARC selected 35 statements for the survey after reviewing scientific literature. Invited participants, selected on the basis of expertise, geographical and gender distribution, were asked to express agreement on the statements. Consensus was defined as a score of ≥6 points (scale 0 to 9) in ≥70% of answers across two scoring rounds. // Results: A-hundred-and-two (72.3%) out of 141 invited experts participated the first round. Their response rate in the second round was 81%. The final consensus definition of “COPD-BE association” was: “The coexistence of (1) specific radiological findings (abnormal bronchial dilatation, airways visible within 1 cm of pleura and/or lack of tapering sign in ≥1 pulmonary segment and in >1 lobe) with (2) an obstructive pattern on spirometry (FEV1/FVC<0.7), (3) at least two characteristic symptoms (cough, expectoration, dyspnoea, fatigue, frequent infections) and (4) current or past exposure to smoke (≥10 pack-years) or other toxic agents (biomass, etc.)”. These criteria form the acronym “ROSE” (Radiology, Obstruction, Symptoms, Exposure). // Conclusions: The Delphi process formulated a European consensus definition of “COPD-BE association”. We hope this definition will have broad applicability across clinical practice and research in the future