Rationale: Smoking-related microvascular loss causes end-organ damage in the kidneys, heart, and brain. Basic research suggests a similar process in the lungs, but no large studies have assessed pulmonary microvascular blood flow (PMBF) in early chronic lung disease.Objectives: To investigate whether PMBF is reduced in mild as well as more severe chronic obstructive pulmonary disease (COPD) and emphysema.Methods: PMBF was measured using gadolinium-enhanced magnetic resonance imaging (MRI) among smokers with COPD and control subjects age 50 to 79 years without clinical cardiovascular disease. COPD severity was defined by standard criteria. Emphysema on computed tomography (CT) was defined by the percentage of lung regions below 2950 Hounsfield units (2950 HU) and by radiologists using a standard protocol. We adjusted for potential confounders, including smoking, oxygenation, and left ventricular cardiac output.Measurements and Main Results: Among 144 participants, PMBF was reduced by 30% in mild COPD, by 29% in moderate COPD, and by 52% in severe COPD (all P , 0.01 vs. control subjects). PMBF was reduced with greater percentage emphysema 2950HU and radiologist-defined emphysema, particularly panlobular and centrilobular emphysema (all P < 0.01). Registration of MRI and CT images revealed that PMBF was reduced in mild COPD in both nonemphysematous and emphysematous lung regions. Associations for PMBF were independent of measures of small airways disease on CT and gas trapping largely because emphysema and small airways disease occurred in different smokers.Conclusions: PMBF was reduced in mild COPD, including in regions of lung without frank emphysema, and may represent a distinct pathological process from small airways disease. PMBF may provide an imaging biomarker for therapeutic strategies targeting the pulmonary microvasculature.

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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 CD311 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. CD311 EMPs were measured using flow cytometry in 180 participants who also underwent CTs and spirometry. CD62E1 EMPs phenotypic for endothelial cell activation were also measured. COPD was defined by standard criteria. Percent emphysema was defined as regions less than 2950 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: CD311 EMPs were elevated in COPD compared with control subjects (P ¼ 0.03) and were notably increased in mild COPD (P ¼ 0.03). CD311 EMPs were positively related to percent emphysema (P ¼ 0.045) and were inversely associated with PMBF (P ¼ 0.047) and diffusing capacity (P ¼ 0.01). In contrast, CD62E1 EMPs were elevated in severe COPD (P ¼ 0.003) and hyperinflation (P ¼ 0.001). Conclusions: CD311 EMPs, suggestive of endothelial cell apoptosis, were elevated in mild COPD and emphysema. In contrast, CD62E 1 EMPs indicative of endothelial activation were elevated in severe COPD and hyperinflation.Keywords: chronic obstructive pulmonary disease; emphysema; antigens, CD31; endothelium; pulmonary disease Chronic obstructive pulmonary disease (COPD) is the third leading cause of death in the United States (1) and is projected to be the third leading cause of death worldwide by 2020 (2). COPD is defined as airflow obstruction that is not fully reversible (3). Many patients with COPD have emphysema, which is characterized by the destruction of alveolar walls with permanent loss of lung architecture and parenchyma (4).Cigarette smoking, the primary cause of COPD (3), is known to cause endothelial dysfunction (5). Cigarette smoke is delivered directly to pulmonary endothelial cells and contains multiple factors including acrolein that cause endothelial apoptosis (6). Increased endothelial cell apoptosis has been observed in the lung tissue of patients with emphysema compared with control subjects (7,8). Additionally, reductions in vascular endothelial growth factor (VEGF) and its receptor have been noted Prior research using animal models has implicated the primary destruction of the pulmonary capillary bed in the patho...