Pulmonary Microvascular Blood Flow in Mild Chronic Obstructive Pulmonary Disease and Emphysema: The MESA COPD Study

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Abstract

Rationale: Smoking-related microvascular loss causes end-organ damageinthekidneys,heart,andbrain.Basicresearchsuggestsasimilar 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%insevereCOPD(allP, 0.01vs.controlsubjects).PMBFwasreduced with greater percentage emphysema2950HU and radiologist-defined emphysema, particularly panlobular and centrilobular emphysema (allP < 0.01).RegistrationofMRIandCTimagesrevealedthatPMBFwas 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.

Keywords: pulmonary microvascular blood flow (PMBF); gadolinium-enhanced MRI; chronic obstructive pulmonary disease (COPD); lung emphysema; small airway disease

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death globally and in the United States (1, 2). Cigarette smoke, the major cause of COPD, has protean effects on the airway epithelium (3) but also causes endothelial damage and loss of the microvasculature in multiple organs, including the brain, kidney, and heart (4). The consequent loss of blood flow causes end-organ damage, and therapies that ameliorate microvascular blood flow, such as angiotensin-receptor blockers, improve function of some of these organs (5). Despite the importance of this preventative and therapeutic target in other organs, there has been little examination of the pulmonary microvasculature early in the course of COPD.

Basic science studies suggest that smoking may have similar...