Pulmonary microvascular perfusion in the Multi-Ethnic Study of Atherosclerosis

The renewal would build upon the findings of R01-HL077612 that demonstrate the clinical and mechanistic importance of emphysema and the pulmonary microvasculature in the general population including among patients without COPD: 1) percent emphysema on computed tomography (CT) was associated independently with dyspnea, reduced exercise tolerance, and all-cause mortality; 2) percent emphysema and the pulmonary vascular volume on non-contrast CT, a measure of large-vessel volume, were major determinants of left ventricular (LV) filling; 3) measures of microvascular damage and coagulopathy were associated with the progression of emphysema over 10 years. Further, therapies targeting the microvasculature were associated with slowed progression of emphysema. This renewal would add state-of-the-art, dual-source CT to assess, for the first time in a population, pulmonary microvascular blood volume (PMBV) in addition to pre/post-bronchodilator spirometry, and would test hypotheses related to natural-killer T (NKT)-cell-related microcoagulopathy, for which adenosine-related treatments are in development.