Defining the role of early pulmonary vascular disease in COPD

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 DESCRIPTION (provided by applicant): Our goal is to understand how thoracic multi detector-row computed tomography (MDCT) combined with innovative image analysis techniques can be used to identify COPD patients at greatest risk. The overall objective of this proposal is to focus on the pulmonary vasculature. We hypothesize that novel quantitative MDCT-based metrics that characterize heterogeneity of pulmonary parenchymal perfusion and pulmonary vascular anatomy in early stage COPD subjects will allow us to identify subjects at greater risk for rapid disease progression. Numerous observations from our own laboratories and others point to an abnormal pulmonary vascular response to smoking induced parenchymal inflammation that leads to the development of emphysema. We have established imaging methods for the quantitative assessment of the pulmonary vascular tree and regional pulmonary parenchymal perfusion status. The former measure takes advantage of volumetric MDCT and the later makes use of dual energy MDCT (DE-MDCT) to provide clinically implementable tools for the interrogation of lung structure and function. Our Specific Aims are as follows: (1) determine whether objective, quantitative measures of increased PBV heterogeneity derived from DE-MDCT, as an index of emphysema susceptibility, will serve as a very early indicator of rapid emphysema progression (assessed by MDCT) and lung function decline; (2) determine whether anatomic changes in pulmonary vascular geometry will identify subjects at risk for more rapid emphysema progression and lung function decline, possibly in more urgent need of intervention; and (3) determine whether early anatomic and functional markers of vascular disease will combine to identify subjects at increased risk for development of frequent exacerbations who require more intense therapy before significant lung function decline has occurred. In this time-sensitive proposal, we will leverage the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS). SPIROMICS offers a unique opportunity to study at risk smokers and individuals with COPD in a longitudinal study that are well-characterized in terms of repeated clinical, physiological and biological evaluations. We propose to insert a baseline DE-MDCT scan to evaluate an index of pulmonary perfusion heterogeneity (Perfused Blood Volume: PBV) in 200 GOLD 0/I subjects at baseline and to insert a 3rd year MDCT exam into the SPIROMICS protocol for these same individuals. We also propose a year 3 MDCT exam in an additional 125 GOLD II-III SPIROMICS subjects. Our over-riding goal is to evaluate early functional and anatomic indices of vascular dysfunction to determine the association between these metrics and rate of emphysema progression, lung function decline and risk of AECOPD.