Pulmonary Vascular Disease as a Contributor to Respiratory Morbidity in Chronic Obstructive Pulmonary Disease

Project Summary/Abstract
Chronic obstructive pulmonary disease (COPD) occurs in over 15 million adults in the US. As many as
35% of those patients develop pulmonary vascular disease (PVD), but the recommendations for assessment
and management of PVD in COPD have been limited by key knowledge gaps. Firstly, assessment of the
pulmonary vasculature has relied upon invasive right heart catheterization as the gold standard, limiting studies
to select populations with severe PVD. Noninvasive techniques, though widely available, have also been
primarily validated in populations with severe PVD applying markers that are likely to reflect end-stage PVD,
such as right ventricular failure. As a result, another key knowledge gap is the unknown contribution of PVD to
COPD morbidity across its observed spectrum of severity. While the concomitant presence of severe PVD is
observed to portend increased morbidity and mortality compared to those with COPD alone, the contribution of
less severe PVD, at potentially more intervenable points in the disease course is less well-understood. This
proposal seeks to address these knowledge gaps in three aims by (SA1) testing the diagnostic accuracy of
three noninvasive markers that are selected for plausible sensitivity to early PVD, (SA2) and applying these
noninvasive markers to understand the contribution of PVD to respiratory morbidity in cross-sectional and
(SA3) longitudinal study designs. This application will add noninvasive markers to a general COPD cohort
unselected for PVD and will further assemble a prospective longitudinal cohort of COPD patients enriched for
PVD with the same noninvasive testing. The results of this proposal will identify novel noninvasive approaches
for assessing PVD, define their clinical relevance across the spectrum of PVD, and establish opportunities to
study the use of noninvasive markers as candidate outcomes in clinical trials targeting the pulmonary
vasculature to manage COPD.
Dr. Balasubramanian’s proposal is a strong training vehicle for her career development, offering her
skills in hands-on cohort study design and execution, advanced biostatistical and epidemiologic methodology,
and noninvasive and invasive assessment of PVD in COPD through numerous modalities including right heart
catheterization, magnetic resonance imaging, speckle-tracking echocardiography, and physiologic
measurements of diffusing capacity of the lung. Dr. Balasubramanian will be supported by a strong multi-
disciplinary mentorship team with expertise in COPD, pulmonary hypertension, cardiology, radiology, and
biostatistics. She further will leverage an exceptional institutional environment with its collaborative and
supportive culture, extensive intellectual and physical resources, and strong history of supporting junior
investigators. This award will establish Dr. Balasubramanian as an independent investigator with a unique
research niche, distinct from her mentorship team, and establish a foundation for future studies evaluating and
managing PVD in COPD.

Grant Number: 5K23HL153778-04
NIH Institute/Center: NIH
Principal Investigator: Aparna Balasubramanian