Pathogenesis and Phenotypes of Pulmonary Vascular Disease in COPD: A Consensus Statement From the Pulmonary Vascular Research Institute's Innovative Drug Development Initiative – PH Group 3 Workstream

Lucilla Piccari, Katarina Zeder, Aparna Balasubramanian, Brian W. Allwood, Stephen John Wort, Shelsey W. Johnson, Reda E. Girgis, Oksana A. Shlobin, Steven H. Abman, Gabor Kovacs, George Washko, Sylvia M. Nikkho, Steven D. Nathan

https://doi.org/10.1002/pul2.70409 

Abstract

Chronic obstructive pulmonary disease (COPD) is frequently associated with pulmonary vascular disease (PVD) yet pulmonary vascular involvement remains underrecognized and incompletely phenotyped. Emerging evidence demonstrates that pulmonary vasculopathy may precede overt emphysema and airflow obstruction, suggesting that vascular remodeling is an early and integral component of COPD pathobiology rather than solely a late consequence of advanced lung disease. Multiple mechanisms contribute to COPD-associated PVD, including genetic susceptibility, abnormal lung development, cigarette smoke and environmental exposures, endothelial dysfunction, hypoxia, inflammation, hyperinflation, and comorbid cardiovascular and infectious diseases, which are discussed in this paper. These processes lead to heterogeneous clinical phenotypes that span a continuum from early pulmonary vascular abnormalities without resting PH to severe hemodynamically defined PH. Conventional spirometry and resting hemodynamics incompletely capture this complexity, whereas advanced imaging, gas-exchange assessment, and exercise testing improve identification of pulmonary vascular involvement. Distinct pulmonary vascular phenotypes may carry important implications for exercise limitation, exacerbation risk, progression, and survival. Recognizing COPD-associated PVD as a continuum rather than a late-stage complication has major implications for screening, phenotyping, and clinical trial design. This article reflects deliberations of the Pulmonary Vascular Research Institute's Innovative Drug Development Initiative (PVRI IDDI) Group 3 Pulmonary Hypertension Workstream on the pathophysiology and phenotypes of PVD in COPD.

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