• Eileen M Harder, Pietro Nardelli, Carrie L Pistenmaa, Samuel Y Ash, Aparna Balasubramanian, Russell P Bowler, Monica Iturrioz Campo, Alejandro A Diaz, Paul M Hassoun, Jane A Leopold, Fernando J Martinez, Steven D Nathan, Imre Noth, Anna J Podolanczuk, Rajan Saggar, Rúben San José Estépar, Oksana A Shlobin, Wei Wang, Aaron B Waxman, Rachel K Putman, George R Washko, Bina Choi, San José EstéparRaúlR0000-0002-3677-1996Brigham and Women's Hospital, Radiology, Boston, Massachusetts, United States., and Farbod N Rahaghi.
• Brigham and Women's Hospital, Boston, Massachusetts, United States; eharder1@bwh.harvard.edu.
• Am. J. Respir. Crit. Care Med. 2024 May 31.

RationaleQuantitative interstitial abnormalities (QIA) are a computed tomography (CT) measure of early parenchymal lung disease associated with worse clinical outcomes including exercise capacity and symptoms. The presence of pulmonary vasculopathy in QIA and its role in the QIA-outcome relationship is unknown.ObjectivesTo quantify radiographic pulmonary vasculopathy in quantitative interstitial abnormalities (QIA) and determine if this vasculopathy mediates the QIA-outcome relationship.MethodsEver-smokers with QIA, outcome, and pulmonary vascular mediator data were identified from the COPDGene cohort. CT-based vascular mediators were: right ventricle-to-left ventricle ratio (RV/LV), pulmonary artery-to-aorta ratio (PA/Ao), and pre-acinar intraparenchymal arterial dilation (PA volume 5-20mm2 in cross-sectional area, normalized to total arterial volume). Outcomes were: six-minute walk distance (6MWD) and modified Medical Council Research Council (mMRC) Dyspnea score ≥2. Adjusted causal mediation analyses were used to determine if the pulmonary vasculature mediated the QIA effect on outcomes. Associations of pre-acinar arterial dilation with select plasma biomarkers of pulmonary vascular dysfunction were examined.Main ResultsAmong 8,200 participants, QIA burden correlated positively with vascular damage measures including pre-acinar arterial dilation. Pre-acinar arterial dilation mediated 79.6% of the detrimental impact of QIA on 6MWD (56.2-100%, p<0.001). PA/Ao was a weak mediator and RV/LV was a suppressor. Similar results were observed in the QIA-mMRC relationship. Pre-acinar arterial dilation correlated with increased pulmonary vascular dysfunction biomarker levels including angiopoietin-2 and NT-proBNP.ConclusionsParenchymal quantitative interstitial abnormalities (QIA) deleteriously impact outcomes primarily through pulmonary vasculopathy. Pre-acinar arterial dilation may be a novel marker of pulmonary vasculopathy in QIA.

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