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Journal Article Ppublish 1 citation

PubMed: 38820122 DOI: 10.1164/rccm.202312-2342OC

Preacinar Arterial Dilation Mediates Outcomes of Quantitative Interstitial Abnormalities in the COPDGene Study.

Am J Respir Crit Care Med 210(9):1132-1142

Authors: Eileen M Harder, Pietro Nardelli, Carrie L Pistenmaa, Samuel Y Ash, Aparna Balasubramanian, Russell P Bowler, Mónica 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, Raúl San José Estépar, Farbod N Rahaghi

Affiliations

  • Division of Pulmonary and Critical Care Medicine.
  • Department of Radiology.
  • Department of Critical Care Medicine, South Shore Hospital, South Weymouth, Massachusetts, and School of Medicine, Tufts University, Boston, Massachusetts.
  • Division of Pulmonary and Critical Care Medicine, Department of Medicine, Johns Hopkins University, Baltimore, Maryland.
  • Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, National Jewish Health, Denver, Colorado.
  • Division of Cardiovascular Medicine, and.
  • Division of Pulmonary and Critical Care Medicine, Department of Medicine, Weill Cornell Medicine, New York City, New York.
  • Inova Advanced Lung Disease and Transplant Program, Inova Fairfax Hospital, Falls Church, Falls Church, Virginia.
  • Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Virginia School of Medicine, Charlottesville, Virginia.
  • Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, University of California, Los Angeles, Los Angeles, California; and.
  • Division of Sleep and Circadian Disorders, Department of Medicine, and Department of Neurology, Brigham and Women's Hospital, Boston, Massachusetts.
  • Division of Sleep Medicine, Harvard Medical School, Boston, Massachusetts.

Abstract

Rationale: Quantitative interstitial abnormalities (QIAs) 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 QIAs and its role in the QIA-outcome relationship is unknown. Objectives: To quantify radiographic pulmonary vasculopathy in QIAs and determine whether this vasculopathy mediates the QIA-outcome relationship. Methods: Ever-smokers with QIAs, outcomes, and pulmonary vascular mediator data were identified from the Genetic Epidemiology of COPD (COPDGene) study cohort. CT-based vascular mediators were right ventricle-to-left ventricle ratio, pulmonary artery-to-aorta ratio, and preacinar intraparenchymal arterial dilation (pulmonary artery volume, 5-20 mm 2 in cross-sectional area, normalized to total arterial volume). Outcomes were 6-minute walk distance and a modified Medical Council Research Council Dyspnea Scale score of 2 or higher. Adjusted causal mediation analyses were used to determine whether the pulmonary vasculature mediated the QIA effect on outcomes. Associations of preacinar arterial dilation with select plasma biomarkers of pulmonary vascular dysfunction were examined. Measurements and Main Results: Among 8,200 participants, QIA burden correlated positively with vascular damage measures, including preacinar arterial dilation. Preacinar arterial dilation mediated 79.6% of the detrimental impact of QIA on 6-minute walk distance (56.2-100%; P < 0.001). Pulmonary artery-to-aorta ratio was a weak mediator, and right ventricle-to-left ventricle ratio was a suppressor. Similar results were observed in the relationship between QIA and modified Medical Council Research Council dyspnea score. Preacinar arterial dilation correlated with increased pulmonary vascular dysfunction biomarker levels, including angiopoietin-2 and N-terminal brain natriuretic peptide. Conclusions: Parenchymal QIAs deleteriously impact outcomes primarily through pulmonary vasculopathy. Preacinar arterial dilation may be a novel marker of pulmonary vasculopathy in QIAs.

MeSH

Respiratory Tract Diseases, Critical Care, Biomarkers, Mediation Analysis, Angiopoietin-2

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