Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Nov 1;210(9):1132-1142.
doi: 10.1164/rccm.202312-2342OC.

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

Eileen M Harder  1 , Pietro Nardelli  2 , Carrie L Pistenmaa  1 , Samuel Y Ash  3 , Aparna Balasubramanian  4 , Russell P Bowler  5 , Mónica Iturrioz Campo  2 , Alejandro A Diaz  1 , Paul M Hassoun  4 , Jane A Leopold  6 , Fernando J Martinez  7 , Steven D Nathan  8 , Imre Noth  9 , Anna J Podolanczuk  7 , Rajan Saggar  10 , Rúben San José Estépar  2 , Oksana A Shlobin  8 , Wei Wang  11   12 , Aaron B Waxman  1 , Rachel K Putman  1 , George R Washko  1 , Bina Choi  1 , Raúl San José Estépar  2 , Farbod N Rahaghi  1
Affiliations

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

Eileen M Harder et al. Am J Respir Crit Care Med. .

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 mm2 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.

Keywords: QIAs; clinical outcomes; interstitial lung disease; pulmonary hypertension; pulmonary vasculopathy.

PubMed Disclaimer

Comment in

Similar articles

See all similar articles

Cited by

References

    1. Washko GR, Hunninghake GM, Fernandez IE, Nishino M, Okajima Y, Yamashiro T, et al. COPDGene Investigators Lung volumes and emphysema in smokers with interstitial lung abnormalities. N Engl J Med . 2011;364:897–906. - PMC - PubMed
    1. Ash SY, Harmouche R, Ross JC, Diaz AA, Hunninghake GM, Putman RK, et al. The objective identification and quantification of interstitial lung abnormalities in smokers. Acad Radiol . 2017;24:941–946. - PMC - PubMed
    1. Choi B, Adan N, Doyle TJ, San José Estépar R, Harmouche R, Humphries SM, et al. COPDGene Study and Pittsburgh Lung Screening Study Investigators Quantitative interstitial abnormality progression and outcomes in the Genetic Epidemiology of COPD and Pittsburgh Lung Screening Study cohorts. Chest . 2023;163:164–175. - PMC - PubMed
    1. Lederer DJ, Enright PL, Kawut SM, Hoffman EA, Hunninghake G, van Beek EJ, et al. Cigarette smoking is associated with subclinical parenchymal lung disease: the Multi-Ethnic Study of Atherosclerosis (MESA)–lung study. Am J Respir Crit Care Med . 2009;180:407–414. - PMC - PubMed
    1. Putman RK, Hatabu H, Araki T, Gudmundsson G, Gao W, Nishino M, et al. Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) Investigators COPDGene Investigators. Association between interstitial lung abnormalities and all-cause mortality. JAMA . 2016;315:672–681. - PMC - PubMed

MeSH terms