Pulmonary Arterial Pruning and Longitudinal Change in Percent Emphysema and Lung Function: The Genetic Epidemiology of COPD Study

COPDGene Investigators

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3 Scopus citations

Abstract

BACKGROUND: Pulmonary endothelial damage has been shown to precede the development of emphysema in animals, and vascular changes in humans have been observed in COPD and emphysema.

RESEARCH QUESTION: Is intraparenchymal vascular pruning associated with longitudinal progression of emphysema on CT imaging or decline in lung function over 5 years?

STUDY DESIGN AND METHODS: The Genetic Epidemiology of COPD Study enrolled ever smokers with and without COPD from 2008 through 2011. The percentage of emphysema-like lung, or "percent emphysema," was assessed at baseline and after 5 years on noncontrast CT imaging as the percentage of lung voxels < -950 Hounsfield units. An automated CT imaging-based tool assessed and classified intrapulmonary arteries and veins. Spirometry measures are postbronchodilator. Pulmonary arterial pruning was defined as a lower ratio of small artery volume (< 5 mm 2 cross-sectional area) to total lung artery volume. Mixed linear models included demographics, anthropomorphics, smoking, and COPD, with emphysema models also adjusting for CT imaging scanner and lung function models adjusting for clinical center and baseline percent emphysema.

RESULTS: At baseline, the 4,227 participants were 60 ± 9 years of age, 50% were women, 28% were Black, 47% were current smokers, and 41% had COPD. Median percent emphysema was 2.1 (interquartile range, 0.6-6.3) and progressed 0.24 percentage points/y (95% CI, 0.22-0.26 percentage points/y) over 5.6 years. Mean FEV 1 to FVC ratio was 68.5 ± 14.2% and declined 0.26%/y (95% CI, -0.30 to -0.23%/y). Greater pulmonary arterial pruning was associated with more rapid progression of percent emphysema (0.11 percentage points/y per 1-SD increase in arterial pruning; 95% CI, 0.09-0.16 percentage points/y), including after adjusting for baseline percent emphysema and FEV 1. Arterial pruning also was associated with a faster decline in FEV 1 to FVC ratio (-0.04%/y per 1-SD increase in arterial pruning; 95% CI, -0.008 to -0.001%/y).

INTERPRETATION: Pulmonary arterial pruning was associated with faster progression of percent emphysema and more rapid decline in FEV 1 to FVC ratio over 5 years in ever smokers, suggesting that pulmonary vascular differences may be relevant in disease progression.

TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT00608764; URL: www.clinicaltrials.gov.

Original languageEnglish (US)
Pages (from-to)470-480
Number of pages11
JournalCHEST
Volume160
Issue number2
DOIs
StatePublished - Aug 2021

Bibliographical note

Funding Information:
Financial/nonfinancial disclosures: The authors have reported to CHEST the following: C. L. P. received research grants from the Alpha1 Foundation and Boehringer Ingelheim and personal fees from Lancet Respiratory Medicine and Horizon CME. S. Y. A. received a research grant from the Pulmonary Fibrosis Foundation and an ownership distribution from Quantitative Imaging Solutions. R. G. B. received research grants from the Foundation for the NIH and COPD Foundation . J. M. W. received research grants from Vertex Pharmaceuticals , Inc., Bayer AG, ARCUS-MED, LLC, and Mereo BioPharma and personal fees from GlaxoSmithKline , Boehringer Ingelheim, and Takeda. G. R. W. received research grants from Boehringer Ingelheim, BTG Interventional Medicine, and Janssen Pharmaceuticals and personal fees from Boehringer Ingelheim, PulmonX, Janssen Pharmaceuticals , and GlaxoSmithKline . R. S. J. E. received personal fees from Toshiba, Boehringer Ingelheim, Eolo Medical, and Leuko Labs. R. S. J. E. and G. R. W. are founders and co-owners of Quantitative Imaging Solutions, a company that provides image-based consulting and develops software to enable data sharing. None declared (P. N., C. E. C., A. A. D., F. N. R., K. A. Y., G. L. K., J. P. S., R. C. W., and J. E. H.).

Funding Information:
FUNDING/SUPPORT: This study was supported by the National Heart, Lung, and Blood Institute, National Institutes of Health [Grants K23 HL141651, R01 HL116931, R01 HL116473, U01 HL089897, and U01 HL089856]. The COPDGene Study is also supported by the COPD Foundation through contributions made to an industry advisory board comprising AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Novartis, Pfizer, Siemens, and Sunovion.Author contributions: C. L. P. is the guarantor of the manuscript, responsible for the content of this manuscript, including the data and analysis. C. L. P. G. R. W. and R. S. J. E. conceived and designed the study. S. Y. A. C. E. C. A. A. D. J. E. H. G. L. K. P. N. F. N. R. R. G. B. J. P. S. K. A. Y. R. C. W. and J. M. W. collected the data. C. L. P. G. R. W. and R. S. J. E. analyzed and interpreted the data and guarantee the data. C. L. P. drafted the manuscript. All authors critically revised and approved the final manuscript. Financial/nonfinancial disclosures: The authors have reported to CHEST the following: C. L. P. received research grants from the Alpha1 Foundation and Boehringer Ingelheim and personal fees from Lancet Respiratory Medicine and Horizon CME. S. Y. A. received a research grant from the Pulmonary Fibrosis Foundation and an ownership distribution from Quantitative Imaging Solutions. R. G. B. received research grants from the Foundation for the NIH and COPD Foundation. J. M. W. received research grants from Vertex Pharmaceuticals, Inc. Bayer AG, ARCUS-MED, LLC, and Mereo BioPharma and personal fees from GlaxoSmithKline, Boehringer Ingelheim, and Takeda. G. R. W. received research grants from Boehringer Ingelheim, BTG Interventional Medicine, and Janssen Pharmaceuticals and personal fees from Boehringer Ingelheim, PulmonX, Janssen Pharmaceuticals, and GlaxoSmithKline. R. S. J. E. received personal fees from Toshiba, Boehringer Ingelheim, Eolo Medical, and Leuko Labs. R. S. J. E. and G. R. W. are founders and co-owners of Quantitative Imaging Solutions, a company that provides image-based consulting and develops software to enable data sharing. None declared (P. N. C. E. C. A. A. D. F. N. R. K. A. Y. G. L. K. J. P. S. R. C. W. and J. E. H.). Role of sponsors: The sponsor had no role in the design of the study, the collection and analysis of the data, or the preparation of the manuscript. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Heart, Lung, and Blood Institute or the National Institutes of Health. ? COPDGene Investigators: Core Units?Administrative Center: James D. Crapo, MD (PI); Edwin K. Silverman, MD, PhD (PI); Barry J. Make, MD; Elizabeth A. Regan, MD, PhD; Genetic Analysis Center: Terri H. Beaty, PhD; Peter J. Castaldi, MD, MSc; Michael H. Cho, MD, MPH; Dawn L. DeMeo, MD, MPH; Adel El Boueiz, MD, MMSc; Marilyn G. Foreman, MD, MS; Auyon Ghosh, MD; Lystra P. Hayden, MD, MMSc; Craig P. Hersh, MD, MPH; Jacqueline Hetmanski, MS; Brian D. Hobbs, MD, MMSc; John E. Hokanson, MPH, PhD; Wonji Kim, PhD; Nan Laird, PhD; Christoph Lange, PhD; Sharon M. Lutz, PhD; Merry-Lynn McDonald, PhD; Dmitry Prokopenko, PhD; Matthew Moll, MD, MPH; Jarrett Morrow, PhD; Dandi Qiao, PhD; Elizabeth A. Regan, MD, PhD; Aabida Saferali, PhD; Phuwanat Sakornsakolpat, MD; Edwin K. Silverman, MD, PhD; Emily S. Wan, MD; Jeong Yun, MD, MPH; Imaging Center: Juan Pablo Centeno; Jean-Paul Charbonnier, PhD; Harvey O. Coxson, PhD; Craig J. Galban, PhD; MeiLan K. Han, MD, MS; Eric A. Hoffman, Stephen Humphries, PhD; Francine L. Jacobson, MD, MPH; Philip F. Judy, PhD; Ella A. Kazerooni, MD; Alex Kluiber; David A. Lynch, MB; Pietro Nardelli, PhD; John D. Newell, Jr, MD; Aleena Notary; Andrea Oh, MD; Elizabeth A. Regan, MD, PhD; James C. Ross, PhD; Raul San Jose Estepar, PhD; Joyce Schroeder, MD; Jered Sieren; Berend C. Stoel, PhD; Juerg Tschirren, PhD; Edwin Van Beek, MD, PhD; Bram van Ginneken, PhD; Eva van Rikxoort, PhD; Gonzalo Vegas Sanchez- Ferrero, PhD; Lucas Veitel; George R. Washko, MD; Carla G. Wilson, MS; PFT QA Center, Salt Lake City, UT: Robert Jensen, PhD; Data Coordinating Center and Biostatistics, National Jewish Health, Denver, CO: Douglas Everett, PhD; Jim Crooks, PhD; Katherine Pratte, PhD; Matt Strand, PhD; Carla G. Wilson, MS; Epidemiology Core, University of Colorado Anschutz Medical Campus, Aurora, CO: John E. Hokanson, MPH, PhD; Erin Austin, PhD; Gregory Kinney, MPH, PhD; Sharon M. Lutz, PhD; Kendra A. Young, PhD; Mortality Adjudication Core: Surya P. Bhatt, MD; Jessica Bon, MD; Alejandro A. Diaz, MD, MPH; MeiLan K. Han, MD, MS; Barry Make, MD; Susan Murray, ScD; Elizabeth Regan, MD; Xavier Soler, MD; Carla G. Wilson, MS; Biomarker Core: Russell P. Bowler, MD, PhD; Katerina Kechris, PhD; Farnoush Banaei- Kashani, PhD; Clinical Centers?Ann Arbor VA: Jeffrey L. Curtis, MD; Perry G. Pernicano, MD; Baylor College of Medicine, Houston, TX: Nicola Hanania, MD, MS; Mustafa Atik, MD; Aladin Boriek, PhD; Kalpatha Guntupalli, MD; Elizabeth Guy, MD; Amit Parulekar, MD; Brigham and Women's Hospital, Boston, MA: Dawn L. DeMeo, MD, MPH; Craig Hersh, MD, MPH; Francine L. Jacobson, MD, MPH; George Washko, MD; Columbia University, New York, NY: R. Graham Barr, MD, DrPH; John Austin, MD; Belinda D'Souza, MD; Byron Thomashow, MD; Duke University Medical Center, Durham, NC: Neil MacIntyre, Jr. MD; H. Page McAdams, MD; Lacey Washington, MD; HealthPartners Research Institute, Minneapolis, MN; Charlene McEvoy, MD, MPH; Joseph Tashjian, MD; Johns Hopkins University, Baltimore, MD: Robert Wise, MD; Robert Brown, MD; Nadia N. Hansel, MD, MPH; Karen Horton, MD; Allison Lambert, MD, MHS; Nirupama Putcha, MD, MHS; Lundquist Institute for Biomedical Innovation at Harbor UCLA Medical Center, Torrance, CA: Richard Casaburi, PhD, MD; Alessandra Adami, PhD; Matthew Budoff, MD; Hans Fischer, MD; Janos Porszasz, MD, PhD; Harry Rossiter, PhD; William Stringer, MD; Michael E. DeBakey VAMC, Houston, TX: Amir Sharafkhaneh, MD, PhD; Charlie Lan, DO; Minneapolis VA: Christine Wendt, MD; Brian Bell, MD; Ken M. Kunisaki, MD, MS; Morehouse School of Medicine, Atlanta, GA: Eric L. Flenaugh, MD; Hirut Gebrekristos, PhD; Mario Ponce, MD; Silanath Terpenning, MD; Gloria Westney, MD, MS; National Jewish Health, Denver, CO: Russell Bowler, MD, PhD; David A. Lynch, MB; Reliant Medical Group, Worcester, MA: Richard Rosiello, MD; David Pace, MD; Temple University, Philadelphia, PA: Gerard Criner, MD; David Ciccolella, MD; Francis Cordova, MD; Chandra Dass, MD; Gilbert D'Alonzo, DO; Parag Desai, MD; Michael Jacobs, PharmD; Steven Kelsen, MD, PhD; Victor Kim, MD; A. James Mamary, MD; Nathaniel Marchetti, DO; Aditi Satti, MD; Kartik Shenoy, MD; Robert M. Steiner, MD; Alex Swift, MD; Irene Swift, MD; Maria Elena Vega-Sanchez, MD; University of Alabama, Birmingham, AL: Mark Dransfield, MD; William Bailey, MD; Surya P. Bhatt, MD; Anand Iyer, MD; Hrudaya Nath, MD; J. Michael Wells, MD; University of California, San Diego, CA: Douglas Conrad, MD; Xavier Soler, MD, PhD; Andrew Yen, MD; University of Iowa, Iowa City, IA: Alejandro P. Comellas, MD; Karin F. Hoth, PhD; John Newell, Jr. MD; Brad Thompson, MD; University of Michigan, Ann Arbor, MI: MeiLan K. Han, MD MS; Ella Kazerooni, MD MS; Wassim Labaki, MD MS; Craig Galban, PhD; Dharshan Vummidi, MD; University of Minnesota, Minneapolis, MN: Joanne Billings, MD; Abbie Begnaud, MD; Tadashi Allen, MD; University of Pittsburgh, Pittsburgh, PA: Frank Sciurba, MD; Jessica Bon, MD; Divay Chandra, MD, MSc; Joel Weissfeld, MD, MPH; University of Texas Health. Additional information: The e-Figure and e-Tables can be found in the Supplemental Materials section of the online article.

Funding Information:
FUNDING/SUPPORT: This study was supported by the National Heart, Lung, and Blood Institute , National Institutes of Health [Grants K23 HL141651 , R01 HL116931 , R01 HL116473 , U01 HL089897 , and U01 HL089856 ]. The COPDGene Study is also supported by the COPD Foundation through contributions made to an industry advisory board comprising AstraZeneca , Boehringer Ingelheim, GlaxoSmithKline , Novartis , Pfizer , Siemens, and Sunovion.

Publisher Copyright:
© 2021 American College of Chest Physicians

Keywords

  • emphysema
  • imaging
  • longitudinal
  • lung function
  • pulmonary circulation

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