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Turning subtypes into disease axes to improve prediction of COPD progression
  1. Junxiang Chen1,
  2. Michael Cho2,3,
  3. Edwin K Silverman2,3,
  4. John E Hokanson4,
  5. Greg L Kinney4,
  6. James D Crapo5,
  7. Stephen Rennard6,7,
  8. Jennifer Dy1,
  9. Peter Castaldi2,8
  1. 1 Department of Electrical and Computer Engineering, Northeastern University, Boston, United States
  2. 2 Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, United States
  3. 3 Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, United States
  4. 4 Colorado School of Public Health, University of Colorado Denver, Aurora, Colorado, USA
  5. 5 Department of Medicine, National Jewish Health, Denver, Colorado, USA
  6. 6 Division of Pulmonary, Critical Care, Sleep and Allergy, University of Nebraska Medical Center, Omaha, United States
  7. 7 IMED Biotech Unit, AstraZeneca, Cambridge, United Kingdom
  8. 8 Division of Primary Care and Internal Medicone, Brigham and Women's Hospital, Boston, United States
  1. Correspondence to Dr Peter Castaldi, Brigham and Women's Hospital Department of Medicine, Boston, MA 02115, USA; peter.castaldi{at}channing.harvard.edu

Abstract

Chronic obstructive pulmonary disease (COPD) is an umbrella definition encompassing multiple disease processes. COPD heterogeneity has been described as distinct subgroups of individuals (subtypes) or as continuous measures of COPD variability (disease axes). There is little consensus on whether subtypes or disease axes are preferred, and the relative value of disease axes and subtypes for predicting COPD progression is unknown. Using a propensity score approach to learn disease axes from pairs of subtypes, we demonstrate that these disease axes predict prospective forced expiratory volume in 1 s decline and emphysema progression more accurately than the subtype pairs from which they were derived.

  • copd epidemiology
  • emphysema
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Footnotes

  • Collaborators Administrative Center: James D. Crapo; Edwin K. Silverman; Barry J. Make; Elizabeth A. Regan; Genetic Analysis Center: Terri Beaty; Ferdouse Begum; Peter J. Castaldi; Michael Cho; Dawn L. DeMeo; Adel R. Boueiz; Marilyn G. Foreman; Eitan Halper-Stromberg; Lystra P. Hayden; Craig P. Hersh; Jacqueline Hetmanski; Brian D. Hobbs; John E. Hokanson; Nan Laird; Christoph Lange; Sharon M. Lutz; Merry-Lynn McDonald; Margaret M. Parker; Dandi Qiao; Elizabeth A. Regan; Edwin K. Silverman; Emily S. Wan; Sungho Won; Phuwanat Sakornsakolpat; Dmitry Prokopenko; Imaging Center: Mustafa Al Qaisi; Harvey O. Coxson; Teresa Gray; MeiLan K. Han; Eric A. Hoffman; Stephen Humphries; Francine L. Jacobson; Philip F. Judy; Ella A. Kazerooni; Alex Kluiber; David A. Lynch; John D. Newell; Elizabeth A. Regan; James C. Ross; Raul San Jose Estepar; Joyce Schroeder; Jered Sieren; Douglas Stinson; Berend C. Stoel; Juerg Tschirren; Edwin Van Beek; Bram van Ginneken; Eva van Rikxoort; George Washko; Carla G. Wilson; PFT QA Center, Salt Lake City, UT: Robert Jensen; Data Coordinating Center and Biostatistics, National Jewish Health, Denver, CO: Douglas Everett; Jim Crooks; Camille Moore; Matt Strand; Carla G. Wilson; Epidemiology Core, University of Colorado Anschutz Medical Campus, Aurora, CO: John E. Hokanson; John Hughes; Gregory Kinney; Sharon M. Lutz; Katherine Pratte; Kendra A. Young; Mortality Adjudication Core: Surya Bhatt; Jessica Bon; MeiLan K. Han; Barry Make; Carlos Martinez; Susan Murray; Elizabeth Regan; Xavier Soler; Carla G. Wilson; Biomarker Core: Russell P. Bowler; Katerina Kechris; Farnoush Banaei-Kashani; COPDGene® Investigators – Clinical Centers: Ann Arbor VA: Jeffrey L. Curtis; Carlos H. Martinez; Perry G. Pernicano; Baylor College of Medicine, Houston, TX: Nicola Hanania; Philip Alapat; Mustafa Atik; Venkata Bandi; Aladin Boriek; Kalpatha Guntupalli; Elizabeth Guy; Arun Nachiappan; Amit Parulekar; Brigham and Women’s Hospital, Boston, MA: Dawn L. DeMeo; Craig Hersh; Francine L. Jacobson; George Washko; Columbia University, New York, NY: R. Graham Barr; John Austin; Belinda D’Souza; Gregory D.N. Pearson; Anna Rozenshtein; Byron Thomashow; Duke University Medical Center, Durham, NC: Neil MacIntyre; H. Page McAdams; Lacey Washington; Health Partners Research Institute, Minneapolis: Charlene McEvoy; Joseph Tashjian; Johns Hopkins University, Baltimore: Robert Wise; Robert Brown; Nadia N. Hansel; Karen Horton; Allison Lambert; Nirupama Putcha; Los Angeles Biomedical Research Institute at Harbor UCLA Medical Center, Torrance, CA: Richard Casaburi; Alessandra Adami; Matthew Budoff; Hans Fischer; Janos Porszasz; Harry Rossiter; William Stringer; Michael E. DeBakey VAMC, Houston, TX: Amir Sharafkhaneh; Charlie Lan; Minneapolis VA: Christine Wendt; Brian Bell; Morehouse School of Medicine, Atlanta, GA: Marilyn G. Foreman; Eugene Berkowitz; Gloria Westney; National Jewish Health, Denver, CO: Russell Bowler; David A. Lynch; Reliant Medical Group, Worcester, MA: Richard Rosiello; David Pace; Temple University, Philadelphia, PA: Gerard Criner; David Ciccolella; Francis Cordova; Chandra Dass; Gilbert D’Alonzo; Parag Desai; Michael Jacobs; Steven Kelsen; Victor Kim; A. James Mamary; Nathaniel Marchetti; Aditi Satti; Kartik Shenoy; Robert M. Steiner; Alex Swift; Irene Swift; Maria Elena Vega-Sanchez; University of Alabama, Birmingham, AL: Mark Dransfield; William Bailey; Surya Bhatt; Anand Iyer; Hrudaya Nath; J. Michael Wells; University of California, San Diego, CA: Joe Ramsdell; Paul Friedman; Xavier Soler; Andrew Yen; University of Iowa, Iowa City, IA: Alejandro P. Comellas; Karin F. Hoth; John Newell; Brad Thompson; University of Michigan, Ann Arbor, MI: MeiLan K. Han; Ella Kazerooni; Carlos H. Martinez; University of Minnesota, Minneapolis, MN: Joanne Billings; Abbie Begnaud; Tadashi Allen; University of Pittsburgh, Pittsburgh, PA: Frank Sciurba; Jessica Bon; Divay Chandra; Carl Fuhrman; Joel Weissfeld; University of Texas Health Science Center at San Antonio, San Antonio, TX: Antonio Anzueto; Sandra Adams; Diego Maselli-Caceres; Mario E. Ruiz.

  • Contributors Study concept and design: JC, GLK, JEH and PC. Acquisition, analysis or interpretation of data: JC, MC, EKS, JDC, SR, JD and PC. Drafting of the manuscript: JC and PC. Critical revision of the manuscript for important intellectual content: All authors. Statistical analysis: JC, JD and PC. Obtained funding: EKS, JDC and PC.

  • Funding The COPDGene project is also supported by the COPD Foundation through contributions made to an Industry Advisory Board comprised of AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Novartis, Pfizer, Siemens and Sunovion. The project described was supported by award number U01 HL089897 and award number U01 HL089856 from the National Heart, Lung and Blood Institute.

  • Disclaimer 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.

  • Competing interests JC reports consulting fees and grant support from GSK and Novartis outside the submitted work. MC has received grant support from GSK. In the past 3 years, EKS received honoraria from Novartis for Continuing Medical Education Seminars and grant and travel support from GlaxoSmithKline.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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