Longitudinal Association Between Muscle Loss and Mortality in Ever Smokers

COPDGene Investigators

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

BACKGROUND: Body composition measures, specifically low weight or reduced muscle mass, are associated with mortality in COPD, but the effect of longitudinal body composition changes is undefined.

RESEARCH QUESTION: Is the longitudinal loss of fat-free mass (FFM) associated with increased mortality, including in those with initially normal or elevated body composition metrics?

STUDY DESIGN AND METHODS: Participants with complete data for at least one visit in the COPDGene study (n = 9,268) and the ECLIPSE study (n = 1,760) were included and monitored for 12 and 8 years, respectively. Pectoralis muscle area (PMA) was derived from thoracic CT scans and used as a proxy for FFM. A longitudinal mixed submodel for PMA and a Cox proportional hazards submodel for survival were fitted on a joint distribution, using a shared random intercept parameter and Markov chain Monte Carlo parameter estimation.

RESULTS: Both cohorts demonstrated a left-shifted distribution of baseline FFM, not reflected in BMI, and an increase in all-cause mortality risk associated with longitudinal loss of PMA. For each 1-cm 2 PMA loss, mortality increased 3.1% (95% CI, 2.4%-3.7%; P < .001) in COPDGene, and 2.4% (95% CI, 0.9%-4.0%; P < .001) in ECLIPSE. Increased mortality risk was independent of enrollment values for BMI and disease severity [BODE (body mass, airflow obstruction, dyspnea, and exercise capacity) index quartiles] and was significant even in participants with initially greater than average PMA.

INTERPRETATION: Longitudinal loss of PMA is associated with increased all-cause mortality, regardless of BMI or initial muscle mass. Consideration of novel screening tests and further research into mechanisms contributing to muscle decline may improve risk stratification and identify novel therapeutic targets in ever smokers.

Original languageEnglish (US)
Pages (from-to)960-970
Number of pages11
JournalCHEST
Volume161
Issue number4
DOIs
StatePublished - Apr 2022

Bibliographical note

Funding Information:
Author contributions: S. E. M. is the guarantor of the manuscript and wrote the manuscript. S. E. M. G. R. W. and M. J. S. were responsible for study design and statistical analysis. R. M.-M. Ru. S. J. E. and Ra. S. J. E. contributed to the computational imaging methodology. R. M.-M. W. W. L. M. J. S. E. A. R. J. B. R. C. M.-L. McD. H. B. R. B. M. M. T. D. M.L. K. H. K. Y. G. K. J. E. H. Ra. S. J. E. J. L. C. K. S. and G. R. W. revised the manuscript for critical intellectual content. Financial/nonfinancial disclosures: M. J. S. H. B. R. M. T. D. M.L. K. H. K. Y. J. L. C. K. S. and Ra. S. J. E. report grants from the National Institutes of Health. H. B. R. reports grant funding from the Tobacco-Related Disease Program. S. E. M. R. M.-M. W. W. L. E. A. R. J. B. Ru. S. J. E. R. C. M.-L. McD. B. M. G. K. J. E. H. and G. R. W.: None declared. For a comprehensive listing of disclosures not related to this work, please see the online article. Role of sponsors: The sponsors had no role in the design of the study, the collection and analysis of the data, or the preparation of the manuscript. ?COPDGene Investigators: Administrative Center: James D. Crapo, MD, Edwin K. Silverman, MD, PhD, Sara Cummings, Kelley Madden, Barry J. Make, MD, Juliet Nabbosa, Emily Port, Serine Rashdi, Elizabeth A. Regan, MD, PhD, Lori Stepp, Shandi Watts, MS, Michael Weaver; Executive Committee: Terri Beaty, PhD, Russell P. Bowler, MD, PhD, James D. Crapo, MD, Jeffrey L. Curtis, MD, MeiLan K. Han, MD, MS, John E. Hokanson, MPH, PhD, David A. Lynch, MB, Barry J. Make, MD, Elizabeth A. Regan, MD, PhD, Edwin K. Silverman, MD, PhD, Matthew J. Strand, PhD; External Advisory Committee: Gary Anderson, PhD, Eugene R. Bleecker, MD, Harvey O. Coxson, PhD, Ronald G. Crystal, MD, James C. Hogg, MD, Michael A. Province, PhD, Stephen I. Rennard, MD; NHLBI: Thomas Croxton, MD, PhD, Weiniu Gan, PhD, Lisa A. Postow, PhD, Lisa M. Viviano, BSN; COPD Foundation: Corinne Costa-Davis, Elisha Malanga, Delia Prieto, Ruth Tal-Singer, PhD; Biorepository Visit 1 (Baltimore): Homayoon Farzadegan, PhD, Akila Hadji; Biorepository Visits 2 & 3 (Boston): Leena Sathe, PhD; Data Coordinating Center: Director: Matthew J. Strand, PhD, David Baraghoshi, Grace Chen, James Crooks, PhD, Ruthie Knowles, MSW, CCRP, Katherine Pratte, PhD, Carla Wilson, MS, Pearlanne T. Zelarney, MS; National Jewish Analysis Group: James D. Crapo, MD, Russell P. Bowler, MD, PhD, Katerina J. Kechris, PhD, Sonia Leach, PhD, Elizabeth A. Regan, MD, PhD; Epidemiology Center: Director: John E. Hokanson, MPH, PhD, Erin E. Austin, PhD, Annika Czizik, Gregory Kinney, MPH, PhD, Yisha Li, Sharon M. Lutz, MPH, PhD, Margaret F. Ragland, MD, MS, Nicole Richmond, MPH, Kendra A. Young, MSPH, PhD; Sequencing and Bioinformatics Center: Director: Michael Cho, MD, Peter J. 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Coxson, PhD, Jennifer G. Dy, PhD, Sean B. Fain, PhD, Shoshana Ginsburg, MS, Eric A. Hoffman, PhD, Stephen Humphries, PhD, Philip F. Judy, PhD, Alex Kluiber Stefanie Mason, MD, Andrea Oh, MD, Clare Poynton, MD, PhD, Joseph M. Reinhardt, PhD, James Ross, PhD, Raul San Jose Estepar, PhD, Joyce D. Schroeder, MD, Arkadiusz Sitek, PhD, Robert M. Steiner, MD, Edwin van Beek, MD, PhD, Med, Bram van Ginneken, PhD, Eva van Rikxoort, PhD, George R. Washko, MD; PFT QA Center: Robert Jensen, PhD, Committees: Ancillary Studies and Publication Committee: Co-Chair: James D. Crapo, MD, Co-Chair: John E. Hokanson, MPH, PhD, Surya P. Bhatt, MD, Richard Casaburi, PhD, MD, Peter J. Castaldi, MD, MSc, Jeffrey L. Curtis, MD, Dawn L. DeMeo, MD, MPH, MeiLan K. Han, MD, MS, Craig P. Hersh, MD, MPH, Stephen Humphries, PhD, Victor Kim, MD, David A. Lynch, MB, Barry J. Make, MD, Nirupama Putcha, MD, MHS, Elizabeth A. Regan, MD, PhD, Edwin K. Silverman, MD, PhD, Matthew J. 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Hoth, PhD, Victor Kim, MD, Allison Lambert, MD, Katherine Lowe, MS, Barry J. Make, MD, Gabriela Oates, PhD, Trisha Parekh, DO, Nirupama Putcha, MD, MHS, Elizabeth A. Regan, MD, PhD, Shandi Watts, Gloria Westney, MD, MS, Kendra Young, MSPH, PhD; Clinical Epidemiology Working Group: Co-Chair: MeiLan K. Han, MD, MS, Co-Chair: Nirupama Putcha, MD, MHS, Antonio Anzueto, MD, Aparna Balasubramanian, MD, Surya P. Bhatt, MD, Jessica Bon, MD, Aladin Boriek, PhD, Russell P. Bowler, MD, PhD, Richard Casaburi, PhD, MD, Michael H. Cho, MD, Douglas Conrad, MD, Jeffrey L. Curtis, MD, Dawn L. DeMeo, MD, MPH, Alejandro A. Diaz, MD, MPH, Mark T. Dransfield, MD, Ashraf Fawzy, MD, MPH, Nicola A. Hanania, MD, MS, Nadia N. Hansel, MD, MPH, Lystra P. Hayden, MD, Craig P. Hersh, MD, MPH, John E. Hokanson, MPH, PhD, Karin F. Hoth, PhD, Francine Jacobson, MD, MPH, Victor Kim, MD, Greg Kinney, MPH, PhD, David C. LaFon, MD, Allison Lambert, MD, Neil MacIntyre, MD, Barry J. Make, MD, Diego Maselli-Caceres, MD, Meredith C. McCormack, MD, MHS, Merry-Lynn McDonald, PhD, Matthew Moll, MD, Trisha Parekh, DO, Elizabeth A. Regan, MD, PhD, Frank Sciurba, MD, Edwin K. Silverman, MD, PhD, Xavier Soler, MD, PhD, Robert M. Steiner, MD, Vickram Tejwani, MD, Edwin JR van Beek, MD, PhD, Raymond C. Wade, MD, Emily S. Wan, MD, George R. Washko, MD, Shandi Watts, Mike Wells, MD, Chris H. Wendt, MD, Kendra Young, MSPH, PhD, Jeong H. Yun, MD, MPH, Jingzhou Zhang, MD, MPH; Clinical Translation Working Group: Chair: James D. Crapo, MD, Erin E. Austin, PhD, Russell P. Bowler, MD, PhD, Peter J. Castaldi, MD, MSc, Lucas Gillenwater, MPH, Med, John E. Hokanson, MPH, PhD, Stephen Humphries, PhD, Greg Kinney, MPH, PhD, Yisha Li, MPH, BPharm, Katherine E. Lowe, MSc, David A. Lynch, MB, Barry J. Make, MD, Matthew Moll, MD, Katherine A. Pratte, PhD, Margaret Ragland, MD, PhD, Elizabeth A. Regan, MD, PhD, Nicole Richmond, MPH, Matthew J. 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Castaldi, MD, MSc, Takis Benos, PhD, Richard Casaburi, PhD, MD, James D. Crapo, MD, Dawn L. DeMeo, MD, MPH, Jennifer G. Dy, PhD, MeiLan K. Han, MD, MS, Lystra P. Hayden, MD, Craig P. Hersh, MD, MPH, Brian D. Hobbs, MD, Greg Kinney, MPH, PhD, Sharon M. Lutz, MPH, PhD, David A. Lynch, MB, Barry J. Make, MD, Bruce E. Miller, PhD, Elizabeth A. Regan, MD, PhD, Stephen I. Rennard, MD, Tara Retson, MD, PhD, James Ross, PhD, Raul San Jose Estepar, PhD, Frank Sciurba, MD, Edwin K. Silverman, MD, PhD, Xavier Soler, MD, PhD, Robert M. Steiner, MD, Edwin JR van Beek, MD, PhD, Emily S. Wan, MD, George R. Washko, MD, Carla Wilson, MS, Kendra Young, MSPH, PhD; Clinical Centers: Ann Arbor VA Medical Center: Jeffrey L. Curtis, MD, Lisa McCloskey BBA, RRT, Perry G. Pernicano, MD; Baylor College of Medicine: Nicola A. Hanania, MD, MS, Mustafa Atik, MD, CCRP, Laura Bertrand, RN, RPFT, Aladin Boriek, PhD, Thomas Monaco, MD, Dharani Narendra, MD, Veronica V. Lenge de Rosen, MD; Brigham and Women's Hospital: Dawn L. DeMeo, MD, MPH, Craig P. Hersh, MD, MPH, Kwame Badu-Danso, BS, Alejandro A. Diaz, MD, MPH, Lystra P. Hayden, MD, Brian D. Hobbs, MD, Francine L. Jacobson, MD, MPH, Laura Kaufman, PA-C, Cherie Maguire, MS, CAGS, Clare Poynton, MD, PhD, Sophie Struble, George R. Washko, MD, Seth Wilson, Jeong H. Yun, MD, MPH, Jingzhou Zhang, MD, MPH; Columbia University Medical Center: R. Graham Barr, MD, DrPH, Casandra Almonte, John H.M. Austin, MD, Maria Lorena Gomez Blum, Belinda M. D'Souza, MD, Emilay Florez, Rodney Martinez; Byron Thomashow, MD; Duke Univ. Medical Center: Neil MacIntyre, Jr. MD, Wendy Curry, BS, RRT, H. Page McAdams, MD, Charlotte V. Reikofski, Lacey Washington, MD; Johns Hopkins University: Robert A. Wise, MD, Aparna Balasubramanian, MD, Robert Brown, MD, Cheryl Clare, Marie Daniel, RN, CCRP, Ashraf Fawzy, MD, MPH, Nadia N. Hansel, MD, MPH, Karen Horton, MD, Cheng Ting ?Tony? Lin, MD, Meredith C. 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Bowler, MD, PhD, Grace Broadhurst, Debra Dyer, MD, Elena Engel, Jay Finigan, MD, Andrew Hill, MS, Alex Jones, Ryan Jones, Jordan Owen, David A. Lynch, MB; Reliant Medical Group (Fallon): Richard Rosiello, MD, Nicole Andries, RN, Mary Charpentier, Diane Kirk, RN, David Pace, MD; Temple University: Gerard J. Criner, MD, David Ciccolella, MD, Francis Cordova, MD, Chandra Dass, MD, Gilbert D'Alonzo, DO, Valena Davis, Parag Desai, MD, Dee Fehrle, BSN, MHA, Carla Grabianowski, RN, BSN, Michael Jacobs, PharmD, Laurie Jameson, Gayle M. Jones, RN, BSN, CCRP, Steven Kelsen, MD, PhD, Victor Kim, MD, A. James Mamary, MD, Nathaniel Marchetti, DO, Francine McGonagle, Aditi Satti, MD, Kartik Shenoy, MD, Regina Sheridan, Maria Vega-Sanchez, MD, Samantha Wallace; University of Alabama, Birmingham: Surya P. Bhatt, MD, Samuel Akinseye-kolapo, William C. Bailey, MD, Matthew Baker, Mark T. Dransfield, MD, Arnissa Goggins, Anand Iyer, MD, David C. LaFon, MD, Anny McClain, Merry-Lynn McDonald, PhD, Takudzwa Mkorombindo, MD, Hrudaya Nath, MD, Gabriela Oates, PhD, Trisha Parekh, DO, Satinder P. Singh, MD, FCCP, Sushil K. Sonavane, MD, Raymond C. Wade, MD, Mike Wells, MD, Elizabeth Westfall, MPH; University of California, San Diego: Douglas Conrad, MD, Marissa Gil, Tarek El Hajjaoui, Albert Hsiao, MD, PhD, Amber Martineau, Jenna Mielke, Karl Perez, Gabriel Querido, Tara Reston, MD, PhD, Xavier Soler, MD, PhD, Andrew Yen, MD; University of Iowa: Alejandro Comellas, MD, Spyridon Fortis, MD, Mauricio Galizia, MD, Eric Garcia, Karin F. Hoth, PhD, Janet Keating, Archana Laroia, MD, Changhyun Lee, MD, PhD, Amber Meyer, Brian Mullan, MD, Prashant Nagpal, MD, Oloigbe Ofori, Kim Sprenger, RN, BS, Sierra Suiter. Additional information: The e-Figures and e-Tables can be found in the Supplemental Materials section of the online article. FUNDING/SUPPORT: This work was supported by National Institutes of Health (NIH) [grants HL089856 and HL089897, and T32 HL007633 (S. E. M.)]; and by the COPD Foundation.

Funding Information:
Financial/nonfinancial disclosures: M. J. S., H. B. R., M. T. D., M.L. K. H., K. Y., J. L. C., K. S., and Ra. S. J. E. report grants from the National Institutes of Health. H. B. R. reports grant funding from the Tobacco-Related Disease Program. S. E. M., R. M.-M., W. W. L., E. A. R., J. B., Ru. S. J. E., R. C., M.-L. McD., B. M., G. K., J. E. H., and G. R. W.: None declared. For a comprehensive listing of disclosures not related to this work, please see the online article.

Funding Information:
FUNDING/SUPPORT: This work was supported by National Institutes of Health (NIH) [grants HL089856 and HL089897, and T32 HL007633 (S. E. M.)]; and by the COPD Foundation.

Publisher Copyright:
© 2021 American College of Chest Physicians

Keywords

  • COPD
  • mortality
  • muscle wasting
  • sarcopenia
  • Body Composition
  • Body Mass Index
  • Pulmonary Disease, Chronic Obstructive/complications
  • Smokers
  • Humans
  • Lung
  • Pectoralis Muscles
  • Longitudinal Studies

PubMed: MeSH publication types

  • Journal Article
  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

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