Longitudinal Association Between Muscle Loss and Mortality in Ever Smokers

COPDGene Investigators

doi:10.1016/j.chest.2021.10.047

Longitudinal Association Between Muscle Loss and Mortality in Ever Smokers

COPDGene Investigators

Research output: Contribution to journal › Article › peer-review

22 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 language	English (US)
Pages (from-to)	960-970
Number of pages	11
Journal	CHEST
Volume	161
Issue number	4
DOIs	https://doi.org/10.1016/j.chest.2021.10.047
State	Published - Apr 1 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. Castaldi, MD, MSc, Kimberly Glass, PhD, Craig Hersh, MD, MPH, Wonji Kim, PhD, Yang-Yu Liu, PhD, Edwin K. Silverman, MD, PhD; Genotyping Centers: Genome-Wide Center: Director: Terri Beaty, PhD; Candidate Genotyping Center: Craig P. Hersh, MD, MPH, Edwin K. Silverman, MD, PhD; Genetic Analysis Center: Director: Edwin K. Silverman, MD, PhD, Terri Beaty, PhD, Jacqueline Bidinger, MS, Peter J. Castaldi, MD, MSc, Michael H. Cho, MD, Douglas Conrad, MD, Dawn L. DeMeo, MD, MPH, Adel R. El-Boueiz, MD, Marilyn G. Foreman, MD, MS, Auyon Ghosh, MD, Georg Hahn, PhD, Nadia N. Hansel, MD, MPH, Lystra P. Hayden, MD, Craig Hersh, MD, MPH, Brian Hobbs, MD, Wonji Kim, PhD, Woori Kim, PhD, Christoph Lange, PhD, Sharon M. Lutz, MPH, PhD, Merry-Lynn McDonald, PhD, Michael McGeachie, PhD, Matthew Moll, MD, Melody Morris, PhD, Nikolaos A. Patsopoulos, MD, PhD, Dandi Qiao, PhD, Elizabeth A. Regan, MD, PhD, Ingo Ruczinski, PhD, Emily S. Wan, MD; Imaging Center: Director: David A. Lynch, MB, Harvey O. 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. Strand, PhD, Shandi Watts, Carla Wilson; Death Adjudication Committee: Chair: MeiLan Han, MD, Surya P. Bhatt, MD, Jessica Bon, MD, Alejandro A. Diaz, MD, MPH, Barry J. Make, MD, Elizabeth Regan, MD, PhD, Carla Wilson; Industry Advisory Committee: AstraZeneca, Bayer, Boehringer-Ingelheim, Genentech, GSK, Novartis, Sunovion; Longitudinal Follow-up Committee: Chair: Elizabeth A. Regan, MD, PhD, Antonio Anzueto, MD, William C. Bailey, MD, Jessica Bon, MD, Russell P. Bowler, MD, PhD, James D. Crapo, MD, Gerard J. Criner, MD, Mark T. Dransfield, MD, MeiLan K. Han, MD, MS, John E. Hokanson, MPH, PhD, Victor Kim, MD, Greg Kinney, MPH, PhD, Barry J. Make, MD, Kim Sprenger, RN, BS, Lori Stepp, Carla Wilson, MS; Working Groups: Age, Race and Gender Working Group: Chair: Dawn L. DeMeo, MD, MPH, Takis Benos, PhD, Surya P. Bhatt, MD, Russell P. Bowler, MD, PhD, Mark T. Dransfield, MD, Marilyn G. Foreman, MD, MS, Nicola A. Hanania, MD, MS, Nadia N. Hansel, MD, MPH, Karin F. 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. Strand, PhD, Kendra Young, MSPH, PhD; Musculoskeletal Working Group: Chair: Elizabeth A. Regan, MD, PhD, Amy Attaway, Jessica Bon, MD, Richard Casaburi, PhD, MD, Dawn L. DeMeo, MD, MPH, Stephen Humphries, PhD, Barry J. Make, MD, Stefanie Mason, MD, Merry-Lynn McDonald, PhD, Harry B. Rossiter, PhD, Punam Kumar Saha, PhD, Raul San Jose Estepar, PhD, George R. Washko, MD, Shandi Watts, Ava Wilson, MS, Kendra Young, MSPH, PhD; Race, Spirometry and Census Data Working Group: Chair: Elizabeth A. Regan, MD, PhD, Hannatu Amaza, Aparna Balasubramanian, MD, Adrienne Baldomero, Surya P. Bhatt, MD, Richard Casaburi, PhD, MD, James Crooks, PhD, Jeffrey L. Curtis, MD, Dawn L. DeMeo, MD, MPH, Alejandro A. Diaz, MD, MPH, Mark T. Dransfield, MD, Marilyn G. Foreman, MD, MS, MeiLan Han, MD, MS, Nicola A. Hanania, MD, MS, Nadia N. Hansel, MD, MPH, Karin F. Hoth, PhD, Victor Kim, MD, Greg Kinney, MPH, PhD, Katherine Lowe, MS, Barry J. Make, MD, A. James Mamary, MD, Gabriela Oates, PhD, James O'Brien, MD, Trisha Parekh, DO, Nirupama Putcha, MD, MHS, Shandi Watts, Gloria Westney, MD, MS, Robert A. Wise, MD, Kendra Young, MSPH, PhD; Social and Behavioral Sciences Working Group: Chair: Karin F. Hoth, PhD, Surya P. Bhatt, MD, Sara Cummings, Annika Czizik, Dawn L. DeMeo, MD, MPH, Mark T. Dransfield, MD, Michelle Eakin, PhD, Jess G. Fiedorowicz, MD, PhD, Marilyn G. Foreman, MD, MS, Nicola A. Hanania, MD, MS, Ben Henkle, MD, MPH, Kristen Holm, PhD, MPH, Karin F. Hoth, PhD, Anand Iyer, MD, Victor Kim, MD, Greg Kinney, MPH, PhD, Ken M. Kunisaki, MD, MS, Katherine Lowe, MS, Barry J. Make, MD, Merry-Lynn McDonald, PhD, Charlene McEvoy, MD, MPH, Takudzwa Mkorombindo, MD, Gabriela Oates, PhD, Trisha Parekh, DO, Elizabeth A. Regan, MD, PhD, Gen Shinozaki, MD, Shandi Watts, Robert A. Wise, MD, Abebaw Yohannes, PhD; Subtyping Working Group: Co-Chair: Michael H. Cho, MD, Co-Chair: Peter J. 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. McCormack, MD, MHS, Tahira Mirza, Nirupama Putcha, MD, MHS, Meagan Scott, Becky Shade; L.A. Biomedical Research Institute: Richard Casaburi, PhD, MD, Matt Budoff, MD, Robert Calmelat, Deborah Cavanaugh, Chris Dailing, Leticia Diaz, Hans Fischer, MD, PhD, Renee Love Indelicato, Janos Porszasz, MD, PhD, Harry B. Rossiter, PhD, April Soriano, William Stringer, MD, Miriam Urrutia; Minneapolis VA Medical Center: Chris H. Wendt, MD, Arianne Baldomero, MD, Brian Bell, MD, Miranda Deconcini, Ken M. Kunisaki, MD, MS; Minnesota HealthPartners ? Twin Cities: Charlene McEvoy, MD, MPH, Linda Loes, Jonathan Phelan, MD, Camille Robichaux, MD, Cheryl Sasse, Joseph H. Tashjian, MD; Morehouse School of Medicine: Eric L. Flenaugh, MD, FCCP, Kema Abson, Marilyn G. Foreman, MD, MS, Hirut Gebrekristos, PhD, Priscilla Johnson, MSN, PhD, Jessica Jordan, Mario Ponce, MD, Silanath Terpenning, MD, Gloria Westney, MD, MS, Derrick Wilson, MS; National Jewish Health: Russell P. 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

Publisher link

10.1016/j.chest.2021.10.047

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@article{97974027780e4bc989865afaabc1bc59,

title = "Longitudinal Association Between Muscle Loss and Mortality in Ever Smokers",

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.",

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

author = "{COPDGene Investigators} and Mason, {Stefanie E.} and Rafael Moreta-Martinez and Labaki, {Wassim W.} and Strand, {Matthew J.} and Regan, {Elizabeth A.} and Jessica Bon and {San Jose Estepar}, Ruben and Richard Casaburi and McDonald, {Merry Lynn} and Rossiter, {Harry B.} and Barry Make and Dransfield, {Mark T.} and Han, {Mei Lan K.} and Kendra Young and Curtis, {Jeffrey L.} and Kathleen Stringer and Greg Kinney and Hokanson, {John E.} and {San Jose Estepar}, Raul and Washko, {George R.} and Crapo, {James D.} and Silverman, {Edwin K.} and Sara Cummings and Kelley Madden and Make, {Barry J.} and Juliet Nabbosa and Emily Port and Serine Rashdi and Lori Stepp and Shandi Watts and Michael Weaver and Terri Beaty and Bowler, {Russell P.} and Lynch, {David A.} and Gary Anderson and Bleecker, {Eugene R.} and Coxson, {Harvey O.} and Crystal, {Ronald G.} and Hogg, {James C.} and Province, {Michael A.} and Rennard, {Stephen I.} and Thomas Croxton and Weiniu Gan and Wendt, {Chris H.} and Ben Henkle and Kunisaki, {Ken M.} and Charlene McEvoy and Arianne Baldomero and Tashjian, {Joseph H.} and Spyridon Fortis",

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. Castaldi, MD, MSc, Kimberly Glass, PhD, Craig Hersh, MD, MPH, Wonji Kim, PhD, Yang-Yu Liu, PhD, Edwin K. Silverman, MD, PhD; Genotyping Centers: Genome-Wide Center: Director: Terri Beaty, PhD; Candidate Genotyping Center: Craig P. Hersh, MD, MPH, Edwin K. Silverman, MD, PhD; Genetic Analysis Center: Director: Edwin K. Silverman, MD, PhD, Terri Beaty, PhD, Jacqueline Bidinger, MS, Peter J. Castaldi, MD, MSc, Michael H. Cho, MD, Douglas Conrad, MD, Dawn L. DeMeo, MD, MPH, Adel R. El-Boueiz, MD, Marilyn G. Foreman, MD, MS, Auyon Ghosh, MD, Georg Hahn, PhD, Nadia N. Hansel, MD, MPH, Lystra P. Hayden, MD, Craig Hersh, MD, MPH, Brian Hobbs, MD, Wonji Kim, PhD, Woori Kim, PhD, Christoph Lange, PhD, Sharon M. Lutz, MPH, PhD, Merry-Lynn McDonald, PhD, Michael McGeachie, PhD, Matthew Moll, MD, Melody Morris, PhD, Nikolaos A. Patsopoulos, MD, PhD, Dandi Qiao, PhD, Elizabeth A. Regan, MD, PhD, Ingo Ruczinski, PhD, Emily S. Wan, MD; Imaging Center: Director: David A. Lynch, MB, Harvey O. 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. Strand, PhD, Shandi Watts, Carla Wilson; Death Adjudication Committee: Chair: MeiLan Han, MD, Surya P. Bhatt, MD, Jessica Bon, MD, Alejandro A. Diaz, MD, MPH, Barry J. Make, MD, Elizabeth Regan, MD, PhD, Carla Wilson; Industry Advisory Committee: AstraZeneca, Bayer, Boehringer-Ingelheim, Genentech, GSK, Novartis, Sunovion; Longitudinal Follow-up Committee: Chair: Elizabeth A. Regan, MD, PhD, Antonio Anzueto, MD, William C. Bailey, MD, Jessica Bon, MD, Russell P. Bowler, MD, PhD, James D. Crapo, MD, Gerard J. Criner, MD, Mark T. Dransfield, MD, MeiLan K. Han, MD, MS, John E. Hokanson, MPH, PhD, Victor Kim, MD, Greg Kinney, MPH, PhD, Barry J. Make, MD, Kim Sprenger, RN, BS, Lori Stepp, Carla Wilson, MS; Working Groups: Age, Race and Gender Working Group: Chair: Dawn L. DeMeo, MD, MPH, Takis Benos, PhD, Surya P. Bhatt, MD, Russell P. Bowler, MD, PhD, Mark T. Dransfield, MD, Marilyn G. Foreman, MD, MS, Nicola A. Hanania, MD, MS, Nadia N. Hansel, MD, MPH, Karin F. 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. Strand, PhD, Kendra Young, MSPH, PhD; Musculoskeletal Working Group: Chair: Elizabeth A. Regan, MD, PhD, Amy Attaway, Jessica Bon, MD, Richard Casaburi, PhD, MD, Dawn L. DeMeo, MD, MPH, Stephen Humphries, PhD, Barry J. Make, MD, Stefanie Mason, MD, Merry-Lynn McDonald, PhD, Harry B. Rossiter, PhD, Punam Kumar Saha, PhD, Raul San Jose Estepar, PhD, George R. Washko, MD, Shandi Watts, Ava Wilson, MS, Kendra Young, MSPH, PhD; Race, Spirometry and Census Data Working Group: Chair: Elizabeth A. Regan, MD, PhD, Hannatu Amaza, Aparna Balasubramanian, MD, Adrienne Baldomero, Surya P. Bhatt, MD, Richard Casaburi, PhD, MD, James Crooks, PhD, Jeffrey L. Curtis, MD, Dawn L. DeMeo, MD, MPH, Alejandro A. Diaz, MD, MPH, Mark T. Dransfield, MD, Marilyn G. Foreman, MD, MS, MeiLan Han, MD, MS, Nicola A. Hanania, MD, MS, Nadia N. Hansel, MD, MPH, Karin F. Hoth, PhD, Victor Kim, MD, Greg Kinney, MPH, PhD, Katherine Lowe, MS, Barry J. Make, MD, A. James Mamary, MD, Gabriela Oates, PhD, James O'Brien, MD, Trisha Parekh, DO, Nirupama Putcha, MD, MHS, Shandi Watts, Gloria Westney, MD, MS, Robert A. Wise, MD, Kendra Young, MSPH, PhD; Social and Behavioral Sciences Working Group: Chair: Karin F. Hoth, PhD, Surya P. Bhatt, MD, Sara Cummings, Annika Czizik, Dawn L. DeMeo, MD, MPH, Mark T. Dransfield, MD, Michelle Eakin, PhD, Jess G. Fiedorowicz, MD, PhD, Marilyn G. Foreman, MD, MS, Nicola A. Hanania, MD, MS, Ben Henkle, MD, MPH, Kristen Holm, PhD, MPH, Karin F. Hoth, PhD, Anand Iyer, MD, Victor Kim, MD, Greg Kinney, MPH, PhD, Ken M. Kunisaki, MD, MS, Katherine Lowe, MS, Barry J. Make, MD, Merry-Lynn McDonald, PhD, Charlene McEvoy, MD, MPH, Takudzwa Mkorombindo, MD, Gabriela Oates, PhD, Trisha Parekh, DO, Elizabeth A. Regan, MD, PhD, Gen Shinozaki, MD, Shandi Watts, Robert A. Wise, MD, Abebaw Yohannes, PhD; Subtyping Working Group: Co-Chair: Michael H. Cho, MD, Co-Chair: Peter J. 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. McCormack, MD, MHS, Tahira Mirza, Nirupama Putcha, MD, MHS, Meagan Scott, Becky Shade; L.A. Biomedical Research Institute: Richard Casaburi, PhD, MD, Matt Budoff, MD, Robert Calmelat, Deborah Cavanaugh, Chris Dailing, Leticia Diaz, Hans Fischer, MD, PhD, Renee Love Indelicato, Janos Porszasz, MD, PhD, Harry B. Rossiter, PhD, April Soriano, William Stringer, MD, Miriam Urrutia; Minneapolis VA Medical Center: Chris H. Wendt, MD, Arianne Baldomero, MD, Brian Bell, MD, Miranda Deconcini, Ken M. Kunisaki, MD, MS; Minnesota HealthPartners ? Twin Cities: Charlene McEvoy, MD, MPH, Linda Loes, Jonathan Phelan, MD, Camille Robichaux, MD, Cheryl Sasse, Joseph H. Tashjian, MD; Morehouse School of Medicine: Eric L. Flenaugh, MD, FCCP, Kema Abson, Marilyn G. Foreman, MD, MS, Hirut Gebrekristos, PhD, Priscilla Johnson, MSN, PhD, Jessica Jordan, Mario Ponce, MD, Silanath Terpenning, MD, Gloria Westney, MD, MS, Derrick Wilson, MS; National Jewish Health: Russell P. 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: {\textcopyright} 2021 American College of Chest Physicians",

year = "2022",

month = apr,

day = "1",

doi = "10.1016/j.chest.2021.10.047",

language = "English (US)",

volume = "161",

pages = "960--970",

journal = "CHEST",

issn = "0012-3692",

publisher = "Elsevier Inc.",

number = "4",

}

TY - JOUR

T1 - Longitudinal Association Between Muscle Loss and Mortality in Ever Smokers

AU - COPDGene Investigators

AU - Mason, Stefanie E.

AU - Moreta-Martinez, Rafael

AU - Labaki, Wassim W.

AU - Strand, Matthew J.

AU - Regan, Elizabeth A.

AU - Bon, Jessica

AU - San Jose Estepar, Ruben

AU - Casaburi, Richard

AU - McDonald, Merry Lynn

AU - Rossiter, Harry B.

AU - Make, Barry

AU - Dransfield, Mark T.

AU - Han, Mei Lan K.

AU - Young, Kendra

AU - Curtis, Jeffrey L.

AU - Stringer, Kathleen

AU - Kinney, Greg

AU - Hokanson, John E.

AU - San Jose Estepar, Raul

AU - Washko, George R.

AU - Crapo, James D.

AU - Silverman, Edwin K.

AU - Cummings, Sara

AU - Madden, Kelley

AU - Make, Barry J.

AU - Nabbosa, Juliet

AU - Port, Emily

AU - Rashdi, Serine

AU - Stepp, Lori

AU - Watts, Shandi

AU - Weaver, Michael

AU - Beaty, Terri

AU - Bowler, Russell P.

AU - Lynch, David A.

AU - Anderson, Gary

AU - Bleecker, Eugene R.

AU - Coxson, Harvey O.

AU - Crystal, Ronald G.

AU - Hogg, James C.

AU - Province, Michael A.

AU - Rennard, Stephen I.

AU - Croxton, Thomas

AU - Gan, Weiniu

AU - Wendt, Chris H.

AU - Henkle, Ben

AU - Kunisaki, Ken M.

AU - McEvoy, Charlene

AU - Baldomero, Arianne

AU - Tashjian, Joseph H.

AU - Fortis, Spyridon

N1 - 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. Castaldi, MD, MSc, Kimberly Glass, PhD, Craig Hersh, MD, MPH, Wonji Kim, PhD, Yang-Yu Liu, PhD, Edwin K. Silverman, MD, PhD; Genotyping Centers: Genome-Wide Center: Director: Terri Beaty, PhD; Candidate Genotyping Center: Craig P. Hersh, MD, MPH, Edwin K. Silverman, MD, PhD; Genetic Analysis Center: Director: Edwin K. Silverman, MD, PhD, Terri Beaty, PhD, Jacqueline Bidinger, MS, Peter J. Castaldi, MD, MSc, Michael H. Cho, MD, Douglas Conrad, MD, Dawn L. DeMeo, MD, MPH, Adel R. El-Boueiz, MD, Marilyn G. Foreman, MD, MS, Auyon Ghosh, MD, Georg Hahn, PhD, Nadia N. Hansel, MD, MPH, Lystra P. Hayden, MD, Craig Hersh, MD, MPH, Brian Hobbs, MD, Wonji Kim, PhD, Woori Kim, PhD, Christoph Lange, PhD, Sharon M. Lutz, MPH, PhD, Merry-Lynn McDonald, PhD, Michael McGeachie, PhD, Matthew Moll, MD, Melody Morris, PhD, Nikolaos A. Patsopoulos, MD, PhD, Dandi Qiao, PhD, Elizabeth A. Regan, MD, PhD, Ingo Ruczinski, PhD, Emily S. Wan, MD; Imaging Center: Director: David A. Lynch, MB, Harvey O. 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. Strand, PhD, Shandi Watts, Carla Wilson; Death Adjudication Committee: Chair: MeiLan Han, MD, Surya P. Bhatt, MD, Jessica Bon, MD, Alejandro A. Diaz, MD, MPH, Barry J. Make, MD, Elizabeth Regan, MD, PhD, Carla Wilson; Industry Advisory Committee: AstraZeneca, Bayer, Boehringer-Ingelheim, Genentech, GSK, Novartis, Sunovion; Longitudinal Follow-up Committee: Chair: Elizabeth A. Regan, MD, PhD, Antonio Anzueto, MD, William C. Bailey, MD, Jessica Bon, MD, Russell P. Bowler, MD, PhD, James D. Crapo, MD, Gerard J. Criner, MD, Mark T. Dransfield, MD, MeiLan K. Han, MD, MS, John E. Hokanson, MPH, PhD, Victor Kim, MD, Greg Kinney, MPH, PhD, Barry J. Make, MD, Kim Sprenger, RN, BS, Lori Stepp, Carla Wilson, MS; Working Groups: Age, Race and Gender Working Group: Chair: Dawn L. DeMeo, MD, MPH, Takis Benos, PhD, Surya P. Bhatt, MD, Russell P. Bowler, MD, PhD, Mark T. Dransfield, MD, Marilyn G. Foreman, MD, MS, Nicola A. Hanania, MD, MS, Nadia N. Hansel, MD, MPH, Karin F. 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. Strand, PhD, Kendra Young, MSPH, PhD; Musculoskeletal Working Group: Chair: Elizabeth A. Regan, MD, PhD, Amy Attaway, Jessica Bon, MD, Richard Casaburi, PhD, MD, Dawn L. DeMeo, MD, MPH, Stephen Humphries, PhD, Barry J. Make, MD, Stefanie Mason, MD, Merry-Lynn McDonald, PhD, Harry B. Rossiter, PhD, Punam Kumar Saha, PhD, Raul San Jose Estepar, PhD, George R. Washko, MD, Shandi Watts, Ava Wilson, MS, Kendra Young, MSPH, PhD; Race, Spirometry and Census Data Working Group: Chair: Elizabeth A. Regan, MD, PhD, Hannatu Amaza, Aparna Balasubramanian, MD, Adrienne Baldomero, Surya P. Bhatt, MD, Richard Casaburi, PhD, MD, James Crooks, PhD, Jeffrey L. Curtis, MD, Dawn L. DeMeo, MD, MPH, Alejandro A. Diaz, MD, MPH, Mark T. Dransfield, MD, Marilyn G. Foreman, MD, MS, MeiLan Han, MD, MS, Nicola A. Hanania, MD, MS, Nadia N. Hansel, MD, MPH, Karin F. Hoth, PhD, Victor Kim, MD, Greg Kinney, MPH, PhD, Katherine Lowe, MS, Barry J. Make, MD, A. James Mamary, MD, Gabriela Oates, PhD, James O'Brien, MD, Trisha Parekh, DO, Nirupama Putcha, MD, MHS, Shandi Watts, Gloria Westney, MD, MS, Robert A. Wise, MD, Kendra Young, MSPH, PhD; Social and Behavioral Sciences Working Group: Chair: Karin F. Hoth, PhD, Surya P. Bhatt, MD, Sara Cummings, Annika Czizik, Dawn L. DeMeo, MD, MPH, Mark T. Dransfield, MD, Michelle Eakin, PhD, Jess G. Fiedorowicz, MD, PhD, Marilyn G. Foreman, MD, MS, Nicola A. Hanania, MD, MS, Ben Henkle, MD, MPH, Kristen Holm, PhD, MPH, Karin F. Hoth, PhD, Anand Iyer, MD, Victor Kim, MD, Greg Kinney, MPH, PhD, Ken M. Kunisaki, MD, MS, Katherine Lowe, MS, Barry J. Make, MD, Merry-Lynn McDonald, PhD, Charlene McEvoy, MD, MPH, Takudzwa Mkorombindo, MD, Gabriela Oates, PhD, Trisha Parekh, DO, Elizabeth A. Regan, MD, PhD, Gen Shinozaki, MD, Shandi Watts, Robert A. Wise, MD, Abebaw Yohannes, PhD; Subtyping Working Group: Co-Chair: Michael H. Cho, MD, Co-Chair: Peter J. 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. McCormack, MD, MHS, Tahira Mirza, Nirupama Putcha, MD, MHS, Meagan Scott, Becky Shade; L.A. Biomedical Research Institute: Richard Casaburi, PhD, MD, Matt Budoff, MD, Robert Calmelat, Deborah Cavanaugh, Chris Dailing, Leticia Diaz, Hans Fischer, MD, PhD, Renee Love Indelicato, Janos Porszasz, MD, PhD, Harry B. Rossiter, PhD, April Soriano, William Stringer, MD, Miriam Urrutia; Minneapolis VA Medical Center: Chris H. Wendt, MD, Arianne Baldomero, MD, Brian Bell, MD, Miranda Deconcini, Ken M. Kunisaki, MD, MS; Minnesota HealthPartners ? Twin Cities: Charlene McEvoy, MD, MPH, Linda Loes, Jonathan Phelan, MD, Camille Robichaux, MD, Cheryl Sasse, Joseph H. Tashjian, MD; Morehouse School of Medicine: Eric L. Flenaugh, MD, FCCP, Kema Abson, Marilyn G. Foreman, MD, MS, Hirut Gebrekristos, PhD, Priscilla Johnson, MSN, PhD, Jessica Jordan, Mario Ponce, MD, Silanath Terpenning, MD, Gloria Westney, MD, MS, Derrick Wilson, MS; National Jewish Health: Russell P. 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

PY - 2022/4/1

Y1 - 2022/4/1

N2 - 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.

AB - 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.

KW - COPD

KW - mortality

KW - muscle wasting

KW - sarcopenia

KW - Body Composition

KW - Body Mass Index

KW - Pulmonary Disease, Chronic Obstructive/complications

KW - Smokers

KW - Humans

KW - Lung

KW - Pectoralis Muscles

KW - Longitudinal Studies

UR - http://www.scopus.com/inward/record.url?scp=85126930089&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85126930089&partnerID=8YFLogxK

U2 - 10.1016/j.chest.2021.10.047

DO - 10.1016/j.chest.2021.10.047

M3 - Article

C2 - 34785234

AN - SCOPUS:85126930089

SN - 0012-3692

VL - 161

SP - 960

EP - 970

JO - CHEST

JF - CHEST

IS - 4

ER -

Longitudinal Association Between Muscle Loss and Mortality in Ever Smokers

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