Emphysema Progression and Lung Function Decline Among Angiotensin Converting Enzyme Inhibitors and Angiotensin-Receptor Blockade Users in the COPDGene Cohort

COPDGene Investigators

doi:10.1016/j.chest.2021.05.007

Emphysema Progression and Lung Function Decline Among Angiotensin Converting Enzyme Inhibitors and Angiotensin-Receptor Blockade Users in the COPDGene Cohort

COPDGene Investigators

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

6 Scopus citations

Abstract

Background: Attenuation of transforming growth factor β by blocking angiotensin II has been shown to reduce emphysema in a murine model. General population studies have demonstrated that the use of angiotensin converting enzyme inhibitors (ACEis) and angiotensin-receptor blockers (ARBs) is associated with reduction of emphysema progression in former smokers and that the use of ACEis is associated with reduction of FEV₁ progression in current smokers. Research Question: Is use of ACEi and ARB associated with less progression of emphysema and FEV₁ decline among individuals with COPD or baseline emphysema? Methods: Former and current smokers from the Genetic Epidemiology of COPD Study who attended baseline and 5-year follow-up visits, did not change smoking status, and underwent chest CT imaging were included. Adjusted linear mixed models were used to evaluate progression of adjusted lung density (ALD), percent emphysema (%total lung volume <–950 Hounsfield units [HU]), 15th percentile of the attenuation histogram (attenuation [in HU] below which 15% of voxels are situated plus 1,000 HU), and lung function decline over 5 years between ACEi and ARB users and nonusers in those with spirometry-confirmed COPD, as well as all participants and those with baseline emphysema. Effect modification by smoking status also was investigated. Results: Over 5 years of follow-up, compared with nonusers, ACEi and ARB users with COPD showed slower ALD progression (adjusted mean difference [aMD], 1.6; 95% CI, 0.34-2.9). Slowed lung function decline was not observed based on phase 1 medication (aMD of FEV₁ % predicted, 0.83; 95% CI, –0.62 to 2.3), but was when analysis was limited to consistent ACEi and ARB users (aMD of FEV₁ % predicted, 1.9; 95% CI, 0.14-3.6). No effect modification by smoking status was found for radiographic outcomes, and the lung function effect was more pronounced in former smokers. Results were similar among participants with baseline emphysema. Interpretation: Among participants with spirometry-confirmed COPD or baseline emphysema, ACEi and ARB use was associated with slower progression of emphysema and lung function decline. Trial Registry: ClinicalTrials.gov; No.: NCT00608764; URL: www.clinicaltrials.gov

Original language	English (US)
Pages (from-to)	1245-1254
Number of pages	10
Journal	CHEST
Volume	160
Issue number	4
DOIs	https://doi.org/10.1016/j.chest.2021.05.007
State	Published - Oct 1 2021

Bibliographical note

Funding Information:
FUNDING/SUPPORT: This study was supported by the National Heart, Lung, and Blood Institute [Grant F32HL149258-01 to V.T.] and the Baurenschmidt Award from the Johns Hopkins Eudowood Foundation (V.T.). M. H. C. was supported by the National Institutes of Health [Grants R01HL135142 , R01 HL137927 , and R01 HL147148 ]. The COPDGene study (NCT00608764) is supported by National Heart, Lung, and Blood Institute [Grants R01 HL089897 and R01 HL089856 ] and the COPD Foundation through contributions made to an industry advisory board comprising AstraZeneca , Boehringer Ingelheim, Novartis , Pfizer , GlaxoSmithKline , Siemens, and Sunovion.

Funding Information:
FUNDING/SUPPORT: This study was supported by the National Heart, Lung, and Blood Institute [Grant F32HL149258-01 to V.T.] and the Baurenschmidt Award from the Johns Hopkins Eudowood Foundation (V.T.). M. H. C. was supported by the National Institutes of Health [Grants R01HL135142, R01 HL137927, and R01 HL147148]. The COPDGene study (NCT00608764) is supported by National Heart, Lung, and Blood Institute [Grants R01 HL089897 and R01 HL089856] and the COPD Foundation through contributions made to an industry advisory board comprising AstraZeneca, Boehringer Ingelheim, Novartis, Pfizer, GlaxoSmithKline, Siemens, and Sunovion.Author contributions: V. T. is the guarantor of the content of the manuscript. V. T. F. R. D. and N. N. H conceived of the presented concept. P. C. M. H. C. K. A. P. and S. A. B. contributed to the study design. D. A. L. and S. M. H. contributed to the radiologic assessments and outcomes. G. L. K. ensured veracity of medication data. V. T. A. F. N. P. and N. N. H. performed biostatistical analysis. All authors discussed the results and contributed to the final manuscript. Financial/nonfinancial disclosures: The authors have reported to CHEST the following: M. H. C. has received grant support from GSK and Bayer and consulting or speaking fees from Genentech, AstraZeneca, and Illumina. None declared (V. T. A. F. N. P. P. C. K. A. P. S. P. B. D. A. L. S. M. H. G. L. K. F. R. D.). ?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 Beaty, PhD; Ferdouse Begum, PhD; Peter J. Castaldi, MD, MSc; Michael Cho, MD; Dawn L. DeMeo, MD, MPH; Adel R. Boueiz, MD; Marilyn G. Foreman, MD, MS; Eitan Halper-Stromberg; Lystra P. Hayden, MD, MMSc; Craig P. Hersh, MD, MPH; Jacqueline Hetmanski, MS, MPH; Brian D. Hobbs, MD; John E. Hokanson, MPH, PhD; Nan Laird, PhD; Christoph Lange, PhD; Sharon M. Lutz, PhD; Merry-Lynn McDonald, PhD; Margaret M. Parker, PhD; Dmitry Prokopenko, Ph.D; Dandi Qiao, PhD; Elizabeth A. Regan, MD, PhD; Phuwanat Sakornsakolpat, MD; Edwin K. Silverman, MD, PhD; Emily S. Wan, MD; Sungho Won, PhD. 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; 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, Ph.D. COPDGene? Investigators ? 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; Alejandro A. Diaz, MD, MPH; Lystra P. Hayden, MD; Brian D. Hobbs, MD; 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. Grady Memorial Hospital, Atlanta, GA: Eric Flenaugh, MD; Silanth Terpenning, 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 Innovationat 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. 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; Carl Fuhrman, MD; Joel Weissfeld, MD, MPH. University of Texas Health, San An, Additional information: The e-Appendix, e-Figure, and e-Tables can be found in the Supplemental Materials section of the online article.

Publisher Copyright:
© 2021 American College of Chest Physicians

Keywords

COPD
angiotensin II
emphysema progression

Publisher link

10.1016/j.chest.2021.05.007

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@article{7aa27134a9754e0fa4dfa23c32137b00,

title = "Emphysema Progression and Lung Function Decline Among Angiotensin Converting Enzyme Inhibitors and Angiotensin-Receptor Blockade Users in the COPDGene Cohort",

abstract = "Background: Attenuation of transforming growth factor β by blocking angiotensin II has been shown to reduce emphysema in a murine model. General population studies have demonstrated that the use of angiotensin converting enzyme inhibitors (ACEis) and angiotensin-receptor blockers (ARBs) is associated with reduction of emphysema progression in former smokers and that the use of ACEis is associated with reduction of FEV1 progression in current smokers. Research Question: Is use of ACEi and ARB associated with less progression of emphysema and FEV1 decline among individuals with COPD or baseline emphysema? Methods: Former and current smokers from the Genetic Epidemiology of COPD Study who attended baseline and 5-year follow-up visits, did not change smoking status, and underwent chest CT imaging were included. Adjusted linear mixed models were used to evaluate progression of adjusted lung density (ALD), percent emphysema (%total lung volume <–950 Hounsfield units [HU]), 15th percentile of the attenuation histogram (attenuation [in HU] below which 15% of voxels are situated plus 1,000 HU), and lung function decline over 5 years between ACEi and ARB users and nonusers in those with spirometry-confirmed COPD, as well as all participants and those with baseline emphysema. Effect modification by smoking status also was investigated. Results: Over 5 years of follow-up, compared with nonusers, ACEi and ARB users with COPD showed slower ALD progression (adjusted mean difference [aMD], 1.6; 95% CI, 0.34-2.9). Slowed lung function decline was not observed based on phase 1 medication (aMD of FEV1 % predicted, 0.83; 95% CI, –0.62 to 2.3), but was when analysis was limited to consistent ACEi and ARB users (aMD of FEV1 % predicted, 1.9; 95% CI, 0.14-3.6). No effect modification by smoking status was found for radiographic outcomes, and the lung function effect was more pronounced in former smokers. Results were similar among participants with baseline emphysema. Interpretation: Among participants with spirometry-confirmed COPD or baseline emphysema, ACEi and ARB use was associated with slower progression of emphysema and lung function decline. Trial Registry: ClinicalTrials.gov; No.: NCT00608764; URL: www.clinicaltrials.gov",

keywords = "COPD, angiotensin II, emphysema progression",

author = "{COPDGene Investigators} and Vickram Tejwani and Ashraf Fawzy and Nirupama Putcha and Castaldi, {Peter J.} and Cho, {Michael H.} and Pratte, {Katherine A.} and Bhatt, {Surya P.} and Lynch, {David A.} and Humphries, {Stephen M.} and Kinney, {Gregory L.} and D'Alessio, {Franco R.} and Hansel, {Nadia N.} and Crapo, {James D.} and Silverman, {Edwin K.} and Make, {Barry J.} and Regan, {Elizabeth A.} and Terri Beaty and Ferdouse Begum and Michael Cho and DeMeo, {Dawn L.} and Boueiz, {Adel R.} and Foreman, {Marilyn G.} and Eitan Halper-Stromberg and Hayden, {Lystra P.} and Hersh, {Craig P.} and Jacqueline Hetmanski and Hobbs, {Brian D.} and Hokanson, {John E.} and Nan Laird and Christoph Lange and Lutz, {Sharon M.} and McDonald, {Merry Lynn} and Parker, {Margaret M.} and Dmitry Prokopenko and Dandi Qiao and Phuwanat Sakornsakolpat and Wan, {Emily S.} and Sungho Won and Centeno, {Juan Pablo} and Charbonnier, {Jean Paul} and Coxson, {Harvey O.} and Galban, {Craig J.} and Han, {Mei Lan K.} and Charlene McEvoy and Joseph Tashjian and Christine Wendt and Kunisaki, {Ken M.} and Joanne Billings and Abbie Begnaud and Tadashi Allen",

note = "Funding Information: FUNDING/SUPPORT: This study was supported by the National Heart, Lung, and Blood Institute [Grant F32HL149258-01 to V.T.] and the Baurenschmidt Award from the Johns Hopkins Eudowood Foundation (V.T.). M. H. C. was supported by the National Institutes of Health [Grants R01HL135142 , R01 HL137927 , and R01 HL147148 ]. The COPDGene study (NCT00608764) is supported by National Heart, Lung, and Blood Institute [Grants R01 HL089897 and R01 HL089856 ] and the COPD Foundation through contributions made to an industry advisory board comprising AstraZeneca , Boehringer Ingelheim, Novartis , Pfizer , GlaxoSmithKline , Siemens, and Sunovion. Funding Information: FUNDING/SUPPORT: This study was supported by the National Heart, Lung, and Blood Institute [Grant F32HL149258-01 to V.T.] and the Baurenschmidt Award from the Johns Hopkins Eudowood Foundation (V.T.). M. H. C. was supported by the National Institutes of Health [Grants R01HL135142, R01 HL137927, and R01 HL147148]. The COPDGene study (NCT00608764) is supported by National Heart, Lung, and Blood Institute [Grants R01 HL089897 and R01 HL089856] and the COPD Foundation through contributions made to an industry advisory board comprising AstraZeneca, Boehringer Ingelheim, Novartis, Pfizer, GlaxoSmithKline, Siemens, and Sunovion.Author contributions: V. T. is the guarantor of the content of the manuscript. V. T. F. R. D. and N. N. H conceived of the presented concept. P. C. M. H. C. K. A. P. and S. A. B. contributed to the study design. D. A. L. and S. M. H. contributed to the radiologic assessments and outcomes. G. L. K. ensured veracity of medication data. V. T. A. F. N. P. and N. N. H. performed biostatistical analysis. All authors discussed the results and contributed to the final manuscript. Financial/nonfinancial disclosures: The authors have reported to CHEST the following: M. H. C. has received grant support from GSK and Bayer and consulting or speaking fees from Genentech, AstraZeneca, and Illumina. None declared (V. T. A. F. N. P. P. C. K. A. P. S. P. B. D. A. L. S. M. H. G. L. K. F. R. D.). ?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 Beaty, PhD; Ferdouse Begum, PhD; Peter J. Castaldi, MD, MSc; Michael Cho, MD; Dawn L. DeMeo, MD, MPH; Adel R. Boueiz, MD; Marilyn G. Foreman, MD, MS; Eitan Halper-Stromberg; Lystra P. Hayden, MD, MMSc; Craig P. Hersh, MD, MPH; Jacqueline Hetmanski, MS, MPH; Brian D. Hobbs, MD; John E. Hokanson, MPH, PhD; Nan Laird, PhD; Christoph Lange, PhD; Sharon M. Lutz, PhD; Merry-Lynn McDonald, PhD; Margaret M. Parker, PhD; Dmitry Prokopenko, Ph.D; Dandi Qiao, PhD; Elizabeth A. Regan, MD, PhD; Phuwanat Sakornsakolpat, MD; Edwin K. Silverman, MD, PhD; Emily S. Wan, MD; Sungho Won, PhD. 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; 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, Ph.D. COPDGene? Investigators ? 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; Alejandro A. Diaz, MD, MPH; Lystra P. Hayden, MD; Brian D. Hobbs, MD; 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. Grady Memorial Hospital, Atlanta, GA: Eric Flenaugh, MD; Silanth Terpenning, 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 Innovationat 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. 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; Carl Fuhrman, MD; Joel Weissfeld, MD, MPH. University of Texas Health, San An, Additional information: The e-Appendix, e-Figure, and e-Tables can be found in the Supplemental Materials section of the online article. Publisher Copyright: {\textcopyright} 2021 American College of Chest Physicians",

year = "2021",

month = oct,

day = "1",

doi = "10.1016/j.chest.2021.05.007",

language = "English (US)",

volume = "160",

pages = "1245--1254",

journal = "CHEST",

issn = "0012-3692",

publisher = "American College of Chest Physicians",

number = "4",

}

TY - JOUR

T1 - Emphysema Progression and Lung Function Decline Among Angiotensin Converting Enzyme Inhibitors and Angiotensin-Receptor Blockade Users in the COPDGene Cohort

AU - COPDGene Investigators

AU - Tejwani, Vickram

AU - Fawzy, Ashraf

AU - Putcha, Nirupama

AU - Castaldi, Peter J.

AU - Cho, Michael H.

AU - Pratte, Katherine A.

AU - Bhatt, Surya P.

AU - Lynch, David A.

AU - Humphries, Stephen M.

AU - Kinney, Gregory L.

AU - D'Alessio, Franco R.

AU - Hansel, Nadia N.

AU - Crapo, James D.

AU - Silverman, Edwin K.

AU - Make, Barry J.

AU - Regan, Elizabeth A.

AU - Beaty, Terri

AU - Begum, Ferdouse

AU - Cho, Michael

AU - DeMeo, Dawn L.

AU - Boueiz, Adel R.

AU - Foreman, Marilyn G.

AU - Halper-Stromberg, Eitan

AU - Hayden, Lystra P.

AU - Hersh, Craig P.

AU - Hetmanski, Jacqueline

AU - Hobbs, Brian D.

AU - Hokanson, John E.

AU - Laird, Nan

AU - Lange, Christoph

AU - Lutz, Sharon M.

AU - McDonald, Merry Lynn

AU - Parker, Margaret M.

AU - Prokopenko, Dmitry

AU - Qiao, Dandi

AU - Sakornsakolpat, Phuwanat

AU - Wan, Emily S.

AU - Won, Sungho

AU - Centeno, Juan Pablo

AU - Charbonnier, Jean Paul

AU - Coxson, Harvey O.

AU - Galban, Craig J.

AU - Han, Mei Lan K.

AU - McEvoy, Charlene

AU - Tashjian, Joseph

AU - Wendt, Christine

AU - Kunisaki, Ken M.

AU - Billings, Joanne

AU - Begnaud, Abbie

AU - Allen, Tadashi

N1 - Funding Information: FUNDING/SUPPORT: This study was supported by the National Heart, Lung, and Blood Institute [Grant F32HL149258-01 to V.T.] and the Baurenschmidt Award from the Johns Hopkins Eudowood Foundation (V.T.). M. H. C. was supported by the National Institutes of Health [Grants R01HL135142 , R01 HL137927 , and R01 HL147148 ]. The COPDGene study (NCT00608764) is supported by National Heart, Lung, and Blood Institute [Grants R01 HL089897 and R01 HL089856 ] and the COPD Foundation through contributions made to an industry advisory board comprising AstraZeneca , Boehringer Ingelheim, Novartis , Pfizer , GlaxoSmithKline , Siemens, and Sunovion. Funding Information: FUNDING/SUPPORT: This study was supported by the National Heart, Lung, and Blood Institute [Grant F32HL149258-01 to V.T.] and the Baurenschmidt Award from the Johns Hopkins Eudowood Foundation (V.T.). M. H. C. was supported by the National Institutes of Health [Grants R01HL135142, R01 HL137927, and R01 HL147148]. The COPDGene study (NCT00608764) is supported by National Heart, Lung, and Blood Institute [Grants R01 HL089897 and R01 HL089856] and the COPD Foundation through contributions made to an industry advisory board comprising AstraZeneca, Boehringer Ingelheim, Novartis, Pfizer, GlaxoSmithKline, Siemens, and Sunovion.Author contributions: V. T. is the guarantor of the content of the manuscript. V. T. F. R. D. and N. N. H conceived of the presented concept. P. C. M. H. C. K. A. P. and S. A. B. contributed to the study design. D. A. L. and S. M. H. contributed to the radiologic assessments and outcomes. G. L. K. ensured veracity of medication data. V. T. A. F. N. P. and N. N. H. performed biostatistical analysis. All authors discussed the results and contributed to the final manuscript. Financial/nonfinancial disclosures: The authors have reported to CHEST the following: M. H. C. has received grant support from GSK and Bayer and consulting or speaking fees from Genentech, AstraZeneca, and Illumina. None declared (V. T. A. F. N. P. P. C. K. A. P. S. P. B. D. A. L. S. M. H. G. L. K. F. R. D.). ?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 Beaty, PhD; Ferdouse Begum, PhD; Peter J. Castaldi, MD, MSc; Michael Cho, MD; Dawn L. DeMeo, MD, MPH; Adel R. Boueiz, MD; Marilyn G. Foreman, MD, MS; Eitan Halper-Stromberg; Lystra P. Hayden, MD, MMSc; Craig P. Hersh, MD, MPH; Jacqueline Hetmanski, MS, MPH; Brian D. Hobbs, MD; John E. Hokanson, MPH, PhD; Nan Laird, PhD; Christoph Lange, PhD; Sharon M. Lutz, PhD; Merry-Lynn McDonald, PhD; Margaret M. Parker, PhD; Dmitry Prokopenko, Ph.D; Dandi Qiao, PhD; Elizabeth A. Regan, MD, PhD; Phuwanat Sakornsakolpat, MD; Edwin K. Silverman, MD, PhD; Emily S. Wan, MD; Sungho Won, PhD. 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; 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, Ph.D. COPDGene? Investigators ? 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; Alejandro A. Diaz, MD, MPH; Lystra P. Hayden, MD; Brian D. Hobbs, MD; 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. Grady Memorial Hospital, Atlanta, GA: Eric Flenaugh, MD; Silanth Terpenning, 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 Innovationat 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. 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; Carl Fuhrman, MD; Joel Weissfeld, MD, MPH. University of Texas Health, San An, Additional information: The e-Appendix, e-Figure, and e-Tables can be found in the Supplemental Materials section of the online article. Publisher Copyright: © 2021 American College of Chest Physicians

PY - 2021/10/1

Y1 - 2021/10/1

N2 - Background: Attenuation of transforming growth factor β by blocking angiotensin II has been shown to reduce emphysema in a murine model. General population studies have demonstrated that the use of angiotensin converting enzyme inhibitors (ACEis) and angiotensin-receptor blockers (ARBs) is associated with reduction of emphysema progression in former smokers and that the use of ACEis is associated with reduction of FEV1 progression in current smokers. Research Question: Is use of ACEi and ARB associated with less progression of emphysema and FEV1 decline among individuals with COPD or baseline emphysema? Methods: Former and current smokers from the Genetic Epidemiology of COPD Study who attended baseline and 5-year follow-up visits, did not change smoking status, and underwent chest CT imaging were included. Adjusted linear mixed models were used to evaluate progression of adjusted lung density (ALD), percent emphysema (%total lung volume <–950 Hounsfield units [HU]), 15th percentile of the attenuation histogram (attenuation [in HU] below which 15% of voxels are situated plus 1,000 HU), and lung function decline over 5 years between ACEi and ARB users and nonusers in those with spirometry-confirmed COPD, as well as all participants and those with baseline emphysema. Effect modification by smoking status also was investigated. Results: Over 5 years of follow-up, compared with nonusers, ACEi and ARB users with COPD showed slower ALD progression (adjusted mean difference [aMD], 1.6; 95% CI, 0.34-2.9). Slowed lung function decline was not observed based on phase 1 medication (aMD of FEV1 % predicted, 0.83; 95% CI, –0.62 to 2.3), but was when analysis was limited to consistent ACEi and ARB users (aMD of FEV1 % predicted, 1.9; 95% CI, 0.14-3.6). No effect modification by smoking status was found for radiographic outcomes, and the lung function effect was more pronounced in former smokers. Results were similar among participants with baseline emphysema. Interpretation: Among participants with spirometry-confirmed COPD or baseline emphysema, ACEi and ARB use was associated with slower progression of emphysema and lung function decline. Trial Registry: ClinicalTrials.gov; No.: NCT00608764; URL: www.clinicaltrials.gov

AB - Background: Attenuation of transforming growth factor β by blocking angiotensin II has been shown to reduce emphysema in a murine model. General population studies have demonstrated that the use of angiotensin converting enzyme inhibitors (ACEis) and angiotensin-receptor blockers (ARBs) is associated with reduction of emphysema progression in former smokers and that the use of ACEis is associated with reduction of FEV1 progression in current smokers. Research Question: Is use of ACEi and ARB associated with less progression of emphysema and FEV1 decline among individuals with COPD or baseline emphysema? Methods: Former and current smokers from the Genetic Epidemiology of COPD Study who attended baseline and 5-year follow-up visits, did not change smoking status, and underwent chest CT imaging were included. Adjusted linear mixed models were used to evaluate progression of adjusted lung density (ALD), percent emphysema (%total lung volume <–950 Hounsfield units [HU]), 15th percentile of the attenuation histogram (attenuation [in HU] below which 15% of voxels are situated plus 1,000 HU), and lung function decline over 5 years between ACEi and ARB users and nonusers in those with spirometry-confirmed COPD, as well as all participants and those with baseline emphysema. Effect modification by smoking status also was investigated. Results: Over 5 years of follow-up, compared with nonusers, ACEi and ARB users with COPD showed slower ALD progression (adjusted mean difference [aMD], 1.6; 95% CI, 0.34-2.9). Slowed lung function decline was not observed based on phase 1 medication (aMD of FEV1 % predicted, 0.83; 95% CI, –0.62 to 2.3), but was when analysis was limited to consistent ACEi and ARB users (aMD of FEV1 % predicted, 1.9; 95% CI, 0.14-3.6). No effect modification by smoking status was found for radiographic outcomes, and the lung function effect was more pronounced in former smokers. Results were similar among participants with baseline emphysema. Interpretation: Among participants with spirometry-confirmed COPD or baseline emphysema, ACEi and ARB use was associated with slower progression of emphysema and lung function decline. Trial Registry: ClinicalTrials.gov; No.: NCT00608764; URL: www.clinicaltrials.gov

KW - COPD

KW - angiotensin II

KW - emphysema progression

UR - http://www.scopus.com/inward/record.url?scp=85115941159&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85115941159&partnerID=8YFLogxK

U2 - 10.1016/j.chest.2021.05.007

DO - 10.1016/j.chest.2021.05.007

M3 - Article

C2 - 34029566

AN - SCOPUS:85115941159

SN - 0012-3692

VL - 160

SP - 1245

EP - 1254

JO - CHEST

JF - CHEST

IS - 4

ER -

Emphysema Progression and Lung Function Decline Among Angiotensin Converting Enzyme Inhibitors and Angiotensin-Receptor Blockade Users in the COPDGene Cohort

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