Emphysema Progression and Lung Function Decline Among Angiotensin Converting Enzyme Inhibitors and Angiotensin-Receptor Blockade Users in the COPDGene Cohort
Vickram Tejwani, Ashraf Fawzy, Nirupama Putcha, Peter J Castaldi, Michael H Cho, Katherine A Pratte, Surya P Bhatt, David A Lynch, Stephen M Humphries, Gregory L Kinney, Franco R D'Alessio, Nadia N Hansel, COPDGene Investigators, James D Crapo, Edwin K Silverman, Barry J Make, Elizabeth A Regan, Terri Beaty, Ferdouse Begum, Peter J Castaldi, Michael Cho, Dawn L DeMeo, Adel R Boueiz, Marilyn G Foreman, Eitan Halper-Stromberg, Lystra P Hayden, Craig P Hersh, Jacqueline Hetmanski, Brian D Hobbs, John E Hokanson, Nan Laird, Christoph Lange, Sharon M Lutz, Merry-Lynn McDonald, Margaret M Parker, Dmitry Prokopenko, Dandi Qiao, Elizabeth A Regan, Phuwanat Sakornsakolpat, Edwin K Silverman, Emily S Wan, Sungho Won, Juan Pablo Centeno, Jean-Paul Charbonnier, Harvey O Coxson, Craig J Galban, MeiLan K Han, Eric A Hoffman, Stephen Humphries, Francine L Jacobson, Philip F Judy, Ella A Kazerooni, Alex Kluiber, David A Lynch, Pietro Nardelli, John D Newell Jr, Aleena Notary, Andrea Oh, Elizabeth A Regan, James C Ross, Raul San Jose Estepar, Joyce Schroeder, Jered Sieren, Berend C Stoel, Juerg Tschirren, Edwin Van Beek, Bramvan Ginneken, Eva van Rikxoort, Gonzalo Vegas Sanchez-Ferrero, Lucas Veitel, George R Washko, Carla G Wilson, Robert Jensen, Douglas Everett, Jim Crooks, Katherine Pratte, Matt Strand, Carla G Wilson, John E Hokanson, Gregory Kinney, Sharon M Lutz, Kendra A Young, Surya P Bhatt, Jessica Bon, Alejandro A Diaz, MeiLan K Han, Barry Make, Susan Murray, Elizabeth Regan, Xavier Soler, Carla G Wilson, Russell P Bowler, Katerina Kechris, Farnoush Banaei-Kashani, Jeffrey L Curtis, Perry G Pernicano, Nicola Hanania, Mustafa Atik, Aladin Boriek, Kalpatha Guntupalli, Elizabeth Guy, Amit Parulekar, Dawn L DeMeo, Alejandro A Diaz, Lystra P Hayden, Brian D Hobbs, Craig Hersh, Francine L Jacobson, George Washko, R Graham Barr, John Austin, Belinda D'Souza, Byron Thomashow, Neil MacIntyre Jr, H Page McAdams, Lacey Washington, Eric Flenaugh, Silanth Terpenning, Charlene McEvoy, Joseph Tashjian, Robert Wise, Robert Brown, Nadia N Hansel, Karen Horton, Allison Lambert, Nirupama Putcha, Richard Casaburi, Alessandra Adami, Matthew Budoff, Hans Fischer, Janos Porszasz, Harry Rossiter, William Stringer, Amir Sharafkhaneh, Charlie Lan, Christine Wendt, Brian Bell, KenM Kunisaki, Russell Bowler, David A Lynch, Richard Rosiello, David Pace, Gerard Criner, David Ciccolella, Francis Cordova, Chandra Dass, Gilbert D'Alonzo, Parag Desai, Michael Jacobs, Steven Kelsen, Victor Kim, A James Mamary, Nathaniel Marchetti, Aditi Satti, Kartik Shenoy, Robert M Steiner, Alex Swift, Irene Swift, Maria Elena Vega-Sanchez, Mark Dransfield, William Bailey, Surya P Bhatt, Anand Iyer, Hrudaya Nath, J Michael Wells, Douglas Conrad, Xavier Soler, Andrew Yen, Alejandro P Comellas, Karin F Hoth, John Newell Jr, Brad Thompson, MeiLan K Han, Ella Kazerooni, Wassim Labaki, Craig Galban, Dharshan Vummidi, Joanne Billings, Abbie Begnaud, Tadashi Allen, Frank Sciurba, Jessica Bon, Divay Chandra, Carl Fuhrman, Joel Weissfeld, Vickram Tejwani, Ashraf Fawzy, Nirupama Putcha, Peter J Castaldi, Michael H Cho, Katherine A Pratte, Surya P Bhatt, David A Lynch, Stephen M Humphries, Gregory L Kinney, Franco R D'Alessio, Nadia N Hansel, COPDGene Investigators, James D Crapo, Edwin K Silverman, Barry J Make, Elizabeth A Regan, Terri Beaty, Ferdouse Begum, Peter J Castaldi, Michael Cho, Dawn L DeMeo, Adel R Boueiz, Marilyn G Foreman, Eitan Halper-Stromberg, Lystra P Hayden, Craig P Hersh, Jacqueline Hetmanski, Brian D Hobbs, John E Hokanson, Nan Laird, Christoph Lange, Sharon M Lutz, Merry-Lynn McDonald, Margaret M Parker, Dmitry Prokopenko, Dandi Qiao, Elizabeth A Regan, Phuwanat Sakornsakolpat, Edwin K Silverman, Emily S Wan, Sungho Won, Juan Pablo Centeno, Jean-Paul Charbonnier, Harvey O Coxson, Craig J Galban, MeiLan K Han, Eric A Hoffman, Stephen Humphries, Francine L Jacobson, Philip F Judy, Ella A Kazerooni, Alex Kluiber, David A Lynch, Pietro Nardelli, John D Newell Jr, Aleena Notary, Andrea Oh, Elizabeth A Regan, James C Ross, Raul San Jose Estepar, Joyce Schroeder, Jered Sieren, Berend C Stoel, Juerg Tschirren, Edwin Van Beek, Bramvan Ginneken, Eva van Rikxoort, Gonzalo Vegas Sanchez-Ferrero, Lucas Veitel, George R Washko, Carla G Wilson, Robert Jensen, Douglas Everett, Jim Crooks, Katherine Pratte, Matt Strand, Carla G Wilson, John E Hokanson, Gregory Kinney, Sharon M Lutz, Kendra A Young, Surya P Bhatt, Jessica Bon, Alejandro A Diaz, MeiLan K Han, Barry Make, Susan Murray, Elizabeth Regan, Xavier Soler, Carla G Wilson, Russell P Bowler, Katerina Kechris, Farnoush Banaei-Kashani, Jeffrey L Curtis, Perry G Pernicano, Nicola Hanania, Mustafa Atik, Aladin Boriek, Kalpatha Guntupalli, Elizabeth Guy, Amit Parulekar, Dawn L DeMeo, Alejandro A Diaz, Lystra P Hayden, Brian D Hobbs, Craig Hersh, Francine L Jacobson, George Washko, R Graham Barr, John Austin, Belinda D'Souza, Byron Thomashow, Neil MacIntyre Jr, H Page McAdams, Lacey Washington, Eric Flenaugh, Silanth Terpenning, Charlene McEvoy, Joseph Tashjian, Robert Wise, Robert Brown, Nadia N Hansel, Karen Horton, Allison Lambert, Nirupama Putcha, Richard Casaburi, Alessandra Adami, Matthew Budoff, Hans Fischer, Janos Porszasz, Harry Rossiter, William Stringer, Amir Sharafkhaneh, Charlie Lan, Christine Wendt, Brian Bell, KenM Kunisaki, Russell Bowler, David A Lynch, Richard Rosiello, David Pace, Gerard Criner, David Ciccolella, Francis Cordova, Chandra Dass, Gilbert D'Alonzo, Parag Desai, Michael Jacobs, Steven Kelsen, Victor Kim, A James Mamary, Nathaniel Marchetti, Aditi Satti, Kartik Shenoy, Robert M Steiner, Alex Swift, Irene Swift, Maria Elena Vega-Sanchez, Mark Dransfield, William Bailey, Surya P Bhatt, Anand Iyer, Hrudaya Nath, J Michael Wells, Douglas Conrad, Xavier Soler, Andrew Yen, Alejandro P Comellas, Karin F Hoth, John Newell Jr, Brad Thompson, MeiLan K Han, Ella Kazerooni, Wassim Labaki, Craig Galban, Dharshan Vummidi, Joanne Billings, Abbie Begnaud, Tadashi Allen, Frank Sciurba, Jessica Bon, Divay Chandra, Carl Fuhrman, Joel Weissfeld
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.
Copyright © 2021 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.
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Source: PubMed