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

2021; Elsevier BV; Volume: 160; Issue: 4 Linguagem: Inglês

10.1016/j.chest.2021.05.007

1931-3543

Emily S. Wan, Ashraf Fawzy, Nirupama Putcha, Peter J. Castaldi, Michael H. Cho, Katherine Pratte, Surya P. Bhatt, David A. Lynch, Stephen M. Humphries, Gregory L. Kinney, Franco R. D’Alessio, Nadia N. Hansel, James D. Crapo, Edwin K. Silverman, Barry J. Make, Elizabeth A. Regan, Terri H. Beaty, Ferdouse Begum, Peter J. Castaldi, Michael H. Cho, Dawn L. DeMeo, Adel R. Boueiz, Marilyn G. Foreman, Eitan Halper-Stromberg, Lystra P. Hayden, Craig P. Hersh, Jacqueline B. Hetmanski, Brian D. Hobbs, John E. Hokanson, Nan M. 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. Galbán, MeiLan K. Han, Eric A. Hoffman, Stephen M. Humphries, Francine L. Jacobson, Philip F. Judy, Ella A. Kazerooni, Alex Kluiber, David A. Lynch, Pietro Nardelli, John D. Newell, Aleena Notary, Andrea Oh, Elizabeth A. Regan, James C. Ross, Raúl San Jośe Estépar, Joyce Schroeder, Jered Sieren, Berend C. Stoel, Juerg Tschirren, Edwin J.R. van Beek, Bramvan Ginneken, Eva M. van Rikxoort, Gonzalo Vegas‐Sánchez‐Ferrero, Lucas Veitel, George R. Washko, Carla G. Wilson, Robert L. Jensen, Douglas Curran‐Everett, Jim Crooks, Katherine Pratte, Matthew Strand, Carla G. Wilson, John E. Hokanson, Gregory L. Kinney, Sharon M. Lutz, Kendra A. Young, Surya P. Bhatt, Jessica Bon, Alejandro A. Díaz, MeiLan K. Han, Barry J. Make, Susan Murray, Elizabeth A. Regan, Xavier Soler, Carla G. Wilson, Russell P. Bowler, Katerina Kechris, Farnoush Banaei‐Kashani, Jeffrey L. Curtis, Perry G. Pernicano, Nicola A. Hanania, Mustafa Atik, Aladin M. Boriek, Kalpatha Guntupalli, Elizabeth Guy, Amit Parulekar, Dawn L. DeMeo, Alejandro A. Díaz, Lystra P. Hayden, Brian D. Hobbs, Craig P. Hersh, Francine L. Jacobson, George R. Washko, R. Graham Barr, John Austin, Belinda D’Souza, Byron Thomashow, Neil MacIntyre, H. Page McAdams, Lacey Washington, Eric L. Flenaugh, Silanth Terpenning, Charlene McEvoy, Joseph Tashjian, Robert A. Wise, Robert H. Brown, Nadia N. Hansel, Karen M. Horton, Allison Lambert, Nirupama Putcha, Richard Casaburi, Alessandra Adami, Matthew J. Budoff, H. Keith Fischer, János Pórszász, Harry B. Rossiter, William W. Stringer, Amir Sharafkhaneh, Charlie Lan, Christine Wendt, Brian Bell, Ken M. Kunisaki, Russell P. Bowler, David A. Lynch, Richard Rosiello, David Pace, Gerard J. Criner, David Ciccolella, Francis Cordova, Chandra Dass, Gilbert E. D’Alonzo, Parag Desai, Michael R. Jacobs, Steven Kelsen, V. Kim, A. James Mamary, Nathaniel Marchetti, Aditi Satti, Kartik Shenoy, Robert M. Steiner, Alex Swift, Irene Swift, Maria Elena Vega‐Sanchez, Mark T. Dransfield, William C. 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, Brad Thompson, MeiLan K. Han, Ella A. Kazerooni, Wassim W. Labaki, Craig J. Galbán, Dharshan Vummidi, Joanne Billings, Abbie Begnaud, Tadashi Allen, Frank C. Sciurba, Jessica Bon, Divay Chandra, Carl R. Fuhrman, Joel L. Weissfeld,

Pulmonary Hypertension Research and Treatments

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 FEV 1 progression in current smokers. Research Question Is use of ACEi and ARB associated with less progression of emphysema and FEV 1 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 FEV 1 % predicted, 0.83; 95% CI, –0.62 to 2.3), but was when analysis was limited to consistent ACEi and ARB users (aMD of FEV 1 % 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