Estimated Ventricular Size, Asthma Severity, and Exacerbations: The Severe Asthma Research Program III Cohort

Samuel Y. Ash; Gonzalo Vegas Sanchez-Ferrero; Mark L. Schiebler; Farbod N. Rahaghi; Ashish Rai; Carolyn E. Come; James C. Ross; Alysha G. Colon; Juan Carlos Cardet; Eugene R. Bleecker; Mario Castro; John V. Fahy; Sean B. Fain; Benjamin M. Gaston; Eric A. Hoffman; Nizar N. Jarjour; Jason K. Lempel; David T. Mauger; Matthew C. Tattersall; Sally E. Wenzel; Bruce D. Levy; George R. Washko; Elliot Israel; Raul San Jose Estepar; Bruce Levy; George Washko; Manuela Cernadas; Wanda Phipatanakul; Sally Wenzel; Merritt Fajt; Benjamin Gaston; James Chmiel; W. Gerald Teague; Anne Marie Irani; Serpil Erzurum; Sumita Khatri; Suzy Comhair; Raed Dweik; Kristie Ross; Ross Myers; Wendy Moore; Deborah Meyers; Eugene Bleecker; Stephen Peters; Annette Hastie; Victor Ortega; Greg Hawkins; Xingan Li; Anne Fitzpatrick; Nazar Jarjour; Loren Denlinger; Sean Fain; Ronald Sorkness; Leonard Bacharier; David Gierada; Kenneth Schechtman; Jason Woods; John Fahy; Prescott Woodruff; Ngoc Ly; David Mauger

doi:10.1016/j.chest.2019.08.2185

Estimated Ventricular Size, Asthma Severity, and Exacerbations: The Severe Asthma Research Program III Cohort

Samuel Y. Ash, Gonzalo Vegas Sanchez-Ferrero, Mark L. Schiebler, Farbod N. Rahaghi, Ashish Rai, Carolyn E. Come, James C. Ross, Alysha G. Colon, Juan Carlos Cardet, Eugene R. Bleecker, Mario Castro, John V. Fahy, Sean B. Fain, Benjamin M. Gaston, Eric A. Hoffman, Nizar N. Jarjour, Jason K. Lempel, David T. Mauger, Matthew C. Tattersall, Sally E. WenzelBruce D. Levy, George R. Washko, Elliot Israel, Raul San Jose Estepar, Bruce Levy, George Washko, Manuela Cernadas, Wanda Phipatanakul, Sally Wenzel, Merritt Fajt, Benjamin Gaston, James Chmiel, W. Gerald Teague, Anne Marie Irani, Serpil Erzurum, Sumita Khatri, Suzy Comhair, Raed Dweik, Kristie Ross, Ross Myers, Wendy Moore, Deborah Meyers, Eugene Bleecker, Stephen Peters, Annette Hastie, Victor Ortega, Greg Hawkins, Xingan Li, Anne Fitzpatrick, Nazar Jarjour, Loren Denlinger, Sean Fain, Ronald Sorkness, Leonard Bacharier, David Gierada, Kenneth Schechtman, Jason Woods, John Fahy, Prescott Woodruff, Ngoc Ly, David Mauger

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

3 Scopus citations

Abstract

Background: Relative enlargement of the pulmonary artery (PA) on chest CT imaging is associated with respiratory exacerbations in patients with COPD or cystic fibrosis. We sought to determine whether similar findings were present in patients with asthma and whether these findings were explained by differences in ventricular size. Methods: We measured the PA and aorta diameters in 233 individuals from the Severe Asthma Research Program III cohort. We also estimated right, left, and total epicardial cardiac ventricular volume indices (eERVVI, eELVVI, and eETVVI, respectively). Associations between the cardiac and PA measures (PA-to-aorta [PA/A] ratio, eERVVI-to-eELVVI [eRV/eLV] ratio, eERVVI, eELVVI, eETVVI) and clinical measures of asthma severity were assessed by Pearson correlation, and associations with asthma severity and exacerbation rate were evaluated by multivariable linear and zero-inflated negative binomial regression. Results: Asthma severity was associated with smaller ventricular volumes. For example, those with severe asthma had 36.1 mL/m² smaller eETVVI than healthy control subjects (P = .003) and 14.1 mL/m² smaller eETVVI than those with mild/moderate disease (P = .011). Smaller ventricular volumes were also associated with a higher rate of asthma exacerbations, both retrospectively and prospectively. For example, those with an eETVVI less than the median had a 57% higher rate of exacerbations during follow-up than those with eETVVI greater than the median (P = .020). Neither PA/A nor eRV/eLV was associated with asthma severity or exacerbations. Conclusions: In patients with asthma, smaller cardiac ventricular size may be associated with more severe disease and a higher rate of asthma exacerbations. Trial Registry: ClinicalTrials.gov; No.: NCT01761630; URL: www.clinicaltrials.gov

Original language	English
Pages (from-to)	258-267
Number of pages	10
Journal	CHEST
Volume	157
Issue number	2
DOIs	https://doi.org/10.1016/j.chest.2019.08.2185
State	Published - Feb 2020

Keywords

CT imaging
asthma
heart

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10.1016/j.chest.2019.08.2185

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Ash, S. Y., Sanchez-Ferrero, G. V., Schiebler, M. L., Rahaghi, F. N., Rai, A., Come, C. E., Ross, J. C., Colon, A. G., Cardet, J. C., Bleecker, E. R., Castro, M., Fahy, J. V., Fain, S. B., Gaston, B. M., Hoffman, E. A., Jarjour, N. N., Lempel, J. K., Mauger, D. T., Tattersall, M. C., ... Mauger, D. (2020). Estimated Ventricular Size, Asthma Severity, and Exacerbations: The Severe Asthma Research Program III Cohort. CHEST, 157(2), 258-267. https://doi.org/10.1016/j.chest.2019.08.2185

@article{9f6d68d46cdf43618cb9a9bd517e5d0e,

title = "Estimated Ventricular Size, Asthma Severity, and Exacerbations: The Severe Asthma Research Program III Cohort",

abstract = "Background: Relative enlargement of the pulmonary artery (PA) on chest CT imaging is associated with respiratory exacerbations in patients with COPD or cystic fibrosis. We sought to determine whether similar findings were present in patients with asthma and whether these findings were explained by differences in ventricular size. Methods: We measured the PA and aorta diameters in 233 individuals from the Severe Asthma Research Program III cohort. We also estimated right, left, and total epicardial cardiac ventricular volume indices (eERVVI, eELVVI, and eETVVI, respectively). Associations between the cardiac and PA measures (PA-to-aorta [PA/A] ratio, eERVVI-to-eELVVI [eRV/eLV] ratio, eERVVI, eELVVI, eETVVI) and clinical measures of asthma severity were assessed by Pearson correlation, and associations with asthma severity and exacerbation rate were evaluated by multivariable linear and zero-inflated negative binomial regression. Results: Asthma severity was associated with smaller ventricular volumes. For example, those with severe asthma had 36.1 mL/m2 smaller eETVVI than healthy control subjects (P = .003) and 14.1 mL/m2 smaller eETVVI than those with mild/moderate disease (P = .011). Smaller ventricular volumes were also associated with a higher rate of asthma exacerbations, both retrospectively and prospectively. For example, those with an eETVVI less than the median had a 57% higher rate of exacerbations during follow-up than those with eETVVI greater than the median (P = .020). Neither PA/A nor eRV/eLV was associated with asthma severity or exacerbations. Conclusions: In patients with asthma, smaller cardiac ventricular size may be associated with more severe disease and a higher rate of asthma exacerbations. Trial Registry: ClinicalTrials.gov; No.: NCT01761630; URL: www.clinicaltrials.gov",

keywords = "CT imaging, asthma, heart",

author = "Ash, {Samuel Y.} and Sanchez-Ferrero, {Gonzalo Vegas} and Schiebler, {Mark L.} and Rahaghi, {Farbod N.} and Ashish Rai and Come, {Carolyn E.} and Ross, {James C.} and Colon, {Alysha G.} and Cardet, {Juan Carlos} and Bleecker, {Eugene R.} and Mario Castro and Fahy, {John V.} and Fain, {Sean B.} and Gaston, {Benjamin M.} and Hoffman, {Eric A.} and Jarjour, {Nizar N.} and Lempel, {Jason K.} and Mauger, {David T.} and Tattersall, {Matthew C.} and Wenzel, {Sally E.} and Levy, {Bruce D.} and Washko, {George R.} and Elliot Israel and {San Jose Estepar}, Raul and Bruce Levy and George Washko and Manuela Cernadas and Wanda Phipatanakul and Sally Wenzel and Merritt Fajt and Benjamin Gaston and James Chmiel and Teague, {W. Gerald} and Irani, {Anne Marie} and Serpil Erzurum and Sumita Khatri and Suzy Comhair and Raed Dweik and Kristie Ross and Ross Myers and Wendy Moore and Deborah Meyers and Eugene Bleecker and Stephen Peters and Annette Hastie and Victor Ortega and Greg Hawkins and Xingan Li and Anne Fitzpatrick and Nazar Jarjour and Loren Denlinger and Sean Fain and Ronald Sorkness and Leonard Bacharier and David Gierada and Kenneth Schechtman and Jason Woods and John Fahy and Prescott Woodruff and Ngoc Ly and David Mauger",

note = "Funding Information: FUNDING/SUPPORT: Supported by grants from the National Heart, Lung, and Blood Institute, National Institutes of Health (NIH), to the Severe Asthma Research Program (SARP) Principal Investigators, Clinical Centers, and Data Coordinating Center as follows: U10 HL109164 (E. R. B.), U10 HL109257 (M. C.), U10 HL109250 (B. M. G.), U10 HL109146 (J. V. F.), U10 HL109250 (B. M. G.), U10 HL109172 (E. I. and B. D. L.), U10 HL109168 (N. N. J.), U10 HL109152 (S. E. W.), and U10 HL109086 (D. T. M.). In addition, this program is supported through the following NIH National Center for Advancing Translational Sciences awards: UL1 TR000448 (Washington University), UL1 TR001420 (Wake Forest University), UL1 TR000427 (University of Wisconsin), and UL1 TR001102 (Harvard University). Additional support was provided by R01 HL116473 (R. S. J. E. and G. R. W.), K23 HL136905 (F. N. R.), K23 HL114735 (C. E. C.), K23 AI125785 (J. C. C), T32 HL007633 (S. Y. A.), and K08 HL145118 (S. Y. A). Funding Information: FUNDING/SUPPORT: Supported by grants from the National Heart, Lung, and Blood Institute, National Institutes of Health (NIH), to the Severe Asthma Research Program (SARP) Principal Investigators, Clinical Centers, and Data Coordinating Center as follows: U10 HL109164 (E. R. B.), U10 HL109257 (M. C.), U10 HL109250 (B. M. G.), U10 HL109146 (J. V. F.), U10 HL109250 (B. M. G.), U10 HL109172 (E. I. and B. D. L.), U10 HL109168 (N. N. J.), U10 HL109152 (S. E. W.), and U10 HL109086 (D. T. M.). In addition, this program is supported through the following NIH National Center for Advancing Translational Sciences awards: UL1 TR000448 (Washington University), UL1 TR001420 (Wake Forest University), UL1 TR000427 (University of Wisconsin), and UL1 TR001102 (Harvard University). Additional support was provided by R01 HL116473 (R. S. J. E. and G. R. W.), K23 HL136905 (F. N. R.), K23 HL114735 (C. E. C.), K23 AI125785 (J. C. C), T32 HL007633 (S. Y. A.), and K08 HL145118 (S. Y. A).Author contributions: S. Y. A. G. V. S.-F. and R. S. J. E. had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. S. Y. A. G. V. S.-F. G. R. W. E. I. and R. S. J. E. are responsible for the study concept and design. G. V. S.-F. F. N. R. and R. S. J. E. developed the cardiac segmentation tool. S. Y. A. performed the statistical analyses. G. R. W. E. I. and R. S. J. E. supervised the study. All authors contributed to the acquisition, analysis, or interpretation of data. All authors contributed to the drafting of the manuscript. All authors contributed to the intellectual content. The authors meet criteria for authorship as recommended by the International Committee of Medical Journal Editors. 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. Financial/nonfinancial disclosures: The authors reported to CHEST the following: E. R. B. reports having undertaken clinical trials through his employer, Wake Forest School of Medicine and the University of Arizona, for AstraZeneca, MedImmune, Boehringer Ingelheim, Cephalon/Teva, Genentech, Johnson & Johnson (Janssen), Novartis, Regeneron, and Sanofi Genzyme. He has also served as a paid consultant for AstraZeneca, MedImmune, Boehringer Ingelheim, GlaxoSmithKline, Novartis, Regeneron, and Sanofi Genzyme outside the submitted work. M. C. reports grants from the National Institutes of Health (NIH) and the American Lung Association during the conduct of the study; personal fees from Aviragen, Boehringer Ingelheim, Boston Scientific, Elsevier, Genentech, GlaxoSmithKline, Nuvaira, and Teva; grants from Amgen, Boehringer Ingelheim, Genentech, Gilead, GlaxoSmithKline, Invion, Medimmune, Sanofi-Aventis, and Vectura; all outside the submitted work. J. V. F. reports receiving consultant fees from Boehringer Ingelheim, Pieris, Entrinsic Health Solutions, and Sanofi Genzyme; all outside the submitted work. G. R. W. reports grants from the NIH, grants and other from Boehringer Ingelheim, other from Genentech, other from Quantitative Imaging Solutions, other from PulmonX, other from Regeneron, other from ModoSpira, grants from BTG Interventional Medicine, grants and other from Janssen Pharmaceuticals, other from Toshiba, other from GlaxoSmithKline; all outside the submitted work; and G. R. W.{\textquoteright}s spouse works for Biogen, which is focused on developing therapies for fibrotic lung disease. E. I. reports personal fees from AstraZeneca, personal fees from Novartis, personal fees from Philips Respironics, personal fees from Regeneron Pharmaceuticals, personal fees from Teva Specialty Pharmaceuticals, grants from Genentech, nonfinancial support from Boehringer Ingelheim, nonfinancial support from GlaxoSmithKline, nonfinancial support from Merck, nonfinancial support from Sunovion, nonfinancial support from Teva, grants from Sanofi, personal fees from Bird Rock Bio, personal fees from Nuvelution Pharmaceuticals, personal fees from Vitaeris, grants from Boehringer Ingelheim, nonfinancial support from Teva Specialty Pharmaceuticals, personal fees from Sanofi, personal fees from Merck, personal fees from Entrinsic Health Solutions, personal fees from GlaxoSmithKline, other from Vorso Corp. personal fees from Pneuma Respiratory, personal fees from 4D Pharma, outside the submitted work. S. B. F. reports grants from GE Healthcare, outside the submitted work; and served as a paid consultant advising on quantitative CT protocols for the COPD Gene Project. E. A. H. is a founder and shareholder of VIDA Diagnostics, a company commercializing lung image analysis software developed, in part, at the University of Iowa. S. E. W. reports grants and personal fees from AstraZeneca, grants from Boehringer Ingelheim, grants from GlaxoSmithKline, grants and personal fees from Sanofi, grants from Novartis, personal fees from Pieris, personal fees from Up to Date, outside the submitted work. None declared (S. Y. A. G. V. S.-F. M. L. S. F. N. R. A. R. C. E. C. J. C. R. N. N. J. B. M. G. B. D. L. and A. G. C.). SARP Investigators: Elliot Israel MD, Bruce Levy MD, George Washko MD, Manuela Cernadas MD, Wanda Phipatanakul MD, Sally Wenzel MD, Merritt Fajt MD, Benjamin Gaston MD, James Chmiel MD, W. Gerald Teague MD, Anne-Marie Irani MD, Serpil Erzurum MD, Sumita Khatri MD, Suzy Comhair MD, Raed Dweik MD, Kristie Ross MD, Ross Myers MD, Wendy Moore MD, Deborah Meyers PhD, Eugene Bleecker MD, Stephen Peters MD, Annette Hastie MD, Victor Ortega MD, Greg Hawkins PhD, Xingan Li MD, Anne Fitzpatrick PhD, Nazar Jarjour MD, Loren Denlinger MD PhD, Sean Fain PhD, Ronald Sorkness PhD, Mario Castro MD MPH, Leonard Bacharier MD, David Gierada MD, Kenneth Schechtman PhD, Jason Woods PhD, John Fahy MD, Prescott Woodruff MD MPH, Ngoc Ly MD MPH, David Mauger PhD. Additional Information: The e-Appendix, e-Figures, and e-Tables can be found in the Supplemental Materials section of the online article. Publisher Copyright: {\textcopyright} 2019 American College of Chest Physicians",

year = "2020",

month = feb,

doi = "10.1016/j.chest.2019.08.2185",

language = "English",

volume = "157",

pages = "258--267",

journal = "Chest",

issn = "0012-3692",

number = "2",

}

Ash, SY, Sanchez-Ferrero, GV, Schiebler, ML, Rahaghi, FN, Rai, A, Come, CE, Ross, JC, Colon, AG, Cardet, JC, Bleecker, ER, Castro, M, Fahy, JV, Fain, SB, Gaston, BM, Hoffman, EA, Jarjour, NN, Lempel, JK, Mauger, DT, Tattersall, MC, Wenzel, SE, Levy, BD, Washko, GR, Israel, E, San Jose Estepar, R, Levy, B, Washko, G, Cernadas, M, Phipatanakul, W, Wenzel, S, Fajt, M, Gaston, B, Chmiel, J, Teague, WG, Irani, AM, Erzurum, S, Khatri, S, Comhair, S, Dweik, R, Ross, K, Myers, R, Moore, W, Meyers, D, Bleecker, E, Peters, S, Hastie, A, Ortega, V, Hawkins, G, Li, X, Fitzpatrick, A, Jarjour, N, Denlinger, L, Fain, S, Sorkness, R, Bacharier, L, Gierada, D , Schechtman, K, Woods, J, Fahy, J, Woodruff, P, Ly, N & Mauger, D 2020, 'Estimated Ventricular Size, Asthma Severity, and Exacerbations: The Severe Asthma Research Program III Cohort', CHEST, vol. 157, no. 2, pp. 258-267. https://doi.org/10.1016/j.chest.2019.08.2185

TY - JOUR

T1 - Estimated Ventricular Size, Asthma Severity, and Exacerbations

T2 - The Severe Asthma Research Program III Cohort

AU - Ash, Samuel Y.

AU - Sanchez-Ferrero, Gonzalo Vegas

AU - Schiebler, Mark L.

AU - Rahaghi, Farbod N.

AU - Rai, Ashish

AU - Come, Carolyn E.

AU - Ross, James C.

AU - Colon, Alysha G.

AU - Cardet, Juan Carlos

AU - Bleecker, Eugene R.

AU - Castro, Mario

AU - Fahy, John V.

AU - Fain, Sean B.

AU - Gaston, Benjamin M.

AU - Hoffman, Eric A.

AU - Jarjour, Nizar N.

AU - Lempel, Jason K.

AU - Mauger, David T.

AU - Tattersall, Matthew C.

AU - Wenzel, Sally E.

AU - Levy, Bruce D.

AU - Washko, George R.

AU - Israel, Elliot

AU - San Jose Estepar, Raul

AU - Levy, Bruce

AU - Washko, George

AU - Cernadas, Manuela

AU - Phipatanakul, Wanda

AU - Wenzel, Sally

AU - Fajt, Merritt

AU - Gaston, Benjamin

AU - Chmiel, James

AU - Teague, W. Gerald

AU - Irani, Anne Marie

AU - Erzurum, Serpil

AU - Khatri, Sumita

AU - Comhair, Suzy

AU - Dweik, Raed

AU - Ross, Kristie

AU - Myers, Ross

AU - Moore, Wendy

AU - Meyers, Deborah

AU - Bleecker, Eugene

AU - Peters, Stephen

AU - Hastie, Annette

AU - Ortega, Victor

AU - Hawkins, Greg

AU - Li, Xingan

AU - Fitzpatrick, Anne

AU - Jarjour, Nazar

AU - Denlinger, Loren

AU - Fain, Sean

AU - Sorkness, Ronald

AU - Bacharier, Leonard

AU - Gierada, David

AU - Schechtman, Kenneth

AU - Woods, Jason

AU - Fahy, John

AU - Woodruff, Prescott

AU - Ly, Ngoc

AU - Mauger, David

N1 - Funding Information: FUNDING/SUPPORT: Supported by grants from the National Heart, Lung, and Blood Institute, National Institutes of Health (NIH), to the Severe Asthma Research Program (SARP) Principal Investigators, Clinical Centers, and Data Coordinating Center as follows: U10 HL109164 (E. R. B.), U10 HL109257 (M. C.), U10 HL109250 (B. M. G.), U10 HL109146 (J. V. F.), U10 HL109250 (B. M. G.), U10 HL109172 (E. I. and B. D. L.), U10 HL109168 (N. N. J.), U10 HL109152 (S. E. W.), and U10 HL109086 (D. T. M.). In addition, this program is supported through the following NIH National Center for Advancing Translational Sciences awards: UL1 TR000448 (Washington University), UL1 TR001420 (Wake Forest University), UL1 TR000427 (University of Wisconsin), and UL1 TR001102 (Harvard University). Additional support was provided by R01 HL116473 (R. S. J. E. and G. R. W.), K23 HL136905 (F. N. R.), K23 HL114735 (C. E. C.), K23 AI125785 (J. C. C), T32 HL007633 (S. Y. A.), and K08 HL145118 (S. Y. A). Funding Information: FUNDING/SUPPORT: Supported by grants from the National Heart, Lung, and Blood Institute, National Institutes of Health (NIH), to the Severe Asthma Research Program (SARP) Principal Investigators, Clinical Centers, and Data Coordinating Center as follows: U10 HL109164 (E. R. B.), U10 HL109257 (M. C.), U10 HL109250 (B. M. G.), U10 HL109146 (J. V. F.), U10 HL109250 (B. M. G.), U10 HL109172 (E. I. and B. D. L.), U10 HL109168 (N. N. J.), U10 HL109152 (S. E. W.), and U10 HL109086 (D. T. M.). In addition, this program is supported through the following NIH National Center for Advancing Translational Sciences awards: UL1 TR000448 (Washington University), UL1 TR001420 (Wake Forest University), UL1 TR000427 (University of Wisconsin), and UL1 TR001102 (Harvard University). Additional support was provided by R01 HL116473 (R. S. J. E. and G. R. W.), K23 HL136905 (F. N. R.), K23 HL114735 (C. E. C.), K23 AI125785 (J. C. C), T32 HL007633 (S. Y. A.), and K08 HL145118 (S. Y. A).Author contributions: S. Y. A. G. V. S.-F. and R. S. J. E. had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. S. Y. A. G. V. S.-F. G. R. W. E. I. and R. S. J. E. are responsible for the study concept and design. G. V. S.-F. F. N. R. and R. S. J. E. developed the cardiac segmentation tool. S. Y. A. performed the statistical analyses. G. R. W. E. I. and R. S. J. E. supervised the study. All authors contributed to the acquisition, analysis, or interpretation of data. All authors contributed to the drafting of the manuscript. All authors contributed to the intellectual content. The authors meet criteria for authorship as recommended by the International Committee of Medical Journal Editors. 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. Financial/nonfinancial disclosures: The authors reported to CHEST the following: E. R. B. reports having undertaken clinical trials through his employer, Wake Forest School of Medicine and the University of Arizona, for AstraZeneca, MedImmune, Boehringer Ingelheim, Cephalon/Teva, Genentech, Johnson & Johnson (Janssen), Novartis, Regeneron, and Sanofi Genzyme. He has also served as a paid consultant for AstraZeneca, MedImmune, Boehringer Ingelheim, GlaxoSmithKline, Novartis, Regeneron, and Sanofi Genzyme outside the submitted work. M. C. reports grants from the National Institutes of Health (NIH) and the American Lung Association during the conduct of the study; personal fees from Aviragen, Boehringer Ingelheim, Boston Scientific, Elsevier, Genentech, GlaxoSmithKline, Nuvaira, and Teva; grants from Amgen, Boehringer Ingelheim, Genentech, Gilead, GlaxoSmithKline, Invion, Medimmune, Sanofi-Aventis, and Vectura; all outside the submitted work. J. V. F. reports receiving consultant fees from Boehringer Ingelheim, Pieris, Entrinsic Health Solutions, and Sanofi Genzyme; all outside the submitted work. G. R. W. reports grants from the NIH, grants and other from Boehringer Ingelheim, other from Genentech, other from Quantitative Imaging Solutions, other from PulmonX, other from Regeneron, other from ModoSpira, grants from BTG Interventional Medicine, grants and other from Janssen Pharmaceuticals, other from Toshiba, other from GlaxoSmithKline; all outside the submitted work; and G. R. W.’s spouse works for Biogen, which is focused on developing therapies for fibrotic lung disease. E. I. reports personal fees from AstraZeneca, personal fees from Novartis, personal fees from Philips Respironics, personal fees from Regeneron Pharmaceuticals, personal fees from Teva Specialty Pharmaceuticals, grants from Genentech, nonfinancial support from Boehringer Ingelheim, nonfinancial support from GlaxoSmithKline, nonfinancial support from Merck, nonfinancial support from Sunovion, nonfinancial support from Teva, grants from Sanofi, personal fees from Bird Rock Bio, personal fees from Nuvelution Pharmaceuticals, personal fees from Vitaeris, grants from Boehringer Ingelheim, nonfinancial support from Teva Specialty Pharmaceuticals, personal fees from Sanofi, personal fees from Merck, personal fees from Entrinsic Health Solutions, personal fees from GlaxoSmithKline, other from Vorso Corp. personal fees from Pneuma Respiratory, personal fees from 4D Pharma, outside the submitted work. S. B. F. reports grants from GE Healthcare, outside the submitted work; and served as a paid consultant advising on quantitative CT protocols for the COPD Gene Project. E. A. H. is a founder and shareholder of VIDA Diagnostics, a company commercializing lung image analysis software developed, in part, at the University of Iowa. S. E. W. reports grants and personal fees from AstraZeneca, grants from Boehringer Ingelheim, grants from GlaxoSmithKline, grants and personal fees from Sanofi, grants from Novartis, personal fees from Pieris, personal fees from Up to Date, outside the submitted work. None declared (S. Y. A. G. V. S.-F. M. L. S. F. N. R. A. R. C. E. C. J. C. R. N. N. J. B. M. G. B. D. L. and A. G. C.). SARP Investigators: Elliot Israel MD, Bruce Levy MD, George Washko MD, Manuela Cernadas MD, Wanda Phipatanakul MD, Sally Wenzel MD, Merritt Fajt MD, Benjamin Gaston MD, James Chmiel MD, W. Gerald Teague MD, Anne-Marie Irani MD, Serpil Erzurum MD, Sumita Khatri MD, Suzy Comhair MD, Raed Dweik MD, Kristie Ross MD, Ross Myers MD, Wendy Moore MD, Deborah Meyers PhD, Eugene Bleecker MD, Stephen Peters MD, Annette Hastie MD, Victor Ortega MD, Greg Hawkins PhD, Xingan Li MD, Anne Fitzpatrick PhD, Nazar Jarjour MD, Loren Denlinger MD PhD, Sean Fain PhD, Ronald Sorkness PhD, Mario Castro MD MPH, Leonard Bacharier MD, David Gierada MD, Kenneth Schechtman PhD, Jason Woods PhD, John Fahy MD, Prescott Woodruff MD MPH, Ngoc Ly MD MPH, David Mauger PhD. Additional Information: The e-Appendix, e-Figures, and e-Tables can be found in the Supplemental Materials section of the online article. Publisher Copyright: © 2019 American College of Chest Physicians

PY - 2020/2

Y1 - 2020/2

N2 - Background: Relative enlargement of the pulmonary artery (PA) on chest CT imaging is associated with respiratory exacerbations in patients with COPD or cystic fibrosis. We sought to determine whether similar findings were present in patients with asthma and whether these findings were explained by differences in ventricular size. Methods: We measured the PA and aorta diameters in 233 individuals from the Severe Asthma Research Program III cohort. We also estimated right, left, and total epicardial cardiac ventricular volume indices (eERVVI, eELVVI, and eETVVI, respectively). Associations between the cardiac and PA measures (PA-to-aorta [PA/A] ratio, eERVVI-to-eELVVI [eRV/eLV] ratio, eERVVI, eELVVI, eETVVI) and clinical measures of asthma severity were assessed by Pearson correlation, and associations with asthma severity and exacerbation rate were evaluated by multivariable linear and zero-inflated negative binomial regression. Results: Asthma severity was associated with smaller ventricular volumes. For example, those with severe asthma had 36.1 mL/m2 smaller eETVVI than healthy control subjects (P = .003) and 14.1 mL/m2 smaller eETVVI than those with mild/moderate disease (P = .011). Smaller ventricular volumes were also associated with a higher rate of asthma exacerbations, both retrospectively and prospectively. For example, those with an eETVVI less than the median had a 57% higher rate of exacerbations during follow-up than those with eETVVI greater than the median (P = .020). Neither PA/A nor eRV/eLV was associated with asthma severity or exacerbations. Conclusions: In patients with asthma, smaller cardiac ventricular size may be associated with more severe disease and a higher rate of asthma exacerbations. Trial Registry: ClinicalTrials.gov; No.: NCT01761630; URL: www.clinicaltrials.gov

AB - Background: Relative enlargement of the pulmonary artery (PA) on chest CT imaging is associated with respiratory exacerbations in patients with COPD or cystic fibrosis. We sought to determine whether similar findings were present in patients with asthma and whether these findings were explained by differences in ventricular size. Methods: We measured the PA and aorta diameters in 233 individuals from the Severe Asthma Research Program III cohort. We also estimated right, left, and total epicardial cardiac ventricular volume indices (eERVVI, eELVVI, and eETVVI, respectively). Associations between the cardiac and PA measures (PA-to-aorta [PA/A] ratio, eERVVI-to-eELVVI [eRV/eLV] ratio, eERVVI, eELVVI, eETVVI) and clinical measures of asthma severity were assessed by Pearson correlation, and associations with asthma severity and exacerbation rate were evaluated by multivariable linear and zero-inflated negative binomial regression. Results: Asthma severity was associated with smaller ventricular volumes. For example, those with severe asthma had 36.1 mL/m2 smaller eETVVI than healthy control subjects (P = .003) and 14.1 mL/m2 smaller eETVVI than those with mild/moderate disease (P = .011). Smaller ventricular volumes were also associated with a higher rate of asthma exacerbations, both retrospectively and prospectively. For example, those with an eETVVI less than the median had a 57% higher rate of exacerbations during follow-up than those with eETVVI greater than the median (P = .020). Neither PA/A nor eRV/eLV was associated with asthma severity or exacerbations. Conclusions: In patients with asthma, smaller cardiac ventricular size may be associated with more severe disease and a higher rate of asthma exacerbations. Trial Registry: ClinicalTrials.gov; No.: NCT01761630; URL: www.clinicaltrials.gov

KW - CT imaging

KW - asthma

KW - heart

UR - http://www.scopus.com/inward/record.url?scp=85075447824&partnerID=8YFLogxK

U2 - 10.1016/j.chest.2019.08.2185

DO - 10.1016/j.chest.2019.08.2185

M3 - Article

C2 - 31521672

AN - SCOPUS:85075447824

SN - 0012-3692

VL - 157

SP - 258

EP - 267

JO - Chest

JF - Chest

IS - 2

ER -

Estimated Ventricular Size, Asthma Severity, and Exacerbations: The Severe Asthma Research Program III Cohort

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