AJRCCM Articles in Press. Published on 11-June-2015 as 10.1164/rccm.201411-2120OC
Page 1 of 70
Pulmonary microvascular blood flow in mild chronic obstructive pulmonary disease and emphysema. The MESA COPD Study
Katja Hueper, MD,1,2* Jens Vogel-Claussen, MD,1,2* Megha A Parikh, MS,3 John HM Austin, MD,4 David A Bluemke, MD PhD,5 James Carr, MD MS,6 Jiwoong Choi, PhD,7 Thomas A Goldstein, PhD,8 Antoinette S. Gomes, MD,9 Eric A Hoffman, PhD,10 Steven M Kawut, MD MS,11 Joao Lima, MD,1,12 Erin D Michos, MD MHS,12 Wendy S. Post, MD,12 Ming Jack Po,13 Martin R Prince, MD PhD,4 Kiang Liu, PhD,14 Dan Rabinowitz, PhD,15 Jan Skrok, MD,1 Ben M Smith, MD,3 Karol Watson, MD PhD,17 Youbing Yin, PhD,18 Alan M Zambeli-Ljepovic,13 R Graham Barr, MD DrPH3,19
Authors’ affiliations: 1
Department of Radiology, Johns Hopkins University, Baltimore, MD
2
Department of Radiology, Hannover Medical School, Hannover, Germany
3
Department of Medicine, Columbia University Medical Center, New York, NY
4
Department of Radiology, Columbia University Medical Center, New York, NY
5
Radiology and Imaging Sciences, NIH Clinical Center, Bethesda, MD
6
Department of Radiology, Northwestern University, Chicago, IL
7
Department of Radiology and IIHR-Hydroscience & Engineering, University of Iowa, Iowa
City, IA 8
Department of Biomedical Engineering, Stanford University, Stanford, CA
9
Department of Radiology, University of California at Los Angeles, Los Angeles, CA
10
Departments of Radiology, Medicine and Biomedical Engineering, University of Iowa,
Iowa City, IA 11
Department of Medicine, University of Pennsylvania, Philadelphia, PA
12
Department of Medicine, Johns Hopkins University, Baltimore, MD 1 Copyright © 2015 by the American Thoracic Society
AJRCCM Articles in Press. Published on 11-June-2015 as 10.1164/rccm.201411-2120OC
13
Department of Biomedical Engineering, Columbia University, New York, NY
14
Department of Biostatistics, Northwestern University, Chicago, IL
15
Department of Statistics, Columbia University, New York, NY
17
Department of Medicine, University of California-Los Angeles, Los Angeles, CA
18
VIDA Diagnostics, Coralville, IA
19
Department of Epidemiology, Columbia University Medical Center, New York, NY
Page 2 of 70
* These authors contributed equally to the manuscript.
Correspondence: R Graham Barr MD DrPH Presbyterian Hospital 9 East 105 Columbia University Medical Center 630 West 168th St New York, NY 10032 E-mail: [email protected]
Short title: Pulmonary microvascular blood flow in mild COPD and emphysema
Descriptors: Chronic obstructive pulmonary disease, emphysema, MRI, pulmonary microvascular blood flow (9.0, 8.16/17)
Funding: National Institutes of Health R01-HL093081, R01-HL077612, R01-HL075476, N01-HC95159-HC95169, and UL1 RR024156
Word Count: 3466
2 Copyright © 2015 by the American Thoracic Society
Page 3 of 70
AJRCCM Articles in Press. Published on 11-June-2015 as 10.1164/rccm.201411-2120OC
Abstract Word Count: 250
This article has an online data supplement, which is accessible from this issue's table of content online at www.atsjournals.org
Conception and design: JVC, DB, EH, SK, JL, RGB; Data collection: KH, JA, DB, JC, JC, TG, AG, EH, JL, EM, WP, MJP, MAP, KL, JS, BS, KW, YJ, AZL, RGB; Analysis and interpretation: MAP, DR, RGB; Obtaining of funding: EH, JL, WP, MJP, KL, KW, RGB; Drafting the manuscript: KH, JVC; Critical revision of the manuscript for important intellectual content: All authors.
3 Copyright © 2015 by the American Thoracic Society
AJRCCM Articles in Press. Published on 11-June-2015 as 10.1164/rccm.201411-2120OC
Page 4 of 70
ABSTRACT Introduction: Smoking-related microvascular loss causes end-organ damage in the kidneys, heart and brain. Basic research suggests a similar process in the lungs but no large studies have assessed pulmonary microvascular blood flow (PMBF) in early chronic lung disease. We hypothesized that PMBF is reduced in mild as well as more severe COPD and emphysema. Materials and Methods: PMBF was measured using gadolinium-enhanced magnetic resonance imaging (MRI) among smokers with COPD and controls age 50–79 years without clinical cardiovascular disease. COPD severity was defined by standard criteria. Emphysema on computed tomography (CT) was defined by percent of lung regions
Page 1 of 70
Pulmonary microvascular blood flow in mild chronic obstructive pulmonary disease and emphysema. The MESA COPD Study
Katja Hueper, MD,1,2* Jens Vogel-Claussen, MD,1,2* Megha A Parikh, MS,3 John HM Austin, MD,4 David A Bluemke, MD PhD,5 James Carr, MD MS,6 Jiwoong Choi, PhD,7 Thomas A Goldstein, PhD,8 Antoinette S. Gomes, MD,9 Eric A Hoffman, PhD,10 Steven M Kawut, MD MS,11 Joao Lima, MD,1,12 Erin D Michos, MD MHS,12 Wendy S. Post, MD,12 Ming Jack Po,13 Martin R Prince, MD PhD,4 Kiang Liu, PhD,14 Dan Rabinowitz, PhD,15 Jan Skrok, MD,1 Ben M Smith, MD,3 Karol Watson, MD PhD,17 Youbing Yin, PhD,18 Alan M Zambeli-Ljepovic,13 R Graham Barr, MD DrPH3,19
Authors’ affiliations: 1
Department of Radiology, Johns Hopkins University, Baltimore, MD
2
Department of Radiology, Hannover Medical School, Hannover, Germany
3
Department of Medicine, Columbia University Medical Center, New York, NY
4
Department of Radiology, Columbia University Medical Center, New York, NY
5
Radiology and Imaging Sciences, NIH Clinical Center, Bethesda, MD
6
Department of Radiology, Northwestern University, Chicago, IL
7
Department of Radiology and IIHR-Hydroscience & Engineering, University of Iowa, Iowa
City, IA 8
Department of Biomedical Engineering, Stanford University, Stanford, CA
9
Department of Radiology, University of California at Los Angeles, Los Angeles, CA
10
Departments of Radiology, Medicine and Biomedical Engineering, University of Iowa,
Iowa City, IA 11
Department of Medicine, University of Pennsylvania, Philadelphia, PA
12
Department of Medicine, Johns Hopkins University, Baltimore, MD 1 Copyright © 2015 by the American Thoracic Society
AJRCCM Articles in Press. Published on 11-June-2015 as 10.1164/rccm.201411-2120OC
13
Department of Biomedical Engineering, Columbia University, New York, NY
14
Department of Biostatistics, Northwestern University, Chicago, IL
15
Department of Statistics, Columbia University, New York, NY
17
Department of Medicine, University of California-Los Angeles, Los Angeles, CA
18
VIDA Diagnostics, Coralville, IA
19
Department of Epidemiology, Columbia University Medical Center, New York, NY
Page 2 of 70
* These authors contributed equally to the manuscript.
Correspondence: R Graham Barr MD DrPH Presbyterian Hospital 9 East 105 Columbia University Medical Center 630 West 168th St New York, NY 10032 E-mail: [email protected]
Short title: Pulmonary microvascular blood flow in mild COPD and emphysema
Descriptors: Chronic obstructive pulmonary disease, emphysema, MRI, pulmonary microvascular blood flow (9.0, 8.16/17)
Funding: National Institutes of Health R01-HL093081, R01-HL077612, R01-HL075476, N01-HC95159-HC95169, and UL1 RR024156
Word Count: 3466
2 Copyright © 2015 by the American Thoracic Society
Page 3 of 70
AJRCCM Articles in Press. Published on 11-June-2015 as 10.1164/rccm.201411-2120OC
Abstract Word Count: 250
This article has an online data supplement, which is accessible from this issue's table of content online at www.atsjournals.org
Conception and design: JVC, DB, EH, SK, JL, RGB; Data collection: KH, JA, DB, JC, JC, TG, AG, EH, JL, EM, WP, MJP, MAP, KL, JS, BS, KW, YJ, AZL, RGB; Analysis and interpretation: MAP, DR, RGB; Obtaining of funding: EH, JL, WP, MJP, KL, KW, RGB; Drafting the manuscript: KH, JVC; Critical revision of the manuscript for important intellectual content: All authors.
3 Copyright © 2015 by the American Thoracic Society
AJRCCM Articles in Press. Published on 11-June-2015 as 10.1164/rccm.201411-2120OC
Page 4 of 70
ABSTRACT Introduction: Smoking-related microvascular loss causes end-organ damage in the kidneys, heart and brain. Basic research suggests a similar process in the lungs but no large studies have assessed pulmonary microvascular blood flow (PMBF) in early chronic lung disease. We hypothesized that PMBF is reduced in mild as well as more severe COPD and emphysema. Materials and Methods: PMBF was measured using gadolinium-enhanced magnetic resonance imaging (MRI) among smokers with COPD and controls age 50–79 years without clinical cardiovascular disease. COPD severity was defined by standard criteria. Emphysema on computed tomography (CT) was defined by percent of lung regions
