{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T05:47:25Z","timestamp":1793166445973,"version":"4.5.0"},"reference-count":69,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000002g","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01-HL093081"],"award-info":[{"award-number":["R01-HL093081"]}],"id":[{"id":"10.13039\/100000002g","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002g","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01-HL077612"],"award-info":[{"award-number":["R01-HL077612"]}],"id":[{"id":"10.13039\/100000002g","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002g","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01-HL075476"],"award-info":[{"award-number":["R01-HL075476"]}],"id":[{"id":"10.13039\/100000002g","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002g","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01-HL-112986"],"award-info":[{"award-number":["R01-HL-112986"]}],"id":[{"id":"10.13039\/100000002g","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002g","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["N01-HC95159-HC95169"],"award-info":[{"award-number":["N01-HC95159-HC95169"]}],"id":[{"id":"10.13039\/100000002g","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002g","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["UL1 RR024156"],"award-info":[{"award-number":["UL1 RR024156"]}],"id":[{"id":"10.13039\/100000002g","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To investigate whether PMBF is reduced in mild as well as more severe chronic obstructive pulmonary disease (COPD) and emphysema.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>PMBF was measured using gadolinium-enhanced magnetic resonance imaging (MRI) among smokers with COPD and control subjects age 50 to 79 years without clinical cardiovascular disease. COPD severity was defined by standard criteria. Emphysema on computed tomography (CT) was defined by the percentage of lung regions below \u2212950 Hounsfield units (\u2212950 HU) and by radiologists using a standard protocol. We adjusted for potential confounders, including smoking, oxygenation, and left ventricular cardiac output.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and Main Results<\/jats:title>\n                    <jats:p>Among 144 participants, PMBF was reduced by 30% in mild COPD, by 29% in moderate COPD, and by 52% in severe COPD (all P\u2009&amp;lt;\u20090.01 vs. control subjects). PMBF was reduced with greater percentage emphysema\u2212950HU and radiologist-defined emphysema, particularly panlobular and centrilobular emphysema (all P\u2009\u2264\u20090.01). Registration of MRI and CT images revealed that PMBF was reduced in mild COPD in both nonemphysematous and emphysematous lung regions. Associations for PMBF were independent of measures of small airways disease on CT and gas trapping largely because emphysema and small airways disease occurred in different smokers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>PMBF was reduced in mild COPD, including in regions of lung without frank emphysema, and may represent a distinct pathological process from small airways disease. PMBF may provide an imaging biomarker for therapeutic strategies targeting the pulmonary microvasculature.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1164\/rccm.201411-2120oc","type":"journal-article","created":{"date-parts":[[2015,6,11]],"date-time":"2015-06-11T12:36:25Z","timestamp":1434026185000},"page":"570-580","source":"Crossref","is-referenced-by-count":168,"title":["Pulmonary Microvascular Blood Flow in Mild Chronic Obstructive Pulmonary Disease and Emphysema. The MESA COPD Study"],"prefix":"10.1093","volume":"192","author":[{"given":"Katja","family":"Hueper","sequence":"first","affiliation":[{"name":"Department of Radiology and"},{"name":"Department of Radiology and Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Member of the German Center for Lung Research, Hannover Medical School, Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens","family":"Vogel-Claussen","sequence":"additional","affiliation":[{"name":"Department of Radiology and"},{"name":"Department of Radiology and Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Member of the German Center for Lung Research, Hannover Medical School, Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megha A.","family":"Parikh","sequence":"additional","affiliation":[{"name":"Department of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John H. M.","family":"Austin","sequence":"additional","affiliation":[{"name":"Department of Radiology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Bluemke","sequence":"additional","affiliation":[{"name":"Radiology and Imaging Sciences, National Institutes of Health Clinical Center, Bethesda, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Carr","sequence":"additional","affiliation":[{"name":"Department of Radiology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiwoong","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Radiology"},{"name":"IIHR\u2013Hydroscience & Engineering"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas A.","family":"Goldstein","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Stanford University, Stanford, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antoinette S.","family":"Gomes","sequence":"additional","affiliation":[{"name":"Department of Radiology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric A.","family":"Hoffman","sequence":"additional","affiliation":[{"name":"Department of Radiology"},{"name":"Department of Medicine, and"},{"name":"Department of Biomedical Engineering, University of Iowa, Iowa City, Iowa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven M.","family":"Kawut","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joao","family":"Lima","sequence":"additional","affiliation":[{"name":"Department of Radiology and"},{"name":"Department of Medicine, Johns Hopkins University, Baltimore, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erin D.","family":"Michos","sequence":"additional","affiliation":[{"name":"Department of Medicine, Johns Hopkins University, Baltimore, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wendy S.","family":"Post","sequence":"additional","affiliation":[{"name":"Department of Medicine, Johns Hopkins University, Baltimore, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming Jack","family":"Po","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin R.","family":"Prince","sequence":"additional","affiliation":[{"name":"Department of Radiology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiang","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Northwestern University, Chicago, Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Rabinowitz","sequence":"additional","affiliation":[{"name":"Department of Statistics, Columbia University, New York, New York; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Skrok","sequence":"additional","affiliation":[{"name":"Department of Radiology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ben M.","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karol","family":"Watson","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California at Los Angeles, Los Angeles, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youbing","family":"Yin","sequence":"additional","affiliation":[{"name":"VIDA Diagnostics, Coralville, Iowa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan M.","family":"Zambeli-Ljepovic","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. Graham","family":"Barr","sequence":"additional","affiliation":[{"name":"Department of Medicine"},{"name":"Department of Epidemiology, Columbia University Medical Center, New York, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2015,9,1]]},"reference":[{"key":"2026032100160386600_bib1","doi-asserted-by":"crossref","first-page":"2095","DOI":"10.1016\/S0140-6736(12)61728-0","article-title":"Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010","volume":"380","author":"Lozano","year":"2012","journal-title":"Lancet"},{"key":"2026032100160386600_bib2","first-page":"1","article-title":"Death in the United States, 2010","volume":"99","author":"Minino","year":"2012","journal-title":"NCHS Data Brief"},{"key":"2026032100160386600_bib3","doi-asserted-by":"crossref","first-page":"2749","DOI":"10.1172\/JCI60324","article-title":"Pathogenesis of chronic obstructive pulmonary disease","volume":"122","author":"Tuder","year":"2012","journal-title":"J Clin Invest"},{"key":"2026032100160386600_bib4","doi-asserted-by":"crossref","first-page":"524","DOI":"10.2174\/1570161111311040016","article-title":"Vascular pathology from smoking: look at the microcirculation!","volume":"11","author":"Leone","year":"2013","journal-title":"Curr Vasc Pharmacol"},{"key":"2026032100160386600_bib5","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1007\/s00125-011-2398-8","article-title":"Reno-protective effects of renin-angiotensin system blockade in type 2 diabetic patients: a systematic review and network meta-analysis","volume":"55","author":"Vejakama","year":"2012","journal-title":"Diabetologia"},{"key":"2026032100160386600_bib6","doi-asserted-by":"crossref","first-page":"276","DOI":"10.2174\/157016107782023406","article-title":"Structural and functional alteration of blood vessels caused by cigarette smoking: an overview of molecular mechanisms","volume":"5","author":"Rahman","year":"2007","journal-title":"Curr Vasc Pharmacol"},{"key":"2026032100160386600_bib7","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1183\/09031936.00105110","article-title":"Effects of cigarette smoke and hypoxia on pulmonary circulation in the guinea pig","volume":"38","author":"Ferrer","year":"2011","journal-title":"Eur Respir J"},{"key":"2026032100160386600_bib8"},{"key":"2026032100160386600_bib9","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1164\/rccm.200605-724OC","article-title":"Prostacyclin prevents pulmonary endothelial cell apoptosis induced by cigarette smoke","volume":"175","author":"Nana-Sinkam","year":"2007","journal-title":"Am J Respir Crit Care Med"},{"key":"2026032100160386600_bib10","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1038\/nm1238","article-title":"Ceramide upregulation causes pulmonary cell apoptosis and emphysema-like disease in mice","volume":"11","author":"Petrache","year":"2005","journal-title":"Nat Med"},{"key":"2026032100160386600_bib11","first-page":"67","article-title":"Pulmonary emphysema with special reference to vascular changes","volume":"80","author":"Liebow","year":"1959","journal-title":"Am Rev Respir Dis"},{"key":"2026032100160386600_bib12","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1183\/09031936.02.00245902","article-title":"Characterization of pulmonary vascular remodelling in smokers and patients with mild COPD","volume":"19","author":"Santos","year":"2002","journal-title":"Eur Respir J"},{"key":"2026032100160386600_bib13","first-page":"L908","article-title":"Endothelial dysfunction in pulmonary arteries of patients with mild COPD","volume":"274","author":"Peinado","year":"1998","journal-title":"Am J Physiol"},{"key":"2026032100160386600_bib14","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1002\/(SICI)1522-2594(199912)42:6<1033::AID-MRM7>3.0.CO;2-7","article-title":"Quantitative assessment of pulmonary perfusion with dynamic contrast-enhanced MRI","volume":"42","author":"Hatabu","year":"1999","journal-title":"Magn Reson Med"},{"key":"2026032100160386600_bib15","doi-asserted-by":"crossref","first-page":"7485","DOI":"10.1073\/pnas.0913880107","article-title":"Heterogeneity of pulmonary perfusion as a mechanistic image-based phenotype in emphysema susceptible smokers","volume":"107","author":"Alford","year":"2010","journal-title":"Proc Natl Acad Sci USA"},{"key":"2026032100160386600_bib16","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1002\/jmri.20137","article-title":"Quantitative assessment of regional pulmonary perfusion in the entire lung using three-dimensional ultrafast dynamic contrast-enhanced magnetic resonance imaging: preliminary experience in 40 subjects","volume":"20","author":"Ohno","year":"2004","journal-title":"J Magn Reson Imaging"},{"key":"2026032100160386600_bib17","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1097\/RLI.0b013e31816901ab","article-title":"Quantitatively assessed dynamic contrast-enhanced magnetic resonance imaging in patients with chronic obstructive pulmonary disease: correlation of perfusion parameters with pulmonary function test and quantitative computed tomography","volume":"43","author":"Jang","year":"2008","journal-title":"Invest Radiol"},{"key":"2026032100160386600_bib18","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1164\/rccm.201301-0162OC","article-title":"Computed tomographic measures of pulmonary vascular morphology in smokers and their clinical implications","volume":"188","author":"Est\u00e9par","year":"2013","journal-title":"Am J Respir Crit Care Med"},{"key":"2026032100160386600_bib19","doi-asserted-by":"crossref","first-page":"1234","DOI":"10.1007\/s00330-012-2729-2","article-title":"Capability of differentiating smokers with normal pulmonary function from COPD patients: a comparison of CT pulmonary volume analysis and MR perfusion imaging","volume":"23","author":"Fan","year":"2013","journal-title":"Eur Radiol"},{"key":"2026032100160386600_bib20","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1111\/crj.12033","article-title":"Characteristic features of pulmonary function test, CT volume analysis and MR perfusion imaging in COPD patients with different HRCT phenotypes","volume":"8","author":"Fan","year":"2014","journal-title":"Clin Respir J"},{"key":"2026032100160386600_bib21","doi-asserted-by":"crossref","first-page":"510","DOI":"10.3109\/15412555.2014.948990","article-title":"Dynamic contrast enhanced magnetic resonance perfusion imaging in high-risk smokers and smoking-related COPD: correlations with pulmonary function tests and quantitative computed tomography","volume":"11","author":"Xia","year":"2014","journal-title":"COPD"},{"issue":"S 01","key":"2026032100160386600_bib22","doi-asserted-by":"crossref","first-page":"VO318_1","DOI":"10.1055\/s-0032-1311254","article-title":"Ver\u00e4nderungen der lungenperfusion bei patienten mit chronisch obstruktiver Lungenerkrankung (COPD): die MESA COPD Studie [abstract]","volume":"184","author":"Hueper","year":"2012","journal-title":"Fortschr R\u00f6ntgenstr"},{"key":"2026032100160386600_bib23","article-title":"Pulmonary parenchymal blood flow in early chronic obstructive pulmonary disease (COPD): the MESA COPD Study [abstract]","volume":"0624","author":"Hueper","year":"2012","journal-title":"Proc Intl Soc Mag Reson Med"},{"key":"2026032100160386600_bib24","first-page":"A4345","article-title":"Pulmonary parenchymal perfusion in early chronic obstructive pulmonary disease (COPD): the MESA COPD Study [abstract]","volume":"185","author":"Hueper","year":"2012","journal-title":"Am J Respir Crit Care Med"},{"key":"2026032100160386600_bib25","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1093\/aje\/kwf113","article-title":"Multi-ethnic study of atherosclerosis: objectives and design","volume":"156","author":"Bild","year":"2002","journal-title":"Am J Epidemiol"},{"key":"2026032100160386600_bib26","doi-asserted-by":"crossref","first-page":"1200","DOI":"10.1164\/rccm.200707-980OC","article-title":"Impaired flow-mediated dilation is associated with low pulmonary function and emphysema in ex-smokers: the Emphysema and Cancer Action Project (EMCAP) Study","volume":"176","author":"Barr","year":"2007","journal-title":"Am J Respir Crit Care Med"},{"key":"2026032100160386600_bib27","doi-asserted-by":"crossref","first-page":"201","DOI":"10.7326\/0003-4819-152-4-201002160-00004","article-title":"The association of pipe and cigar use with cotinine levels, lung function, and airflow obstruction: a cross-sectional study","volume":"152","author":"Rodriguez","year":"2010","journal-title":"Ann Intern Med"},{"key":"2026032100160386600_bib28","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1097\/RLI.0b013e318281057d","article-title":"Quantitative and semiquantitative measures of regional pulmonary microvascular perfusion by magnetic resonance imaging and their relationships to global lung perfusion and lung diffusing capacity: the multiethnic study of atherosclerosis chronic obstructive pulmonary disease study","volume":"48","author":"Hueper","year":"2013","journal-title":"Invest Radiol"},{"key":"2026032100160386600_bib29","doi-asserted-by":"crossref","first-page":"2123","DOI":"10.1152\/jappl.1996.81.5.2123","article-title":"Morphometry of the human pulmonary vasculature","volume":"81","author":"Huang","year":"1996","journal-title":"J Appl Physiol (1985)"},{"key":"2026032100160386600_bib30","first-page":"208","article-title":"A quantitative approach to the morphologic study of the peripheral pulmonary vasculature","volume":"19","author":"Weibel","year":"1962","journal-title":"Med Thorac"},{"key":"2026032100160386600_bib31","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1183\/09031936.05.00034805","article-title":"Standardisation of spirometry","volume":"26","author":"Miller","year":"2005","journal-title":"Eur Respir J"},{"key":"2026032100160386600_bib32","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1378\/chest.09-0919","article-title":"Performance of American Thoracic Society-recommended spirometry reference values in a multiethnic sample of adults: the Multi-Ethnic Study of Atherosclerosis (MESA) lung study","volume":"137","author":"Hankinson","year":"2010","journal-title":"Chest"},{"key":"2026032100160386600_bib33","doi-asserted-by":"crossref","first-page":"932","DOI":"10.1183\/09031936.04.00014304","article-title":"Standards for the diagnosis and treatment of patients with COPD: a summary of the ATS\/ERS position paper","volume":"23","author":"Celli","year":"2004","journal-title":"Eur Respir J"},{"key":"2026032100160386600_bib34","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1164\/rccm.201204-0596PP","article-title":"Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary","volume":"187","author":"Vestbo","year":"2013","journal-title":"Am J Respir Crit Care Med"},{"key":"2026032100160386600_bib35","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1164\/ajrccm.159.1.9712108","article-title":"Spirometric reference values from a sample of the general U.S. population","volume":"159","author":"Hankinson","year":"1999","journal-title":"Am J Respir Crit Care Med"},{"key":"2026032100160386600_bib36","article-title":"CT Imaging Protocol Standardization for use in a Multicenter Study: SPIROMICS","author":"Sieren","year":"2011"},{"key":"2026032100160386600_bib37","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1164\/ajrccm.152.2.7633722","article-title":"Comparison of computed density and macroscopic morphometry in pulmonary emphysema","volume":"152","author":"Gevenois","year":"1995","journal-title":"Am J Respir Crit Care Med"},{"key":"2026032100160386600_bib38","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1513\/AnnalsATS.201310-364OC","article-title":"Variation in the percent of emphysema-like lung in a healthy, nonsmoking multiethnic sample. The MESA lung study","volume":"11","author":"Hoffman","year":"2014","journal-title":"Ann Am Thorac Soc"},{"key":"2026032100160386600_bib39","doi-asserted-by":"crossref","first-page":"94, e7","DOI":"10.1016\/j.amjmed.2013.09.020","article-title":"Pulmonary emphysema subtypes on computed tomography: the MESA COPD Study","volume":"127","author":"Smith","year":"2014","journal-title":"Am J Med"},{"key":"2026032100160386600_bib40","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1183\/09031936.05.00034905","article-title":"Standardisation of the single-breath determination of carbon monoxide uptake in the lung","volume":"26","author":"Macintyre","year":"2005","journal-title":"Eur Respir J"},{"key":"2026032100160386600_bib41","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1183\/09031936.05.00035005","article-title":"Standardisation of the measurement of lung volumes","volume":"26","author":"Wanger","year":"2005","journal-title":"Eur Respir J"},{"key":"2026032100160386600_bib42"},{"key":"2026032100160386600_bib43","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1148\/radiology.216.2.r00au14597","article-title":"Left ventricular mass and volume: fast calculation with guide-point modeling on MR images","volume":"216","author":"Young","year":"2000","journal-title":"Radiology"},{"key":"2026032100160386600_bib44","doi-asserted-by":"crossref","first-page":"2000","DOI":"10.1016\/j.jacc.2014.07.991","article-title":"Cor pulmonale parvus in chronic obstructive pulmonary disease and emphysema: the MESA COPD study","volume":"64","author":"Kawut","year":"2014","journal-title":"J Am Coll Cardiol"},{"key":"2026032100160386600_bib45","doi-asserted-by":"crossref","first-page":"1503","DOI":"10.1161\/CIRCULATIONAHA.113.001653","article-title":"Pulmonary hyperinflation and left ventricular mass: the Multi-Ethnic Study of Atherosclerosis COPD Study","volume":"127","author":"Smith","year":"2013","journal-title":"Circulation"},{"key":"2026032100160386600_bib46","doi-asserted-by":"crossref","first-page":"1902","DOI":"10.1152\/japplphysiol.00085.2009","article-title":"Ventilation-perfusion imbalance and chronic obstructive pulmonary disease staging severity","volume":"106","author":"Rodr\u00edguez-Roisin","year":"2009","journal-title":"J Appl Physiol (1985)"},{"key":"2026032100160386600_bib47","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1007\/s12149-007-0137-5","article-title":"Assessment of anatomic relation between pulmonary perfusion and morphology in pulmonary emphysema with breath-hold SPECT-CT fusion images","volume":"22","author":"Suga","year":"2008","journal-title":"Ann Nucl Med"},{"key":"2026032100160386600_bib48","doi-asserted-by":"crossref","first-page":"1344","DOI":"10.1007\/s00259-011-1757-5","article-title":"Ventilation\/perfusion SPECT in chronic obstructive pulmonary disease: an evaluation by reference to symptoms, spirometric lung function and emphysema, as assessed with HRCT","volume":"38","author":"J\u00f6gi","year":"2011","journal-title":"Eur J Nucl Med Mol Imaging"},{"key":"2026032100160386600_bib49","doi-asserted-by":"crossref","first-page":"2834","DOI":"10.1007\/s00330-009-1475-6","article-title":"Assessment of lobar perfusion in smokers according to the presence and severity of emphysema: preliminary experience with dual-energy CT angiography","volume":"19","author":"Pansini","year":"2009","journal-title":"Eur Radiol"},{"key":"2026032100160386600_bib50","doi-asserted-by":"crossref","first-page":"H388","DOI":"10.1152\/ajpheart.00868.2010","article-title":"Chronic cigarette smoking causes hypertension, increased oxidative stress, impaired NO bioavailability, endothelial dysfunction, and cardiac remodeling in mice","volume":"300","author":"Talukder","year":"2011","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"2026032100160386600_bib51","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1165\/rcmb.2012-0132OC","article-title":"Cigarette smoke-induced CXCR3 receptor up-regulation mediates endothelial apoptosis","volume":"47","author":"Green","year":"2012","journal-title":"Am J Respir Cell Mol Biol"},{"key":"2026032100160386600_bib52","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1164\/ajrccm.164.4.2101023","article-title":"Reduced expression of endothelial nitric oxide synthase in pulmonary arteries of smokers","volume":"164","author":"Barber\u00e0","year":"2001","journal-title":"Am J Respir Crit Care Med"},{"key":"2026032100160386600_bib53","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1177\/0003319707306141","article-title":"Endothelial dysfunction in chronic obstructive pulmonary disease","volume":"59","author":"Moro","year":"2008","journal-title":"Angiology"},{"key":"2026032100160386600_bib54","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1164\/rccm.201012-2061OC","article-title":"Circulating endothelial microparticles as a measure of early lung destruction in cigarette smokers","volume":"184","author":"Gordon","year":"2011","journal-title":"Am J Respir Crit Care Med"},{"key":"2026032100160386600_bib55","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.1136\/thoraxjnl-2011-201395","article-title":"Increased circulating endothelial microparticles in COPD patients: a potential biomarker for COPD exacerbation susceptibility","volume":"67","author":"Takahashi","year":"2012","journal-title":"Thorax"},{"key":"2026032100160386600_bib56","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1164\/rccm.201209-1697OC","article-title":"Endothelial microparticles in mild chronic obstructive pulmonary disease and emphysema: the Multi-Ethnic Study of Atherosclerosis Chronic Obstructive Pulmonary Disease study","volume":"188","author":"Thomashow","year":"2013","journal-title":"Am J Respir Crit Care Med"},{"key":"2026032100160386600_bib57","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/path.1711170102","article-title":"The pathology of elastase-induced panacinar emphysema in hamsters","volume":"117","author":"Hayes","year":"1975","journal-title":"J Pathol"},{"key":"2026032100160386600_bib58","doi-asserted-by":"crossref","first-page":"1222","DOI":"10.1164\/rccm.200512-1842OC","article-title":"A novel antiapoptotic role for \u03b11-antitrypsin in the prevention of pulmonary emphysema","volume":"173","author":"Petrache","year":"2006","journal-title":"Am J Respir Crit Care Med"},{"key":"2026032100160386600_bib59","first-page":"687","article-title":"The effects of weekly augmentation therapy in patients with PiZZ \u03b11-antitrypsin deficiency","volume":"7","author":"Schmid","year":"2012","journal-title":"Int J Chron Obstruct Pulmon Dis"},{"key":"2026032100160386600_bib60","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1165\/rcmb.2012-0515OC","article-title":"\u03b1\u2081-Antitrypsin modulates lung endothelial cell inflammatory responses to TNF-\u03b1","volume":"49","author":"Lockett","year":"2013","journal-title":"Am J Respir Cell Mol Biol"},{"key":"2026032100160386600_bib61","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1007\/s00428-007-0469-5","article-title":"Association of progressive structural changes in the bronchial epithelium with subepithelial fibrous remodeling: a potential role for hypoxia","volume":"451","author":"Polosukhin","year":"2007","journal-title":"Virchows Arch"},{"key":"2026032100160386600_bib62","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1056\/NEJMoa0808836","article-title":"Percent emphysema, airflow obstruction, and impaired left ventricular filling","volume":"362","author":"Barr","year":"2010","journal-title":"N Engl J Med"},{"key":"2026032100160386600_bib63","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1164\/ajrccm.151.1.7812577","article-title":"Association of chronic obstructive pulmonary disease and sleep apnea syndrome","volume":"151","author":"Chaouat","year":"1995","journal-title":"Am J Respir Crit Care Med"},{"key":"2026032100160386600_bib64","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1164\/rccm.2203046","article-title":"Sleep and sleep-disordered breathing in adults with predominantly mild obstructive airway disease","volume":"167","author":"Sanders","year":"2003","journal-title":"Am J Respir Crit Care Med"},{"key":"2026032100160386600_bib65","doi-asserted-by":"crossref","first-page":"1948","DOI":"10.1056\/NEJMoa012369","article-title":"Abnormal subendocardial perfusion in cardiac syndrome X detected by cardiovascular magnetic resonance imaging","volume":"346","author":"Panting","year":"2002","journal-title":"N Engl J Med"},{"key":"2026032100160386600_bib66","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1016\/j.jacc.2005.09.036","article-title":"Coronary risk factors and myocardial perfusion in asymptomatic adults: the Multi-Ethnic Study of Atherosclerosis (MESA)","volume":"47","author":"Wang","year":"2006","journal-title":"J Am Coll Cardiol"},{"key":"2026032100160386600_bib67","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.1164\/rccm.201202-0223OC","article-title":"Spirometric predictors of lung function decline and mortality in early chronic obstructive pulmonary disease","volume":"185","author":"Drummond","year":"2012","journal-title":"Am J Respir Crit Care Med"},{"key":"2026032100160386600_bib68","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/j.cell.2011.08.035","article-title":"Inducible NOS inhibition reverses tobacco-smoke-induced emphysema and pulmonary hypertension in mice","volume":"147","author":"Seimetz","year":"2011","journal-title":"Cell"},{"key":"2026032100160386600_bib69","doi-asserted-by":"crossref","first-page":"1359","DOI":"10.1164\/rccm.201311-2037OC","article-title":"Stimulation of soluble guanylate cyclase prevents cigarette smoke-induced pulmonary hypertension and emphysema","volume":"189","author":"Weissmann","year":"2014","journal-title":"Am J Respir Crit Care Med"}],"container-title":["American Journal of Respiratory and Critical Care Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ajrccm\/article-pdf\/192\/5\/570\/67214531\/ajrccm_192_5_570.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ajrccm\/article-pdf\/192\/5\/570\/67214531\/ajrccm_192_5_570.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T04:16:13Z","timestamp":1774066573000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ajrccm\/article\/192\/5\/570\/8504791"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,9,1]]},"references-count":69,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2015,9,1]]},"published-print":{"date-parts":[[2015,9,1]]}},"URL":"https:\/\/doi.org\/10.1164\/rccm.201411-2120oc","relation":{},"ISSN":["1073-449X","1535-4970"],"issn-type":[{"value":"1073-449X","type":"print"},{"value":"1535-4970","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2015,9]]},"published":{"date-parts":[[2015,9,1]]}}}