title: Pulmonary Microvascular Blood Flow in Mild Chronic Obstructive Pulmonary Disease and Emphysema. The MESA COPD Study.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  To investigate whether PMBF is reduced in mild as well as more severe chronic obstructive pulmonary disease (COPD) and emphysema.
  
  
  METHODS
  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 -950 Hounsfield units (-950 HU) and by radiologists using a standard protocol. We adjusted for potential confounders, including smoking, oxygenation, and left ventricular cardiac output.
  
  
  RESULTS
  Among 144 participants, PMBF was reduced by 30% in mild COPD, by 29% in moderate COPD, and by 52% in severe COPD (all P < 0.01 vs. control subjects). PMBF was reduced with greater percentage emphysema-950HU and radiologist-defined emphysema, particularly panlobular and centrilobular emphysema (all P ≤ 0.01). 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 1 Department of Radiology and.|2 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.
authors.forename: Katja
authors.initials: K
authors.lastname: Hueper
authors.affiliation: 1 Department of Radiology and.|2 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.
authors.forename: Jens
authors.initials: J
authors.lastname: Vogel-Claussen
authors.affiliation: 3 Department of Medicine.
authors.forename: Megha A
authors.initials: MA
authors.lastname: Parikh
authors.affiliation: 4 Department of Radiology, and.
authors.forename: John H M
authors.initials: JH
authors.lastname: Austin
authors.affiliation: 5 Radiology and Imaging Sciences, National Institutes of Health Clinical Center, Bethesda, Maryland.
authors.forename: David A
authors.initials: DA
authors.lastname: Bluemke
authors.affiliation: 6 Department of Radiology and.
authors.forename: James
authors.initials: J
authors.lastname: Carr
authors.affiliation: 7 Department of Radiology.|8 IIHR-Hydroscience & Engineering.
authors.forename: Jiwoong
authors.initials: J
authors.lastname: Choi
authors.affiliation: 9 Department of Biomedical Engineering, Stanford University, Stanford, California.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Goldstein
authors.affiliation: 10 Department of Radiology and.
authors.forename: Antoinette S
authors.initials: AS
authors.lastname: Gomes
authors.affiliation: 7 Department of Radiology.|11 Department of Medicine, and.|12 Department of Biomedical Engineering, University of Iowa, Iowa City, Iowa.
authors.forename: Eric A
authors.initials: EA
authors.lastname: Hoffman
authors.affiliation: 13 Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Steven M
authors.initials: SM
authors.lastname: Kawut
authors.affiliation: 1 Department of Radiology and.|14 Department of Medicine, Johns Hopkins University, Baltimore, Maryland.
authors.forename: Joao
authors.initials: J
authors.lastname: Lima
authors.affiliation: 14 Department of Medicine, Johns Hopkins University, Baltimore, Maryland.
authors.forename: Erin D
authors.initials: ED
authors.lastname: Michos
authors.affiliation: 14 Department of Medicine, Johns Hopkins University, Baltimore, Maryland.
authors.forename: Wendy S
authors.initials: WS
authors.lastname: Post
authors.affiliation: 15 Department of Biomedical Engineering and.
authors.forename: Ming Jack
authors.initials: MJ
authors.lastname: Po
authors.affiliation: 4 Department of Radiology, and.
authors.forename: Martin R
authors.initials: MR
authors.lastname: Prince
authors.affiliation: 16 Department of Biostatistics, Northwestern University, Chicago, Illinois.
authors.forename: Kiang
authors.initials: K
authors.lastname: Liu
authors.affiliation: 17 Department of Statistics, Columbia University, New York, New York; and.
authors.forename: Dan
authors.initials: D
authors.lastname: Rabinowitz
authors.affiliation: 1 Department of Radiology and.
authors.forename: Jan
authors.initials: J
authors.lastname: Skrok
authors.affiliation: 3 Department of Medicine.
authors.forename: Ben M
authors.initials: BM
authors.lastname: Smith
authors.affiliation: 18 Department of Medicine, University of California at Los Angeles, Los Angeles, California.
authors.forename: Karol
authors.initials: K
authors.lastname: Watson
authors.affiliation: 19 VIDA Diagnostics, Coralville, Iowa.
authors.forename: Youbing
authors.initials: Y
authors.lastname: Yin
authors.affiliation: 15 Department of Biomedical Engineering and.
authors.forename: Alan M
authors.initials: AM
authors.lastname: Zambeli-Ljepovic
authors.affiliation: 3 Department of Medicine.|20 Department of Epidemiology, Columbia University Medical Center, New York, New York.
authors.forename: R Graham
authors.initials: RG
authors.lastname: Barr
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D005682:Gadolinium; D006801:Humans; D008168:Lung / Q000098:blood supply* / Q000000981:diagnostic imaging / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008297:Male; D055806:Microvessels / Q000473:pathology*; D008875:Middle Aged; D055420:Perfusion Imaging; D011446:Prospective Studies; D011652:Pulmonary Circulation; D029424:Pulmonary Disease, Chronic Obstructive / Q000000981:diagnostic imaging / Q000473:pathology; D011656:Pulmonary Emphysema / Q000000981:diagnostic imaging / Q000473:pathology*; D012720:Severity of Illness Index; D012907:Smoking / Q000473:pathology*; D013147:Spirometry; D014057:Tomography, X-Ray Computed
chemical_list: D005682:Gadolinium
keywords: chronic obstructive pulmonary disease (COPD); gadolinium-enhanced MRI; lung emphysema; pulmonary microvascular blood flow (PMBF); small airway disease