title: High attenuation areas on chest computed tomography in community-dwelling adults: the MESA study.
abstract: Evidence suggests that lung injury, inflammation and extracellular matrix remodelling precede lung fibrosis in interstitial lung disease (ILD). We examined whether a quantitative measure of increased lung attenuation on computed tomography (CT) detects lung injury, inflammation and extracellular matrix remodelling in community-dwelling adults sampled without regard to respiratory symptoms or smoking.We measured high attenuation areas (HAA; percentage of lung voxels between -600 and -250 Hounsfield Units) on cardiac CT scans of adults enrolled in the Multi-Ethnic Study of Atherosclerosis.HAA was associated with higher serum matrix metalloproteinase-7 (mean adjusted difference 6.3% per HAA doubling, 95% CI 1.3-11.5), higher interleukin-6 (mean adjusted difference 8.8%, 95% CI 4.8-13.0), lower forced vital capacity (FVC) (mean adjusted difference -82 mL, 95% CI -119--44), lower 6-min walk distance (mean adjusted difference -40 m, 95% CI -1--80), higher odds of interstitial lung abnormalities at 9.5 years (adjusted OR 1.95, 95% CI 1.43-2.65), and higher all cause-mortality rate over 12.2 years (HR 1.58, 95% CI 1.39-1.79).High attenuation areas are associated with biomarkers of inflammation and extracellular matrix remodelling, reduced lung function, interstitial lung abnormalities, and a higher risk of death among community-dwelling adults.
authors.affiliation: Dept of Medicine, Columbia University Medical Center, New York, NY, USA.|Both authors contributed equally to this work.
authors.forename: Anna J
authors.initials: AJ
authors.lastname: Podolanczuk
authors.affiliation: Dept of Medicine, Columbia University Medical Center, New York, NY, USA.|Both authors contributed equally to this work.
authors.forename: Elizabeth C
authors.initials: EC
authors.lastname: Oelsner
authors.affiliation: Dept of Medicine, Columbia University Medical Center, New York, NY, USA.|Dept of Epidemiology, Columbia University Medical Center, New York, NY, USA.
authors.forename: R Graham
authors.initials: RG
authors.lastname: Barr
authors.affiliation: Depts of Radiology, Medicine and Biomedical Engineering, University of Iowa Carver College of Medicine, Iowa City, IA, USA.
authors.forename: Eric A
authors.initials: EA
authors.lastname: Hoffman
authors.affiliation: Dept of Epidemiology, Columbia University Medical Center, New York, NY, USA.
authors.forename: Hilary F
authors.initials: HF
authors.lastname: Armstrong
authors.affiliation: Dept of Radiology, Columbia University Medical Center, New York, NY, USA.
authors.forename: John H M
authors.initials: JH
authors.lastname: Austin
authors.affiliation: Dept of Medicine, Columbia University Medical Center, New York, NY, USA.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Basner
authors.affiliation: Dept of Rehabilitation Medicine, Albert Einstein College of Medicine/Montefiore Medical Center, Bronx, NY, USA.
authors.forename: Matthew N
authors.initials: MN
authors.lastname: Bartels
authors.affiliation: Dept of Medicine and the Center for Translational Lung Biology, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Jason D
authors.initials: JD
authors.lastname: Christie
authors.affiliation: Dept of Epidemiology, University of Arizona, Tucson, AZ, USA.
authors.forename: Paul L
authors.initials: PL
authors.lastname: Enright
authors.affiliation: National Human Genome Research Institute, Bethesda, MD, USA.
authors.forename: Bernadette R
authors.initials: BR
authors.lastname: Gochuico
authors.affiliation: Dept of Biostatistics, University of Washington, Seattle, WA, USA.
authors.forename: Karen
authors.initials: K
authors.lastname: Hinckley Stukovsky
authors.affiliation: Dept of Medicine, University of Washington, Seattle, WA, USA.
authors.forename: Joel D
authors.initials: JD
authors.lastname: Kaufman
authors.affiliation: Dept of Radiology, University of Alabama, South Birmingham, AL, USA.
authors.forename: P
authors.initials: P
authors.lastname: Hrudaya Nath
authors.affiliation: Depts of Radiology, Medicine and Biomedical Engineering, University of Iowa Carver College of Medicine, Iowa City, IA, USA.
authors.forename: John D
authors.initials: JD
authors.lastname: Newell
authors.affiliation: Duke Clinical Research Institute, Duke University, Durham, NC, USA.
authors.forename: Scott M
authors.initials: SM
authors.lastname: Palmer
authors.affiliation: Dept of Statistics, Columbia University, New York, NY, USA.
authors.forename: Dan
authors.initials: D
authors.lastname: Rabinowitz
authors.affiliation: Dept of Medicine, University of Washington, Seattle, WA, USA.
authors.forename: Ganesh
authors.initials: G
authors.lastname: Raghu
authors.affiliation: Dept of Medicine, Columbia University Medical Center, New York, NY, USA.
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Sell
authors.affiliation: VIDA Diagnostics, Inc., Coralville, IA, USA.
authors.forename: Jered
authors.initials: J
authors.lastname: Sieren
authors.affiliation: Dept of Radiology, University of Alabama, South Birmingham, AL, USA.
authors.forename: Sushil K
authors.initials: SK
authors.lastname: Sonavane
authors.affiliation: Dept of Pathology, University of Vermont, Colchester, VT, USA.
authors.forename: Russell P
authors.initials: RP
authors.lastname: Tracy
authors.affiliation: Dept of Radiology, University of Alabama, South Birmingham, AL, USA.
authors.forename: Jubal R
authors.initials: JR
authors.lastname: Watts
authors.affiliation: Dept of Medicine, University of Washington, Seattle, WA, USA.
authors.forename: Kayleen
authors.initials: K
authors.lastname: Williams
authors.affiliation: Dept of Medicine and the Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Steven M
authors.initials: SM
authors.lastname: Kawut
authors.affiliation: Dept of Medicine, Columbia University Medical Center, New York, NY, USA davidlederer@columbia.edu.|Dept of Epidemiology, Columbia University Medical Center, New York, NY, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Lederer
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis; D015444:Exercise; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D005355:Fibrosis; D006801:Humans; D007249:Inflammation; D015850:Interleukin-6 / Q000097:blood; D008168:Lung / Q000000981:diagnostic imaging* / Q000503:physiopathology; D017563:Lung Diseases, Interstitial / Q000097:blood / Q000000981:diagnostic imaging; D008297:Male; D020783:Matrix Metalloproteinase 7 / Q000097:blood; D008875:Middle Aged; D016016:Proportional Hazards Models; D013902:Radiography, Thoracic; D012907:Smoking; D013147:Spirometry / Q000379:methods; D014057:Tomography, X-Ray Computed
chemical_list: D015415:Biomarkers; C508600:IL6 protein, human; D015850:Interleukin-6; D002097:C-Reactive Protein; C060932:MMP7 protein, human; D020783:Matrix Metalloproteinase 7