title: A comparison of visual and quantitative methods to identify interstitial lung abnormalities.
abstract: BACKGROUND
  Evidence suggests that individuals with interstitial lung abnormalities (ILA) on a chest computed tomogram (CT) may have an increased risk to develop a clinically significant interstitial lung disease (ILD). Although methods used to identify individuals with ILA on chest CT have included both automated quantitative and qualitative visual inspection methods, there has been not direct comparison between these two methods. To investigate this relationship, we created lung density metrics and compared these to visual assessments of ILA.
  
  
  METHODS
  To provide a comparison between ILA detection methods based on visual assessment we generated measures of high attenuation areas (HAAs, defined by attenuation values between -600 and -250 Hounsfield Units) in >4500 participants from both the COPDGene and Framingham Heart studies (FHS). Linear and logistic regressions were used for analyses.
  
  
  RESULTS
  Increased measures of HAAs (in ≥ 10 % of the lung) were significantly associated with ILA defined by visual inspection in both cohorts (P < 0.0001); however, the positive predictive values were not very high (19 % in COPDGene and 13 % in the FHS). In COPDGene, the association between HAAs and ILA defined by visual assessment were modified by the percentage of emphysema and body mass index. Although increased HAAs were associated with reductions in total lung capacity in both cohorts, there was no evidence for an association between measurement of HAAs and MUC5B promoter genotype in the FHS.
  
  
  CONCLUSIONS
  Our findings demonstrate that increased measures of lung density may be helpful in determining the severity of lung volume reduction, but alone, are not strongly predictive of ILA defined by visual assessment. Moreover, HAAs were not associated with MUC5B promoter genotype.
authors.affiliation: From the Pulmonary and Critical Care Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. kliment.corrine@gmail.com.
authors.forename: Corrine R
authors.initials: CR
authors.lastname: Kliment
authors.affiliation: Department of Radiology, Brigham and Women's Hospital, Boston, MA, USA. taraki@partners.org.
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Araki
authors.affiliation: From the Pulmonary and Critical Care Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. tjdoyle@partners.org.
authors.forename: Tracy J
authors.initials: TJ
authors.lastname: Doyle
authors.affiliation: Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA. gaowei@bu.edu.
authors.forename: Wei
authors.initials: W
authors.lastname: Gao
authors.affiliation: Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA. dupuis@bu.edu.|The National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, Massachusetts, Boston, MA, USA. dupuis@bu.edu.
authors.forename: Josée
authors.initials: J
authors.lastname: Dupuis
authors.affiliation: Department of Medicine, Boston University, Boston, MA, USA. jlatoure@bu.edu.|Department of Neurology, Boston University, Boston, MA, USA. jlatoure@bu.edu.
authors.forename: Jeanne C
authors.initials: JC
authors.lastname: Latourelle
authors.affiliation: From the Pulmonary and Critical Care Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. efren_zazueta89@hotmail.com.
authors.forename: Oscar E
authors.initials: OE
authors.lastname: Zazueta
authors.affiliation: From the Pulmonary and Critical Care Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. isis.fernandez@helmholtz-muenchen.de.
authors.forename: Isis E
authors.initials: IE
authors.lastname: Fernandez
authors.affiliation: Department of Radiology, Brigham and Women's Hospital, Boston, MA, USA. Mizuki_Nishino11@dfci.harvard.edu.|Center for Pulmonary Functional Imaging, Brigham and Women's Hospital, Boston, MA, USA. Mizuki_Nishino11@dfci.harvard.edu.
authors.forename: Mizuki
authors.initials: M
authors.lastname: Nishino
authors.affiliation: Department of Radiology, Brigham and Women's Hospital, Boston, MA, USA. ykokaji@gmail.com.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Okajima
authors.affiliation: Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA. jross@bwh.harvard.edu.|Surgical Planning Laboratory, Department of Radiology, Brigham and Women's Hospital, Boston, MA, USA. jross@bwh.harvard.edu.
authors.forename: James C
authors.initials: JC
authors.lastname: Ross
authors.affiliation: Center for Pulmonary Functional Imaging, Brigham and Women's Hospital, Boston, MA, USA. rjosest@bwh.harvard.edu.|Surgical Planning Laboratory, Department of Radiology, Brigham and Women's Hospital, Boston, MA, USA. rjosest@bwh.harvard.edu.
authors.forename: Raúl San José
authors.initials: RS
authors.lastname: Estépar
authors.affiliation: From the Pulmonary and Critical Care Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. adiaz6@partners.org.|Department of Pulmonary Diseases, Pontificia Universidad Católica de Chile, Santiago, Chile. adiaz6@partners.org.
authors.forename: Alejandro A
authors.initials: AA
authors.lastname: Diaz
authors.affiliation: Division of Pulmonary and Critical Care, College of Physicians and Surgeons, Columbia University, New York, NY, USA. dl427@cumc.columbia.edu.|Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA. dl427@cumc.columbia.edu.
authors.forename: David J
authors.initials: DJ
authors.lastname: Lederer
authors.affiliation: Department of Medicine, University of Colorado, Denver, CO, USA. David.Schwartz@ucdenver.edu.
authors.forename: David A
authors.initials: DA
authors.lastname: Schwartz
authors.affiliation: From the Pulmonary and Critical Care Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. eksilverman@partners.org.|Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA. eksilverman@partners.org.
authors.forename: Edwin K
authors.initials: EK
authors.lastname: Silverman
authors.affiliation: From the Pulmonary and Critical Care Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. irosas@rics.bwh.harvard.edu.
authors.forename: Ivan O
authors.initials: IO
authors.lastname: Rosas
authors.affiliation: From the Pulmonary and Critical Care Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. gwashko@partners.org.|Center for Pulmonary Functional Imaging, Brigham and Women's Hospital, Boston, MA, USA. gwashko@partners.org.
authors.forename: George R
authors.initials: GR
authors.lastname: Washko
authors.affiliation: The National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, Massachusetts, Boston, MA, USA. George.O'Connor@bmc.org.|Pulmonary Center, Department of Medicine, Boston University School of Medicine, Boston, MA, USA. George.O'Connor@bmc.org.
authors.forename: George T
authors.initials: GT
authors.lastname: O'Connor
authors.affiliation: Department of Radiology, Brigham and Women's Hospital, Boston, MA, USA. HHatabu@Partners.org.|Center for Pulmonary Functional Imaging, Brigham and Women's Hospital, Boston, MA, USA. HHatabu@Partners.org.
authors.forename: Hiroto
authors.initials: H
authors.lastname: Hatabu
authors.affiliation: From the Pulmonary and Critical Care Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. ghunninghake@partners.org.|Center for Pulmonary Functional Imaging, Brigham and Women's Hospital, Boston, MA, USA. ghunninghake@partners.org.
authors.forename: Gary M
authors.initials: GM
authors.lastname: Hunninghake
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015992:Body Mass Index; D015331:Cohort Studies; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods*; D016014:Linear Models; D016015:Logistic Models; D008168:Lung / Q000000981:diagnostic imaging* / Q000503:physiopathology; D017563:Lung Diseases, Interstitial / Q000000981:diagnostic imaging* / Q000235:genetics / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D055257:Mucin-5B / Q000235:genetics; D011401:Promoter Regions, Genetic; D029424:Pulmonary Disease, Chronic Obstructive / Q000000981:diagnostic imaging / Q000235:genetics / Q000503:physiopathology; D011656:Pulmonary Emphysema / Q000000981:diagnostic imaging* / Q000235:genetics / Q000503:physiopathology; D013147:Spirometry; D014057:Tomography, X-Ray Computed; D014109:Total Lung Capacity; D014797:Vital Capacity
chemical_list: C524578:MUC5B protein, human; D055257:Mucin-5B