title: Association Between Interstitial Lung Abnormalities and All-Cause Mortality.
abstract: OBJECTIVE
  Interstitial lung abnormalities have been associated with lower 6-minute walk distance, diffusion capacity for carbon monoxide, and total lung capacity. However, to our knowledge, an association with mortality has not been previously investigated.
  
  
  OBJECTIVE
  To investigate whether interstitial lung abnormalities are associated with increased mortality.
  
  
  METHODS
  Prospective cohort studies of 2633 participants from the FHS (Framingham Heart Study; computed tomographic [CT] scans obtained September 2008-March 2011), 5320 from the AGES-Reykjavik Study (Age Gene/Environment Susceptibility; recruited January 2002-February 2006), 2068 from the COPDGene Study (Chronic Obstructive Pulmonary Disease; recruited November 2007-April 2010), and 1670 from ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints; between December 2005-December 2006).
  
  
  METHODS
  Interstitial lung abnormality status as determined by chest CT evaluation.
  
  
  METHODS
  All-cause mortality over an approximate 3- to 9-year median follow-up time. Cause-of-death information was also examined in the AGES-Reykjavik cohort.
  
  
  RESULTS
  Interstitial lung abnormalities were present in 177 (7%) of the 2633 participants from FHS, 378 (7%) of 5320 from AGES-Reykjavik, 156 (8%) of 2068 from COPDGene, and in 157 (9%) of 1670 from ECLIPSE. Over median follow-up times of approximately 3 to 9 years, there were more deaths (and a greater absolute rate of mortality) among participants with interstitial lung abnormalities when compared with those who did not have interstitial lung abnormalities in the following cohorts: 7% vs 1% in FHS (6% difference [95% CI, 2% to 10%]), 56% vs 33% in AGES-Reykjavik (23% difference [95% CI, 18% to 28%]), and 11% vs 5% in ECLIPSE (6% difference [95% CI, 1% to 11%]). After adjustment for covariates, interstitial lung abnormalities were associated with a higher risk of death in the FHS (hazard ratio [HR], 2.7 [95% CI, 1.1 to 6.5]; P = .03), AGES-Reykjavik (HR, 1.3 [95% CI, 1.2 to 1.4]; P < .001), COPDGene (HR, 1.8 [95% CI, 1.1 to 2.8]; P = .01), and ECLIPSE (HR, 1.4 [95% CI, 1.1 to 2.0]; P = .02) cohorts. In the AGES-Reykjavik cohort, the higher rate of mortality could be explained by a higher rate of death due to respiratory disease, specifically pulmonary fibrosis.
  
  
  CONCLUSIONS
  In 4 separate research cohorts, interstitial lung abnormalities were associated with a greater risk of all-cause mortality. The clinical implications of this association require further investigation.
authors.affiliation: Pulmonary and Critical Care Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
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authors.initials: RK
authors.lastname: Putman
authors.affiliation: Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts3Center for Pulmonary Functional Imaging, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
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authors.affiliation: Center for Pulmonary Functional Imaging, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
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authors.affiliation: Department of Respiratory Medicine and Sleep, Landspital University Hospital, University of Iceland, Reykjavik, Iceland.
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authors.affiliation: Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts.
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authors.affiliation: Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts3Center for Pulmonary Functional Imaging, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
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authors.affiliation: Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts6Department of Radiology, St. Luke's International Hospital, Tokyo, Japan.
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authors.affiliation: Pulmonary Center, Department of Medicine, Boston University, Boston, Massachusetts9Department of Neurology, Boston University, Boston, Massachusetts.
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authors.affiliation: Pulmonary and Critical Care Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts10Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
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authors.affiliation: Pulmonary and Critical Care Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
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authors.affiliation: Department of Radiology, University of British Columbia, Vancouver, BC, Canada.
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authors.affiliation: Pulmonary and Critical Care Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
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authors.affiliation: Pulmonary and Critical Care Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts12Comprehensive Pneumology Center, Ludwig-Maximilians-University, University Hospital Grosshadern, Munich, Germany13Helmholtz Zentrum München.
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authors.initials: IE
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authors.affiliation: Pulmonary and Critical Care Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
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authors.affiliation: Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts14Surgical Planning Laboratory, Department of Radiology, Brigham and Women's Hospital, Boston, Massachusetts.
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authors.affiliation: Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts14Surgical Planning Laboratory, Department of Radiology, Brigham and Women's Hospital, Boston, Massachusetts.
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authors.affiliation: Pulmonary and Critical Care Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
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authors.affiliation: Icelandic Heart Association, Kopavogur, Iceland.
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authors.affiliation: Icelandic Heart Association, Kopavogur, Iceland.
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authors.forename: Gudny
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authors.affiliation: Icelandic Heart Association, Kopavogur, Iceland16University of Iceland, Reykjavik, Iceland.
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authors.affiliation: Department of Medicine, Los Angeles Biomedical Research Institute at Harbor-UCLA, Torrance, California.
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authors.initials: MJ
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authors.affiliation: Department of Epidemiology, Colorado School of Public Health, University of Colorado Denver, Denver, Colorado.
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authors.affiliation: Department of Epidemiology, Colorado School of Public Health, University of Colorado Denver, Denver, Colorado.
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authors.affiliation: University of Edinburgh/British Heart Foundation Centre for Cardiovascular Science, Edinburgh, Scotland.
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authors.affiliation: National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, Massachusetts23Cardiovascular Epidemiology and Human Genomics Branch, NHLBI Division of Intramural Research, Bethesda, Maryland.
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authors.initials: TB
authors.lastname: Harrris
authors.affiliation: Icelandic Heart Association, Kopavogur, Iceland16University of Iceland, Reykjavik, Iceland.
authors.forename: Vilmundur
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authors.lastname: Gudnason
authors.affiliation: Pulmonary and Critical Care Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts10Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
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authors.initials: EK
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mesh_terms: D002423:Cause of Death; D015331:Cohort Studies; D003324:Coronary Artery Disease / Q000453:epidemiology / Q000401:mortality; D005260:Female; D006801:Humans; D008297:Male; D009369:Neoplasms / Q000401:mortality; D015995:Prevalence; D016016:Proportional Hazards Models; D011446:Prospective Studies; D029424:Pulmonary Disease, Chronic Obstructive / Q000000981:diagnostic imaging / Q000453:epidemiology / Q000401:mortality*; D011656:Pulmonary Emphysema / Q000453:epidemiology / Q000401:mortality; D011859:Radiography; D012907:Smoking / Q000453:epidemiology