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JAMA. 2016 Feb 16;315(7):672-81. doi: 10.1001/jama.2016.0518.

Association Between Interstitial Lung Abnormalities and All-Cause Mortality.

Author information

  • 1Pulmonary and Critical Care Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
  • 2Department 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.
  • 3Center for Pulmonary Functional Imaging, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
  • 4Department of Respiratory Medicine and Sleep, Landspital University Hospital, University of Iceland, Reykjavik, Iceland.
  • 5Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts.
  • 6Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts6Department of Radiology, St. Luke's International Hospital, Tokyo, Japan.
  • 7Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts7National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, Massachusetts.
  • 8Pulmonary Center, Department of Medicine, Boston University, Boston, Massachusetts9Department of Neurology, Boston University, Boston, Massachusetts.
  • 9Pulmonary 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.
  • 10Department of Radiology, University of British Columbia, Vancouver, BC, Canada.
  • 11Pulmonary 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.
  • 12Channing 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.
  • 13Pulmonary and Critical Care Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts14Surgical Planning Laboratory, Department of Radiology, Brigham and Women's Hospital, Boston, Massachusetts.
  • 14Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts14Surgical Planning Laboratory, Department of Radiology, Brigham and Women's Hospital, Boston, Massachusetts.
  • 15Icelandic Heart Association, Kopavogur, Iceland.
  • 16Icelandic Heart Association, Kopavogur, Iceland16University of Iceland, Reykjavik, Iceland.
  • 17Department of Medicine, Los Angeles Biomedical Research Institute at Harbor-UCLA, Torrance, California.
  • 18Department of Epidemiology, Colorado School of Public Health, University of Colorado Denver, Denver, Colorado.
  • 19University of Edinburgh/British Heart Foundation Centre for Cardiovascular Science, Edinburgh, Scotland.
  • 20Royal Infirmary of Edinburgh, University of Edinburgh, Edinburgh, Scotland.
  • 21Centre for Inflammation Research, University of Edinburgh, Edinburgh, Scotland.
  • 22Cardiac MR PET CT Program, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
  • 23National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, Massachusetts23Cardiovascular Epidemiology and Human Genomics Branch, NHLBI Division of Intramural Research, Bethesda, Maryland.
  • 24Intramural Research Program, National Institute of Aging, NIH, Bethesda, Maryland.
  • 25National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, Massachusetts8Pulmonary Center, Department of Medicine, Boston University, Boston, Massachusetts.
  • 26Pulmonary and Critical Care Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts3Center for Pulmonary Functional Imaging, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.

Abstract

IMPORTANCE:

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.

DESIGN, SETTING, AND POPULATION:

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).

EXPOSURES:

Interstitial lung abnormality status as determined by chest CT evaluation.

MAIN OUTCOMES AND MEASURES:

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 AND RELEVANCE:

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.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT00292552.

PMID:
26881370
[PubMed - indexed for MEDLINE]
PMCID:
PMC4828973
Free PMC Article

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