TY - JOUR
T1 - Association Between Interstitial Lung Abnormalities and All-Cause Mortality
AU - ECLIPSE Investigator
AU - COPDGene Investigator
AU - Putman, Rachel K.
AU - Hatabu, Hiroto
AU - Araki, Tetsuro
AU - Gudmundsson, Gunnar
AU - Gao, Wei
AU - Nishino, Mizuki
AU - Okajima, Yuka
AU - Dupuis, Josee
AU - Latourelle, Jeanne C.
AU - Cho, Michael H.
AU - El-Chemaly, Souheil
AU - Coxson, Harvey O.
AU - Celli, Bartolome R.
AU - Fernandez, Isis E.
AU - Zazueta, Oscar E.
AU - Ross, James C.
AU - Harmouche, Rola
AU - Estepar, Raul San Jose
AU - Diaz, Alejandro A.
AU - Sigurdsson, Sigurdur
AU - Gudmundsson, Elias F.
AU - Eiriksdottir, Gudny
AU - Aspelund, Thor
AU - Budoff, Matthew J.
AU - Kinney, Gregory L.
AU - Hokanson, John E.
AU - Williams, Michelle
AU - Murchison, John T.
AU - MacNee, William
AU - Hoffmann, Udo
AU - O'Donnell, Christopher J.
AU - Launer, Lenore J.
AU - Harrris, Tamara B.
AU - Gudnason, Vilmundur
AU - Silverman, Edwin K.
AU - O'Connor, George T.
AU - Washko, George R.
AU - Rosas, Ivan O.
AU - Hunninghake, Gary M.
PY - 2016/2/16
Y1 - 2016/2/16
N2 - 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]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, 1.1to 2.8]; P = .01), and ECLIPSE (HR, 1.4 [95% CI, 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.
AB - 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]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, 1.1to 2.8]; P = .01), and ECLIPSE (HR, 1.4 [95% CI, 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.
KW - IDIOPATHIC PULMONARY-FIBROSIS
KW - MUC5B PROMOTER POLYMORPHISM
KW - EXERCISE CAPACITY
KW - DISEASE
KW - SUSCEPTIBILITY
KW - EPIDEMIOLOGY
KW - PREVALENCE
U2 - 10.1001/jama.2016.0518
DO - 10.1001/jama.2016.0518
M3 - Article
SN - 0098-7484
VL - 315
SP - 672
EP - 681
JO - Journal of the American Medical Association
JF - Journal of the American Medical Association
IS - 7
ER -