Association Between Interstitial Lung Abnormalities and All-Cause Mortality
Rachel K Putman, Hiroto Hatabu, Tetsuro Araki, Gunnar Gudmundsson, Wei Gao, Mizuki Nishino, Yuka Okajima, Josée Dupuis, Jeanne C Latourelle, Michael H Cho, Souheil El-Chemaly, Harvey O Coxson, Bartolome R Celli, Isis E Fernandez, Oscar E Zazueta, James C Ross, Rola Harmouche, Raúl San José Estépar, Alejandro A Diaz, Sigurdur Sigurdsson, Elías F Gudmundsson, Gudny Eiríksdottír, Thor Aspelund, Matthew J Budoff, Gregory L Kinney, John E Hokanson, Michelle C Williams, John T Murchison, William MacNee, Udo Hoffmann, Christopher J O'Donnell, Lenore J Launer, Tamara B Harrris, Vilmundur Gudnason, Edwin K Silverman, George T O'Connor, George R Washko, Ivan O Rosas, Gary M Hunninghake, Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) Investigators, COPDGene Investigators, Rachel K Putman, Hiroto Hatabu, Tetsuro Araki, Gunnar Gudmundsson, Wei Gao, Mizuki Nishino, Yuka Okajima, Josée Dupuis, Jeanne C Latourelle, Michael H Cho, Souheil El-Chemaly, Harvey O Coxson, Bartolome R Celli, Isis E Fernandez, Oscar E Zazueta, James C Ross, Rola Harmouche, Raúl San José Estépar, Alejandro A Diaz, Sigurdur Sigurdsson, Elías F Gudmundsson, Gudny Eiríksdottír, Thor Aspelund, Matthew J Budoff, Gregory L Kinney, John E Hokanson, Michelle C Williams, John T Murchison, William MacNee, Udo Hoffmann, Christopher J O'Donnell, Lenore J Launer, Tamara B Harrris, Vilmundur Gudnason, Edwin K Silverman, George T O'Connor, George R Washko, Ivan O Rosas, Gary M Hunninghake, Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) Investigators, COPDGene Investigators
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.
Conflict of interest statement
Conflict of Interest Disclosures:
No other disclosures are reported.
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Source: PubMed