Lung abnormalities increase mortality risk

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The presence of interstitial lung abnormalities are associated with a greater risk of all-cause mortality, according to a new study.

Interstitial lung abnormalities are defined as specific patterns of increased lung density noted on chest computed tomography (CT) scans identified in participants with no prior history of interstitial lung disease (a large group of disorders characterised by progressive scarring of the lung tissue between and supporting the air sacs). In studies of adults, interstitial lung abnormalities are present in approximately 2% to 10% of research participants (and 7% of a general population sample) and are associated with reductions in lung capacity and exercise capacity.

Dr Ivan O Rosas, of Brigham and Women’s Hospital, Harvard Medical School, Boston, and colleagues examined whether interstitial lung abnormalities are associated with increased mortality. The study included 2,633 participants from the FHS (Framingham Heart Study), 5,320 from the AGES-Reykjavik Study (Age Gene/Environment Susceptibility), 2,068 from the COPDGene Study (Chronic Obstructive Pulmonary Disease), and 1,670 from ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints).

Interstitial lung abnormalities were present in 7% of the FHS participants, 7% from AGES-Reykjavik, 8% from COPDGene, and 9% 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: 7% vs 1% in FHS, 56% vs 33% in AGES-Reykjavik, and 11% vs 5% in ECLIPSE. Interstitial lung abnormalities were associated with a higher risk of death in all groups. 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. The associations between interstitial lung abnormalities and mortality were not lessened after adjustment for smoking, cancer, COPD, or coronary artery disease.

“These findings, in conjunction with those previously published, demonstrate that despite often being undiagnosed and asymptomatic, interstitial lung abnormalities may be associated with lower survival rates among older persons,” the authors write. “The clinical implications of this association require further investigation.”

“Follow-up studies should determine the risk factors for and the events that lead to death among persons with interstitial lung abnormalities. Given the ability to treat more advanced stages of pulmonary fibrosis, future clinical trials attempting to reduce the overall mortality associated with pulmonary fibrosis should consider including early stages of the disease.”

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.

JAMA material
JAMA abstract


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