HealthDay News – Interstitial lung abnormalities correlate with increased risk of all-cause mortality, according to research published in the Feb. 16 issue of the Journal of the American Medical Association.

Rachel K. Putman, MD, from the Brigham and Women’s Hospital in Boston, and colleagues examined whether interstitial lung abnormalities are associated with increased mortality in four prospective cohort studies. Data were included for 2,633 participants from the Framingham Heart Study (FHS); 5,320 from the Age Gene/Environment Susceptibility (AGES)-Reykjavik Study; 2,068 from the Chronic Obstructive Pulmonary Disease (COPD)Gene study; and 1,670 from the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) study. The authors examined all-cause mortality during a median follow-up of about three to nine years.

These imaging abnormalities were defined as specific patterns of increased lung density affecting more than 5% of any lung zone and included reticular or ground-glass abnormalities, diffuse centrilobular nodularity, nonemphysematous cysts, honeycombing, traction bronchiectasis, or pulmonary parenchymal architectural distortion diagnostic of fibrotic lung disease. They were identified in approximately 7% of the 11,691 study participants

Continue Reading

The researchers found that 7, 7, 8, and 9% of participants from FHS, AGES-Reykjavik, COPDGene, and ECLIPSE, respectively, had interstitial lung abnormalities. More deaths were seen among participants with, versus those without, interstitial lung abnormalities in FHS, AGES-Reykjavik, and ECLIPSE.

The absolute rates of all-cause mortality were significantly higher among participants who had interstitial lung abnormalities than among those who did not. Mortality rates were 7% vs. 1% in the FHS, 56% vs. 33% in AGES-Reykjavik, 16% vs. 11% in COPDGene, and 11% vs. 5% in ECLIPSE. After the data were adjusted to account for confounding factors such as age, sex, race, body-mass index, current smoking status, and pack-years of smoking, the lung abnormalities remained strongly associated with a higher risk of death in the FHS (hazard ratio, 2.7), AGES-Reykjavik (HR, 1.3), COPDGene (HR, 1.8), and ECLIPSE (HR, 1.4) studies.The higher rate of mortality seen in the AGES-Reykjavik cohort was attributed to a higher rate of death due to respiratory diseases, particularly pulmonary fibrosis.

The association remained robust in further analyses restricted only to nonsmoking participants

Summary and Clinical Applicability

Though interstitial lung abnormalities have been associated with lower diffusion capacity for carbon monoxide (DLCO) and total lung capacity (TLC),  an association with mortality had not been previously investigated prior to this study. This study found that In 4 separate large, independent research cohorts, interstitial lung abnormalities were associated with a greater risk of all-cause mortality.

The study findings, taken together with those of previous research, “demonstrate that despite often being undiagnosed and asymptomatic, interstitial lung abnormalities may be associated with lower survival rates among older persons,” said Dr. Rachel K. Putman of the pulmonary and critical care division at Brigham and Women’s Hospital and Harvard Medical School.

This is significant because several rheumatic disease are associated with the development of interstitial lung disease, and the increased mortality associated with interstitial lung disease should be recognized. 


Putman RK, Hatabu H, Araki T, et al. Association Between Interstitial Lung Abnormalities and All-Cause Mortality.JAMA. 2016;315(7):672-681. doi:10.1001/jama.2016.0518.