Interstitial Lung Abnormalities Tied to Increased Mortality

Ricki Lewis, PhD

February 16, 2016

Interstitial lung abnormalities are associated with lower survival rates, according to results of a study published in the February 16 issue of JAMA.

Interstitial lung abnormalities are distinct patterns of increased lung density imaged on chest computed tomography scans in individuals with no history of interstitial lung disease and include more than 100 distinct clinical entities.

In addition to computed tomography imaging evidence, interstitial lung abnormalities are associated with lower diffusion capacity for carbon monoxide, lower 6-minute walk distance, reduced total lung capacity, and reduced exercise capacity. These signs and symptoms are also diagnostic of idiopathic pulmonary fibrosis.

In the current study, Rachel K. Putman, MD, from the Pulmonary and Critical Care Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, and colleagues hypothesize that some cases of interstitial lung abnormalities are early or mild manifestations of idiopathic pulmonary fibrosis, and that if so, these cases might be associated with increased risk for mortality. To find out, the researchers tested the possible association between interstitial lung abnormalities and increased all-cause mortality.

They identified participants using chest computed tomography scan data from four cohorts: 2633 participants in the Framingham Heart Study (FHS), 5320 patients from the Age Gene/Environment Susceptibility (AGES-Reykjavik) Study, 2068 participants from the Chronic Obstructive Pulmonary Disease Gene Study (COPDGene), and 1670 individuals from the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) study. Patients were followed for 3 to 9 years. The AGES-Reykjavik study also included cause of death and captured an older population.

Overall, 177 (7%) of the FHS participants had interstitial lung abnormalities, as did 378 (7%) of the AGES-Reykjavik patients, 156 (8%) of the COPDGene study, and 157 (9%) from ECLIPSE.

During the follow-up periods, more deaths occurred among participants with interstitial lung abnormalities than among those without them in three of the four cohorts: 7% vs 1% in the FHS (6% difference; 95% confidence interval [CI], 2% - 10%), 56% vs 33% for AGES-Reykjavik (23% difference; 95% CI, 18% - 28%), and 11% vs 5% for ECLIPSE (6% difference; 95% CI, 1% - 11%). There was, however, no difference in absolute mortality rate between those with and without interstitial lung abnormalities in the COPDGene study (16% vs 11%; difference, 5%; 95% CI, −1% to 11%).

After covariate adjustment (smoking, cancer, COPD, or coronary artery disease), interstitial lung abnormalities were associated with a higher risk for death in all cohorts: FHS (hazard ratio [HR], 2.7; 95% CI, 1.1 - 6.5; P = .03), AGES-Reykjavik (HR, 1.3; 95% CI, 1.2 - 1.4; P < .001), COPDGene (HR, 1.8; 95% CI, 1.1 - 2.8; P = .01), and ECLIPSE (HR, 1.4; 95% CI, 1.1 - 2.0; P = .02) studies.

The authors note that in the AGES-Reykjavik cohort, death from respiratory causes was more common among participants with vs without interstitial lung abnormalities (13% vs 4%), and pulmonary fibrosis accounted for nearly half of those in the group with interstitial lung abnormalities.

The study could not distinguish computed tomography changes that reflect normal aging from those resulting from early pathology and could not explain the high prevalence of interstitial lung abnormalities and rarity of idiopathic pulmonary fibrosis.

The investigators suggest follow-up studies to identify risk factors for and the events that precede death among individuals 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," they conclude.

One coauthor receives grant funding from General Electric. Another coauthor receives support from AstraZeneca and is on advisory boards for GlaxoSmithKline (GSK), Boehringer-Ingelheim, AstraZeneca, Almirall, and Takeda. Another coauthor receives funds from GSK and is on the boards of GSK and Samsung. Another coauthor receives support from Canon USA and Toshiba Medical Inc. Another coauthor consults for Medna LLC and the George Lehman Group and is on the board of Patients Like Me and Genentech. Another coauthor receives grant support from Canon Inc and consults for Bristol-Myers Squibb. Another coauthor receives honoraria and consulting fees from Merck, grant support and consulting fees from GSK, and honoraria from Novartis. Another coauthor has consulted for Merck and GSK. The other authors have disclosed no relevant financial relationships.

JAMA. 2016;315:672-681. Abstract

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