Presumptive Agent Orange exposure ups risk for IPF

In a large cohort of male Vietnam veterans, presumptive exposure to Agent Orange led to an increased risk for developing idiopathic pulmonary fibrosis, according to a study.

“This study is the first to identify an epidemiological association between Agent Orange, a toxin used in war, and an increased risk of IPF in exposed Veterans,” Bhavika Kaul, MD, MAS, study investigator and assistant professor at the University of California, San Francisco, told Healio.

According to Kaul, the pathway to chronic lung disease is complex and the medical community is in the early stages of understanding how exposures increase the risk for lung fibrosis.

“In particular, the role that military exposures play in the development of lung fibrosis is unknown,” she said.

In the study, which was published in the American Journal of Respiratory and Critical Care Medicine, Kaul and colleagues examined a nationwide cohort of U.S. military veterans and characterized the risk for IPF linked to Agent Orange exposure. They included data for 3.6 million male Vietnam veterans who received care through the Veteran Health Administration between 2010 and 2019; among veterans, 26% had presumptive Agent Orange exposure. The median age at study commencement of veterans with vs. without Agent Orange exposure was 62.7 years vs. 62.9 years.

Findings indicated that IPF occurred more frequently among veterans with Agent Orange exposure compared with those without exposure (2.2% vs. 1.9%; OR = 1.14; 95% CI, 1.12-1.16), a result that remained after adjusting for known IPF risk factors (adjusted OR = 1.08; 95% CI, 1.06-1.1).

In all, the attributable IPF risk for exposed veterans was 7% (95% CI, 5.3%-8.7%).

The risk for IPF remained elevated in sensitivity analyses that restricted the cohort to Vietnam veterans who served in the army as a surrogate measure for dose response (unadjusted OR = 1.15; 95% CI, 1.13-1.18), when using a more specific definition of IPF (unadjusted OR = 1.17; 95% CI, 1.12-1.23) and using the prior criteria plus adjustment for IPF risk factors (aOR = 1.17; 95% CI, 1.09-1.25). When they accounted for the competing risk for death, veterans with Agent Orange exposure remained more likely to develop IPF (subdivision HR = 1.13; 95% CI, 1.1-1.15).

“We found a greater risk of IPF among veterans exposed to Agent Orange,” Kaul concluded. “[Our study] establishes a premise for future work that examines the role of exposures in the development of fibrotic lung diseases.”