Agent Orange Exposure and Risk of Idiopathic Pulmonary Fibrosis among U.S. Veterans

Abstract

Rationale: There is limited literature exploring the relationship between military exposures and idiopathic pulmonary fibrosis (IPF). Objectives: To evaluate whether exposure to Agent Orange is associated with an increased risk of IPF among veterans. Methods: We used Veterans Health Administration data to identify patients diagnosed with IPF between 2010 and 2019. We restricted the cohort to male Vietnam veterans and performed multivariate logistic regression to examine the association between presumptive Agent Orange exposure and IPF. We conducted sensitivity analyses restricting the cohort to army veterans (highest theoretical burden of exposure, surrogate for dose response) and a more specific case definition of IPF. Fine-Gray competing risk models were used to evaluate age to IPF diagnosis. Measurements and Main Results: Among 3.6 million male Vietnam veterans, 948,103 (26%) had presumptive Agent Orange exposure. IPF occurred in 2.2% of veterans with Agent Orange exposure versus 1.9% without exposure (odds ratio, 1.14; 95% confidence interval [CI], 1.12-1.16; P < 0.001). The relationship persisted after adjusting for known IPF risk factors (odds ratio, 1.08; 95% CI, 1.06-1.10; P < 0.001). The attributable risk among exposed veterans was 7% (95% CI, 5.3-8.7%; P < 0.001). Numerically greater risk was observed when restricting the cohort to 1) Vietnam veterans who served in the army and 2) a more specific definition of IPF. After accounting for the competing risk of death, veterans with Agent Orange exposure were still more likely to develop IPF. Conclusions: Presumptive Agent Orange exposure is associated with greater risk of IPF. Future research should validate this association and investigate the biological mechanisms involved.

Keywords: Veterans health; epidemiology; interstitial lung disease.

Figure 1.

Cohort identification. ICD = International Classification of Disease; IPF = idiopathic pulmonary fibrosis; VHA = Veterans Health Administration.

Figure 2.

Cumulative incidence of idiopathic pulmonary fibrosis (IPF) in veterans with and without Agent Orange exposure. Time to event was calculated using age as the time scaler from the beginning of the study period (January 1, 2010) to the date of IPF diagnosis, death, or the end of the study period (December 31, 2019), assuming independent left truncation. CI = confidence interval; sHR = subdistribution hazard ratio.