JOURNAL OF MEDICAL & CLINICAL CASE REPORTS

Introduction

We are conducting a study to look at the possible impact of presumed Agent Orange Exposure (AOE) on mobility and balance. This was part of an ongoing Clinical Innovations Project funded by the National Office of Geriatrics and Extended Care of the Veterans Health Administration, initially funded in 2023. Presumably, 2.7 million US Military may have been exposed to AO between 1962 -71 [2]. It is estimated that over 300,000 US Veterans and over 400,000 Vietnamese died from AOE between 1962 and 1971. The US sprayed 20 times more AO than the manufacturer recommended. AO is 2,3,7,8- tetrachlorodibenzo-p-dioxin (TCDD or Dioxin) and persists in humans for a half-life of 7-11 years and persists indefinitely in the environment. “The Vietnamese Red Cross estimates that 3 million Vietnamese have been affected by dioxin, including at least 150,000 children born after the war with serious birth defects” (Wells-Dang A, usip.org/publications). Presumptive conditions of AOE have demonstrated an increase in healthcare utilization, and the PACT Act was passed in August 2022 to expand healthcare and benefits to Veterans with presumed toxic exposures like burn pits or AO. Presumptive conditions from AOE are listed on this website: https://www.pendercountync.gov/va/agent-orange-presumptive-conditions/ , and we intend to look further into possible impact on cognition and mobility. This project and Gerofit are quality improvement/quality assurance projects and approved by the institutional review board at the VA Greater Los Angeles Healthcare System, and participants are not required to sign consents.

In a literature search and discussion with national experts to detect presumed AOE, we came up with a Qualitative (Does Veteran have no, minor, moderate, or significant concern) and a Quantitative Veteran Herbicide Exposure Index based on 6 questions that rate their presumed exposure risk as negative, low, moderate, or high ([3], see Figure 1).

Figure: 1

We widely distributed brochures about this program with the intention of enrolling Vietnam Veterans in our Gerofit Exercise program [4], provided seminars to Veterans Service Organizations and primary care providers at our VA Facility to engage with Veterans with presumed exposure to AO, with the goal of enrolling them into Gerofit. For those identified with presumed AOE, we facilitated filing Claims with the Veterans Benefits Administration if they had not previously filed a claim and wanted to.

As we began to accumulate presumed AOE Veterans, it was subjectively noticed that presumed AOE Veterans had active bladder symptoms, or Lower Urinary Tract Symptoms (LUTS). A literature search did not identify any human studies or reports, but we found 3 rodent studies in which TCDD exposure occurred In Utero and/or during lactation to the mother, resulting in dysfunction of the lower urinary tract in adulthood. The bladders of the exposed mice were significantly heavier, and urodynamic voiding behavior showed a marked reduction in intervoid interval. It was found that the TCDD exposure resulted in enhanced recruitment of noradrenergic neurons with a permanent increase in noradrenergic axon density and excessive prostatic and urethral smooth muscle tone [5]. In speaking to some experts in LUTS, the Lower Urinary Tract Dysfunction Research Network developed the Symptom Index-10 (LURN SI-10), with a max score of 38, which was felt to be the best screening method for LUTS (Cella D Neurourology & Urodynamics 2019, see Figure 2). This was given to the Veterans. We compared the LURN SI-10 scores of three comparison groups:

• Negative Presumed AOE: Qualitative and Quantitative scores=0
• Presumed AOE:
  • Qualitative AND Quantitative AOE risk questionnaires both >0,
  • Qualitative OR Quantitative >0

Figure: 2