“Gulf War and Health: Depleted Uranium, Pyridostigmine Bromide, Sarin, and Vaccines” (2009)

After returning to the United States, countless Gulf War veterans began reporting illnesses that remain undiagnosed and unexplained by medical science.  These illnesses include, but are not limited to, chronic fatigue syndrome, muscle and joint pain, loss of concentration, forgetfulness, headaches, and rashes.  Due to the uncertainty surrounding these medical conditions, people have begun to wonder if Gulf War veterans were exposed to chemical agents that may have caused these unknown illnesses.  In an effort to respond to these health concerns of veterans and their families, VA contracted with the Institute of Medicine (IOM) to study the scientific evidence concerning associations between the chemical agents to which Gulf War veterans may have been exposed and adverse health effects. This study focused on four main agents including: depleted uranium, sarin, pyridostigmine bromide, and vaccinations against both botulinum toxin and anthrax.  Overall, the goal of this study was to determine whether exposure to these agents is correlated with the negative health outcomes in Gulf War veterans.  The results of this study were published in “Gulf War and Health: Volume 1. Depleted Uranium, Pyridostigmine Bromide, Sarin, and Vaccines”.  Importantly, the IOM is required to update this report as new evidence appears.

How was the study conducted?

The main method of this study involved conducting a review of the available and relevant scientific literature regarding possible health effects of chemical agents to which Gulf War veterans may have been exposed.  The report used five categories to describe the different strengths of association between exposure to a specific agent and a health outcome.  The following categories are listed from strongest association to weakest association in decreasing order:

• “Sufficient Evidence of a Causal Relationship: evidence is sufficient to conclude that a causal relationship exists between the exposure to a specific agent and a health outcome in humans.

• Sufficient Evidence of an Association: evidence is sufficient to conclude that there is a positive association. A positive association has been observed between an exposure and health outcome in human studies in which chance, bias, and confounding could be ruled out with reasonable confidence.

• Limited/Suggestive Evidence of an Association: evidence is suggestive of an association between exposure to a specific agent and a health outcome in humans, but is limited because chance, bias, and confounding could not be ruled out with confidence.

• Inadequate/Insufficient Evidence to Determine Whether an Association Does or Does Not Exist: the available studies are of insufficient quality, consistency, or statistical power to permit a conclusion regarding the presence or absence of an association between exposure and a health outcome in humans.

• Limited/Suggestive Evidence of No Association: there are several adequate studies that are mutually consistent in not showing a positive association between exposure to a specific agent and a health outcome at any level of exposure.”

 Depleted Uranium

Depleted uranium is a component of naturally occurring uranium.  Although the chemical properties are the same, depleted uranium is about 40 percent less radioactive than natural uranium.  The military used depleted uranium in the Gulf War for both offensive and defensive purposes.  For example, tanks had a layer of depleted uranium armor to increase protection and it was also used in ammunition rounds.  As a result, veterans may have been exposed to this agent as a result of participation in both defensive and offensive operations.  The primary forms of exposure occur through ingestion or inhalation, and the amount of depleted uranium retained in the body depends on the amount of exposure.

Conclusion: The report concluded that there was limited/suggestive evidence of no association between exposure to depleted uranium and lung cancer at lower levels of exposure.  Namely, previous medical research shows that there is no increase in the incidence of lung cancer among those exposed to this agent.

However, there is inadequate/insufficient evidence to determine whether or not there is an association at higher levels of exposure.  This conclusion also applies for other health outcomes, noting that there were only a few studies on this agent and its health effects.  Therefore, no other conclusions could be formed.

Sarin

Sarin is a highly toxic nerve agent, in vapor or liquid form, that is used for chemical warfare.  High-level exposure to sarin can be fatal within minutes to hours.  Sarin can be inhaled or absorbed across the skin, eyes, or mucous membranes.  During the Gulf War, United States troops conducted a demolition operation at a large munitions storage complex in Khamisiyah, Iraq.  The Department of Defense later released reports related to the operations at Khamisiyah detailing the risk of exposure to sarin and cyclosarin, which filled the explosives at the storage complex.

Conclusion: The report concluded that there is limited/suggestive evidence of an association between sarin at levels of acute, high-dose exposure and health complications such as coughing and breathing problems, loss of consciousness, seizures, paralysis, and respiratory/nervous system failure.  However, there is inadequate/insufficient evidence to determine an association between sarin and adverse health outcomes when exposed at low levels.

Pyridostigmine Bromide

Pyridostigmine Bromide (PB) is primarily a medication used to improve muscle strength in individuals with certain muscle diseases.  In the Gulf War, it was used as a pre-treatment for exposure to nerve agents.  The relevant scientific literature establishes several side effects related to large doses including: vomiting, diarrhea, abdominal cramps, and weakness.  The DoD reported that approximately 250,000 servicemembers took PB during the Gulf War.  Among those who took PB, there were acute accidental poisonings that resulted in mild to moderate symptoms occurring within several minutes of ingestion and lasting up to 24 hours.

Conclusion: As indicated above, there is sufficient evidence of an association between PB and temporary acute effects in doses normally used for treatment.  While the study produced this finding, there was inadequate/insufficient evidence to determine whether an association does or does not exist between PB exposure and long-term health effects.

Vaccines

During the Gulf War, military personnel often received multiple vaccinations to prevent against potential diseases or exposures to biological threats.  Specifically, it is estimated that at least 150,000 troops received at least one dose of the anthrax vaccine.  Furthermore, approximately 8,000 troops received the botulinum toxoid vaccine.

Conclusion: In both cases, the report concluded that there was sufficient evidence of an association between these vaccines and temporary symptoms typically associated with regular vaccination.  For example, many servicemembers experienced symptoms such as fever, redness, and swelling shortly after receiving the vaccine. However, there is inadequate/insufficient evidence to determine if an association does or does not exist between these vaccines and long-term health effects.

What are the limitations of this study?

While the IOM used all of the available and relevant medical research at its disposal, there were still significant limitations within the study.  Namely, while the IOM was able to draw conclusions in regards to the strength of associations, it was unable to measure the actual likelihood that Gulf War veterans’ health problems are caused by those agents.  In order to do this, the IOM would need to compare rates of health effects in Gulf War veterans who were exposed to the agents with rates of those who were not exposed.  However, this requires specific information about who was exposed and to what extent, which is unavailable.  Additionally, most of the evidence that the IOM used to form its conclusions come from studies of populations that were exposed to these agents in occupational and clinical settings.  Therefore, it is difficult to say how exposure to these agents and resulting health outcomes might differ in the Gulf War veteran population.

Future Recommendations

Towards the end of the report, the IOM offers several recommendations as to how this research can become more effective in the future.  It suggests that future studies need to look at the total impact of all exposures, or the effects of such agents in combination, rather than the effects of each agent individually.  It is possible that veterans were exposed to multiple agents on multiple occasions throughout the Gulf War.  Therefore, an isolated account of each agent’s effects might not accurately represent the full scope of health risks posed to Gulf War veterans.