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Department of Health & Human Services
Centers for Disease Control and Prevention
Atlanta, GA 30341-3724
United States

March 24, 1999

Dear Conference Attendee:

     Thank you very much for your participation in the meeting convened in Atlanta from February 28 through March 2, The Health Impact of Chemical Exposures During the Gulf War: A Research Planning Conference. Our Impression was that it was a very successful meeting that provided a unique opportunity for veterans and scientists to interact and share their concerns regarding the direction of future research. An enormous amount of material was presented during this meeting and it will take some time to sort through.
     In short term, we are enclosing a summary of the presentations given by the Workgroup Chairs during the final session of conference. These summaries represent a broad overview of each workgroup deliberations. Over the next few months, the Executive Planning Committee will be reviewing and prioritizing each workgroup's proposed research recommendations, along with other information provided during the conference. We then plan to work with appropriate agencies to move forward on closing the knowledge gaps associated with illnesses among Gulf War veterans.
     Additionally, we have placed the background document prepared by Syracuse Research Corporation, Background Document on Gulf War-Related Research for The Health Impact of Chemical Exposures During the Gulf War: A Research Planning Conference on the Internet (http://www.cdc.ov/nech/meetings/1999/gulfwar/). We also plan to place the full transcript from the conference this same Internet site. (For privacy reasons, the transcripts on the Internet will not include the names of persons providing input.) We anticipate that this transcript will be online within the next two to three months. In addition, a summary of the proceedings from the conference will be prepared and mailed to all conference attendees as soon as it is complete. Finally, we anticipate that the Executive Planning Committee's report on research recommendations will be completed within six months.
     On behalf of the Executive Planning Committee, thank you for your interest in our efforts to develop future research for addressing the health concerns of Gulf War veterans.

Sincerely yours,

Due H. Barrett, Ph.D.
Chair, Conference Executive Planning Committee
Chief, Veterans' Health Activity Working Group
Division of Environmental Hazards and Health Effects
National Center For Environmental Health

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Health Impact of Chemical Exposures During the Gulf War:
A Research Planning Conference

February 28-March 2, 1999-Atlanta, Georgia

     Summary of Pathophysiology/Etiology Workgroup Chair Presentation During Final Session of Conference

1. Environmental Exposures (these exposures such be investigated with respect to a number of parameters, including individual vs. combined effects, dose response relationships, timing and duration of exposure):

Depleted uranium (chemical and radioactive effects)
Drugs (e.g., pyridostigmine bromide)
Vaccines and experimental adjutants
Nerve and blister agents
Heavy metals (e.g., lead)
Pesticides (e.g., organophosphates, pyrethroids, linden)
Insect repellents (e.g., DEET)
Petroleum (e.g., solvents, fuels, Kuwaiti crude)
Oil fires (e.g., soot, oil rain)
Carbon monoxide
Bioactive properties of contaminated fine sand
Chemical agent resistant coating (CARC) paint
Heat, exertion and other stresses
Infectious agents

2. Human Studies

Analysis of deployment and other defined cohorts
Analysis of exposed Gulf War veteran populations from other countries and
related experiences
Neurological, central nervous system, neuromuscular and aging studies
Immunological studies
Pulmonary/respiratory studies
Circulatory and heatopoietic system studies
Dermal and gastrointestinal studies
Other organ systems (e.g., reticuloendothelial system)
Genetic screening for known risk factors (e.g., cholinesterase's and
Birth defects and reproductive toxicity
Chemical sensitivity
Gender effects
Treatment-driven research strategies

3. Animal Studies:

Synergistic effects of exposures
Sub clinical effects of exposures
Low-level, chronic exposures
Multigenerational exposures
Gene expression
Delayed expression of environmental
Sex differences

4. Developmental of Biomarkers of Susceptibility, Exposure and Effect:

Susceptibility to chemical sensitivity
Biomarkers of stress
Biomarkers for chemical agent exposures

5. New Methodologies:
Quantitative structure activity relationships (QSAR) approach to molecular interactions
Multifactorial statistical models (gene-environment interactions, exposure cofounders)
Transgenic and knockouts for studies of genetic susceptibility
Imaging techniques
Anti-sense DNA technologies
Alternatives to animal systems (cell and tissue culture)

6. Related Exposure-Driven Studies (examples):

Studies of potential health effects of destruction of chemical warfare agents in
the U.S.
Pesticide exposures
Oil fire exposures

7. Special needs:

Centralized Gulf War research library and data repository (electronic access
Controlled-environment medical research units

NOTE:*= New directions or initiatives

1. Case Definition

     Establish a process by which case definitions can be developed for symptom
based illnesses such as Gulf War illnesses and can be compared to existing
definitions of disorders such as multiple chemical sensitivity (MCS), fibromyalgia
(FM), and chronic fatigue syndrome (DFS). (short term)
Delineate the definitions of Gulf War illnesses that are implicit in existing
studies. Compare methods of diagnostic determination in these studies. (short
     Define subtypes of Gulf War-related illnesses based on existing and future
data. (long term)
     Individual symptoms and symptom clusters that cannot be subsumed under a
diagnosis or disorder should be tracked and studied with regard to relevant
independent variables such as exposure. (long term)

2. Chronic Mullet-System Disorders

          Compare the prevalence and overlap of several different conditions (e.g., Gulf
War illnesses, CFS, FM, MCS, somatization, sick building syndrome,
post-traumatic stress disorder, neurasthenia) in Gulf War veterans to prevalence
in other relevant populations (e.g., Persian Gulf area indigenous populations,
coalitions forces, active duty personnel prepped for deployment, Russian
liquidates, other relevant populations). (long term)

     Carry out case control studies among Gulf War veterans. (short term)
     Examine field data on casualties and illnesses in the war theater. (long term)
     Use laboratory models to explore illnesses and symptoms experienced by Gulf
War veterans. Novel techniques such as use of environmental control units,
applications of imaging and functional imaging techniques, development of
models of neuralgic disorders without peripheral nervous system damage and
studies of exposed populations are encouraged (for example, looking for
markers of illness). (long term)
     Animal models of Gulf War-related disorders should be pursued. These could
include study of polymorphisms that mediate exposure effects and animal strains
bred to express relevant symptomatology. (long term)
     Investigation of barriers preventing Department of Veterans Affairs (VA)
physicians from applying the diagnoses of chronic multi-system disorders to
patients, reliability of VA application of these diagnoses, and the potential for
training physicians how to apply the diagnoses. (long term)

3. Well Defined Disorders
     Medical disorders in research protocols should be classified using International
Classification of Diseases criteria (ICD-9).
     Psychiatric diagnoses should be classified using Diagnostic and Statistical
Manual of Mental Disorders criteria (DSM-IV).
     Adverse reproductive outcomes should be classified with the Centers for
Disease Control and Prevention classification of birth defects.
     Cancer diagnoses should be made according to Surveillance, Epidemiology, and
End Results (SEER) recognized classifications.
     Studies should record the existence of the following using standard criteria:
physical trauma, infectious diseases, autoimmune disorders, vocal chord
dysfunction, reactive airways dysfunction syndrome (RADS)/asthma, rhinitis and
     All diagnoses for research purposes should be based upon gold standard
     Any research into MCS should consider the possible overlap with other
well-defined ICD-9 disorders whose signs or symptoms are already associated
with chemical exposures in the published literature such as asthma,
mastocytosis, and disorders of porphyrin metabolism.

4. Overlap of Conditions
     When investigators assess overlapping conditions, they must operationalize the
definition of the condition, define the exclusionary criteria used for labeling
subjects with each condition, and use standard criteria for diagnosing the
condition whenever possible (including concrete statements about how the
criteria were measured).
     Evaluate the overlap between specific chronic mullet-system conditions and
other such conditions as well as well-defined conditions. (long term)
     Investigators must develop and specify the methods by which they handle
overlap in symptoms and overlap in diagnoses. (long term)
     Explore determinants of patient treatment seeking. Do they affect the
characteristics of study populations when treatment seeking patients are the
subjects? Explore characteristics of patients seeking care at different types of
health care facilities. (long term)
     It is important to carry out research on non-treatment seeking populations. (short
     Examine the existence of relationships between pre-existing disorders (both
well-defined and chronic multi-system disorders) and the expression of chronic
multi-system disorders after Gulf War service. (long term)
     The role of gender in the development of disorders in Gulf War veterans should
be specifically considered. There is a higher rate of some conditions among
males in the Gulf War veteran population than in some other populations. (long

5. Biomarkers

     Identification of biomarkers is necessary for comparison of Gulf War-related disorders to other disorders, identification of genetic polymorphisms for susceptibility to disorders, and definitive diagnosis of disorders.
     Develop biomarkers for past toxicant exposures. (long term)
     Study existing biomarkers and perform new research on existing biomarkers for
single disorders and for combinations of chronic multi-system disorders. (long

6. Assessment and Diagnosis
     Assessment techniques employed in research should reflect specific
hypotheses about relationships between chemical exposures and structural
changes or functional abnormalities. (long term)
     Behavioral or physiological challenge studies that allow expression of pathology
in well compensated subjects are recommended. (long term)
     Development of new laboratory tests of chemical effects is recommended.
Studies should include evaluation of reliability, repeatability, validity and
specificity. (long term)
     Combinations of assessment and diagnostic techniques aimed evaluation of the
same organ structures should be employed in research. For example, a study of
the central nervous system might include structural imaging, neuropsychological
testing neurophysiologic measures, and functional imaging. (long term)
     Comprehensive assessment may be required to accurately measure variables of
interest, to evaluate confounders and to assess the same domains in different
ways. (long term)
     Clinically non-routine assessment probes are recommended for consideration in
research such as environmental control units, carbon dioxide challenges, blind
olfactory challenges, autonomic nervous system assessment, and response to
treatment. (long term)
     Use of tests for which there are normative and validity data for the general U.S.
population or carefully matched control groups is recommended.
     *A research project assessing longitudinal health changes across time in a
normal population is suggested. (long term)
     Careful assessment of confounders and effect modifiers is necessary. (For
example, research should control for medication history.)
     *Assessment of family members and significant others is recommended for
independent verification of partner health outcome and risk factors, in order to
ascertain whether there is a biological basis for symptom transmission, and in
order to explore environmental exposure histories at home. (long term)
     Assessment of events following the death of a Gulf War veteran is suggested in
order to track factors that might lie behind the death and the death certificate
diagnosis. (long term)
     Protocol driven autopsy studies are recommended following the death of a Gulf
War veteran. (long term)

7. Validation

     Identification of appropriate populations for validation and cross validation of
study results on Gulf War populations should consider groups deployed
elsewhere, non-deployed military personnel, and other exposed populations.
Military controls may not always be appropriate because they may have the
same exposures as deployed veterans.
Standardized instruments revised for use in Gulf War populations need
revalidation. (long term)
     Use of convenience samples in order to develop hypotheses about Gulf
War-related disorders is appropriate with retesting on a larger representative
sample if provocative results are obtained. (long term)
     Validation of a case definition can be carried out at three levels (from lowest to

-derivation on a single Gulf War population
-replication in a second Gulf War population
-association of findings with appropriate biomarkers

General Recommendations

     It is recommended that the Department of Defense should continue to declassify
and disseminate all classified scientific field investigations and clinical studies
to enable a better understanding of Gulf War veterans'; illnesses and their
possible causes.


     1. Develop short term (now) and longer term strategies to bring new treatments to bear
to improve the health of ALL Gulf War veterans.

     Maintain appropriate study methods.

     2. Develop ways to educate physicians and all other health care professionals to
understand the needs of Gulf War veterans.


     Urgent need for treatment; review process needs to be expedited and less
     If alternative causes and treatments found, all veterans should be screened for
these conditions and treated appropriately.

1. Pharmacologic Treatment:

     Test symptom-based treatments (e.g., pain, cognitive symptoms).
     Examine role of neutrally mediated cardiovascular changes and treatments with
drugs (e.g., calcium channel blockers).
     Consider trials of nutritional supplements/vitamins.

2. Treatment for Toxic Exposures and Intolerances:

Testing for intolerances to and avoiding inhalants, foods, drugs.
Drug elimination trial in veterans with polypharmacy for symptoms.

Short term Recommendations:

A. Immediate implementation.
B. Utilize existing clinics as appropriate.
C. Assess efficacy in tiered way (do no delay treatment for stringent studies)

Long Term Recommendations:

A. Expand availability as indicated.
B. Environmental control unit(s) for research and treatment.

3. Non-Pharmacologic (NP) Treatment:
     Challenge: Current structure of VA-DOD care does not accommodate NP strategies
well. Response-Alter structure/organization of services.

Short Term Recommendations:
A. Population-based needs assessments.

-ALL veterans of the Gulf War
-Information needs, information capabilities (PC, Internet, Etc.)
-Health needs

B. Self-help literature targeting veterans'  identified needs.

-Group with standard self-help literature
-Group with tailored literature

Primary care/collaborative primary care.

-Empanel veterans based on need.
-Use primary care practice teams

D. Intensive multidisciplinary care for chronic symptoms and disability.

-Exercise/behavior Therapy trial underway
-VA demonstration projects
-Other approaches (evidence-based)

     Outcomes to be considered: satisfaction, quality of life, health status, etc.
Long Term Recommendations:
A. Innovative care strategies.
-Alternative medicine
-Pilot studies -> randomize control trials
B. Program of quality research.

4. Treatment:

     Purpose: Establish a central body (Logistic and Communication NetworK-LOK-N) to
coordinate communications, education and outreach efforts necessary for effective
conduct of treatment trial and research programs for Gulf War-related illness.
Furthermore, LOK-N will facilitate communication channels between service members,
veterans, Gulf War coordinators, health care professionals, researchers, and

Short Term Recommendations:

A. Establish LOK-N that consists of all appropriate parties (researchers, health care
providers, veterans, Gulf War coordinators, and members of advocate groups, etc.)
committed to enhance communication channels between service members, veterans,
health care professionals, researchers, and administrators.

-Establish organizational structure and members of LOK-N
-Establish goals and aims
-Establish central data band of completed/ongoing research treatment protocols
-Establish website/newsletter
-Needs assessment survey

Long Term Recommendations:
A. Educational tools for veterans, family, health care professionals, and administrators.
B. Develop effective occupational/environment toxicology expertise for VA, DoD and
community health providers.
C. Establish informational communication channels between health care providers,
researchers, veterans, administrators, Gulf War coordinators, etc.

Key Prevention Messages:
     Evaluate effectiveness and evidence of what has already been done (e.g.,
depleted uranium and hazard communication)

-what worked
-what did not work
-lessons learned
-best practices
-evaluation research

Assess other exemplary national and international models of prevention strategies and outcomes (e.g., capture of identifiable diseases like cancer or reproductive endpoints)

Ways to Do Prevention Research (e.g., assess comprehensive safety and health
management program and use best practice standards):

Identify data gaps
Assess effectiveness of prevention strategies
-content (e.g., vaccines)
Hierarchy of Controls:
> Substitution
> Engineering

Health Education
Risk Communication
Record Keeping & Registries
Work Practices
Personal Protective Equipment

1. Substitution
Identify less toxic substances and their interactive effects.
Restrict number of pesticides.
Optimize vaccine potency, formulation, dose and duration.
2. Engineering:
Evaluate the current design and operation of equipment to minimize hazards to
troops (e.g., weapon systems).
Design containment for transport of contaminated materiel (e.g., depleted

3. Health Education
Identify and segment key audiences.
Determine appropriate instructional strategies.
Identify barriers to understanding the importance and impact of health education
messages on readiness.

4. Risk Communication:
Develop and test message content and channels (e.g., reproductive health).
Identify multiple audiences and information sources.
Assess communication of scientific uncertainty and technical information.
Assess comprehension, utility, and value of risk information.
Identify methods to communicate comparative risk issues.

5. Environmental Surveillance:
Develop enhanced instrumentation for nuclear, biological, chemical and
environmental exposure assessment.
Establish exposure limits that take into account the multiple operating
Characterize the environment of deployment.

6. Medical/Biomonitoring Surveillance:
Develop a data gathering tool that spans the life of the service member, that
accompanies person from DOD to VA to civilian life, and that links both the
exposure and health outcome.
Validate self-reported environmental exposures (e.g., Canada).
Develop an effective prospective surveillance for multiple endpoints.
Develop methods for surveillance for low level exposure.
Develop methods for archiving biological specimens.

7. Work Practices:

Evaluate existing health hazard protocols and develop metrics to compare wok
practice risks.
Explore the impact on negative health outcomes of varied work organization
structures (i.e., Reserve forces vs. full-time).

8. Personal Protective Equipment (PPE):

Design protective clothing that is durable, viable, and ergonomically flexible.
Develop and validate data/standards for PPE compliance that strive to adhere to
the existing regulatory standards (e.g., Occupational Safety and Health
Administration (OSHA), Mine Safety and Health Administration (MSHA).

High Priority Recommendations
Assessment of what has already been done since 1991.
Comprehensive safety and health management program.
Metrics for implementation and effectiveness.
Personal Protective Equipment.
Vaccine efficacy and safety.

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