The Problem: Gulf War Illness is an important but poorly defined clinical disorder. For unknown reasons, veterans who have the disorder often have many symptoms including fatigue, joint pain, memory loss, and/or severe headaches. There is no clear consensus or understanding of the cause and no specific objective diagnostic tests for the syndrome and, accordingly, Gulf War Illness remains difficult to definitively diagnose, monitor, treat and prevent. Thus, there is great need for gaining new knowledge regarding the cause and consequences of the disorder. One of the best ways to accomplish this objective will be to develop tests that can objectively generate biomarkers that can be used to characterize the disorder and to select and evaluate potential therapies for Gulf War Illness afflicted individuals.

Our Approach: We propose to use a powerful new technology to study Gulf War Illness to gain new understanding and develop distinguishing biomarkers for Gulf War Illness. One of our collaborators, John Hall, Ph.D., shared the 2005 Nobel Prize in Physics for his discovery of this innovative technique that is called Frequency Comb Spectroscopy. The advantages of the approach are that multiple molecules can be measured non-invasively, simultaneously, sequentially, repeatedly, accurately and with great sensitivity (in parts per billion) on small samples of exhaled breath gas.

Our Objectives: We will use this new technique to measure exhaled gas breath samples from rats that have inhaled pesticides, combustion generated small airborne particles, and/or been treated with pyridostigmine: These three insults have all been implicated as contributors to Gulf War Illness. In addition, we will use this novel biomarker technique to determine and compare biomarker molecules in the breath of Gulf War Illness afflicted individuals with healthy veterans, cigarette smokers, smoke-exposed individuals, and healthy human subjects.

Potential Results, Clinical Application, Rationale and Impact: We anticipate that exhaled gas breath measurements made using this new non-invasive biomarker technology will (1) distinguish individuals with Gulf War Illness from normal healthy subjects thereby providing a needed objective biomarker for classifying and determining any progression in the syndrome, (2) provide new understanding regarding any potential underlying abnormality which might be reflected by exhaled biomarkers and contribute to the symptoms of Gulf War Illness veterans, (3) show the effects of three implicated insults on molecules in the exhaled breath of well-controlled experimental rat models and in the process provide a way to directly compare the exhaled gas biomarker findings in humans with Gulf War Illness to the exhaled gas biomarker patterns from rats that have been exposed in controlled experiments to Gulf War insults, (4) produce new insights that might be useful in developing new treatment and/or prevention strategies for Gulf War Illness and (5) provide biomarker analysis as a way to sequentially measure the effectiveness of various therapies in Gulf War Illness.

It is anticipated that we will generate convincing results regarding the potential of this new Nobel-Prize winning technology during the three year period of study. For this and other reasons, commercial companies are interested in developing a simplified model which can make these measurements relatively inexpensively and be located in many convenient locations nationally. The ability to produce objective criteria for diagnosing and monitoring individuals with Gulf War Illness holds great promise for improving the lives of these important veterans and perhaps preventing this type of condition in the future.