symptom inventory that included symptom severity (mild, moderate, or severe) and duration (less than 6 months or 6 months or longer) and randomly divided the 3255 participants who had answered all symptom questions into subsamples of 1631 and 1624. They used factor analysis to organize symptoms into a case definition for the CDC. The case definition consisted of having one or more chronic symptoms (present for 6 months or longer) in each of at least two of three categories: fatigue, mood-cognition (symptoms of feeling depressed, difficulty in remembering or concentrating, feeling moody, feeling anxious, trouble in finding words, and difficulty in sleeping), and musculoskeletal (symptoms of joint pain, joint stiffness, and muscle pain). A case was classified as severe if each reported symptom that was used to meet the case definition was rated as severe.

Of the survey participants, those deployed to the Gulf War experienced a higher prevalence of chronic symptoms than nondeployed veterans (33 of 35 symptoms with more than 6-month duration were reported to be more prevalent). According to the case definition, 39% of Gulf War-deployed veterans and 14% of nondeployed veterans had mild to moderate cases, and 6% and 0.7%, respectively, had severe cases. On the basis of a total of 158 clinical examinations performed in one Air National Guard unit, there were no abnormal physical or laboratory findings that differentiated those who met the case definition from those who did not meet the case definition. Case subjects, however, reported significantly lower functioning and well-being. Because such a large fraction (14%) of nondeployed veterans met the definition of mild to moderate cases, the investigators concluded that the case definition could not specifically characterize Gulf War veterans who had unexplained illnesses (Fukuda et al. 1998).

The study has several limitations, including the fact that its coverage of only current Air Force personnel several years after the Gulf War makes it difficult to generalize its results to other branches of service and to those who might have left the service because of illness. The use of self-reported symptoms introduced the possibility of reporting bias, and the low participation rates in two of the four units (62% and 35%) introduced the possibility of selection bias. Nonetheless, symptom reporting and prevalence were similar among the four units. A particular strength of the study was its use of a symptom inventory rather than asking veterans about specific diagnoses, such as CFS, multiple chemical sensitivity, depression, and various neurologic abnormalities. Its use of a more intensive examination of Gulf War veterans from one unit—including an additional clinical questionnaire, a variety of laboratory tests, and interviewer-administered modules on major depression, somatization disorder, and panic disorder—provided important additional data even though participation rates were low (62%).

A nested case-control secondary study of the Fukuda et al. (1998) cohort (n = 1002) sought to identify self-reported exposures associated with cases of chronic mutisymptom illness (Nisenbaum et al. 2000). Having an injury requiring medical attention was associated with having a severe case of chronic mutisymptom illness. Symptom clustering in the Fort Devens cohort was studied in 1997 with CDC's case definition of chronic mutisymptom illness (Wolfe et al. 2002). The case definition was applied to findings from use of the 52-item health checklist. About 60% of respondents met the CDC case definition. That group was divided between “mild to moderate” and “severe” cases. Both Nisenbaum et al. (2000) and Wolfe et al. (2002) found that many Gulf War exposures—including exposure to pyridostigmine bromide, anthrax vaccination, tent-heater exhaust, oil-fire smoke, and chemical odors—and psychologic distress such as fear of a chemical attack, were associated with meeting the case definition of chronic mutisymptom illness.

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