Fukuda and colleagues (1998) used factor analysis and other methods to assess the health status of Gulf War Air Force veterans in response to a request from DOD, VA, and the state of Pennsylvania. Their focus was to assess the prevalence and causes of an unexplained illness in members of one Air National Guard unit. By studying that unit and three comparison Air Force populations, the investigators aimed to organize symptoms into a case definition and to carry out clinical evaluations on participants from the index Air National Guard unit. They administered a 35-item symptom inventory that included symptom severity (mild, moderate, or severe) and duration (less than 6 months or 6 months or longer) and divided the 3,255 participants who had answered all symptom questions into two subsamples of 1,631 and 1,624. They conducted an exploratory factor analysis of the first subsample that yielded 10 factors with eigenvalues greater than 1.0; three of the factors accounted for 39.1% of the total variance. When the three were examined in a confirmatory factor analysis in the second subsample, two could be confirmed. The first, called mood-cognition-fatigue, consisted of the symptoms: feeling depressed, feeling anxious, feeling moody, difficulty in remembering or concentrating, trouble in finding words, difficulty in sleeping, and fatigue. The second, called musculoskeletal, consisted of the symptoms: joint stiffness, joint pain, and muscle pain. They used those 10 symptoms from the two confirmed factors to develop a preliminary case definition having a combined factor score in the top 25th percentile. That was compared with an alternative clinical case definition of having one or more symptoms in each of two of three symptom categories: fatigue, mood-cognition, and musculoskeletal. Forty-five percent of deployed veterans met the factor-score-based case definition, whereas only 15% of nondeployed veterans met it. The same percentages met the clinical case definition, which because of its greater clinical simplicity than the factor-score-based case definition, was then used to create a case definition of chronic multisymptom illness. The new definition, which was used in later studies, was having one or more chronic symptoms (present for 6 months or longer) from at least 2 of the 3 categories: fatigue, mood-cognition16, and musculoskeletal17. A case was classified as severe if each symptom reported that was used to meet the case definition was rated as severe.
Of the participants surveyed, those deployed to the Gulf War experienced a higher prevalence of chronic symptoms (33 of 35 symptoms with more than 6-month duration were reported to be more prevalent) than nondeployed veterans. According to the case definition of chronic multisymptom disease, 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 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. Cases, however, reported significantly lower functioning and well-being.
Because such a large fraction (14%) of nondeployed veterans met the mild-to-moderate case definition, the investigators concluded that the case definition could not specifically characterize Gulf War veterans who had unexplained illnesses (Fukuda et al. 1998). The study, however, had several limitations, the most important of which was its coverage of only current