are transient and characteristically mild. Idiosyncratic reactions occur at a much lower rate.
The committee concludes that there is sufficient evidence of an association between PB and transient acute cholinergic effects in doses normally used in treatment and for diagnostic purposes.
Since unexplained Gulf War-related illnesses have been chronic, possible long-term effects of PB are of great interest. There are no reports of chronic toxicity related to human PB exposure in clinical or military populations. Haley and Kurt (1997) suggested that unexplained Gulf War-related symptoms could be a unique manifestation of organophosphate-induced delayed neuropathy associated with PB exposure alone or in combination with other wartime exposures, in the absence of acute symptoms of organophosphate toxicity. There is evidence that some AChE inhibitors may be associated with chronic neurological changes. Haley and Kurt provide evidence that a small number of ill Gulf War veterans have neurological impairment compared to a small number of well veterans from the same unit. The committee felt that the validity of this association, and the possible causal relationship between PB and the neurological findings, are uncertain. Among the reasons for withholding judgment are the large potential for selection and information biases4 in this study population, the lack of a nondeployed comparison group, and the lack of clinical validity in the measures of neurological damage. Haley and Kurt’s hypothesis requires further investigation.
Haley and Kurt (1997) have also suggested that chronic neuropsychological syndromes derived from factor analysis are linked to acute responses to administration of PB. The evidence that they present has several shortcomings. The major limitation was the lack of comparable studies in a nondeployed group of veterans. There is uncertainty about how the authors selected, administered, and interpreted the neuropsychological tests. The study population consisted of self-selected individuals who replied to a survey (41 percent of the battalion). The data on exposure to PB were self-reports of events that had occurred many years before.
The epidemiologic data do not provide evidence of a link between PB and chronic illness in Gulf War veterans. Most epidemiologic studies of Gulf War veterans have focused on whether a unique Gulf War syndrome exists and defining its characteristics. Only two epidemiologic studies specifically investigated the possible association of PB use and chronic symptoms among Gulf War veterans (Haley and Kurt, 1997; Unwin et al., 1999). This summary has already noted the limitations of the small, selected population studied by Haley and colleagues. Based on factor analysis, they defined three syndromes associated with
Selection bias can occur in the recruitment of study subjects to a cohort when the study and control groups differ from each other by a factor, often unknown, that is likely to affect the results. Information bias results from the way in which the data are collected (e.g., measurement errors, imprecise measurement, misdiagnosis). Bias may also result from misclassification of study subjects with respect to the outcome variable.