et al. 2001b; Nisenbaum et al. 2004; Simmons et al. 2004; Unwin et al. 1999), Canada (Goss Gilroy Inc. 1998), Australia (Kelsall et al. 2004b), or Denmark (Ishoy et al. 1999b)—have found that, several years after deployment, deployed veterans report higher levels of respiratory symptoms and of self-reported respiratory illnesses than nondeployed troops. Of particular interest is the UK cohort study reported in Nisenbaum et al. (2004) and Unwin et al. (1999) which found substantially higher prevalences of respiratory symptoms and self-reports of respiratory disease among those deployed in the Gulf War than among those deployed in another war theater, Bosnia.

Associations of Respiratory Symptoms, Signs, and Illnesses with Specific Exposures Experienced by Gulf War Veterans During Their Deployment

The study of Gulf War veterans of Cowan et al. (2002), which used objective exposure measure and methods, found associations between oil-well-fire smoke and doctor-assigned diagnosis of asthma in veterans. Limitations of the study include the lack of pulmonary function data and of specified criteria for the diagnosis of asthma and the self-selection into the DOD registry. Exposures were well estimated and high but brief, and the exposed population was healthier than in most studies of combustion products. At least aggravation of asthma appears biologically plausible as effect of this exposure, and causation of asthma less certain (the Cowan study did not include questions that would have enabled differentiation of aggravation from causation). The other key Gulf War study of oil-well-fire smoke, based on the Iowa cohort (Lange et al. 2002), which found no relationship between the same objective exposure and respiratory health outcomes, had the advantage of avoiding the potential selection biases of the Cowan et al. study. However, its definitions of respiratory diseases were based entirely on self-reports of symptoms and cannot be viewed as adequate. The study of Smith et al. (2002) found no significant associations between the same objective measures of exposure to smoke from oil-well fires and hospitalization for asthma, acute bronchitis, chronic bronchitis, or emphysema. Limitations of the study include the lack of information on tobacco-smoking, and that most adults in the study age range are seldom hospitalized for those diagnoses which imply that most cases would not be expected to be captured.

The study by Gray and collaborators (1999b) found a small increase in postwar hospitalization for respiratory system disease associated with modeled exposure to nerve agents at Khamisiyah. Limitations of the study include the likely exposure misclassification based on later revised DOD exposure estimates, lack of control for tobacco-smoking, lack of a clear dose-response pattern, and low biologic plausibility of effects on the respiratory system. Karlinsky et al. (2004) found no associations between pulmonary function measures and exposure to nerve agents at Khamisiyah based on the improved DOD exposure estimates developed in 2002; the lack of finding casts further doubt on the validity of the findings of the Gray et al. study.

In conclusion, as is the case for a number of other organ systems, respiratory symptoms and self-reported diseases are strongly associated with Gulf War deployment in most studies addressing this question and used comparison groups of nondeployed veterans. However, the findings of no statistical association of objective pulmonary function measures with Gulf War deployment, in the four cohorts in which this has been investigated, leaves the clinical interpretation of the increased symptoms and self-reported diseases uncertain.

With respect to associations of specific exposures in the Gulf War Theater with pulmonary outcomes, the positive study by Cowan et al. of objective measures of oil-well fire smoke and doctor-assigned respiratory diagnoses is methodologically the strongest to have



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