Catherine Unwin

Health of UK servicemen who served in Persian Gulf War

BACKGROUND Various symptoms in military personnel in the Persian Gulf War 1990-91 have caused international speculation and concern. We investigated UK servicemen. METHODS We did a cross-sectional postal survey on a random sample of Gulf War veterans (Gulf War cohort, n=4248) and, stratified for age and rank, servicemen deployed to the Bosnia conflict (Bosnia cohort, n=4250) and those serving during the Gulf War but not deployed there (Era cohort, n=4246). We asked about deployment, exposures, symptoms, and illnesses. We analysed men only. Our outcome measures were physical health, functional capacity (SF-36), the general health questionnaire, the Centers for Disease Control and Prevention (CDC) multisymptom criteria for Gulf War illness, and post-traumatic stress reactions. FINDINGS There were 8195 (65.1%) valid responses. The Gulf War cohort reported symptoms and disorders significantly more frequently than those in the Bosnia and Era cohorts, which were similar. Perception of physical health and ability were significantly worse in the Gulf War cohort than in the other cohorts, even after adjustment for confounders. Gulf War veterans were more likely than the Bosnia cohort to have substantial fatigue (odds ratio 2.2 [95% CI 1.9-2.6]), symptoms of post-traumatic stress (2.6 [1.9-3.4]), and psychological distress (1.6 [1.4-1.8]), and were nearly twice as likely to reach the CDC case definition (2.5 [2.2-2.8]). In the Gulf War, Bosnia, and Era cohorts, respectively, 61.9%, 36.8%, and 36.4% met the CDC criteria, which fell to 25.3%, 11.8%, and 12.2% for severe symptoms. Potentially harmful exposures were reported most frequently by the Gulf War cohort. All exposures showed associations with all of the outcome measures in the three cohorts. Exposures specific to the Gulf were associated with all outcomes. Vaccination against biological warfare and multiple routine vaccinations were associated with the CDC multisymptom syndrome in the Gulf War cohort. INTERPRETATION Service in the Gulf War was associated with various health problems over and above those associated with deployment to an unfamiliar hostile environment. Since associations of ill health with adverse events and exposures were found in all cohorts, however, they may not be unique and causally implicated in Gulf-War-related illness. A specific mechanism may link vaccination against biological warfare agents and later ill health, but the risks of illness must be considered against the protection of servicemen.

Is there a Gulf War syndrome

Summary Background UK veterans of the Gulf War report more ill health than servicemen who were not deployed to the Gulf War. We investigated whether the pattern of symptom reporting by veterans of the Gulf War differed from that in active servicemen who had not fought in the Gulf War or who had fought in other conflicts. Methods We used a population-based cross-sectional design. We sent a standardised survey that asked about 50 physical symptoms to three UK military cohorts; men who had served in the Gulf War, those who had served in the Bosnia conflict, and men who had been in active service but not deployed to the Gulf War (Era cohort). We used exploratory factor analysis to identify underlying factors and describe the factor structure of the symptoms reported in the Gulf War cohort. Confirmatory factor analysis was used to test the fit of this factor structure in the Bosnia and Era cohorts. Findings Three factors in the Gulf War cohort together accounted for about 20% of the common variance. We labelled the factors mood, respiratory system, and peripheral nervous system, according to the symptoms that loaded on to them. In the confirmatory factor analysis, the factor structure identified in the Gulf War cohort fitted reasonably well in the Bosnia and Era cohorts. Interpretation Although results from complex modelling procedures need to be interpreted with caution, our findings do not support a unique Gulf War syndrome. The mechanisms behind increased self-reporting of symptoms need further investigation. Lancet 1999; 353: 179‐82 See Commentary page ???

Role of vaccinations as risk factors for ill health in veterans of the Gulf war: cross sectional study

Abstract Objectives: To explore the relation between ill health after the Gulf war and vaccines received before or during the conflict. To test the hypothesis that such ill health is limited to military personnel who received multiple vaccines during deployment and that pesticide use modifies any effect. Design: Cross sectional study of Gulf war veterans followed for six to eight years after deployment. Setting: UK armed forces. Participants: Military personnel who served in the Gulf and who still had their vaccine records. Main outcome measures: Multisymptom illness as classified by the Centers for Disease Control and Prevention; fatigue; psychological distress; post-traumatic stress reaction; health perception; and physical functioning. Results: The response rate for the original survey was 70.4% (n=3284). Of these, 28% (923) had vaccine records. Receipt of multiple vaccines before deployment was associated with only one of the six health outcomes (post-traumatic stress reaction). By contrast five of the six outcomes (all but post-traumatic stress reaction) were associated with multiple vaccines received during deployment. The strongest association was for the multisymptom illness (odds ratio 5.0; 95% confidence interval 2.5 to 9.8). Conclusion: Among veterans of the Gulf war there is a specific relation between multiple vaccinations given during deployment and later ill health. Multiple vaccinations in themselves do not seem to be harmful but combined with the “stress” of deployment they may be associated with adverse health outcomes. These results imply that every effort should be made to maintain routine vaccines during peacetime.

The mental health of UK Gulf war veterans: phase 2 of a two phase cohort study

Abstract Objectives: To examine the prevalence of psychiatric disorders in veterans of the Gulf war with or without unexplained physical disability (a proxy measure of ill health) and in similarly disabled veterans who had not been deployed to the Gulf war (non-Gulf veterans). Design: Two phase cohort study. Setting: Current and ex-service UK military personnel. Participants: Phase 1 consisted of three randomly selected samples of Gulf veterans, veterans of the 1992-7 Bosnia peacekeeping mission, and UK military personnel not deployed to the Gulf war (Era veterans) who had completed a postal health questionnaire. Phase 2 consisted of randomly selected subsamples from phase 1 of Gulf veterans who reported physical disability (n=111) or who did not report disability (n=98) and of Bosnia (n=54) and Era (n=79) veterans who reported physical disability. Main outcome measure: Psychiatric disorders assessed by the schedule for clinical assessment in neuropsychiatry and classified by the Diagnostic and Statistical Manual of Mental Disorders, fourth edition. Results: Only 24% (n=27) of the disabled Gulf veterans had a formal psychiatric disorder (depression, anxiety, or alcohol related disorder). The prevalence of psychiatric disorders in non-disabled Gulf veterans was 12%. Disability and psychiatric disorders were weakly associated in the Gulf group when confounding was adjusted for (adjusted odds ratio 2.4, 99% confidence interval 0.8 to 7.2, P=0.04). The prevalence of psychiatric disorders was similar in disabled non-Gulf veterans and disabled Gulf veterans (19% v 24%; 1.3, 0.5 to 3.4). All groups had rates for post-traumatic stress disorder of between 1% and 3%. Conclusions: Most disabled Gulf veterans do not have a formal psychiatric disorder. Post-traumatic stress disorder is not higher in Gulf veterans than in other veterans. Psychiatric disorders do not fully explain self reported ill health in Gulf veterans; alternative explanations for persistent ill health in Gulf veterans are needed.

Gulf War illness - better, worse or just the same? A cohort study

Abstract Objectives Firstly, to describe changes in the health of Gulf war veterans studied in a previous occupational cohort study and to compare outcome with comparable non-deployed military personnel. Secondly, to determine whether differences in prevalence between Gulf veterans and controls at follow up can be explained by greater persistence or greater incidence of disorders. Design Occupational cohort study in the form of a postal survey. Participants Military personnel who served in the 1991 Persian Gulf war; personnel who served on peacekeeping duties to bosnia; military personnel who were deployed elsewhere (“Era” controls). All participants had responded to a previous survey. Setting United Kingdom. Main outcome measures Self reported fatigue measured on the Chalder fatigue scale; psychological distress measured on the general health questionnaire, physical functioning and health perception on the SF-36; and a count of physical symptoms. Results Gulf war veterans experienced a modest reduction in prevalence of fatigue (48.8% at stage 1, 43.4% at stage 2) and psychological distress (40.0% stage 1, 37.1% stage 2) but a slight worsening of physical functioning on the SF-36 (90.3 stage 1, 88.7 stage 2). Compared with the other cohorts Gulf veterans continued to experience poorer health on all outcomes, although physical functioning also declined in bosnia veterans. Era controls showed both lower incidence of fatigue than Gulf veterans, and both comparison groups showed less persistence of fatigue compared with Gulf veterans. Conclusions Gulf war veterans remain a group with many symptoms of ill health. The excess of illness at follow up is explained by both higher incidence and greater persistence of symptoms.

Neurophysiologic analysis of neuromuscular symptoms in UK Gulf War veterans A controlled study

Background: UK veterans who were deployed to the Gulf in 1990 to 1991 reported higher prevalence of neuromuscular symptoms. Objective: To investigate whether these Gulf War-related symptoms were associated with objective evidence of neuromuscular dysfunction. Methods: Forty-nine Gulf War veterans with more than four neuromuscular symptoms (Gulf-ill), 26 Gulf-well veterans, 13 symptomatic Bosnian veterans (Bosnia-ill), and 22 symptomatic veterans who were not deployed to the Gulf (Era-ill) underwent detailed neurophysiologic assessment: nerve conduction studies, quantitative sensory and autonomic testing, and concentric needle and single-fiber electromyography (EMG). Results: Nerve conduction studies detected carpal tunnel syndrome in two Gulf-ill, two Gulf-well, one Bosnia-ill, and three Era-ill veterans. Ulnar neuropathy was detected in one Gulf-ill and two Era-ill veterans. However, results of detailed nerve conduction studies of the Gulf-ill veterans were comparable with results observed in the other three groups. Quantitative sensory and autonomic assessments also failed to show any specific abnormalities in the Gulf-ill group. Similarly, quantitative assessment of concentric needle and single-fiber EMG detected no chronic denervation or myopathic changes or any abnormalities of neuromuscular transmission in the Gulf-ill veterans. Conclusion: Gulf War-related neuromuscular symptoms are not associated with specific impairments of peripheral nerves, neuromuscular junctions, or skeletal muscles.

Occupational risk factors for ill health in Gulf veterans of the United Kingdom

OBJECTIVES To study the association between occupational factors specific to the Armed Forces (rank, functional roles, Service, regular or reservist status and deployment factors) and symptomatic health problems in Gulf veterans, after sociodemographic and lifestyle factors have been accounted for. DESIGN A postal cross sectional survey of randomly selected UK Gulf veterans was conducted six to seven years after the Gulf conflict. Physical ill health was measured using the Fatigue Questionnaire and a measure of the Centers for Disease Control and Prevention (CDC) multi-symptom syndrome. Psychological ill health was measured using the General Health Questionnaire and a post-traumatic stress measure. SETTING Population of servicemen who were serving in the UK Armed Forces during the Gulf conflict between 1 September 1990 and 30 June 1991. PARTICIPANTS 3297 Gulf veterans. MAIN RESULTS In multivariate logistic regression, there was an inverse relation between higher rank and psychological and physical ill health (test of trend: General Health Questionnaire, p=0.004 ; post-traumatic stress, p=0.002; fatigue, p=0.015; CDC case, p=0.002). Having left the Armed Forces was associated with a two to three times increase in reporting ill health. Of the deployment factors, there was a weak association between being deployed as an individual reinforcement in a combat role and post-traumatic stress but there was no association between receiving pre-deployment training or post-deployment leave and ill health. Marital status and smoking were associated with psychological and physical ill health. CONCLUSIONS Rank was the main occupational factor associated with both psychological and physical ill health in Gulf veterans. This may parallel the associations between socioeconomic status and morbidity in civilian populations. Ill health seems to be greater in those who return to civilian life. Sociodemographic factors also seem to be important in ill health in Gulf veterans.

Cellular Immune Activation in Gulf War Veterans

The etiology and pathology of illnesses related to the first Persian Gulf War are unclear. Among the constellation of symptoms noted in sick veterans, some, such as skin rashes, musculoskeletal pains, and neuropsychiatric problems, have been proposed to reflect an underlying immune dysfunction. In this study we explored the hypothesis that sickness following deployment to the Gulf in 1991 is associated with altered immune function, and we examine possible associated exposures. In particular, we focused on peripheral blood Th1/Th2 balance by measuring intracellular production of IFN-γ, IL-2 (Th1), IL-4 (Th2), and IL-10 by CD4 T cells, using a nested case control study design within a large epidemiological survey. We compared symptomatic Gulf War veterans (sGWV) with well GWVs (wGWV), and a second control group of symptomatic veterans who served in Bosnia or were nondeployed military personnel of the same era. We found evidence for an altered immune status in sGWV in comparison to the other study groups. In particular, ongoing Th1-type immune activation was associated with multisymptom illness in GWVs, with sick veterans having significantly elevated levels of IFN-γ and IL-2 producing CD4+ cells in the absence of in vitro stimulation compared with wGWVs (P = 0.01 and P =0.001). In vitro polyclonal activation revealed significantly elevated levels of IL-10 producing memory CD4 cells in sGWVs (P <0.001), but other cytokines were normal. In terms of possible exposures that might influence immune function, we found a trend for reduced levels of IFN-γ producing cells after polyclonal activation with increasing numbers of vaccines administered (P <0.05) but no changes in other cytokines. These data show that multisymptom illness in Gulf War veterans is characterized by ongoing Th1-type immune activation and a biased generation of memory cells secreting the suppressor cytokine, IL-10.

Prevalence of Gulf war veterans who believe they have Gulf war syndrome: questionnaire study

Abstract Objectives: To determine how many veterans in a random sample of British veterans who served in the Gulf war believe they have “Gulf war syndrome,” to examine factors associated with the presence of this belief, and to compare the health status of those who believe they have Gulf war syndrome with those who do not. Design: Questionnaire study asking British Gulf war veterans whether they believe they have Gulf war syndrome and about symptoms, fatigue, psychological distress, post-traumatic stress, physical functioning, and their perception of health. Participants: 2961 respondents to questionnaires sent out to a random sample of 4250 Gulf war veterans (69.7%). Main outcome measure: The proportion of veterans who believe they have Gulf war syndrome. Results: Overall, 17.3% (95% confidence interval 15.9 to 18.7) of the respondents believed they had Gulf war syndrome. The belief was associated with the veteran having poor health, not serving in the army when responding to the questionnaire, and having received a high number of vaccinations before deployment to the Gulf. The strongest association was knowing another person who also thought they had Gulf war syndrome. Conclusions: Substantial numbers of British Gulf war veterans believe they have Gulf war syndrome, which is associated with psychological distress, a high number of symptoms, and some reduction in activity levels. A combination of biological, psychological, and sociological factors are associated with the belief, and these factors should be addressed in clinical practice. What is already known on this topic The term Gulf war syndrome has been used to describe illnesses and symptoms experienced by veterans of the 1991 Gulf war Concerns exist over the validity of Gulf war syndrome as a unique entity What this study adds 17% of Gulf war veterans believe they have Gulf war syndrome Holding the belief is associated with worse health outcomes Knowing someone else who believes they have Gulf war syndrome and receiving more vaccinations were associated with holding the belief

Paraoxonase in Persian Gulf War veterans

Learning ObjectivesSummarize what previous studies have shown about possible causes of low serum paraoxonase (PON1).Recall what this study showed about serum PON1 activity in Gulf War veterans, in veterans deployed elsewhere, and its relation to symptoms.Present possible explanations of group differences in serum PON1 activity. Serum paraoxonase (PON1) is responsible for the metabolism of organophosphates in serum, and PON1 activity is a major determinant of their toxicity in humans. There have been reports linking lowered PON1 activity to physical symptoms after deployment to the Persian Gulf War (PGW) of 1990 to 1991. Therefore, the object of this study was to determine (1) whether PON1 activity was decreased among symptomatic PGW veterans compared with asymptomatic PGW veterans and (2) to determine whether PGW veterans as a whole had lower PON1 activity compared with other military control groups. This was a case control study nested in occupational cohort study of military personnel. Four groups of military personnel were identified from a large epidemiological study of health effects of deployment to the PGW and Bosnia: (1) symptomatic PGW veterans, n = 115; (2) healthy PGW veterans, n = 95; (3) symptomatic Bosnia peacekeeping veterans, n = 52; and (4) symptomatic nondeployed military controls, n = 85. The main outcome measures were PON1 activity and genotype for PON1–55 and -192. We found significant differences in PON1 activity among these four groups, and although the two Gulf groups did not differ in PON1 activity, those deployed to the Gulf had significantly lower PON1 activity compared with the non-PGW groups (median difference = 70.9; 95% CI: 20.2, 121.5, P = 0.012). These differences were not explained by a range of potential confounders, or differences in PON1 coding region polymorphisms. PON1 activity is reduced in PGW veterans compared with military control groups. The effect is independent of ill health in PGW veterans.