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Gulf war illness—better, worse, or just the same? A cohort study
M Hotopf, Anthony S David, Lisa Hull, Vasilis Nikalaou, Catherine Unwin, Simon Wessely
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 repor ted 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.
Introduction
Consensus exists that service in the 1991 Persian Gulf war
resulted in increased symptomatic ill health among those
deployed.
1–8
We know of no studies on the prognosis of
symptoms among Gulf war veterans. In 1997 we studied a large
random sample of members of the armed forces who served in
the 1991 Gulf war,
1
including those who had left the services. We
compared the “Gulf cohort” with two military control cohorts.
This study assesses the outcomes of these cohorts four years
later. Our two main aims were, firstly, to compare the prevalence
of various health outcomes over time and between cohorts, and,
secondly, to determine rates of incidence and remission for clini-
cally important fatigue and psychological distress after adjusting
for potential confounders.
Method
Participants
Our original study consisted of three groups: personnel who
served in the Persian Gulf war between 1 September 1990 and
30 June 1991 (the Gulf cohort); personnel who served on UN
peacekeeping duties in Bosnia between 1 April 1992 and 6 Feb-
ruary 1997 (the Bosnia cohort); and personnel who were serving
in the armed forces on 1 January 1991 but who were not
deployed to the Gulf (the “Era” cohort).
1
We took a random
sample of all Gulf veterans, with oversampling of women.
Sampling of the other two cohorts was frequency matched in
terms of sex, age, reservist status, officer status, service (Royal
Navy, Army, or Royal Air Force), and a measure of fitness.
Of 8196 participants who responded to the first survey 503
refused permission for future contact and 449 failed to complete
the relevant section of the questionnaire. We used random strati-
fied sampling to select respondents from stage 1 into the present
study. All women were selected. We stratified the sampling on the
severity of fatigue at stage 1. The selection process included all
male veterans with a fatigue score greater than 8 (511 Gulf, 115
Bosnia, and 120 Era); for Gulf, a 50% sample of veterans with
fatigue scores of 4-8 (484 veterans), along with all those in Bosnia
(n = 333) and Era (n = 364) who scored in this range; and an
approximately one in eight sample of veterans with fatigue
scores less than 4 in order to represent asymptomatic individuals
(n = 250 in each group).
Mailing method
We used three mailings. To trace non-responders we used the
NHS central registry to obtain health authority ciphers and cur-
rent addresses. We used the online electoral registry “Cameo” to
check addresses. Service pension and discharge sources supplied
updated addresses. We sent the second and third mailings via
commanding officers, asking for their help in disseminating the
questionnaires on our behalf. Following an agreement with the
War Pensions Agency, the UK Depar tment of Social Security
sent two further mailings. In order to comply with data
protection regulation, we were not informed which addresses the
Department of Social Security had on their records.
Questionnaire and outcomes
The questionnaire included a fatigue scale
9
; the 12 item general
health questionnaire (a screening questionnaire for common
mental disorders)
10
; the SF-36 instrument for physical health and
functional capacity
11–13
; and a list of 50 common symptoms. We
defined cases of fatigue as having a score on the fatigue scale of
greater than 3 and cases of psychological distress as having a
score greater than 2 on the general health questionnaire. We
defined cases of “stress reaction” from a checklist of symptoms
described in previous work.
1
Editor ial by Clauw and p 1373
page 1 of 4BMJ VOLUME 327 13 DECEMBER 2003 bmj.com
Statistical analyses
Response bias—We defined four groups
—
responders, “refus-
ers,” “returns to sender” (where questionnaires were returned to
us), and “no information” (where no reply was forthcoming). We
compared the frequency of these four outcomes by cohort. We
determined whether response bias was present by comparing
demographic variables and stage 1 health outcomes across
cohorts, using Scheffé’s test.
14
Follow up health outcomes
—
To take account of the sampling
strategy all analyses used sampling weights and robust standard
errors by using the appropriate commands in Stata (StataCorp,
College Station, TX). We calculated the prevalence of binary out-
come variables and present these in relation to baseline scores.
For binary outcomes we present the matched odds ratio, which is
the proportion of incident cases to recovered cases for each out-
come. For continuous outcomes we present stage 1 and 2 scores
and mean differences with 95% confidence intervals.
Results
Response rates
The response rate for those eligible to receive a questionnaire
was 71.6% (table 1). The response rate was higher in the Gulf
cohort than in the other two cohorts (P = 0.03). A similar pattern
emerged in terms of types of non-respondents in Gulf and
Bosnia, but the Era group had a higher proportion of refusers
than the other two cohorts. Response rates were lower in men,
younger participants, and those who were unmarried. Non-
responders rated their health as poorer at stage 1 for physical
disability and general health perception but were less likely to
have been cases on the general health questionnaire.
Table 2 shows the sociodemographic characteristics of the
participants and indicates that Gulf and Era were broadly similar.
The Bosnia group were younger, less likely to be married, more
likely to have remained in service, and only from the Army.
Table 3 shows the prevalence of categorical outcomes at
stages 1 and 2. We report the prevalence of stage 1 outcomes
within the sample studied at stage 2, not for the entire cohort
—
hence the prevalence figures we report for stage 1 are similar, but
not identical to, those shown in our previous paper.
1
Table 3
shows that Gulf had higher rates of the disorders under study
than the other two cohorts, and this difference is maintained
between stages 1 and 2. For Gulf we found a modest reduction in
the prevalence of fatigue, post-traumatic stress reaction, general
health questionnaire cases, and self reported “Gulf war
syndrome.” For Bosnia and Era we found no changes other than
an increase in the prevalence of post-traumatic stress reaction in
the Era group, which was not significant (P > 0.05).
Table 4 shows the scores on continuous measures at each time
point for the three cohorts. The Gulf cohort was less healthy than
the other two cohorts at both stages. A decline in physical
functioning affected each of the three cohorts (non-significant for
Era). Health perception declined for both Bosnia and Era but not
Table 1 Characteristics of responders and non-responders in a cohort study among Gulf war veterans. Values are numbers (percentages) unless otherwise
indicated
Responders v all non-responders Responders v type of non-responder
Responders
(n=2370)
All non-responders
(n=935) Statistic
Refuser
(n=246)
No information
(n=433)
Return to sender
(n=256) Statistic
Cohort:
Gulf 1089 (74.0)
1
383 (26.0)
2
=6.8 (df=2) (P=0.03)
88 (6.0)
2
191 (13.0)
2
104 (7.0)
1
2
=25.4 (df=6) P<0.001
Bosnia 638 (70.2) 271 (29.8) 59 (6.5) 133 (14.6) 79 (8.7)
Era 643 (69.6) 281 (30.4) 99 (10.7) 109 (11.8) 73 (7.9)
Male sex (%) 1873 (79.0)
3
791 (84.6)
2
=13.3 (df=1) P<0.001 209 (85.0) 374 (86.4)
3
208 (81.3)
2
=16.0 (df=3) P=0.001
Age in years in 2002 (SD) 37.7 (7.4)
a
36.3 (6.9) I=4.8 P<0.0001 37.9 (7.3)
b
35.6 (6.9)
a, b
36.2 (6.4) F
3
, 3301=13.1
P<0.0001
Commissioned officers 416 (17.6)
4
90 (9.6)
2
=32.5 (df=1) P<0.001 30 (12.2)
6
26 (6.0)
4, 5, 6
34 (13.3)
5
2
=40.8 (df=3) P<0.001
Marital status:
Married or cohabiting 1640 (69.9) 596 (64.6)
2
=9.1 (df=2) P=0.01
170 (70.0) 268 (63.1) 158 (62.0)
2
=14.6 (df=6) P=0.02
Never married 481 (20.5) 218 (23.6) 52 (21.4) 102 (24.0) 64 (25.1)
Widowed, separated, or divorced 224 (9.6) 109 (11.8) 21 (8.6) 55 (12.9) 33 (12.9)
Still serving 1444 (60.9)
7
541 (57.9)
2
=2.6 (df=1) P=0.1 141 (57.3) 229 (52.9)
7, 8
171 (66.8)
8
2
=15.6 (df=3) P=0.001
SF-36 physical functioning (SD) 89.2 (18.3)
c
86.9 (20.9) t=3.1
P=0.002
83.9
(17.4)
cd
86.9 (20.8) 89.8 (17.4)
d
F 3, 3225=7.00
P<0.0001
SF-36 health perception (SD) 64.7 (26.0)
e
62.1 (27.2) t=2.6
P=0.01
61.8
(27.5)
60.2 (28.3)
e
65.5 (24.8) F
3
, 3297=4.4
P=0.004
General health questionnaire case 1193 (51.1) 432 (47.3)
2
=3.8 (df=1) P=0.05 115 (47.5) 197 (47.0) 120 (47.6)
2
=3.8 (df=3) P=0.3
Fatigue case 832 (35.3) 323 (34.7)
2
=0.1 (df=1) P=0.7 246 (37.4) 133 (30.9) 98 (37.4)
2
=5.3 (df=3) P=0.15
a, b, c, d, e
: Scheffé test
14
, P<0.01;
1-8
: specific contrasts on
2
, P<0.01.
Table 2 Characteristics of the three cohorts. Values are numbers (percentages) unless otherwise indicated
Stage 1 variables Gulf (n=1089) Bosnia (n=638) Era (n=643)
Men 918 (84.5) 484 (76.6) 502 (78.2)
Mean age (SD) 39.2 (6.9) 33.7 (6.7) 39.8 (7.5)
Service:
Royal Navy 80 (7.4) — 56 (8.7)
Army 881 (81.0) 632 (100)* 470 (73.2)
Royal Air Force 127 (11.7) — 116 (18.1)
Officers 166 (15.8) 123 (19.7) 142 (24.1)
Married 809 (74.8) 355 (57.1) 633 (74.4)
Still serving at stage 1 583 (54.7) 558 (88.4) 319 (54.1)
*Bosnia was selected only from Army.
Papers
page 2 of 4 BMJ VOLUME 327 13 DECEMBER 2003 bmj.com
for Gulf. The Gulf v eterans showed a modest reduction in fatigue
scores and non-significant but small reductions in general health
questionnaire scores and total symptoms. The other tw o cohorts
show ed a general tendency to experience more symptoms ov er
time; six changes were significant (P < 0.05).
Because it was possible that differences in prevalence
between cohorts could have been explained by either higher
incidence, or greater persistence, of symptoms this was explored
in table 5. The incidence risk for fatigue and general health ques-
tionnaire caseness was lower in Era than the other two cohorts.
Controlling for stage 1 sociodemographic variables reduced the
differences, but the Era group remained less likely to experience
new fatigue than the Gulf group. The Gulf group were more
likely to experience persistent fatigue compared with the Era
and Bosnia cohorts, an effect that remained significant after con-
trolling for potential confounders (P = 0.009).
Discussion
Main findings
Gulf war v eterans continue to experience symptoms that are con-
siderably worse than would be expected in an equivalent cohort of
military personnel. However, Gulf war veterans are not deteriorat-
ing and do not have a higher incidence of new illnesses.
Our study had two main aims. Firstly , w e wanted to describe
the outcome of Gulf war veterans three to four years after we first
surv eyed them. Our results show a disappointing stability in the
prevalence of the main disorders we studied. Although the preva-
Table 3 Prevalence of categorical outcomes in the three cohorts. Values are percentages (95% confidence intervals) unless otherwise indicated
Gulf Bosnia Era
Stage 1 Stage 2
Ratio* (new
cases/recovered
cases) Stage 1 Stage 2
Ratio* (new
cases/
recovered
cases) Stage 1 Stage 2
Ratio* (new
cases/recovered
cases)
Fatigue cases 48.8
(45.4 to 52.2)
43.4
(39.9 to 46.8)
0.65
(0.45 to 0.85)
29.0
(25.6 to 32.4)
32.7
(28.6 to 36.8)
1.21
(0.83 to 1.59)
22.8
(20.0 to 25.6)
22.0
(18.6 to 25.4)
0.91
(0.56-1.26)
Post-traumatic
stress reaction
cases
12.4
(10.7 to 14.2)
10.8
(9.1 to 12.5)
0.73
(0.47 to 0.99)
5.7
(4.0 to 7.4)
6.0
(4.2 to 7.8)
1.07
(0.49 to 1.65)
4.0
(2.6 to 5.3)
6.6
(4.8 to 8.4)
2.45
(0.88-4.02)
General health
questionnaire
cases
40.0
(36.8 to 43.2)
37.1
(33.8 to 40.4)
0.79
(0.59 to 1.00)
29.2
(25.5 to 32.9)
31.5
(27.4 to 35.6)
1.25
(0.84 to 1.67)
25.3
(21.7 to 28.9)
23.8
(20.1 to 27.6)
0.88
(0.56-1.20)
Self reported
Gulf war
syndrome
18.6
(16.2 to 21.1)
15.8
(13.3 to 18.2)
0.58
(0.25 to 0.90)
All prevalence estimates are weighted for sampling.
*Values of <1 indicate declining prevalence. Ratios are weighted for sampling.
Table 4 Scores (95% confidence intervals) for continuous measures by cohort and stage
Gulf Bosnia Era
Stage 1 Stage 2 Difference Stage 1 Stage 2 Difference Stage 1 Stage 2 Difference
SF-36* physical
function
90.3
(88.3 to 91.3)
88.7
(87.6 to 89.9)
−1.6
(−2.5 to −0.7)
95.4
(94.4 to 96.4)
92.9
(91.6 to 94.1)
−2.6
(−3.8 to −1.3)
92.1
(90.6 to 93.6)
90.8
(89.2 to 92.3)
−1.3
(−2.7 to 0.1)
SF-36* health
perception
65.8
(64.1 to 67.5)
65.9
(64.2 to 67.6)
0.1
(−1.2 to 1.4)
76.2
(74.4 to 77.9)
72.9
(71.0 to 74.8)
−3.3
(−5.1 to −1.6)
76.8
(75.0 to 78.6)
74.4
(72.4 to 76.4)
−2.4
(−4.2 to −0.6)
General health
questionnaire
14.5
(14.1 to 14.9)
14.2
(13.8 to 14.5)
−0.3
(0.1, −0.6)
13.1
(12.7 to 13.6)
13.2
(12.7 to 13.7)
0.1
(−0.4 to 0.6)
12.4
(12.0 to 12.8)
12.9
(12.5 to 13.3)
0.5
(0.05 to 1.0)
Fatigue 17.8
(17.4 to 18.1)
16.9
(16.5 to 17.2)
−0.9
(−1.2 to −0.6)
15.6
(15.2 to 16.0)
15.3
(14.9 to 15.7)
−0.3
(−0.7 to 0.2)
14.7
(14.3 to 15.0)
14.9
(14.5 to 15.3)
0.2
(−0.2 to 0.6)
Total symptoms 11.0
(10.4 to 11.6)
10.7
(10.1 to 11.3)
−0.3
(−0.8 to 0.1)
6.2
(5.6 to 6.8)
7.9
(7.3 to 8.5)
1.7
(1.2 to 2.3)
5.3
(4.8 to 5.8)
6.4
(5.8 to 7.0)
1.1
(0.6 to 1.6)
All scores are weighted for sampling.
*SF-36 scales range from 0-100, with higher scores indicating better health.
For SF-36 scores, negative differences in mean indicate a worsening in health. For other scales, negative scores indicate an improvement in health.
Table 5 Incidence and persistence of outcomes. Values are presented with 95% confidence intervals
Cohort
Incidence Persistence
Risk Crude odds ratio Corrected odds ratio* Risk Crude odds ratio Corrected odds ratio*
General health questionnaire cases:
Gulf 20.2 (16.4 to 24.0) 1.0 1.0 61.8 (57.3 to 66.3) 1.0 1.0
Bosnia 21.2 (16.7 to 25.8) 1.1 (0.7 to 1.5) 0.9 (0.6 to 1.4) 58.9 (51.9 to 65.8) 0.9 (0.6 to 1.1) 1.1 (0.7 to 1.6)
Era 15.4 (11.4 to 19.4) 0.7 (0.5 to 1.1) 0.7 (0.5 to 1.1) 48.4 (41.0 to 55.9) 0.8 (0.6 to 1.1) 0.6 (0.4 to 0.8)
Fatigue cases:
Gulf 18.8 (14.4 to 23.1) 1.0 1.0 69.7 (66.4 to 73.0) 1.0 1.0
Bosnia 19.8 (15.1 to 24.4) 1.1 (0.7 to 1.6) 0.9 (0.6 to 1.5) 59.9 (54.2 to 65.6) 0.6 (0.5 to 0.9) 0.7 (0.5 to 1.0)
Era 11.2 (7.5 to 15.0) 0.6 (0.3 to 0.9) 0.5 (0.3 to 0.9) 58.2 (53.1 to 63.4) 0.6 (0.5 to 0.8) 0.7 (0.5 to 0.9)
Post-traumatic stress reaction cases:
Gulf 5.0 (3.6 to 6.4) 1.0 1.0 51.8 (44.8 to 58.9) 1.0 1.0
Bosnia 4.0 (2.5 to 5.5) 0.8 (0.5 to 1.3) 0.8 (0.4 to 1.5) 38.9 (24.3 to 53.3) 0.6 (0.3 to 1.2) 0.8 (0.4 to 1.8)
Era 4.6 (3.0 to 6.2) 0.9 (0.6 to 1.5) 0.9 (0.5 to 1.5) 54.8 (37.8 to 71.9) 1.1 (0.5 to 2.4) 1.2 (0.6 to 2.7)
*Controlled for demographic variables (age, sex, rank, marital status).
Paper s
page 3 of 4BMJ VOLUME 327 13 DECEMBER 2003 bmj.com
lence of the symptom based disorders lessened for Gulf veterans,
physical functioning and health perception measured on the
SF-36 barely changed. The reduced physical functioning may have
been due to increasing age. The two comparison groups had some
worsening in health on the SF-36 scales and more physical symp-
toms. This implies that some w orsening of these health outcomes
is expected ov er time, presumably due to advancing age. At each
wave the prevalence between Gulf and the two comparison groups
differs, and, although the gap narrowed slightly, the Gulf v eterans
continued to experience poorer health on all measures.
Our second aim was to examine whether the raised prevalence
in Gulf veterans was explained by a greater incidence of disorders
or more persistence. No clear pattern emerged. We found some
evidence that the incidence of fatigue and caseness on the general
health questionnaire was higher in the two deployed groups
(Bosnia and Gulf) than in Era but that the difference for the
general health questionnaire was explained by confounding. F or
fatigue we found evidence that the Gulf group continued to have
greater incidence than the Era group , and this was not explained
by confounding. For persistence we found a strong trend for
Gulf veterans with fatigue to be more likely to remain fatigued at
follow up.
Limitations of the study
We achieved a follow up rate of just over 70%, which leaves room
for bias. Because follow up rates were worse in participants with
poorer health at stage 1 we have probably slightly underesti-
mated the prevalence of the disorders under study. The effect of
this bias seems to have been similar across cohorts, which makes
it unlikely that the non-response bias would have led to the Gulf
group having still higher than expected prevalence figures at
stage 1. We believe that the missing values are unlikely to have
changed the main findings of this study. We measured health on
a range of self report items, which are open to reporting biases.
Implications
The nature of Gulf war illness remains ambiguous. If the illness
represented the prodrome of a known disease (such as a neuro-
logical disorder), even with the passage of time, this has yet to
declare itself.
15 16
We think that the non-specific increase in
symptoms reported by our and other studies is likely to remain
poorly understood in terms of conventional biomedical diseases.
This study did not have the statistical power to assess mortality in
Gulf war veterans, and this was not our aim. Other studies in the
United Kingdom and the United States, however, have failed to
find higher than expected death rates.
17 18
Finally, as time passes
it becomes increasingly difficult to find causes of illnesses in vet-
erans of the 1990-1 Gulf war. We suspect that different
psychosocial, military and environmental risk factors may deter-
mine onset and recovery, and this is the topic of future research.
We thank Nick Blatchley and Simon Satchell from the Gulf Veterans Illness
Unit of the Ministry of Defence for assistance in tracking participants,
Michael Dewey for statistical advice, and the participants for their patience
in once again completing lengthy questionnaires.
Contributors: MH, ASD, and SW designed the study. CU snf LH were
responsible for data collection under the supervision of SW, ASD, and MH.
MH and VN ptrformed the statistical analyses. MH wrote the paper and is
the guarantor. All authors provided comments.
Funding: US Department of Defense, UK Medical Research Council.
Competing interests: None declared.
Ethical approval: The study received approval from the relevant research
ethics committees.
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(Accepted 14 October)
bmj.com 2003;327:1370
Gulf War Illnesses Research Unit, Department of Psychological Medicine, Guy’s,
King’s, and St Thomas’s School of Medicine, London SE5 8AZ
Matthew Hotopf reader
Anthony S David professor
Lisa Hull research assistant
Vasilis Nikalaou statistician
Catherine Unwin study coordinator
Simon Wessely professor
Correspondence to: M Hotopf
m.hotopf@iop.kcl.ac.uk
What is already known on this topic
Veterans of the 1990-1 Gulf war experience poorer health
on most subjective outcomes than non-deployed military
personnel
No satisfactory follow up studies have assessed outcome of
veterans of the Gulf war over more than one wave of data
collection, so it is unclear whether veterans are getting
worse, staying the same, or getting better
What this study adds
Gulf war veterans still have considerably poorer subjective
health than appropriate military controls
The health of Gulf war veterans has improved, but this
improvement is relatively minor
For comparison groups there has been a worsening of
health on some outcomes, which is probably due to ageing
The health gap between Gulf war veterans and comparison
groups has therefore narrowed slightly
Papers
page 4 of 4 BMJ VOLUME 327 13 DECEMBER 2003 bmj.com
