American Journal of Epidemiology
Copyright 0 1 9 9 9 by The Johns Hopkins University School of Hygiene and Public Health
All rights reserved
vol. 150, No. 5
Printed In U.SA.
The Postwar Hospitalization Experience of Gulf War Veterans Possibly
Exposed to Chemical Munitions Destruction at Khamisiyah, Iraq
Gregory C. Gray,1 Tyler C. Smith,1 James D. Knoke,1 and Jack M. Heller2
Using Department of Defense hospital data, the authors examined the postwar hospitalization experience
from March 1991 through September 1995 of US Guff War veterans who were near Khamisiyah, Iraq, during
nerve agent munition destruction in March 1991. Multiple sources of meteorologic, munition, and toxicology data
were used to circumscribe geographic areas of low level, vaporized nerve agent for 4 days after the destruction.
Plume estimates were overlaid on military unit positions, and exposure was estimated for the 349,291 US Army
Gulf War veterans. Exposure was classified as not exposed (n = 224,804), uncertain low dose exposure (n =
75,717), and specific estimated subclinical exposure (n = 48,770) categorized into three groups for doseresponse evaluation. Using Cox proportional hazard modeling, the authors compared the postwar experiences
of these exposure groups for hospitalization due to any cause, for diagnoses in 15 unique categories, and for
specific diagnoses an expert panel proposed as most likely to reflect latent disease from such subclinical
exposure. There was little evidence that veterans possibly exposed to the nerve agent plumes experienced
unusual postwar morbidity. While there were several differences in hospitalization risk, none of the models
suggested a dose-response relation or neurologic sequelae. These data, having a number of limitations, do not
support the hypothesis that Gulf War veterans are suffering postwar morbidity from subclinical nerve agent
exposure. Am J Epidemiol 1999; 150:532-40.
environmental exposure; hospitalization; military medicine; military personnel; morbidity; Persian Gulf syndrome;
veterans
During the Persian Gulf War, Iraq was known to possess chemical weapons (1, 2). Shortly after the 1991
fighting ended, expert panels evaluated available exposure and medical data and concluded that there was no
evidence that Iraq used these weapons of mass destruction during the conflict (3). In June 1996 (4), the US
Department of Defense announced United Nations'
findings that chemical agents had been destroyed by
US forces near Khamisiyah, Iraq, during March 1991.
In a series of follow-up reports, the Department of
Defense announced that US soldiers who were near
Khamisiyah may have been exposed to the plume from
munition destruction (5). Subsequently, there has been
speculation that Gulf War veterans located under the
plume may be suffering increased postwar morbidity
as a result of this exposure (6-8). This report documents our investigation into the postwar hospitalization experience of these veterans.
MATERIALS AND METHODS
Objective
The objective for this investigation was to compare
the postwar hospitalization experience of Gulf War
veterans who were possibly exposed to a plume from
munition destruction at Khamisiyah, Iraq, in March
1991, with that of other Gulf War veterans who were
not likely to have been exposed.
Received for publication June 16, 1998, and accepted for publication January 22, 1999.
Abbreviations: ICD-9, International Classification of Diseases,
Ninth Revision; RR, risk ratio.
1
Emerging Illness Division, Department of Health Sciences and
Epidemiology, Naval Health Research Center, San Diego, CA.
2
Deployment Environmental Surveillance Program, US Army
Center for Health Promotion and Preventive Medicine, Aberdeen
Proving Ground, MD.
Reprint requests to Dr. Gregory C. Gray, Naval Health Research
Center, Emerging Illness Division, P.O. Box 85122, San Diego, CA
92186-5122.
Data sources
This study was conducted in accordance with
Protection of Human Subjects' guidelines from the US
Department of the Navy. As previously described
(9-11), demographic, hospitalization, and deployment
data for the Gulf War veterans were obtained from the
Defense Manpower Data Center, Monterey Bay,
California. Geographic information system data were
532
Gulf War Veterans and Khamisiyah
compiled by the US Army Center for Health
Promotion and Preventive Medicine, Aberdeen
Proving Ground, Maryland.
Descriptive data
Descriptive data available for analysis included the
social security number, sex, date of birth, pay grade,
race, ethnicity, home of record, service branch, service
type, marital status (during deployment period),
Department of Defense primary occupational specialty, active-duty service entry date, beginning and
ending date of Gulf War service, and date of separation
from military service. The service branch (Navy/Coast
Guard, Army, Air Force, Marine Corps) was coded to
reflect military service on February 21, 1991. Age, as
of September 30, 1990, was categorized so as to form
approximate quartile age groups: 17-21 years, 22-25
years, 26-31 years, and ^32 years. Occupation (226
unique codes) was divided into 10 major groups, as
defined by the Department of Defense Occupational
Conversion Manual (12). In an effort to be consistent
with previous military categorizations and yet maintain group size for robust modeling, we combined race
and ethnicity into one variable with four categories:
White, Black, Hispanic, and other. Length of service,
calculated from the active-duty service entry date and
date of separation variables, was categorized into 0-2
years, 3-4 years, 5-9 years, and 10-42 years. Pay
grade was categorized into enlisted, warrant officer,
and commissioned officer. Length of service and pay
grade were then used to define a five-category monthly
salary variable: less than $1,000, $1,000-$ 1,399,
$1,400-$2,099, $2,100-$3,199, and >$3,199. Marital
status was categorized into married or not married.
533
Geographic information system data
Troop locations on specific days were recorded
using an Oracle Relational Database Management
System (Oracle Corporation, Redwood Shores,
California) and Intergraph Modular GIS Environment
software (Intergraph Corporation, Huntsville,
Alabama) on a Windows NT-based Intergraph TD
Series computer (Intergraph Corporation). Geographic
information system data were compiled from troop
movement information (US Armed Services Center for
Research of Unit Records, Springfield, Virginia),
linked by Unit Identification Codes to the roster of
Persian Gulf War veterans. As individual veteran location data were not available on a daily basis, troop
movement was normally tracked by companies of
from 50 to 120 individuals. Generally, these companies or units traveled together with a geographic
spread not exceeding 400 m. However, some individuals and small groups of veterans did occasionally separate from their unit.
The geographic information system contained all
records of daily unit locations (latitude and longitude) that could be found following the war. These
data had limitations. Not all units reported daily location data in their journals, logs, and messages. Units
were widely dispersed throughout the region, and
constructing the geographic information system from
thousands of paper records was difficult and not
without possible error. During 1997 and 1998, the
Office of the Special Assistant to the Deputy
Secretary of Defense for Gulf War Illnesses interviewed approximately 150 military operational officers to optimize troop movement data for March
10-13, 1991, the time frame of the Khamisiyah
munitions destruction.
Hospitalizatlon data
Hospitalization data were captured from all
Department of Defense hospitals from March 10,
1991, through September 30, 1995, and included date
of admission, up to eight individual discharge diagnoses, and disposition after hospital discharge.
Additionally, as per previous research (9,10), a prewar
hospitalization covariate (coded as yes or no) was used
to reflect a hospital admission during the 12 months
prior to August 1,1990. Diagnoses were coded according to the International Classification of Diseases,
Ninth Revision (ICD-9) (13). For these analyses, we
ignored the decimal component of ICD-9 diagnoses
and considered diagnoses with the same whole number
(up to three digits) to be the same. No hospitalization
data were available from hospitals outside the
Department of Defense system. No outpatient data
were available.
Am J Epidemiol Vol. 150, No. 5, 1999
Nerve agent exposure estimates
Intelligence information (14) and demolitions (5)
concerning Khamisiyah have been previously
reported in detail. In summary, Khamisiyah was a
large ammunition storage facility, located in southern
Iraq, approximately 25 km southeast of the city of An
Nasiriyah. The site contained numerous ammunition
bunkers, storage buildings, pits, and sand mounds to
protect stored weapons. During March 1991, Army
engineers operating from remote sites destroyed many
of the bunkers, warehouses, and stored weapons at the
facility. The chief focus of concern regarding
Khamisiyah is the March 10, 1991, destruction of a
cache of 1,250 rockets, which were stored in an open
pit. At that time, Army engineers did not have evidence that any of the munitions stored at Khamisiyah
contained nerve agents. However, in May 1996, the
534
Gray et al.
United Nations Special Commission inspectors examined demolition debris and determined that some of
the destroyed rockets contained the nerve agents sarin
and cyclosarin.
Rocket destruction modeling
An estimated 1,250 rockets were present at
Khamisiyah, each containing 6.3 kg of 50 percent
sarin and cyclosarin at a 3:1 ratio. Lacking empiric
data on the nerve agent release caused by open-air
detonation of these rockets, the Department of
Defense and Central Intelligence Agency jointly conducted destruction testing using simulated rockets
containing simulated nerve agent. The rocket destruction modeling was used to determine how much nerve
agent was released instantaneously and how much
was released over time by evaporation. This simulation, combined with intelligence data, led to the estimate that 342 gallons (1,294.57 liters) of nerve agent
were released on March 10, 1990, from 500 damaged
rockets (15). It was further determined, from interviews with the engineers that placed the charges at
Khamisiyah and from the multiple simulations, that 2
percent of the agent was released instantaneously (1
percent as droplets and 1 percent as vapor), and that
16 percent was released over time by evaporation
from the soil (6 percent) and from wooden rocket
packing crates (10 percent).
Meteorologic transport and diffusion modeling
All Khamisiyah modeling was guided by an expert
panel composed of numerous nonfederal and federal
experts in meteorology and atmospheric modeling.
Meteorologic modeling was conducted to simulate
the weather conditions in the vicinity of Khamisiyah
on March 10, 1991, and succeeding days. Results
from three global (synoptic) weather models and
three regional (mesoscale) high resolution weather
models were used (15). The meteorologic reconstruction was based upon a number of data sources including the following: global observation data from the
Persian Gulf region during March 1991, Saudi
Arabian surface and radiosonde observations, declassified surface data collected by the US Air Force and
Special Forces in the Khamisiyah region, and Navy
ship and satellite data. In addition, soot vector patterns from the Khamisiyah bunker explosions and
fires and smoke dispersion from the Kuwait oil fires
were used to validate the modeling result. The meteorologic models used in this effort were a combination of civilian university models and military models, many of which have been peer reviewed and
published.
Three Department of Defense transport and diffusion models were selected by an expert committee for
exposure modeling. Two of the diffusion models have
been validated, one in a series of field tests in the midwestern United States, and one by field trial data from
at least 60 reports on chemical and biologic agent simulation releases. These methods have historically been
used by the Department of Defense to model chemical
agent dispersion for military tactical analysis. The
three dispersion models were combined with the meteorologic models to generate five estimates or simulations of daily plume coverage (15).
Exposure plumes and exposure estimates
Since no US personnel were known to have died or
to have been incapacitated during the time period of
concern, the Department of Defense defined two lesser
nerve agent concentrations of interest (15). The first
noticeable effects concentration, 1 mg-minute/m3, was
defined as the dosage expected to cause mild symptoms, such as rhinorrhea, muscle twitching, chest
tightness, and headache. The general population limit
(hereafter termed low level exposure) concentration,
0.0126 mg-minute/m3, was the dosage below which
the general population, including children and the
elderly, could endure for at least 72 hours without
symptoms.
Two different types of chemical agent plumes were
used in these analyses. The union of five different
meteorologic/dispersion model simulations, termed
the notification plume, was used to inform Gulf War
veterans in early 1997 of potential chemical agent
exposure. These model simulation contours represent a
99 percent probability that persons exposed to the general population limit dosage would fall within that
perimeter (15). This union methodology was selected
upon advice from an independent expert review panel.
After much deliberation in November 1997, a similar independent expert panel recommended that a
smaller epidemiologic plume model be constructed
from the combination of the "best" meteorologic and
dispersion models for unit-specific dose estimation.
This epidemiologic plume or footprint enabled epidemiologists to estimate individual exposure by quantifying the nerve agent concentration at specific troop
locations over time. Because an updated mesoscale
meteorologic model was used with one of the three
dispersion models, the epidemiologic plume was not
completely contained in the notification plume. In the
future, the Department of Defense plans to redefine the
notification plume to include the new exposure estimate (epidemiology plume).
Plumes were estimated for each day for the period
March 10-13, 1991. The daily locations of the vapor
Am J Epidemiol Vol. 150, No. 5, 1999
Gulf War Veterans and Khamisiyah
plumes were overlaid on a geographic information system troop unit location base map (figure 1).
symptoms, signs, and ill-defined conditions; and
injury and poisoning.
The aggregation of many diagnoses into large ICD9 categories might mask population risk differences
due to individual diagnoses. We therefore also chose to
examine specific ICD-9 diagnoses, suggested by an
expert panel as possible manifestations of subtle, nerve
agent-induced, neurophysiologic effects: mononeuritis, peripheral neuropathy, toxic neuropathy, and
myoneural disorders and myopathies (6).
For each veteran, hospitalizations (if any) were
scanned in chronologic order, and diagnostic fields
were scanned in numeric order for the ICD-9 codes of
interest. Only the first hospitalization meeting the outcome criteria was counted for each veteran. Only
women were included in the analyses for the complications of pregnancy, childbirth, and the puerperium
category.
Study outcomes
With a focus on vapor plume exposure, risks of
hospitalization for "any cause" and hospitalization
with a diagnosis in each of 15 broad ICD-9 diagnostic categories (13) were examined: infection and parasitic diseases; neoplasms; endocrine, nutritional, and
metabolic diseases and immunity disorders; diseases
of the blood and blood-forming organs; mental disorders; diseases of the nervous system and sense
organs; diseases of the circulatory system; diseases of
the respiratory system; diseases of the digestive system; diseases of the genitourinary system; complications of pregnancy, childbirth, and the puerperium;
diseases of the skin and subcutaneous tissue; diseases
of the musculoskeletal system and connective tissue;
Day 1 - March 10,1991
Iraq
Day 2 - March 11,1991
-Khamisiyah
Saudi Arabia
Notification
Footprint
Khamisiyah
Iraq
Iran
Epidemiologic
Footprint
535
Iran
Epidemiologic
Footprint
Notification
Footprint
Saudi Arabia
V Aii%
), Persian *
Gulf
0
50
100
200 Km
100 150 Miles
I00
0
Day 3 - March 12,1991
50
100
150
Day 4 - March 13,1991
-Khamisiyah
Khamisiyah
Iran
Epidemiologic
Footprint
(See Inset- Right)
Saudi Arabia
0
0
50
100
200 Km
100 150 Miles
FIGURE 1. Geographic information system plots of US Army units with plume estimate overlays after the March 10, 1991, munition destruction at Khamisiyah, Iraq.
Am J Epidemiol
Vol. 150, No. 5, 1999
536
Gray et al.
Statistical analyses
Using SAS software (Version 6.12; SAS Institute,
Inc., Cary, North Carolina), Cox proportional hazard
modeling was used to obtain risk ratios, 95 percent
confidence intervals, and probabilities of hospitalization as a function of time (at the mean value of the
included covariates). Follow-up time was calculated
from March 10, 1991, until hospitalization, separation
from service, or September 30, 1995, whichever
occurred first. Because no separation data were available for reserve personnel, they were assumed to have
remained in active service until June 10, 1991 (at
which time most veterans had returned home), and
then were removed from further modeling consideration (censored).
RESULTS
No units were identified as having been exposed to
the first noticeable effects concentration or higher in the
vapor plume modeling. However, considering the union
of the notification and epidemiologic plumes, complete
data were available for 124,487 Army Gulf War veterans (95,402 (76.6 percent) regular active-duty and
29,085 (23.4 percent) reserve) who were determined to
have the possibility of at least low level exposure during the period March 10-13, 1991 (figure 1). Possibly
exposed Gulf War veterans were categorized into four
groups: uncertain low dose exposure (n = 75,717);
0.0-0.01256 mg-minute/m3 (exposure 1, n = 18,952);
0.01257-0.09656 mg-minute/m3 (exposure 2, n =
23,061); and 0.09657-0.51436 mg-minute/m3 (exposure 3, n = 6,757). As all of these possibly exposed individuals were US Army personnel, they were compared
with 224,804 other Army Gulf War veterans (177,343
(78.9 percent) regular active-duty and 47,461 (21.1 percent) reserve) who had complete data and were
deployed to the Gulf War theater (9) at the same time
but whose units were not under the circumscribed vapor
plumes (not exposed). More than 99.5 percent of all
Army Gulf War veterans had complete data.
During the 54 months of observation of regular
active-duty personnel, hospitalizations occurred in
21.6 percent of the not exposed group; 21.5 percent of
the uncertain low dose group; 23.0 percent of the
exposure 1 group; 21.0 percent of the exposure 2
group; and 21.5 percent of the exposure 3 group.
Similarly, considering only regular active-duty personnel, 48.4 percent of the not exposed group, 49.1 percent of the uncertain low dose group, 49.6 percent of
the exposure 1 group, 47.0 percent of the exposure 2
group, and 49.9 percent of the exposure 3 group
remained on active duty during the entire 54 months of
observation.
Based upon univariate comparisons for hospitalizations occurring during the study period and preliminary Cox proportional hazard modeling with all
covariates, the following covariates were selected for
the further multivariate modeling: sex, service type,
age group, marital status, race/ethnicity, occupational
category, pay grade, prewar hospitalization, and vapor
plume exposure. Home of record and length of service
covariates were not important to the model. Salary was
dropped from the analyses because of colinearity with
age group. Race/ethnicity was reduced to two categories: White and other. The occupational category
was reduced to nine categories by combining undesignated with missing. The records missing marital status
were aggregated with those in the single category.
The four groups of possibly exposed veterans had
similar adjusted risks of "any cause" hospitalization
during the March 10, 1991, to September 30, 1995,
time period compared with not exposed veterans (table
1), and the corresponding probability plots were nearly
parallel for the 54 months of follow-up (figure 2).
However, the multivariate model (table 1) revealed
other better predictors of postwar hospitalization,
which included female sex (risk ratio (RR) = 2.63),
prewar hospitalization (RR = 1.65), enlisted pay grade
(RR = 1.50), and reserve service type (RR = 1.33).
Cox proportional hazard modeling for each of the 15
diagnostic categories over the 54 months was performed (table 2). There was no evidence that possible
nerve agent exposure was associated with postwar hospitalizations. In a similar fashion, Cox proportional
hazard modeling was also conducted for diagnoses
thought most likely to be associated with subtle, nerve
agent-induced, neurophysiologic effects (6). These
analyses revealed no increased risk for personnel possibly exposed to the vapor plume (table 3).
Additionally, when several such diagnoses were combined, there was no indication of an increase in risk
among the possibly exposed groups.
Similarly, Cox proportional hazard models using
only the notification plume data (yes or no exposure)
and only the epidemiologic plume data (yes or no
exposure) were performed for "any cause" and the 15
diagnostic category hospitalizations (data not
shown). Only one of these 32 additional models suggested an association of possible exposure and postwar morbidity. Possibly exposed veterans, as defined
by the notification plume alone, were slightly at
increased risk (RR = 1.07) of hospitalizations due to
mental disorder diagnoses (data not shown). Further
modeling for the 10 most frequent diagnoses in this
category revealed that possibly exposed veterans
were more likely to be hospitalized because of the
mental disorder diagnoses' adjustment reaction (RR =
Am J Epidemiol Vol. 150, No. 5, 1999
Gulf War Veterans and Khamisiyah 537
TABLE 1. Adjusted risk ratios for "any cause" postwar
hospttallzation among regular active-duty US Army Gulf War
veterans In Department of Defense hospitals, March 10,1991,
to September 30,1995
Descriptive
characteristic
Under plume*
Uncertain low dose vs. not exposed
Exposure 1 vs. not exposed
Exposure 2 vs. not exposed
Exposure 3 vs. not exposed
Prewar hospltalization
Yes vs. no
Reserve
Yes vs. no
Sex
Female vs. male
Age (years)
17-21 vs. 26-31
22-25 vs. 26-31
32-83 vs. 26-31
Married
Yes vs. no
Race
White vs. other
Pay grade
Enlisted vs. officer
Warrant officer vs. officer
Occupationt
Infantry, gun crews
Communications and intelligence
Health care
Other technical
Administration
Electrical and mechanical repair
Construction and related trades
Supply handlers
Undesignated and missing
Risk
ratio
95%
confidence
interval
0.95
0.96
0.93
1.02
0.93, 0.97
0.92, 0.99
0.90, 0.96
0.96, 1.08
1.65
1.61,1.69
1.33
1.27,1.40
2.63
2.57, 2.70
1.10
1.07
1.18
1.07, 1.13
1.04, 1.09
1.15, 1.20
1.07
1.04, 1.09
0.93
0.91,0.94
1.50
1.45, 1.55
1.15, 1.30
1.22
1.07
1.01
1.25
1.06
1.02
1.04
1.16
1.12
1.18
1.03,
0.97,
1.19,
0.99,
0.98,
0.99,
1.08,
1.07,
1.12,
1.12
1.06
.31
1.13
.07
.09
.24
.17
.23
• Reflects nerve agent exposure estimates: uncertain low dose;
exposure
1 (0.0-0.01256
mg-minute/m3); exposure 2
(0.01257-0.09656 mg-mlnute/m1); exposure 3 (0.09657-0.51436
mg-minute/m3).
t Referenced to electronic equipment repair personnel.
1.11) and nondependent use of drugs (RR = 1.27)
(data not shown).
DISCUSSION
The acute and long-term effects of sarin and
cyclosarin, as well as other chemical agents, have been
previously reviewed (3, 6, 16, 17). Both nerve agents
are organophosphate compounds and acutely cause
miosis, a runny nose, increased salivation, muscle contractions, headache, convulsions, and respiratory
paralysis. Expert panels have reviewed intelligence
and military data and concluded that there was no evidence that Iraq used such chemical agents during the
Gulf War (3, 6). Although the probability is arguably
low (16), the lack of evidence of acute poisoning
Am J Epidemiol
Vol. 150, No. 5, 1999
among US military personnel does not rule out the
possibility of subclinical, low-level exposure to these
agents after weapon destruction.
Data are sparse regarding the long-term effects of
low-dose sarin or cyclosarin exposure. Organophosphates cause subtle electroencephalographic changes in
some subjects, but the general health implications of
these changes are uncertain (16). Limited data from
these nerve and other organophosphates suggest that, if
chronic manifestations were associated with low-level
nerve agent exposure, they would likely be manifested
as neurophysiologic (especially sensory neuropathies)
or neuropsychologic effects (6). However, other specific
diagnostic associations cannot easily be ruled out
Hence, we sought to broadly and specifically compare
the postwar hospitalization morbidity of GuLf War veterans who were possibly exposed to the vapor plume
from the munition destructions with that of other similar Gulf War veterans.
We examined three exposure modeling strategies and
performed Cox proportional hazard models for "any
cause" and large diagnostic category postwar hospitalizations' outcomes. Consistent with other hospitalization
analyses (9), women, married personnel, persons who
were hospitalized before the war, health care personnel,
and enlisted personnel were at increased risk of hospitalization for "any cause" after the war. However, only
one of 48 models suggested an increased postwar risk.
This finding (using the notification plume exposure estimate alone) was small in magnitude and due to adjustment reaction and nondependent drug abuse diagnoses
known to be associated with combat (9, 18, 19). It is
quite probable that Army personnel possibly exposed to
the nerve agent plumes in Iraq experienced more combat
stress than many of their not exposed Army Gulf War
veteran counterparts who remained in Saudi Arabia.
The benefits (20) and limitations (21) of epidemiologic studies of hospitalization data have been previously described. These data permit the comparison of
morbidity severe enough to warrant hospital admission.
Milder morbidity could not be compared. Often Gulf
War veterans have complained of symptoms not requiring hospital admission (22, 23). However, symptom
studies are easily confounded by other factors, such as
recall bias (9, 24), psychologic disorders (25), stress
reactions (17, 26), desires for compensation (26), and
media influence (27). More severe morbidity, such as
that causing hospitalization, requires validation by a
health care delivery team and is a more objective comparison of health differences. Additionally, where symptom studies may suffer from low participation (23, 28,
29) and missing data, hospitalization data are much
more complete, because active-duty personnel have
ready access to medical care and are rarely hospitalized
538
Gray et al.
0.4 n
0.3
0.2
Not exposed (A)
Uncertain,
low dose (B)
0.1-
Exposure 1 ( Q
Exposure 2 (D)
Exposure 3 (E)
00.0
Years from March 10, 1991
FIGURE 2. Probability of hospitaiization for "any cause" in US Department of Defense hospitals during the period March 10, 1991, to
September 30, 1995, by possible nerve agent plume exposure in March 1991.
TABLE 2. Adjusted exposure risk ratios for postwar hospitaiization due to diagnoses In large International Classification of
Diseases, Ninth Revision (ICD-9), categories among regular active-duty US Army Gulf War veterans In Department of Defense
hospitals, March 10,1991, to September 30,1995
Major ICD-9
diagnostic
categories
Infection and parasitic diseases
Neoplasms
Endocrine, nutritional, and metabolic diseases
Blood diseases
Mental disorders
Nervous system diseases
Circulatory system diseases
Respiratory system diseases
Digestive system diseases
Genitourinary system diseases
Complications of pregnancy§
Skin diseases
Musculoskeletal system diseases
Symptoms, signs, and ill-defined conditions
Injury and poisoning
Risk ratio*
Uncertain low
closet vs.
not exposed
Exposure 1f
vs.
not exposed
Exposure 2t
vs.
not exposed
Exposure 3t
vs.
not exposed
0.86 (0.78, 0.94)$
1.00(0.90,1.12)
0.75 (0.62, 0.92)
1.06(0.78, 1.45)
1.07(1.01, 1.15)
0.94(0.85,1.04)
0.94(0.85, 1.05)
0.92 (0.85, 0.99)
0.98(0.93,1.03)
0.93 (0.86, 1.00)
0.96(0.89, 1.02)
1.06(0.95,1.19)
0.90 (0.86, 0.94)
1.04(0.95,1.13)
0.95 (0.90, 0.99)
0.90(0.75,1.07)
1.24(1.04, 1.47)
0.75(0.52, 1.07)
0.52(0.25, 1.12)
1.00(0.88, 1.13)
0.96(0.80, 1.15)
1.12 (0.93, 1.33)
0.90(0.77, 1.04)
1.03(0.94, 1.12)
1.07(0.95,1.21)
0.80 (0.72, 0.89)
0.77 (0.60, 0.98)
0.90 (0.83, 0.98)
1.07(0.92,1.24)
1.00(0.91,1.09)
0.79 (0.67, 0.94)
1.04(0.87, 1.24)
0.63 (0.44, 0.90)
0.71 (0.38, 1.30)
0.95(0.85, 1.07)
0.85(0.72,1.02)
0.98(0.83, 1.17)
0.89(0.79,1.02)
0.99(0.92,1.08)
0.97(0.86,1.10)
0.82 (0.73, 0.91)
0.92(0.76, 1.13)
0.90 (0.83, 0.96)
1.03(0.90, 1.19)
0.98(0.90, 1.06)
1.20(0.95, 1.51)
0.74(0.52, 1.07)
0.88(0.52, 1.50)
1.33(062,2.83)
0.99(0.82,1.19)
1.04(0.79,1.36)
1.11 (0.84,1.45)
1.26(1.05,1.51)
1.01 (0.88,1.15)
0.89(0.70,1.11)
0.73 (0.57, 0.94)
0.93(0.67,1.30)
0.98(0.87,1.09)
1.08(0.85,1.36)
1.12(0.99, 1.27)
* Risk ratios were adjusted for sex, age group, prewar hospitaiization, race, service type, marital status, pay grade, and occupation using
Cox proportional hazard modeling.
t Reflects nerve agent exposure estimates: uncertain low dose; exposure 1 (0.0-0.01256 mg-minute/m*); exposure 2 (0.01257-0.09656
mg-minute/m3); exposure 3 (0.09657-0.51436 mg-minute/m1).
t Numbers In parentheses, 95% confidence interval.
§ Only women were considered.
Am J Epidemiol Vol. 150, No. 5, 1999
Gulf War Veterans and Khamisiyah
539
TABLE 3. Adjusted risk ratios for hospltallzatlon in US Department of Defense facilities with select neurologic conditions
thought likely to be associated with subtle, nerve agent-induced, neurophyslologlc effects, March 10,1991, to September 30,1995
Specific
diagnosis
ICD-9*
code
354
355
356
357
358
359
AN
Mononeuritis of upper limb
Mononeuritis of lower limb
Hereditary and idiopathic peripheral
neuropathy
Inflammatory and toxic neuropathy
Myoneural disorders
Muscular dystrophies and other
myopathies
All of the above diagnoses
Total
347
258
23
9
5
9
637
Cases
among
not
exposed
Riskratiot
Uncertain low
doset vs.
not exposed
Exposure ^t
vs.
not exposed
Exposure^
vs.
not exposed
Exposure 3t
vs.
not exposed
0.90 (0.68, 1.18)§
225 0.90(0.68,
1.18) 1.41 (0.95, 2.09) 0.80 (0.50, 1.28) 1.28 (0.66, 2.50)
169 0.95 (0.70, 1.29) 1.03 (0.60, 1.79) 1.05 (0.65, 1.71) 0.69 (0.25, 1.85)
16
6
4
D
7
421 0.88(0.72, 1.08)
1.24(0.91,1.69) 0.85(0.61,1.19) 0.94(0.54,1.63)
* ICD-9, International Classification of Diseases, Ninth Revision.
t Risk ratios were adjusted for sex, age group, prewar hospitalization, race, service type, marital status, pay grade, and occupation
using Cox proportional hazard modeling.
$ Reflects nerve agent exposure estimates: uncertain low dose; exposure 1 (0.0-0.01256 mg-minute/m3); exposure 2 (0.01257-0.09656
mg-minute/m3); exposure 3 (0.09657-0.51436 mg-minute/m3).
§ Numbers In parentheses, 95% confidence interval.
H Empty cells reflect inability to compare risk due to sparse outcome data.
outside the Department of Defense system (9, 30).
Routine periodic physical screening and frequent physical fitness testing of military personnel reinforce the
detection of severe morbidity and the likelihood of hospitalization when appropriate. Even so, it is possible that
some Gulf War veterans, fearing separation for medical
disability, may have not sought medical care for symptoms related to Gulf War exposures. It is also possible
that hospital admission and perhaps medical evaluation
may have been somehow related to geographic exposure and mask important exposure-hospitalization associations. However, such biases are unlikely, because
potential plume exposures at Khamisiyah were not recognized until 1996, after the end of the study period.
These data permit only the comparison of Gulf War
veterans who remained on active duty after the conflict
or who retired with medical benefits. Hospital data are
not available to evaluate personnel who left military
service or military medical care. However, a recent
study of the nonfederal hospitalization experience of
Gulf War veterans did not demonstrate an association
of neurologic conditions and Gulf War service (31).
Additionally, military service data from the present
study do not support the hypothesis that possibly
exposed veterans were leaving the military faster
because of illnesses. Finally, there was no difference in
cohort participation in the Department of Defense's
Gulf War veteran health registry (27) (data not shown).
Study data are also time limited in that 54 months of
study are a brief time to detect chronic disease development. More definitive evaluation of exposure and
subsequent chronic disease development would
require future studies of alternative design.
Am J Epidemiol
Vol. 150, No. 5, 1999
Our analyses have numerous unique characteristics.
They represent the first combined use of operational
data (temporal and geographic) with dispersion and
meteorologic data to estimate an exposure during the
Gulf War. These analyses represent one of the first epidemiologic studies of Gulf War veterans to use other
Gulf War veterans as a comparison group, thereby
reducing potential confounding such as that due to a
transient healthy worker selection effect (9, 30). These
data also are important in that they include reserve personnel in the analysis. This study's large populations
and numerous covariates permitted much statistical
power to detect differences in hospitalization risk due
to the estimated exposure. If plume-induced disease
manifestations meriting hospitalization were common
among possibly exposed veterans, it is very likely that
these analyses would have detected this effect.
Additionally, the adjusted risk ratio results for demographic and operational covariates were consistent
with those of other postwar hospitalization studies (9,
10), suggesting model validation.
In summary, we compared the postwar hospitalization experience of veterans with possible exposure to
low-level, subclinical nerve agent vapor concentrations
with that, of other Gulf War veterans. Our analyses
included broad outcomes (any hospitalization and diagnoses from 15 large diagnostic categories) as well as
specific diagnoses suggested by expert panels most
likely to reflect new, chronic manifestations of subclinical acute nerve agent microexposure. None of these
models suggested an increased risk among the possibly
exposed. We next repeated the "any cause" and large
diagnostic category models using each of two unique
540
Gray et al.
plume component exposure estimates and found that
only one of these 32 models suggested an increase in
risk among the possibly exposed. This slight increase
was due to adjustment reaction and nondependent drug
abuse diagnoses and consistent wim medical literature
regarding combat exposure. These data do not support
the hypothesis that Gulf War veterans who were possibly exposed to nerve agent plumes from the March
1991 munition demolitions at Khamisiyah, Iraq, experienced unusual postwar morbidity.
ACKNOWLEDGMENTS
This represents report no. 97-35, supported by the Office
of Naval Research, Arlington, Virginia, under Naval
Medical Research and Development Command reimbursable work unit 6423.
The authors thank the following individuals for their most
helpful assistance and recommendations in conducting this
research: Dr. Gary D. Gackstetter, Uniformed Services
University of Health Sciences, Bethesda, Maryland; and Jeff
Kirkpatrick and Chris Weir, Deployment Environmental
Surveillance Program, US Army Center for Health Promotion
and Preventive Medicine, Aberdeen Proving Ground,
Maryland.
A preliminary analysis of these data was presented in session 1017 at the 125th Annual Meeting of the American
Public Health Association, San Diego, California, November
10, 1997.
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Am J Epidemiol Vol. 150, No. 5, 1999