Division of Viral and Rickettsial Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30333 USA
Gulf War Illness Research Unit, Guy's, King's, and St Thomas's Medical School, London UK
Abstract
Background
Factor analysis is one of the most used statistical techniques to analyze the inter-relationships among symptoms reported by Gulf War veterans. The objective of this study was to apply factor analyses to binary symptom data from the UK study of Gulf War illness and the US Air Force study of Gulf War veterans, and to compare the symptom domains derived from the distinct samples.
Methods
UK veterans of the 1991 Gulf War (n = 3,454), individuals deployed to Bosnia on U.N. peacekeeping operations (n = 1,979) and Gulf War-era servicemen (n = 2,577) who were not deployed to the Gulf were surveyed in 1997–1998, and US 1991 Gulf War veterans from four Air Force units (n = 1,163) were surveyed in 1995 to collect health characteristics including symptoms. Each sample was randomly split in half for exploratory and confirmatory dichotomous factor analyses with promax oblique rotation.
Results
Four correlated factors were identified in each of the samples. Three factors (Respiratory, Mood-Cognition, Peripheral Nervous) overlapped considerably across the UK cohorts. The Gastrointestinal/Urogenital factor in the UK Gulf cohort was noticeably different from the Gastrointestinal factor identified from the Bosnia and Era cohorts. Symptoms from Gulf War UK and U.S cohorts yielded similar Gastrointestinal, Respiratory and Mood-Cognition factors, despite differences in symptom inventories between the two surveys. A Musculoskeletal factor was only elicited from the US Gulf sample.
Conclusion
Findings of this report are consistent with those from other factor analysis studies that identified similar symptom dimensions between Gulf and non-Gulf War veterans, except that the Gastrointestinal factor in Gulf veterans included other symptom types. Correlations among factors raise the question as to whether there is a general illness, even if not unique to Gulf veterans, representing the common pathway underlying the identified factors. Hierarchical factor analysis models may be useful to address this issue.
Introduction
Reports that veterans of the 1991 Gulf War were suffering from unexplained signs and symptoms started to appear as early as one year after the conflict
Several studies have applied factor analysis (or principal components analysis) to examine and compare the inter-relationships among symptoms reported by veterans
When symptoms are measured on a continuous scale normally distributed, linear factor analysis (e.g. common factor analysis
The objective of this report was to apply dichotomous factor analyses to binary symptom data from two studies, i.e., the UK study of Gulf War illness
Methods
Sources of data
The data used in this report came from two sources: the UK Study of Gulf War illness
Symptoms
In the UK study, we considered the analysis of 50 symptoms that occurred in the preceding month ("
Prevalence (%) of symptoms present in the past month across UK Study: Gulf, Bosnia and Era Cohorts
During the past month have you suffered from:
Gulf* N = 3,454
Bosnia N = 1,979
Era N = 2,577
Feeling unrefreshed after sleep
56.1
32.5
31.5
Irritability/outburst of anger
54.7
32.2†
25.5
Headaches
54.2
36.5
36.8
Fatigue
51.1
26.9
28.2
Sleeping difficulties
47.8
30.5
28.3
Forgetfulness
44.7
19.4†
16.8
Loss of concentration
39.5
16.6
15.0
Joint stiffness
39.3
20.9
22.8
Flatulence or burping
34.0
15.7†
21.0
Pain without swelling or redness in several joints
31.7
13.7
14.2
Feeling distant or cut off from others
27.9
14.4†
10.3
Avoiding doing things/situations
26.5
12.4†
10.1
Feeling jumpy/easily startled
24.7
12.9†
9.4
Chest pain
24.5
12.5
11.6
Tingling in fingers and arms
24.3
8.4†
10.9
Night sweats that soak the bed sheets
23.7
12.0†
9.5
Itchy or painful eyes
22.9
10.5
11.9
Sore throat
22.3
15.1
13.6
Distressing dreams
21.6
13.1†
9.0
Numbness or tingling in fingers or toes
21.4
8.1†
10.9
Ringing in the ears
20.5
10.8
12.5
Wheezing
20.4
10.1
9.7
Diarrhea
20.2
11.1
11.9
Unable to breathe deeply enough
20.0
9.8†
7.8
Unintended weight gain greater than 10 lbs
18.7
10.8†
8.5
Dry mouth
17.4
9.1†
6.6
Loss of interest in sex
17.3
7.1
6.7
Dizziness
17.0
7.0
7.7
Tingling in legs and arms
16.8
5.4†
6.8
Rapid heartbeat
16.4
7.5
7.6
Feeling short of breath at rest
15.3
6.5
5.5
Increased sensitivity to noise
15.0
6.3
5.6
Increased sensitivity to light
14.7
6.0
5.8
Stomach cramp
14.6
7.8
7.5
Passing urine more often
14.3
4.9†
6.3
Persistent cough
13.9
7.8†
5.8
Loss or decrease in appetite
13.3
8.5†
5.2
Intolerance to alcohol
11.9
5.0
4.0
Shaking
11.6
5.3†
3.7
Constipation
10.9
5.9
5.2
Faster breathing than normal
10.4
4.4
3.3
Feeling disoriented
10.3
3.2
3.5
Feeling feverish
8.7
3.5
3.0
Nausea
8.7
3.7
3.7
Lump in throat
8.0
3.8
3.0
Unintended weight loss greater than 10 lbs.
5.5
3.9†
2.6
Double vision
5.4
2.5
2.1
Pain on passing urine
5.2
2.3
1.9
Burning sensation in sex organs
5.0
1.3
1.6
Vomiting
4.7
3.2
2.8
In general would you say your health is (mean, standard deviation) 1=Excellent, 2=Very Good, 3=Good, 4=Fair, 5=Poor
2.8 (1.1)‡
2.3 (1.0)
2.3 (1.0)
* Gulf War veterans significantly different (p < 0.05) from Era and Bosnia veterans with respect to all symptoms
† Bosnia veterans were significantly different (p < 0.05) from Era veterans.
‡ Gulf War veterans significantly different (p < 0.05) from Bosnia and Era veterans
Prevalence (%) of symptoms reported as current health problems in the US Study of Gulf War veterans
Current health problem
Deployed to the Gulf (N = 1,163)
Sinus congestion
51.8
Headache
50.0
Fatigue
42.9
Joint pain
35.5
Difficulty remembering or concentrating
34.4
Joint stiffness
30.4
Difficulty or problems to sleep
27.6
Gas, bloating, cramps or abdominal pain
26.7
Trouble finding words
26.1
Irritability or moodiness
25.5
Skin rashes or sores
23.0
Numbness or tingling in fingers or toes
21.0
Muscle pains
19.9
Hay fever or other allergies
19.0
Depression
18.0
Diarrhea (3 or more loose bowel movements in 24 hours)
17.6
Sore throat
17.4
Cough
17.1
Anxiety
17.0
Unintended weight gain greater than 10 lbs
16.9
Shortness of breath
16.4
Chest pain
15.0
Decreased sexual interest
14.3
Dizziness
13.9
Night sweats that soak your bed sheets
13.3
Fatigue lasting 24 hours after exertion
12.6
Sores inside your nose
10.8
Swollen lymph glands in your neck, armpit, groin
10.1
Inability to tolerate milk
7.1
Episodes of disorientation
6.6
Nausea or vomiting
6.3
Wheezing
5.9
Sensitivity to chemicals
5.2
Fever
4.9
Unintended weight loss greater than 10 lbs
2.7
In general would you say your health is (mean, standard deviation) 1=Excellent, 2=Very Good, 3=Good, 4=Fair, 5=Poor
2.3 (0.9)
Statistical analyses
We used chi-squared tests to compare symptom reporting among the UK Gulf, Bosnia and non-deployed cohorts, and between the UK and US Gulf War veterans. For factor analyses, data from each UK group and US study were randomly split into 2 halves (exploratory and confirmatory samples). Exploratory dichotomous factor analyses
The confirmatory dichotomous model
Results
Description of the samples
The UK Study
Of the 3,454 veterans of the Gulf War, 93.3% were men, 75% were married or living with a partner, 92.5% had regular military status when they were deployed to the Gulf. Their average age was 34.4 years (standard deviation = 6.8). The Bosnia cohort had 1,979 veterans with average age of 29.3 years (standard deviation = 6.7) including 89.4% men, 57.5% married or living with a partner, and 91.1% with regular military status when deployed to Bosnia. The Era cohort included 2,577 veterans (92.7% men, 75.3% married or living with a partner, average age of 35.3 years (standard deviation = 7.2) and 48.8% regular military status).
The US Air Force Study
The US Gulf sample included 1,163 veterans who were 94.0% men, 74.9% married or living with a partner, with an average age of 37.9 years (standard deviation = 8.4).
Symptom distribution
The most common symptoms across all UK groups were feeling unrefreshed after sleep, irritability, headaches, fatigue, sleeping difficulties, forgetfulness, loss of concentration, joint stiffness and flatulence/burping (Table
Equivalence between symptoms in UK and US Studies*
UK Study
US Study
Irritability/outburst of anger
Irritability or moodiness
Headaches
Headaches
Fatigue
Fatigue
Sleeping difficulties
Difficulty or problems to sleep
Forgetfulness OR Loss of concentration
Difficulty remembering or concentrating
Joint stiffness
Joint stiffness
Flatulence or burping OR Stomach cramp
Gas, bloating, cramps or abdominal pain
Pain without swelling or redness in several joints
Joint pain
Chest pain
Chest pain
Night sweats that soak the bed sheets
Night sweats that soak your bed sheets
Sore throat
Sore throat
Numbness or tingling in fingers or toes
Numbness or tingling in fingers or toes
Wheezing
Wheezing
Diarrhea
Diarrhea (3 or more loose bowel movements in 24 hours)
Unintended weight gain greater than 10 lbs
Unintended weight gain greater than 10 lbs
Loss of interest in sex
Decreased sexual interest
Dizziness
Dizziness
Feeling short of breath at rest
Shortness of breath
Persistent cough
Cough
Feeling disoriented
Episodes of disorientation
Feeling feverish
Fever
Nausea OR Vomiting
Nausea or Vomiting
Unintended weight loss greater than 10 lbs.
Unintended weight loss greater than 10 lbs.
Diagnostic Criteria for Anxiety Disorder† Feeling distant or cut off from others OR Feeling jumpy/easily startled OR Unable to breathe deeply enough OR Tingling in legs and arms OR Rapid heartbeat OR Shaking OR Faster breathing than normal OR Lump in throat
Anxiety
16 could not find equivalent: Avoiding doing things/situations, Tingling in fingers and arms, Feeling unrefreshed after sleep, Itchy or painful eyes, Distressing dreams, Ringing in the ears, Dry mouth, Increased sensitivity to noise, Increased sensitivity to light, Passing urine more often, Loss or decrease in appetite, Intolerance to alcohol, Constipation, Double vision, Pain on passing urine, Burning sensation in sex organs
11 could not find equivalent: Trouble finding words, Depression, Muscle pains, Hay fever or other allergies, Fatigue lasting 24 hrs after exertion, Swollen lymph glands in your neck, armpit, groin, Inability to tolerate milk, Sensitivity to chemicals, Sinus congestion, Skin rashes or sores, Sores inside your nose
†All equivalent symptoms were significantly more prevalent among UK Gulf veterans than among UK Gulf veterans, except cough and joint pain that were less prevalent, and diarrhea, numbness or tingling in fingers or toes, shortness of breath, and weight gain that were not different in the 2 samples.
†
Dichotomous Factor Analyses
UK Gulf Cohort
The exploratory sample consisted of 1,783 persons. The scree plot suggested 1 major factor, but it was not clear how many additional factors should be investigated (data available from authors). We removed the first eigenvalue from the plot, to better determine how much each additional factor contributed to the variance, and decided to examine 2 to 5-factor solutions. Although all solutions indicated a good fit between data and model (RMSEA ≤ 0.06), the 2-, and 3- factor models yielded non-interpretable factors, and the 5-factor solution could not be confirmed. Thus, we tested the 4-factor exploratory solution in the confirmatory sample that included 1,671 subjects. We specified the number of factors to be 4, the factor variances to be 1 and the leading symptoms of the first (pain on passing urine), second (loss of concentration), third (unable to breathe deeply enough), and fourth (tingling in fingers and arms) factors. Table
Factor loadings for final 4-factor confirmatory model for symptoms reported in the UK Study-Gulf Cohort (N = 3,454), UK Study-Bosnia Cohort (N = 1,979), and UK Study-Era Cohort (N = 2,577)
During the past month have you suffered from:
Gastrointestinal/Urogenital
Gastrointestinal
Gulf
Bosnia
Era
Nausea
.78
.56
-
Vomiting
.77
-
-
Diarrhea
.76
.76
.76
Stomach cramp
.74
.73
.71
Constipation
.59
.78
.57
Flatulence or burping
.55
.63
.58
Sore throat
.53
.49
-
Feeling feverish
.52
.51
-
Dry mouth
.48
.49
-
Pain on passing urine
.53
-
-
Burning sensation in sex organs
.48
-
-
Headaches
.48
-
-
Loss or decrease in appetite
.47
-
-
Unintended weight loss greater than 10 lbs.
.43
-
-
Respiratory
Gulf
Bosnia
Era
Unable to breathe deeply enough
.89
.87
.89
Wheezing
.77
.75
.91
Feeling short of breath at rest
.73
.89
.81
Faster breathing than normal
.66
.63
.66
Persistent cough
.50
-
.48
Chest pain
-
.61
-
Rapid heartbeat
-
.51
-
Mood-Cognition
Gulf
Bosnia
Era
Loss of concentration
.93
.70
.79
Forgetfulness
.87
.66
.71
Feeling distant or cut off from others
.77
.80
.86
Avoiding doing things/situations
.74
.67
.75
Irritability/outburst of anger
.64
.71
.74
Feeling unrefreshed after sleep
.62
.68
-
Feeling jumpy/easily startled
.60
.73
.79
Sleeping difficulties
.57
.66
.56
Feeling disoriented
.57
.64
.70
Fatigue
.57
.53
-
Increased sensitivity to noise
.56
.58
.63
Distressing dreams
.52
.66
.78
Loss of interest in sex
.51
.54
.65
Intolerance to alcohol
-
.50
.46
Shaking
-
.45
.55
Night sweats
-
-
.52
Peripheral Nervous
Gulf
Bosnia
Era
Tingling in fingers and arms
.97
.99
.91
Numbness or tingling in fingers or toes
.84
.89
.90
Tingling in legs and arms
.77
.80
.89
- Blank entries in the table indicate that symptom had a factor loading < .40 during the exploratory phase and was not considered in the confirmatory model
UK Bosnia Cohort
The Bosnia Cohort exploratory sample included 1,008 subjects and the confirmatory included 971. A 4-factor solution with 32 symptoms was confirmed (goodness-of-fit measures: CFI = 0.961; TLI = 0.986; RMSEA = 0.029; SRMR = 0.045; factor correlations range = 0.44–0.63). Results for all 1,979 subjects are displayed in Table
Although the constructs identified from symptoms reported by Bosnia veterans were similar to those confirmed in the Gulf War veteran sample, we were unable to confirm the Gulf War confirmatory 4-factor solution in the Bosnia sample. Some symptoms from the Gulf cohort Gastrointestinal/Urogenital factor loaded in several Bosnia cohort factors, yielding a structure that was difficult to interpret.
UK Era Cohort
There were 1,325 observations in the exploratory and 1,252 in the confirmatory samples. A confirmatory 4-factor model with 26 symptoms and all 2,577 subjects is displayed in Table
Comparing the factor structures of the UK Gulf Cohort with Bosnia and Era Cohorts
The overlap of symptom composition across samples was remarkable for the Respiratory, Peripheral Nervous and Mood-Cognition factors (Table
US Air Force Gulf War Study
The exploratory sample consisted of 590 subjects and the confirmatory included 573. A 4-factor solution with 26 symptoms was confirmed and results for all 1,163 subjects are displayed in Table
Factor loadings for final confirmatory 4-factor model for symptoms reported in the US Study of Gulf War veterans (N = 1,163)
Current health problem
Factor 1
Factor 2
Factor 3
Factor 4
Gastrointestinal/ Respiratory
Allergies
Mood-Cognition
Musculoskeletal
Nausea or vomiting
.80
.00
.00
.00
Diarrhea (3 or more loose bowel movements in 24 hours)
.73
.06
-.04
.02
Gas, bloating, cramps or abdominal pain
.71
-.01
.06
.02
Skin rashes or sores
.56
-.10
-.05
.20
Sore throat
.54
.36
-.17
.14
Fever
.53
.18
.06
.17
Swollen lymph nodes in your neck, armpit, groin
.52
.23
-.14
.08
Night sweats that soak your bed sheets
.52
-.07
.10
.16
Wheezing
.52
. 22
-.10
.18
Cough
.47
.36
-.16
.13
Chest pain
.44
.16
.13
.12
Sinus congestion
.00
.90
.00
.00
Hay fever or other allergies
-.04
.60
.05
-.09
Difficulty remembering or concentrating
.00
.00
.87
.00
Depression
-.07
.17
.77
-.08
Trouble finding words
. 04
.05
.75
-.11
Irritability or moodiness
-.11
.28
.74
.00
Anxiety
-.05
.29
.73
-.12
Episodes of disorientation
.25
-.01
.66
-.03
Fatigue lasting 24 hours after exertion
.15
.05
.48
.28
Fatigue
.15
.13
.48
.24
Decreased sexual interest
.15
.00
.45
.07
Dizziness
.36
.04
.40
.01
Joint pain
.00
.00
.00
.96
Joint stiffness
.06
.01
.08
.80
Muscle pain
.07
.03
.15
.65
Goodness-of-fit measures: CFI = .970; TLI = .988; RMSEA = .029; SRMR = .043
Inter-factor correlations: Factor1, Factor2 = .474; Factor1, Factor3 = .670; Factor1, Factor4 = .525; Factor2, Factor3 = .388;
Factor2, Factor4 = .488; Factor3, Factor4 = .511
Comparing the factor structures of the UK Gulf Cohort with US Gulf Cohort
We could not directly compare the factor structures because the symptom inventories were so different. For example, 3 peripheral nervous symptoms were asked from the UK veterans (Tingling in fingers and arms, Numbness or tingling in fingers or toes, Tingling in legs and arms) while the US study included only 1 (numbness or tingling in fingers or toes). Thus, a separate factor could not be derived from the US study. Nevertheless, both UK and US data yielded similar constructs, namely a mixed gastrointestinal factor, a mood-cognition factor, and a respiratory-related factor. The main difference was that the musculoskeletal construct could not be confirmed in the UK Gulf cohort, and it represented a separate factor in the US sample (Tables
Discussion
The objective of this report was to identify and compare syndromes among 4 samples collected from UK
We identified and confirmed at most 4 correlated factors in each of the samples. Three of the four constructs (Respiratory, Mood-Cognition, Peripheral Nervous) overlapped considerably across the UK cohorts. These factors were identical to those derived in a linear factor analysis of these data
In addition, despite differences in study designs, methods of data collection, military populations and symptom inventories between the UK and US studies of Gulf War veterans, Gastrointestinal, Respiratory and Mood-cognition factors were identified in both UK and US studies. Of note, although joint pain and joint stiffness were measured in both UK and US samples of Gulf War veterans, a Musculoskeletal factor was only elicited as a separate factor from the US data.
In general, findings of this report were consistent with those from other studies that used factor analysis of symptoms to compare symptom patterns between Gulf and non-Gulf War veterans
In this report, we encountered difficulties confirming the dichotomous factor structures, or reproducing a factor structure in another sample, because many symptoms were rare, which created numerical problems. On the other hand, failure to reproduce factor structures across samples may also be due to different symptom distributions in the samples being considered, as was the case of the UK Gulf and Bosnia cohorts. We also acknowledge the difficulties in analyzing self-report symptom data. However, since the UK and US studies were independent of the military and confidential, we do not believe there was a reason form service personnel to exaggerate symptoms in order to gain compensation or eligibility for veterans.
Finally, it must be noted that, in each of the UK or US cohorts, factors were moderately or highly correlated. Correlated factors are complex to interpret because it is difficult to separate their independent effects
In conclusion, considerable progress has been made in defining medically unexplained illness associated with deployment to the 1991 Gulf War. Our results from independent studies conducted in the UK and US confirmed occurrence of an illness comprised of 4 correlated groups of symptoms (factors) in deployed military personnel from both countries. Similar illness occurred in troops who did not participate in the Gulf War (albeit at lower rates and with different specific characteristics), so we believe that this pattern of symptoms is not unique to Gulf War service nor does it represent a unique illness or "Gulf War syndrome." In fact, similar illnesses to those affecting Gulf War veterans have been noted among veterans of US Civil War
Competing Interests
None declared.
Authors' Contributions
RN conceived of this analysis was responsible for its execution and had primary responsibility for the manuscript; KI was instrumental in the conception and design of the UK veterans' study and had primary responsibility for its analysis; collaborated in analysis and interpretation of the present data and writing the manuscript; SW was Principal Investigator for the UK veterans' study, Collaborated in the concept of the present study and collaborated in analysis, interpretation and the manuscript; CU collaborated in the UK veteran's study and collaborated in analysis and interpretation of data and drafting the manuscript for this study; LH collaborated in the UK veteran's study and collaborated in analysis and interpretation of data and drafting the manuscript for this study; WCR was Principal Investigator of the US Gulf War study, conceived the idea for the present study, served as Principal Investigator for the present study and collaborated in all aspects of data interpretation and writing the manuscript.