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JECET; September-November, 2012; Vol.1, No.3, 286-294. 286 E-ISSN: 2278–179X

JECET; September-November, 2012; Vol.1.No.3, 286-294.

Journal of Environmental Science, Computer Science and Engineering & Technology

Available online at www.jecet.org Environmental Science

Research Article

Symptom Cluster Associated to Immunological Biomarkers of Occupational Workers: An Exploratory Study

T. Tunsaringkarn*,K. Zapuang and A. Rungsiyothin

College of Public Health Sciences, Chulalongkorn University, Bangkok 10330, Thailand Received: 25 August 2012; Revised: 24 September 2012; Accepted: 26 September 2012

Abstract: The symptom cluster study is interesting in immunological field in attempt to improve the quality of life of occupational workers who have risk of volatile organic compounds (VOCs) exposure. The aims of this study were determined the prevalence of symptoms and the association between symptom clusters and immunological biomarkers of occupational workers. One hundred and five gasoline station workers were included for interview and blood collection for baseline physical laboratory examinations. The results showed that most prevalence of symptoms were headache, dizziness and fatigue at 35.2%, 27.6% and 20.0% respectively which they showed strong correlation (Pearson’s correlation, p<0.001). Most of immunological parameters were higher than normal range except platelets. Headache was significantly associated with lymphocytes, monocytes and platelets (Logistic regression analysis, p<0.05, p=0.05 and p<0.001 respectively) while dizziness was significantly associated with lymphocytes, monocytes and eosinophils at p<0.05. But fatigue did not show association with any immunological biomarkers of gasoline workers. Conclusions, the symptom cluster of headache, dizziness and fatigue was associated with immune system. Platelets should be specifically associated with headache symptom while eosinophils may be specifically associated with dizziness.

Keyword: symptom clusters, immunological biomarkers, gasoline workers.

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JECET; September-November, 2012; Vol.1, No.3, 286-294. 287 INTRODUCTION

Volatile Organic Compounds (VOCs) is a major occupational and environmental health concern.

Inhalation of VOCs can cause a wide range of adverse health effects, ranging from simple irritation to systemic diseases. It has been shown that VOCs could also influence immune system such as increasing exposure to VOCs measured as toluene was associated with significant CD4 T lymphocytopenia1, and IgG and IgA counts were significantly lower for the people in the area with higher VOCs than for people in the area with lower VOCs2. The risk assessment of VOCs and the toxicological assessment model remains limited, particularly for studying the effect of VOCs on immune system. White blood cells are cells of the immune system involved in defending the body against both infectious disease and foreign materials3. Most gasoline workers with VOCs exposure have a variety of symptoms which are a major problem of interfering quality of life4. Because the management of these symptoms are often of the workers responsibility themselves. There are defined a “symptom cluster” as three or more concurrent symptoms that are related to each other5-7. In addition, previous study of unrelieved symptoms can have deleterious effects on patient outcomes (e.g., functional status, mood status and quality of life) 8-11. In generally white cells are several different types but all are related to immunity and fighting infection. The number of leukocytes in the blood is often an indicator of disease which are normally between 4×109 and 1.1×1010 cells in a litre of blood. They make up approximately 1% of blood in a healthy adult12. Lymphocytes exist in both the blood and the lymphatic system. They are divided into three types of B lymphocytes (B cells), T lymphocytes (T cells) and Natural killer cells (NK cells) but the differential does not distinguish among them. All lymphocytes differentiate from common lymphoid stem cells in the bone marrow13. Neutrophils normally make up the largest number of circulating WBCs. They move into an area of damaged or infected tissue, where they defend against bacterial or fungal infection.

Eosinophils primarily deal with parasitic infections. Eosinophils are also the predominant inflammatory cells in allergic reactions (hypersensitivities). The most important causes of eosinophilia include allergies such as asthma, hay fever, and hives; and also parasitic infections. Basophils usually make up the fewest number of circulating WBCs and are thought to be chiefly involved in allergic and antigen response by releasing the chemical histamine causing vasodilation. Monocytes similar to neutrophils, move to an area of infection and engulf and destroy bacteria which are much longer lived as they have an additional role.

They are associated more often with chronic rather than acute infections. They are also involved in tissue repair and other functions involving the immune system14. Platelets are produced in the bone marrow, the same as the red cells and most of the white blood cells15. Platelets are the most numerous cell of the blood. The normal platelet count is 150 x 109 – 350 x 109 cells per liter of blood, but since platelets are so small, they make up just a tiny fraction of the blood volume. The principal function of platelets is to prevent bleeding. Platelets are also called thrombocytes. This study aimed to determine the prevalence of symptoms and the association between symptom cluster and immunological biomarkers of gasoline station workers. Symptoms are an indication as to the fact that a person may be suffering from a disease.

EXPERIMENTAL DESIGN AND SET UP

Population study: 105 workers were included from 11 gasoline stations in Pathumwan district, Bangkok, Thailand. They were interviewed (characteristics and symptom clusters) and collected blood samples for baseline laboratory analyses. All subjects have given informed consent before the study. The Ethical Review Committee for Research Involving Human Research Subjects, Health Science Group, Chulalongkorn University approved the study. All subjects were healthy and had worked more than 6 months.

Data collection: All workers were interviewed face to face about their characteristics of age, body mass index (BMI), work duration, cigarette smoking, alcohol drinking and symptoms of headache, dizziness,

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JECET; September-November, 2012; Vol.1, No.3, 286-294. 288 fatigue, sore throat, skin irritation, conjunctivitis, nausea and depression during their work shifts.

Sample collection and analyses: The venous blood samples were collected during the 6-8 h shift work, using plastic heparinized vacuum blood tube for analysed blood parameters [haemoglobin (Hb), total white blood cell (WBC), neutrophils (N), lymphocytes (L), monocytes (Mo), eosinophils (Eo), basophils (Ba) and platelets (Plt)], kidney function [blood urea nitrogen (BUN), creatinine (Cr)], liver function [serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT) and alkaline phosphatase (ALP)]. All blood samples were performed at Department of Microscopy, Faculty of Allied Health Sciences, Chulalongkorn University.

Statistical analysis: The descriptive statistical analysis was used of mean, median, standard error (SE), range (Min - Max) and percentage (%) for the characteristics, symptom clusters and biological parameters of gasoline workers. The logistic regression was done for association between symptom clusters and immunological biomarkers of gasoline station workers. All the statistical analyses were performed by SPSS 17.0 for Windows Program. A probability value of p<0.05 was considered as significant.

RESULTS AND DISCUSSION

There were 76.2% of men and 23.8% of women included in this study. Mean of their age, BMI and duration of work were 29.9 years, 23.2 kg/m2 and 5.3 years respectively. They were 34.3% smoking and 60.0% alcohol drinking (Table-1).

Table-1: Characteristics of gasoline workers

The most symptom clusters were headache, dizziness and fatigue at 35.2%, 27.6% and 20.0%, respectively (Table----2) which supported the other studies16-17. The Pearson’s correlation between symptoms of gasoline workers showed that headache, dizziness and fatigue were significant correlations at p<0.001 (Table-3) as symptom clusters. Headache and dizziness was stronger correlation than fatigue.

The baseline laboratory values of gasoline workers were shown in Table-4. Most of laboratory values of symptom clusters were in normal ranges except immunological biomarkers of neutrophils, lymphocytes, monocytes, eosinophils and basophils.

Parameter Mean ±±±± SE or Percentage

Median Range

Age (years) 29.9 ± 0.9 29.0 15.0 – 59.0

BMI (kg/m2) 23.2 ± 0.5 22.1 16.3 – 41.2

Duration of Work (years) 5.3 ± 0.6 3.0 0.5 – 36.0 Sex

Men n (%) 80 (76.2) - -

Women n (%) 25 (23.8) - -

Smoking n (%) 36 (34.3) - -

Alcohol Drinking n (%) 63 (60.0) - -

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JECET; September-November, 2012; Vol.1, No.3, 286-294. 289 The approximated valued of neutrophils, lymphocytes, monocytes, eosinophils and basophils in symptom clusters were higher than normal range for 7.1, 7.0, 5.2, 11.9 and 4.0 folds respectively. The headache was inversely associated with lymphocytes (p<0.05) and monocytes (p=0.05) but positively associated with platelets (p<0.001) as shown in Table-5. While dizziness was inversely associated with lymphocytes (p<0.05) and monocytes (p<0.05) but positively associated with eosinophils (p<0.05). Fatigue was not showed association with any immunological biomarkers of gasoline workers.

Table 2: Symptom prevalence of gasoline workers

Symptoms n Percentage (%)

Headache 37 35.2

Dizziness 29 27.6

Fatigue 21 20.0

Skin irritation 12 11.4

Sore throat 9 8.6

Depression 9 8.6

Conjunctivitis 8 7.6

Nausea 6 5.7

Table 3: Pearson correlation between symptoms of gasoline workers

Parameter Headache Dizziness Fatigue Skin irritation

Sore throat

Depression Conjuncti- vitis

Nausea

Headache 1 0.434

(p<0.001)

0.429 (p<0.001)

0.111 NS

0.201 (p<0.05)

0.130 NS

0.239 (p<0.05)

0.162 NS

Dizziness 1 0.349

(p<0.001)

-0.005 NS

0.114 NS

0.342 (p<0.001)

0.142 NS

0.122 NS

Fatigue 1 0.195

(p<0.05)

0.102 NS

0.187 NS

0.215 (p<0.05)

0.082 NS

Skin irritation

1 -0.110

NS

-0.003 NS

0.348 (p<0.001)

0.169 (p<0.05) Sore

throat

1 -0.094

NS

0.040 NS

0.071 NS

Depression 1 0.040

NS

0.071 NS

Conjuncti- vitis

1 0.239

(p<0.05)

Nausea 1

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JECET; September-November, 2012; Vol.1, No.3, 286-294. 290 Table-4: Baseline laboratory values of gasoline workers

Laboratory Test Normal Rangesa

Symptom Cluster Total (n=105) Headache

(n=37)

Dizziness (n=29)

Fatigue (n=21) Hemoglobin (g/dl)

Mean

Range 13.0 – 17.0

13.9 13.7 13.8 14.1

6.1 – 17.3 WBC (x109/L)

Mean

Range 5.0 – 10.0

8.5 8.2 8.4 7.8

4.7 – 13.1 Neutrophils (x109/L)

Mean

Range 4.0 – 7.5

53.8 51.5 55.5 52.9

1.0 – 78.0 Lymphocytes(x109/L)

Mean

Range 2.0 – 4.5

31.4 32.1 31.5 34.0

1.0 – 54.0 Monocytes (x109/L)

Mean

Range 0.2 – 1.0

5.3 5.2 5.3 5.7

1.0 – 10.0 Eosinophils (x109/L)

Mean

Range 0.1 – 0.6

6.5 7.6 7.4 6.0

0.0 – 26.0 Basophils (x109/L)

Mean

Range 0.0 – 0.1

0.4 0.5 0.3 0.4

0.0 – 1.0 Platelets (x109/L)

Mean

Range 50.0 – 400.0

293.1 263.7 276.2 256.6

121.0 – 527.0 BUN (mg%)

Mean

Range 6.0 – 20.0

11.8 12.0 11.9 11.8

6.0 – 20.0 Creatinine (mg%)

Mean

Range 0.5 – 1.5

1.0 0.9 0.9 1.0

0.5 – 1.8 SGOT (U/L)

Mean

Range 0.0 – 40.0

25.3 27.1 23.0 26.0

1.0 – 150.0 SGPT (U/L)

Mean

Range 0.0 – 40.0

32.1 32.5 27.2 30.9

2.0 – 165.0 ALP (U/L)

Mean

Range 26.0 – 117.0

63.9 66.8 57.3 71.8

26.0 – 298.0

aStandard reference laboratory of faculty of Allied Health Sciences, Chulalongkorn University

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JECET; September-November, 2012; Vol.1, No.3, 286-294. 291 Table-5: Associations between symptom clusters and immune system biomarkers

Symptoms Biomarkers Logistic Regression Analysisa p-value

B Std.

Error

Exp(B) 95% CI

Headache Neutrophils -0.045 0.032 1.016 0.075 to 1.058 0.458

Lymphocytes -0.085 0.034 0.919 0.859 to 0.983 0.014 Monocytes -0.331 0.170 0.718 0.514 to 1.002 0.052 Eosinophils 0.036 0.040 1.037 0.959 to 1.122 0.365 Basophils -0.136 0.445 0.872 0.365 to 2.088 0.759

Platelets 0.017 0.005 1.017 1.008 to 1.026 0.000 Dizziness Neutrophils -0.010 0.021 0.990 0.950 to 1.033 0.649 Lymphocytes -0.068 0.034 0.047 0.873 to 0.999 0.047 Monocytes -0.505 0.203 0.603 0.406 to 0.898 0.013 Eosinophils 0.084 0.042 1.087 1.002 to 1.179 0.044

Basophils 0.630 0.476 1.878 0.739 to 4.771 0.185 Platelets 0.004 0.003 1.004 0.997 to 1.011 0.250 Fatigue Neutrophils 0.036 0.027 1.037 0.984 to 1.093 0.175 Lymphocytes -0.046 0.035 0.955 0.892 to 1.022 0.184

Monocytes -0.254 0.190 0.776 0.535 to 1.125 0.181 Eosinophils 0.059 0.043 1.061 0.904 to 1.154 0.170 Basophils -0.560 0.552 0.571 0.193 to 1.687 0.311 Platelets 0.006 0.004 1.006 0.000 to 1.013 0.112

aAdjusted for age, BMI, duration of work, smoking and alcohol drinking

Headaches involve problems with the circulation in the veins, vessels and capillaries found in the scalp and in the membrane that surrounds the brain. Some problems with circulation contribute significantly to the amount, frequency and intensity of headaches that are experienced in people with high platelets18. In many cases, headaches may be the first and primary symptom experienced by a people with a high-

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JECET; September-November, 2012; Vol.1, No.3, 286-294. 292 platelet count. When the platelet count increases, it can lead to deep vein thrombosis, stroke or heart attacks. It can also cause transient ischaemic attack. Chest pain, headaches, vision changes, weakness and dizziness are also caused due to this condition19. Dizziness occurs when blood is not getting to the brain quickly enough, or if there is a deficit in the amount of oxygen in the blood. In addition, dizziness may be caused by alcohol or drug use or intoxication, allergic reactions, anxiety or panic, arrhythmias (irregular heartbeats), hypoglycemia (low blood sugar), infections or illnesses such as the cold or flu, medication side effects and mild dehydration20. It should support the association between dizziness and eosinophils in this study. Fatigue, can be described as the lack of energy and motivation (both physical and mental or a combination of the two), is a very common complaint. It may be due to medical causes (such as a thyroid disorder, heart disease or diabetes), lifestyle (such as sleep deprivation, overwork or unhealthy habits) or emotional concerns or stress (such as depression and grief)21. Although this approach to data analysis has not been used to examine symptom cluster in patients, it is widely used to examine symptom patterns in other chronically ill populations. It is possible that one symptom could influence another symptom through its relationship to a third symptom or factor. Path models allow for the examination of both direct and indirect relationships among variables such as a group of symptoms6 which regression techniques be used to examine direct and indirect effects of the variables. Most of differential white blood cells were higher than normal references but the workers were still worked at sites. Both headache and dizziness were inversely related to lymphocytes and monocytes. But headache was associated with platelets while dizziness was associated with eosinophils. So, the presence of symptom cluster showed relation to immunological biomarkers which these symptoms may be was interfered their quality of life as the previous studies1, 22-23.

CONCLUSION

The occupational workers as gasoline station workers have the symptom cluster prevalence of headache, dizziness and fatigue which may relate to immune system. Biochemical parameters are still useful as bio- monitoring which they provide assessment of the impact of health and air pollutant exposure.

ACKNOWLEDGEMENTS

This study was entirely supported by Surveillance Center on Health and Public Health Problem Surveillance Center on Health and Public Health Problem under Centenary Academic Development Project, Chulalongkorn University and the College of Public Health Sciences, Chulalongkorn University.

REFERENCES

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JECET; September-November, 2012; Vol.1, No.3, 286-294. 293 4. T. Tunsaringkarn, S. Soogarun, A. Rungsiyothin, K. Zapuang, R.S. Chapman, Health

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8. J. Glover, C. Miaskowski, S. Dibble, M.J. Dodd, Mood states of oncology outpatients:

does pain make a difference. J. Pain Symptom Manage., 1995, 10, 120–128.

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10. C. Miaskowski, K.A. Lee, Pain, fatigue, and sleep disturbances in oncology outpatients receiving radiation therapy for bone metastasis: a pilot study. J. Pain Symptom Manage., 1999. 17, 320–322.

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13. J.E. Berrington, D. Barge, A.C. Fenton, A.J. Cant, G.P. Spickett, Lymphocyte subsets in term and significantly preterm UK infants in the first year of life analysed by single platform flow cytometry, Clin. Exp. Immunol., 2005, 140 (2), 289–292.

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16. M.S. Abd El Aziz MS, E.M. Abd -El Aal, Occupational Program for Improving the Health of Gasoline Workers, J. Am. Sci., 2012, 8(7), 33-41.

17. A.M.H. Lubbad, A.I. Al-Hindi, A.A.I. Hamad, M.M. Yassin, Exposure of gasoline station workers to leaded gasoline in the Gaza Strip: Awareness and self reported symptoms. Annals of Alquds Medicine, 2010, http://annalqudsmed. files.wordpress.com /2010/05/ leaded -gasoline-manuscript-aaqm-gp2.pdf.

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5484198 _symptoms-high-platelets.html.

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20. R. Klasco, Dizziness: Causes. Better Medicine from Healthgrades, 2011, http://www.localhealth.com/article/dizziness.

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JECET; September-November, 2012; Vol.1, No.3, 286-294. 294 21. K. Australia, Fatigue explained. Better Health Channel, 2012,

http://www.betterhealth.vic.gov.au/bhcv2/bhcarticles.nsf/pages/Fatigue_explained.

22. H. Tatsumi, S. Nakaaki, K. Torii, Y. Shinagawa, N. Watanabe, Y. Murata, J. Sato, M.

Mimura, T.A. Furukawa, Neuropsychiatric symptoms predict change in quality of life of Alzheimer disease patients: a two-year follow-up study, Psychiatry Clin. Neurosci., 2009, 63(3), 374-384.

23. N. Uzma, B.S. Kumar, M.A. Hazari, Exposure to benzene induces oxidative stress, alters the immune response and expression of p53 in gasoline filling workers, Am. J. Ind. Med., 2010, 53(12), 1264-1270.

*Correspondence Author: T. Tunsaringkarn;College of Public Health Sciences, Chulalongkorn University, Institute Building 2-3, Phayathai Rd.Bangkok 10330, Thailand.

E-mail: [email protected]

References

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