This prospective study including 50 patients of pulmonary tuberculosis (TB) and 30 subjects as the control group was conducted to study the status of zinc as a micronutrient in pulmonary TB. There was a statistically significant fall in serum zinc levels with advanced age and disease and the levels improved after institution of antitubercular therapy. We conclude that estimation of serum zinc levels is an important tool in the diagnosis, monitoring of response to treatment in pulmonary TB, and booster of the immunological mechanisms if instituted in the therapy.
Keywords: Antitubercular therapy, pulmonary tuberculosis, zinc
|How to cite this article:
Qureshi W, Hassan G, Kadri S M, Aatif M S, Khan G Q, Ahmad M, Kak M. Status of zinc in pulmonary tuberculosis. Ann Trop Med Public Health 2010;3:45-8
|How to cite this URL:
Qureshi W, Hassan G, Kadri S M, Aatif M S, Khan G Q, Ahmad M, Kak M. Status of zinc in pulmonary tuberculosis. Ann Trop Med Public Health [serial online] 2010 [cited 2020 Oct 27];3:45-8. Available from: https://www.atmph.org/text.asp?2010/3/2/45/77179
Tuberculosis (TB) is as old as the mankind. World Health Organization (WHO) in 1993 declared it as a global emergency with respect to the reemerging menace of TB. Nearly one-third of the world’s population is infected by Mycobacterium tuberculosis, the causative organism of TB. ,,,
The American Thoracic Society has estimated that the current TB morbidity and mortality ranges from a prevalence of 10-30 million cases of active disease to an incidence of 3.7-10 million new cases and 1-2 million deaths annually. , The Centre of Disease control (CDC) predicts that TB will claim 30 million lives in the current decade.  It is again estimated that between 2002 and 2020, approximately 1000 million people will be newly infected, over 150 million will get sick and 36 million will die of TB if proper control measures are not instituted.  In India, around 4.8 million people are suffering from TB infection, of whom 2.2 million are smear positive; annual risk of infection is 1-2% and case fatality rate is 24%. 
Malnutrition is frequently observed in patients with pulmonary TB, but their nutritional status, especially of micronutrients, is still poorly documented.  Among the micronutrients, zinc is essential for human growth, development and immune function, and deficiency of this micronutrient impairs overall immune function and resistance to infection.  Several studies have demonstrated that the serum levels of zinc decrease significantly during active TB and increase following recovery after institution of antitubercular therapy (ATT) and improvement of nutritional status. ,,,,,, In fact, vitamin A and zinc supplementation improves the effect of TB medication after 2 months of ATT and results in earlier sputum smear conversion. Estimation of serum zinc levels during the course of TB could be used as a valuable tool for the clinicians to assess response to therapy or effectiveness of the ongoing ATT. , Even zinc has been documented to increase the PPD induration size in children, irrespective of nutritional status. 
The objective of the present study was to assess the status of serum zinc levels in patients of pulmonary TB in Kashmir valley of India.
|Material and Methods|
The study included 50 patients of pulmonary TB and 30 subjects of age- and sex-matched healthy people as the control group and was conducted in the department of Government Medical College, Srinagar, Kashmir, India. The patients of pulmonary TB were diagnosed on the basis of history, clinical examination, chest radiography, sputum examination, Montoux test and related laboratory parameters.
Since serum zinc levels are affected by many physiological and pathological states and drugs, subjects with these states were excluded. The exclusion criteria included the following:
- pregnant women,
- women on oral contraceptives,
- patients with
- chronic liver disease,
- nontuberculous pulmonary infections,
- extrapulmonary TB,
- indolent ulcers,
- chronic renal failure,
- myocardial infarction,
- metastatic carcinoma,
- nephrotic syndrome,
- malabsorption syndrome,
- cystic fibrosis and
- patients taking zinc as medication.
Parameters like age, sex, body weight, height, body mass index in addition to nutrition details, were recorded in the proforma of every subject of study. Patients were placed in three stages on the basis of chest radiography according to the guidelines of National Tuberculosis Association of USA , as follows.
Stage 1 (minimal)
Lesions which are of slight to moderate density but do not contain demonstrable cavitation. They may involve a small part of one or both lungs, but the total extent, regardless of distribution, should not exceed the volume of lung on one side which is present above the second chondrosternal junction and spine of the 4 th or the body of 5 th thoracic vertebra.
Stage 2 (moderately advanced)
Lesions may be present in one or both lungs, but the total extent should not exceed the following limits: disseminated lesions of slight to moderate density which may extend throughout the total volume of one lung or equivalent in both the lungs; dense and confluent lesions which are limited in extent to one-third the volume of one lung; total diameter of cavitation, if present, must be less than 4 cm.
Stage 3 (far advanced)
Lesions more extensive than “moderately advanced” – The serum zinc levels of the selected patients were estimated before, during and after the completion of ATT. Blood samples from the cases and controls were collected in fasting state via venipuncture to determine total white blood cell count, hematocrit, erythrocyte sedimentation rate (ESR), and various other biochemical parameters. All biochemical tests were carried out on the same day, in accordance with the study of Karyadi et al.
The samples for serum zinc estimation were collected in zinc free plastic syringes and the blood was allowed to clot in acid cleaned glass test tubes and stored at 16°C until collection was completed. The estimation of zinc level was done using atomic absorption spectrophotometery method and the readings were recorded in proforma.
The data were analyzed by using paired students “t” test (95% confidence limits) and chi-square tests, where appropriate. P value of less than 0.05 was considered significant.
Of the 50 cases of pulmonary TB, 23 (46%) cases were in the age group of 30-39 years, 12 (24%) cases in the age group of 40-49 years, 8 (16%) cases were of 50-65 years and 7 (14%) were of 20-29 years. The mean age was 38.4 ± 15.38 (mean ± SD) years. Among the controls, the age ranged from 20 to 55 years with mean of 36 ± 4.2 years. Twenty-one (42%) patients of pulmonary TB and 13 (43.3%) controls were females with age ranging from 23 to 51 years (mean 31 ± 2.3).The serum zinc levels revealed an inverse relationship with age in both the groups, i.e., the levels on average were observed lower with the advancement in age [Table 1]. Such a discrepancy in either of the groups was statistically highly significant. Moreover, when the groups were compared to each other, the pulmonary TB group revealed a significant fall in the zinc levels in contrast to the control group. Overall, the pulmonary TB group prior to therapy showed a significant fall (P value <0.05) in average serum zinc levels in contrast to the control group. In the study group of pulmonary TB, there was progressive fall in the serum zinc level with maximum decrease in the stage 3, which was statistically highly significant. After second month of institution of the ATT and within 2 months after completion of treatment of TB, there was again a significant increase in the serum zinc levels [Table 2]. However, no statistical significance was observed with the serum zinc levels and the sex, body weight and body mass index in either cases or controls.
|Table 1: Serum zinc levels in cases and controls before institution of antitubercular therapy in the study group, as per the age distribution
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|Table 2: Serum zinc levels in relation to stage of pulmonary tuberculosis prior to, during and after the antitubercular therapy
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The study demonstrated diminished serum zinc levels in advanced age and progressed pulmonary TB. Although the literature regarding this is sparse, similar results have been documented in previous studies. ,,,,,,, In India, Ray  and co-workers studied the plasma zinc status of 50 children with TB and compared the observations with 10 healthy and 10 malnourished children without TB at 0, 1, 2, 3 and 6 months of the ATT. The children with TB had significantly lower plasma zinc level than those without the disease, irrespective of the nutritional status. Our results are in agreement with another study from India by Taneja  who found significantly low zinc levels in cases of pulmonary TB. Similarly, Karyadi and the co-authors from Indonesia studied the nutritional status of patients with active pulmonary TB and compared the values with those of healthy controls. The authors found poor nutritional status and significantly low serum zinc levels in TB patients compared to controls. Contrary to previous studies and the present one, Ciftci et al. from Turkey, after studying 22 pulmonary TB patients and 18 healthy subjects, found an increase in the levels of zinc and decrease in Cu/Zn ration. However, the mechanism of this increase in zinc levels was not explained. The possible mechanisms for the lowered zinc levels in cases of pulmonary TB include redistribution of zinc from plasma to other tissues,  reduction of hepatic production of zinc carrier protein X 2 macroglobulin and a rise in the production of metallothionein, a protein that transports zinc to liver.  Rankovic and Drdevic  studied zinc levels in serum and pleural effusion in 104 patients and found higher zinc levels in effusion due to TB compared to that in the serum, and concluded that zinc concentration in the effusion and serum higher than 1.0 reliably indicates the presence of TB pleurisy signifying the diagnostic value of zinc in TB. Again Cuevas  and co-workers in UK studied the effect of zinc on the tuberculin response of 98 children exposed to adults with smear positive TB. They found higher proportion of children as PPD positive in the zinc supplemented group (57.1%) than in placebo group (53.1%). It is postulated that zinc supplementation could work by correcting asymptomatic or marginal zinc deficiencies or as a nonspecific booster of immunity irrespective of zinc deficiency. Overall, the studies conclude that zinc supplementation improves the effect of TB medication after 2 months of ATT, results in earlier sputum smear conversion, and serves as a booster of immunologic process, , and estimation of the zinc levels could be used as a valuable laboratory tool to assess to therapy or the effectiveness of the ongoing ATT. , We suggest that in view of the poor nutritional status in patients of pulmonary TB, zinc supplementation be made a mandatory constituent of the treatment protocol.
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Source of Support: None, Conflict of Interest: None
[Table 1], [Table 2]