Tuberc Respir Dis.  2007 Jul;63(1):17-23. 10.4046/trd.2007.63.1.17.

Diagnostic Value of ADA Multiplied by Lymphocyte to Neutrophil Ratio in Tuberculous Pleurisy

• Jeon EJ
• Kwak HW
• Song JH
• Lee YW
• Jeong JW
• Choi JC
• Shin JW
• Kim JY
• Park IW
• Choi BW

• KMID: 1877313
• DOI: http://doi.org/10.4046/trd.2007.63.1.17

Abstract

BACKGROUND: Many diagnostic approaches for defining the definitive cause of pleurisy should be included due to the large variety of diseases resulting in pleural effusion. Although ADA is a useful diagnostic tool for making a differential diagnosis of pleural effusion, particularly for tuberculous pleural effusion, a definitive diagnostic cut-off value remains problematic in Korea. It was hypothesized that ADA multiplied by the Lymphocyte/Neutrophil ratio(L/N ratio) might be more powerful for making a differential diagnosis of pleural effusion.
METHODS
One hundred and ninety patients, who underwent thoracentesis and treatment in Chung-Ang University Hospital from January, 2005 through to February 2006, were evaluated. The clinical characteristics, radiologic data and the examination of the pleural effusion were analyzed retrospectively.
RESULTS
1. Among the 190 patients, 59 patients (31.1%) were diagnosed with tuberculous pleurisy, 45 patients(23.7%) with parapneumonic effusion, 42 patients(22.1%) with malignant effusions, 36 patients(18.9%) with transudate, and 8 patients(4.2%) with empyema. One hundred and twenty one patients were found to have an ADA activity of 1 to 39 IU/L(63.7%). Twenty-nine were found to have an ADA activity of 40 to 75 IU/L(15.3%) and 40 were found to have an ADA activity of 75 IU/L or greater(21.0%). 2. Among the patients with tuberculous pleurisy, 5(8%), 18(30%) and 36 patients(60%) had an ADA activity ranging from 1 to 39 IU/L, 40 to 75 IU/L, and 75 IU/L or greater, respectively. In those with an ADA activitiy 40 to 75 IU/L, 18 patients(62%) had tuberculous pleurisy, 9(31%) had parapneumonic effusion and empyema, and 1(3.4%) had a malignant effusion. 3. In those with an ADA activity of 40 to 75 IU/L, there was no significant difference between tuberculous pleurisy and non-tuberculous pleural effusion(tuberculous pleurisy : 61.3 +/- 9.2 IU/L, non-tuberculous pleural effusion : 53.3+/-10.5 IU/L). 4. The mean L/N ratio of those with tuberculous pleurisy was 39.1 +/- 44.6, which was significantly higher than non- tuberculous pleural effusion patients (p<0.05). The mean ADA x L/N ratio of the tuberculous pleurisy patients was 2,445.7 +/- 2,818.5, which was significantly higher than the non-tuberculous pleural effusion patients (level p<0.05).5. ROC analysis showed that the ADA x L/N ratio had a higher diagnostic value than the ADA alone in the group with an ADA between 40-75 IU/L.
CONCLUSION
The ADA multiplied by the lymphocyte-to-neutrophil ratio might provide a more definitive diagnosis of tuberculous pleurisy.

Keyword

ADA; Lymphocyte-to-Neutrophil Ratio; Tuberculous Pleurisy

MeSH Terms

Diagnosis
Diagnosis, Differential
Empyema
Exudates and Transudates
Humans
Korea
Lymphocytes*
Neutrophils*
Pleural Effusion
Pleurisy
Retrospective Studies
ROC Curve
Tuberculosis, Pleural*

Figure

• 

  Figure 1 Receiver Operating Characteristic (ROC) Analyis of ADA and ADA × L/N to diagnose tuberculous pleurisy in patients with ADA activity between 40 to 75 IU/L. Difference between areas, 0.357 ± 0.131, 95% Confidence interval, 0.101;0.613, p=0.006 ADA: adenosine deaminase; ADALP: ADA × lymphocyte-to-neutrophil ratio; ADAPL: ADA × neutrophil-to-lymphocyte ratio.

Reference

1. Berger HW, Mejia E. Tuberculous pleurisy. Chest. 1973. 63:88–92.

2. Jay SJ. Diagnostic procedures for pleural disease. Clin Chest Med. 1985. 6:33–48.

3. Piras MA, Gakis C, Budroni M, Andreoni G. Adenosine deaminase activity in pleural effusions: an aid to differential diagnosis. Br Med J. 1978. 2:1571–1572.

4. Maritz FJ, Malan C, Le Roux I. Adenosine deaminase estination in the differentiation of pleural effusions. S Afr Med J. 1982. 62:556–558.

5. Ocana I, Martinez-Vazquez JM, Segura RM, Fernandez-De-Sevilla T, Capdevila JA. Adenosine deaminase in pleural fluids: test for diagnosis of tuberculous pleural effusion. Chest. 1983. 84:51–53.

6. Banales JL, Pineda PR, Fitzgerald JM, Rubio H, Selman M, Salazar-Lezama M. Adenosine deaminase in the diagnosis of tuberculous pleural effusions: a report of 218 patients and review of the literature. Chest. 1991. 99:355–357.

7. San Jose E, Valdes L, Sarandeses A, Alvarez D, Chomon B. Diagnostic value of adenosine deaminase and lysozyme in tuberculous pleurisy. Clin Chim Acta. 1992. 209:73–81.

8. Strankinga WF, Nauta JJ, Straub JP, Stam J. Adenosine deaminase activity in tuberculous pleural effusions: a diagnostic test. Tubercle. 1987. 68:137–140.

9. Valdes L, San Jose E, Alvarez D, Sarandeses A, Pose A, Chomon B, et al. Diagnosis of tuberculous pleurisy using the biologic parameters adenosine deaminase, lysozyme, and interferon gamma. Chest. 1993. 103:458–465.

10. Pettersson T, Ojala K, Weber TH. Adenosine deaminase in the diagnosis of pleural effusions. Acta Med Scand. 1984. 215:299–304.

11. Van Keimpema AR, Slaats EH, Wagenaar JP. Adenosine deaminase activity, not diagnostic for tuberculous pleurisy. Eur J Respir Dis. 1987. 71:15–18.

12. Maartens G, Bateman ED. Tuberculous pleural effusions: increased culture yield with bedside inoculation of pleural fluid and poor diagnostic value of adenosine deaminase. Thorax. 1991. 46:96–99.

13. Antony VB, Godbey SW, Kunkel SL, Hott JW, Hartman DL, Burdick MD, et al. Recruitment of inflammatory cells to the pleural space: chemotactic cytokines, IL-8, and monocyte chemotactic peptide-1 in human pleural fluids. J Immunol. 1993. 151:7216–7223.

14. Saks AM, Posner R. Tuberculosis in HIV positive patients in South Africa: a comparative radiological study with HIV negative patients. Clin Radiol. 1992. 46:387–390.

15. Van der Weyden MB, Kelley WN. Human adenosine deaminase. Distribution and properties. J Biol Chem. 1976. 251:5448–5456.

16. Barton RW, Goldschneider I. Nucleotide-metabolizing enzymes and lymphocyte differentiation. Mol Cell Biochem. 1979. 28:135–147.

17. Shore A, Dosch HM, Gelfand EW. Role of adenosine deaminase in the early stages of T cell maturation. Clin Exp Immunol. 1981. 44:152–155.

18. Fischer D, van der Weyden MB, Snyderman R, Kelley WN. A role for adenosine deaminase in human monocyte maturation. J Clin Invest. 1976. 58:399–407.

19. Light R. Light RW, editor. Parapneumonic effusions and infections of the pleural space. Pleural disease. 1990. 2nd ed. Philadelphia: Lea & Febiger;129–149.

20. Sahn SA. State of the Art: the pleura. Am Rev Respir Dis. 1988. 138:184–234.

21. Light RW, Erozan YS, Ball WC. Cells in pleural fluid: their value in differential diagnosis. Arch Intern Med. 1973. 132:854–860.

22. Yam LT. Diagnostic significance of lymphocytes in pleural effusions. Ann Intern Med. 1967. 66:972–982.

23. Bovornkitti S, Pushpakom R, Maranetra N, Nana A, Charoenratanakul S. Adenosine deaminase and lymphocytic populations. Chest. 1991. 99:789–790.

24. Baganha MF, Pego A, Lima MA, Gaspar EV, Cordeiro AR. Serum and pleural adenosine deaminase: correlation with lymphocytic populations. Chest. 1990. 97:605–610.

25. de Wit D, Maartens G, Steyn L. A comparative study of the polymerase chain reaction and conventional procedures for the diagnosis of tuberculous pleural effusion. Tuber Lung Dis. 1992. 73:262–267.