ROLE OF PLEURAL FLUID ADENOSINE DEAMINASE AND LYMPHOCYTE NEUTROPHIL RATIO IN DIFFERENTIATING TUBERCULOUS PLEURAL EFFUSION FROM OTHER EXUDATIVE EFFUSIONS
DOI:
https://doi.org/10.69980/8yv9yg73Keywords:
Pleural Effusion, Exudative Pleural Effusion, Tuberculosis, Pleural Tuberculosis, EmpyemaAbstract
Tubercular Pleural Effusion is the second most common extrapulmonary tuberculosis with incidence of 3-5% in low burden areas and upto 30% in high burden areas. In general, a cutoff level of between 40 and 45 U/L is used with levels above this being indicative of tuberculosis. An ADA level above 70 U/L in a patient who does not have an empyema or rheumatoid arthritis (RA) is essentially diagnostic of tuberculous pleuritis. (1,2,5,6) High pleural fluid ADA levels have also been reported with a very small percent of other neoplasms, with Q fever, with Brucellosis and with Legionnaire's disease Lymphocyte/Neutrophil (L/N) ratio >0.75 is seen to be more likely of TB pleural effusion. (1,2)
Aim and Objectives:
- To evaluate the role of Adenosine deaminase (ADA) and Lymphocyte Neutrophil Ratio (L/N RATIO) in differentiating Tuberculous pleural effusion from other exudative pleural effusion.
- To study the demographical, clinical, radiological, and microbiological profile in various exudative pleural effusions.
- To assess Sensitivity, Specificity, PPV, NPV of pleural fluid ADA and L/N Ratio in tubercular and other exudative effusions.
Patients and Methods: An Institutional based Prospective Observational study was conducted among the patients attended the tertiary care centre in Warangal from May 2023 to April 2025.
In current study, ADA levels are seen to be elevated (> 40IUL) in all the patients with empyema (100%) followed by patients with tubercular pleural effusion (81.2%). This study demonstrates L/N ratio more than 0.75 in all patients with tubercular pleural effusion (100%) followed by patients with malignancy (95%) and parapneumonic effusion empyema (80%). Whereas, majority (71.4%) patients with empyema had L/N ratio less than 0.75.In present study a pleural fluid ADA has high sensitivity (93.1%), high Specificity (96%), high PPV (84%) and high NPV (66%). Pleural fluid L/N ratio also has high sensitivity (99%), high Specificity (100%), high PPV (89%) and high NPV (91%). Hence combined use of both these biochemical marker increases diagnostic accuracy.
References
1.Light R; Parapneumonic effusion and infection of the pleural space. In light RW editor; Pleura diseases 6th edition, Philadelphia: Lea and febiger, 1990: 129-149.
2.Seaton A, Seaton D, Leitch AG; Crofton and Doughlas’ Respiratory Diseases. 5th edition, 2008
3.3.Alfred P. Fishman, Jack A, Elide, M. D., Jay A. Fishman, M. D., Lawy R. Kaisari. In Fishman’s Pulmonary diseases and disorders, 4th ed. Mc Graw- Hill Education USA; 2008:1391-2.
4.Maskell N. BTS guidelines for the investigation of a unilateral pleural effusion in adults. Thorax- 2022-219784)
5.Behera BK, Sathish K TN. Role of adenosine deaminase and lymphocyte/neutrophil ratio in the diagnosis of tuberculous pleural effusion in patients with exudative pleural effusion. Int J Res Med Sci 2018; 6:144-8.
6.Periwal, S., Kumar, A., Maqusood, M., Nirala, P., & Gupta, V. (2022). To study the diagnostic yield of pleural fluid adenosine deaminase (ADA) combined with Lymphocytic/Neutrophil (L/N) ratio in tubercular pleural effusion at a tertiary care centre. International Journal of Health Sciences, 6(S5), 9085–9095.
7.Rajneesh Jha, Ram Kumar Mehata, Puru Koirala. Lymphocyte-Neutrophil Ratio in the Diagnosis of Tubercular Pleural Effusion in a Tertiary Care Centre: A Descriptive Cross Sectional Study. BJHS 2021;6(2)15. 1517-1521.
8.Mohan K et al. Use of Pleural Fluid Lymphocyte Neutrophil Ratio in Addition to Pleural Fluid Adenosine Deaminase for the Diagnosis of Tuberculous Pleural Effusion, Sch. J. App. Med. Sci., 2014; 2(2A):498-501.
9.Hakani L et al. The Role of Adenosine deaminase and C-reactive protein in differentiating exudative effusions, Int J Res Med Sci. 2016 Apr;4(4):975-979.
10.Cargill TN, Hassan M, Corcoran JP, et al. A systematic review of comorbidities and outcomes of adult patients with pleural infection. Eur Respir J 2019.
11.11)N. Bhatta , K. Bhandari , D.A. Bhattarai, D.R. Mishra , A.B. Acharya , N. Bhatta et al: Presence and Pattern of Comorbidities in Patients with Pleural Effusion: American Journal of Respiratory and Critical Care Medicine 2020;201:A1562
12.Chordia, Rohit Ravindra; Heda, Mamata R.; Dubey, Gaurav R.. Clinical Study of Pleural Effusion in Elderly. Indian Journal of Medical Specialties 15(2):p 114-119.
13.Tewatia P, Kaushik RM, Kaushik R, Kumar S (2020). Tobacco smoking as a risk factor for tuberculous pleural effusion: a case-control study. Global Health, Epidemiology and Genomics 5, e1, 1–8. https:// doi.org/10.1017/gheg.2020.1
14.Chiner, E.; Nomdedeu, M.; Vañes, S.; Pastor, E.; Esteban, V.; Castelló, C.; Boira, I.; Molina, V.; Arriero, J.M.; Sancho-Chust, J.N. Clinical and Epidemiological Features of Tuberculous Pleural Effusion in Alicante, Spain. J. Clin. Med. 2021
15.Sina Parsay. Diagnostic value of pleural fluid adenosine deaminase in patients with pleural tuberculosis. Jour of Clin Cas Rep, Med Image, and Heal Sci 2(1)-2022.
16.Light RW, Ball WC. Glucose and amylase in pleural effusions. JAMA 1973; 225:257-260.
17.Wu RG, Yang PC, Kuo SH, et al. “Fluid color sign”: a useful indicator for discrimination between pleural thickening and pleural effusion. J Ultrasound Med 1995; 767-9.
18.Yilmaz U, Polat G, Sahin N, et al. CT in differential diagnosis of benign and malignantpleural disease. Monaldi Arch Chest Dis 2005; 63:17-22.
19.Traill ZC, Davies RJ, Gleeson FV. Thoracic computed tomography in patients withsuspected malignant pleural effusions. Clin Radiol 2001; 56:193-196.
20.Diacon AH, Van de Wal BW, Wyser C, et al. Diagnostic tools in tuberculous pleurisy: adirect comparative study. Eur Respir J 2003; 22:589-591.
21.Chang S-C, Perng RP. The role of fiberoptic bronchoscopy in evaluating the causes ofpleural effusions. Arch Intern Med 1989;149:855-857
22.Davis S, Gardner F, Qvist G. The shape of a pleural effusion. Br J Med 1963; 1:436-437.
23.Berger HW, Mejia E. Tuberculous pleurisy. Chest 1973; 63:88-92.
24.Bueno CE, Clemente G, Castro BC, et al. Cytologic and bacteriologic analysis of fluid andpleural biopsy specimens with Cope's needle. Arch Intern Med 1990; 150:1190-1194.
25.Gupta UA, Chhabra SK, Hiraki A, et al. Diagnosing tubercular pleural effusions. Chest2005; 127:1078- 1079.
26.Ferrer J. Pleural tuberculosis. Eur Respir J 1997; 10:942–947.
27.Richter C, Perenboom R, Mtoni I, et al. Clinical features of HIV-seropositive and HIV- seronegative patients with tuberculous pleural effusion in Dar es Salaam, Tanzania. Chest 1994; 106:1471-1475.
28.Valdes L, Alvarez D, San Jose E, et al. Tuberculous pleurisy: a study of 254 patients. Arch Intern Med 1998; 158:2017-2021.
29.Jime´nez Castro D, Dı´az Nuevo G, Perez-Rodrı´guez E, et al. Diagnostic value of adenosinedeaminase in nontuberculous lymphocytic pleural effusions. Eur Respir J 2003; 21:220–224.
30.Lee YC, Rogers JT, Rodriguez RM, Miller KD, Light RW. Adenosine deaminase levels innontuberculous lymphocytic pleural effusions. Chest 2001; 120: 356–361.
31.Kataria YP, Khurshid I. Adenosine deaminase in the diagnosis of tuberculous pleuraleffusion. Chest 2001; 120:334–336.
32.Guisti G, Galanti B. Methods in enzymatic analysis. New York, NY: Academic Press, 1974;1092–1096.
33.Blake J, Berman P. Useful of adenosine deaminase determination for the diagnosis of tuberculosis. S Afr Med 1982; 62: 782–786.
34.Gakis C, Calia GM, Naitana AGV, Ortu AR, Contu A. Serum and pleural adenosine deaminase activity: correct interpretation of the findings. Chest 1991; 99: 1555–1556.
35.Riantawan P, Chaowalit P, Wongsangiem M, et al. Diagnostic value of pleural fluid adenosine deaminase in tuberculous pleuritis with reference to HIV coinfection and a Bayesian analysis. Chest 1999; 116:97–103
36.Miller KD, Barnette R, Light RW. Stability of adenosine deaminase during transportation.
37.Piras MA, Gakis C, Badroni M, et al. Adenosine deaminase activity in pleural effusion: an aid to differential diagnosis. BMJ 1978; 4:1751–1752.
38.I.B Singh: Development of Pleura. Human Embryology. 5th edition.
39.B.D. Chaurasia: Human Anatomy- Volume –ǏǏ, Thorax and Abdomen.
40.Robbins and cotrans: Text book of clinical pathology south Asia edition, fourth edition.
41.Collins J, Burwell D, Furmanski S, Lorber P, Steckel R. Minimal Detectable Pleural Effusions. Radiology. 1972;105(1):51-53.
42.Craig Blackmore C, Black W, Dallas R, Crow H. Pleural fluid volume estimation: A chest radiograph prediction rule. Academic Radiology. 1996;3(2):103-109
43.Moskowitz H, Platt R, Schachar R, Mellins H. Roentgen Visualization of Minute Pleural Effusion. Radiology. 1973;109(1):33-35
44.Herth F, Becker H. Transthoracic Ultrasound. Respiration. 2003;70(1):87-94.
45.Gilhotra R, Sehgal S, Jindal SK. Pleural biopsy and adenosine deaminase enzyme activity in effusions of different aetiologies. Lung India 1989; 3:122–124
46.Valdes L, San Jose E, Alvarez D, et al. Diagnosis of tuberculous pleurisy using the biologic parameters adenosine deaminase, lysozyme and interferon gamma. Chest 1993; 103:458–465
47.Ungerer JPJ, Oosthuizen HM, Retief JH, et al. Significance of adenosine, deaminase and its isoenzymes in tuberculous effusions. Chest 1994; 106:33–37
48.Burgess LJ, Maritz FJ, Roux IL, et al. Use of adenosine deaminase as a diagnostic tool for tuberculous pleurisy. Thorax 1995; 50:672–674
49.Valdes L, Alvarez D, San Jose E, et al. Value of adenosine deaminase in the diagnosis of tuberculous pleural effusion in young patients in a region of high prevalence of tuberculosis. Thorax 1995; 50:600–603
50.Baganha MF, Pego A, Lima MA, et al. Serum and pleural adenosine deaminase correlation with lymphocytic populations. Chest 1990; 97:605–610
51.P.C. Mathur, K.K. Tiwari, Sushma Trikha, and Dharmendra Tiwari: Diagnostic value of adenosine deaminase (ADA) activity in tubercular serositis: [Indian J Tuberc 2006; 53:92-95]
52.Ocana I, Martinez-Vazquez JM, Segura RM, et al. Adenosine deaminase in pleural fluids: test for diagnosis of tuberculous pleural effusion. Chest 1983; 84:51-53.
53.Ferrer JS, Munoz XG, Orriols RM, et al. Evolution of idiopathic pleural effusion.A prospective, long-term follow-up study. Chest 1996; 109:1508-1513.
54.Lee YC, Rogers JT, Rodriguez RM, et al. Adenosine deaminase levels in nontuberculous lymphocytic pleural effusions. Chest 2001;120:356-361.
55.Carstens ME et al. Isoenzymes of adenosine deaminase in pleural effusions: a diagnostictool. Int J Tuberculosis Lung Dis 1998 Oct; 2 (10) : 831-835.
56.Shibagaki T. et al. Adenosine deaminase isoenzymes in tuberculous pleural effusion. J Lab Clin Med 1996 Apr., 127 (4): 348-352.
57.Voight MD, Kalvaria L, Trey C, et al. Diagnostic value of ascites adenosine deaminase activity in tuberculous peritonitis. Lancet 1989; 1: 751 – 754.
58.Villena V, Lopez-Encuentros A, Echave-Sustaeta J, et al. Interferon-gamma in 388 immunocompromised and immunocompetent patients for diagnosing pleural tuberculosis. Eur Respir J 1996; 9:2635-2639.
59.Villena V, Lopez-Encuentra A, Pozo F, et al. Interferon gamma levels in pleural fluid for the diagnosis of tuberculosis. Am J Med 2003; 115:365-370.
60.Mehta AA, Gupta AS, Ahmed S, Rajesh V. Diagnostic utility of adenosine deaminase in exudative pleural effusions. Lung India.2014;31(2):142-144. doi:10.4103/0970-2113.129842
61.Bhoumik, S., Rahman, M., Ibrahim, M., Hiron, M., &Ahamad, M. Evaluation of Adenosine Deaminase (ADA) Activity for Diagnosis of Tubercular Pleural Effusion. Bangladesh Journal of Medical Biochemistry, 2014;6(2); 40-48.doi.org/10.3329
62.Shin MK, Ham HS, Lee DW, Cho YJ, JiongY Yetal. The Diagnostic Usefulness of Pleural Fluid Adenosine deaminase with Lymphocyte/Neutrophil Ratio in Tuberculous Pleural Effusion.TubercRespir Dis.2004;57(2):132-137.
63.Greco S, Girardi E, Masciangelo R, et al. Adenosine deaminase and interferon gamma measurements for the diagnosis of tuberculous pleurisy: a meta-analysis. Int J Tuberc Lung Dis 2003; 7:777-786.
64.Dan Longo, Anthony Fauci, Dennis Kasper, Stephen Hauser, J. Larry Jameson, Joseph Loscalzo, Steven Holland, Carol Langford.Harrison’s principle of Internal Medicine; 17th edition. Walker WC, Wright V. Rheumatoid pleuritis. Ann Rheum Dis 1967; 26:467-474
65.Faurschou P, Francis D, Faarup P. Thoracoscopic, histological, and clinical findings in nine cases of rheumatoid pleural effusion. Thorax 1985; 40:371-375.
66.Lillington GA, Carr DT, Mayne JG. Rheumatoid pleurisy with effusion. Arch Intern Med 1971; 128:764-768.
67.Halla JT, Schronhenloher RE, Volanakis JE. Immune complexes and other laboratory features of pleural effusions. Ann Intern Med 1980; 92:748-752.
68.Good JT Jr, King TE, Antony VB, et al. Lupus pleuritis: clinical features and pleural fluid characteristics with special reference to pleural fluid antinuclear antibodies. Chest 1983; 84:714- 718.
69.Ellner JJ. Pleural fluid and peripheral blood lymphocyte function in tuberculosis. Ann Intern Med 1978; 89:932-933.
70.Rossi GA, Balbi B, Manca F. Tuberculous pleural effusions: evidence for selective presence of PPD-specific T-lymphocytes at site of inflammation in the early phase of the infection. Am Rev Respir Dis 1987; 136:575-579
71.Bartlett JG, Gorbach SL, Thadepalli H, et al. Bacteriology of empyema. Lancet 1974; 1:338- 340.
72.Varkey B, Rose HD, Kutty CPK, et al. Empyema thoracis during a ten-year period. Arch Intern Med 1981; 141:1771-1776.
Downloads
Published
Issue
Section
License
Copyright (c) 2026 Author
This work is licensed under a Creative Commons Attribution 4.0 International License.
