Abstract
Tuberculous pleural effusion (TPE) is a common medical condition more frequently encountered in poor countries. It is the second most common form of extra-pulmonary tuberculosis. The diagnosis of TPE is problematic because the clinical features are non-specific, and most laboratory tests are not diagnostic. An accurate diagnosis requires the detection of TB bacilli in the pleural fluid or tissue sample from the pleura, which is not an easy task due to the scarcity of bacilli in the pleural fluid and the need for invasive maneuvers to get pleural tissue for histopathological, bacteriological or molecular confirmation for the TB bacilli.
Different markers in pleural fluid have been evaluated to aid in diagnosing TPE. Among those biomarkers, Adenosine deaminase (ADA) was the most studied marker. It is an enzyme predominantly produced by T-lymphocytes and catalyzes the conversion of adenosine to inosine and deoxyadenosine. It is a hallmark of active cellular immunity. A high level of ADA can be found in exudative effusion of different etiologies such as parapneumonic, tuberculous and malignant effusions.
Although there is still a debate over the diagnostic accuracy of ADA as a marker for TPE, many studies recommend its use. A correct diagnosis is crucial for the start of treatment for TPE. Therefore, it is crucial to assess the diagnostic value of adenosine deaminase in diagnosing tuberculous pleural effusion. The ADA optimal cutoff value is still under investigation.
Graphical Abstract
[1]
World Health Organization. Tuberculosis. 2022. Available from: https://www.who.int/news-room/fact-sheets/detail/tuberculosis
[2]
World Health Organization. Global tuberculosis report. 2021. Available from: https://www.who.int/publications/i/item/
[3]
Antonangelo L, Faria CS, Sales RK. Tuberculous pleural effusion: Diagnosis & management. Expert Rev Respir Med 2019; 13(8): 747-59.
[http://dx.doi.org/10.1080/17476348.2019.1637737] [PMID: 31246102]
[http://dx.doi.org/10.1080/17476348.2019.1637737] [PMID: 31246102]
[4]
Vorster MJ, Allwood BW, Diacon AH, Koegelenberg CF. Tuberculous pleural effusions: Advances and controversies. J Thorac Dis 2015; 7(6): 981-91.
[PMID: 26150911]
[PMID: 26150911]
[5]
Krenke R, Korczyński P. Use of pleural fluid levels of adenosine deaminase and interferon gamma in the diagnosis of tuberculous pleuritis. Curr Opin Pulm Med 2010; 16(4): 367-75.
[http://dx.doi.org/10.1097/MCP.0b013e32833a7154]
[http://dx.doi.org/10.1097/MCP.0b013e32833a7154]
[6]
Daniil ZD, Zintzaras E, Kiropoulos T, et al. Discrimination of exudative pleural effusions based on multiple biological parameters. Eur Respir J 2007; 30(5): 957-64.
[http://dx.doi.org/10.1183/09031936.00126306] [PMID: 17690119]
[http://dx.doi.org/10.1183/09031936.00126306] [PMID: 17690119]
[7]
Light RW. Update on tuberculous pleural effusion. Respirology 2010; 15(3): 451-8.
[http://dx.doi.org/10.1111/j.1440-1843.2010.01723.x] [PMID: 20345583]
[http://dx.doi.org/10.1111/j.1440-1843.2010.01723.x] [PMID: 20345583]
[8]
Gakis C. Adenosine deaminase (ADA) isoenzymes ADA1 and ADA2: Diagnostic and biological role. Eur Respir J 1996; 9(4): 632-3.
[http://dx.doi.org/10.1183/09031936.96.09040632] [PMID: 8726922]
[http://dx.doi.org/10.1183/09031936.96.09040632] [PMID: 8726922]
[9]
Liang QL, Shi HZ, Wang K, Qin SM, Qin XJ. Diagnostic accuracy of adenosine deaminase in tuberculous pleurisy: A meta-analysis. Respir Med 2008; 102(5): 744-54.
[http://dx.doi.org/10.1016/j.rmed.2007.12.007] [PMID: 18222681]
[http://dx.doi.org/10.1016/j.rmed.2007.12.007] [PMID: 18222681]
[11]
Zemlin AE, Burgess LJ, Carstens ME. The diagnostic utility of adenosine deaminase isoenzymes in tuberculous pleural effusions. Int J Tuberc Lung Dis 2009; 13(2): 214-20.
[PMID: 19146750]
[PMID: 19146750]
[12]
Jiménez Castro D, Díaz Nuevo G, Pérez-Rodríguez E, Light RW. Diagnostic value of adenosine deaminase in nontuberculous lymphocytic pleural effusions. Eur Respir J 2003; 21(2): 220-4.
[http://dx.doi.org/10.1183/09031936.03.00051603] [PMID: 12608433]
[http://dx.doi.org/10.1183/09031936.03.00051603] [PMID: 12608433]
[13]
Tay TR, Tee A. Factors affecting pleural fluid adenosine deaminase level and the implication on the diagnosis of tuberculous pleural effusion: A retrospective cohort study. BMC Infect Dis 2013; 13(1): 546.
[http://dx.doi.org/10.1186/1471-2334-13-546] [PMID: 24238276]
[http://dx.doi.org/10.1186/1471-2334-13-546] [PMID: 24238276]
[14]
Yeon KM, Kim CJ, Kim JS, Kim CH. Influence of age on the adenosine deaminase activity in patients with exudative pleural effusion. Tuberc Respir Dis 2002; 53(5): 530-41.
[http://dx.doi.org/10.4046/trd.2002.53.5.530]
[http://dx.doi.org/10.4046/trd.2002.53.5.530]
[15]
Valdés L, Alvarez D, San José E, et al. Value of adenosine deaminase in the diagnosis of tuberculous pleural effusions in young patients in a region of high prevalence of tuberculosis. Thorax 1995; 50(6): 600-3.
[http://dx.doi.org/10.1136/thx.50.6.600] [PMID: 7638798]
[http://dx.doi.org/10.1136/thx.50.6.600] [PMID: 7638798]
[16]
Desai A, Grolleau-Julius A, Yung R. Leukocyte function in the aging immune system. J Leukoc Biol 2010; 87(6): 1001-9.
[http://dx.doi.org/10.1189/jlb.0809542] [PMID: 20200405]
[http://dx.doi.org/10.1189/jlb.0809542] [PMID: 20200405]
[17]
Lee YCG, Rogers JT, Rodriguez RM, Miller MDKD, Light RW. Adenosine deaminase levels in nontuberculous lymphocytic pleural effusions. Chest 2001; 120(2): 356-61.
[http://dx.doi.org/10.1378/chest.120.2.356] [PMID: 11502629]
[http://dx.doi.org/10.1378/chest.120.2.356] [PMID: 11502629]
[18]
Kashiwabara K, Okamoto T, Yamane H. When pleural potassium exceeds 5.0 mEq/L, high pleural adenosine deaminase levels do not necessarily indicate tuberculous pleuritis. Respirology 2012; 17(1): 92-8.
[http://dx.doi.org/10.1111/j.1440-1843.2011.02053.x] [PMID: 21883680]
[http://dx.doi.org/10.1111/j.1440-1843.2011.02053.x] [PMID: 21883680]
[19]
Riantawan P, Chaowalit P, Wongsangiem M, Rojanaraweewong P. Diagnostic value of pleural fluid adenosine deaminase in tuberculous pleuritis with reference to HIV coinfection and a Bayesian analysis. Chest 1999; 116(1): 97-103.
[http://dx.doi.org/10.1378/chest.116.1.97] [PMID: 10424510]
[http://dx.doi.org/10.1378/chest.116.1.97] [PMID: 10424510]
[20]
Baba K, Hoosen AA, Langeland N, Dyrhol-Riise A. Adenosine deaminase activity is a sensitive marker for the diagnosis of tuberculouspleuritis in patients with very low CD4 counts. PloseOne 2008; 3: 1-5.
[21]
Han XF, Han C, Jin F, Wang JL, Wang MS. Factors associated with negative pleural adenosine deaminase results in the diagnosis of childhood pleural tuberculosis. BMC Infect Dis 2021; 21(1): 473.
[http://dx.doi.org/10.1186/s12879-021-06209-1] [PMID: 34034670]
[http://dx.doi.org/10.1186/s12879-021-06209-1] [PMID: 34034670]
[22]
Spencer N, Hopkinson DA, Harris H. Adenosine deaminase polymorphism in man. Ann Hum Genet 1968; 32(1): 9-14.
[http://dx.doi.org/10.1111/j.1469-1809.1968.tb00044.x]
[http://dx.doi.org/10.1111/j.1469-1809.1968.tb00044.x]
[23]
Greco S, Girardi E, Masciangelo R, Capoccetta GB, Saltini C. Adenosine deaminase and interferon gamma measurements for the diagnosis of tuberculous pleurisy: A meta-analysis. Int J Tuberc Lung Dis 2003; 7(8): 777-86.
[PMID: 12921155]
[PMID: 12921155]
[24]
Nariman A. Diagnostic value of adenosine deaminase in tuberculous and malignant pleural effusion. Egypt J Chest Dis Tuberc 2012; 61(4): 413-7.
[http://dx.doi.org/10.1016/j.ejcdt.2012.08.004]
[http://dx.doi.org/10.1016/j.ejcdt.2012.08.004]
[25]
Aggarwal AN, Agarwal R, Sehgal IS, Dhooria S, Behera D. Meta-analysis of Indian studies evaluating adenosine deaminase for diagnosing tuberculous pleural effusion. Int J Tuberc Lung Dis 2016; 20(10): 1386-91.
[http://dx.doi.org/10.5588/ijtld.16.0298] [PMID: 27725052]
[http://dx.doi.org/10.5588/ijtld.16.0298] [PMID: 27725052]
[26]
Morisson P, Neves DD. Evaluation of adenosine deaminase in the diagnosis of pleural tuberculosis: A Brazilian meta-analysis. J Bras Pneumol 2008; 34(4): 217-24.
[http://dx.doi.org/10.1590/S1806-37132008000400006] [PMID: 18425258]
[http://dx.doi.org/10.1590/S1806-37132008000400006] [PMID: 18425258]
[27]
Gopi A, Madhavan SM, Sharma SK, Sahn SA. Diagnosis and treatment of tuberculous pleural effusion in 2006. Chest 2007; 131(3): 880-9.
[http://dx.doi.org/10.1378/chest.06-2063] [PMID: 17356108]
[http://dx.doi.org/10.1378/chest.06-2063] [PMID: 17356108]
[28]
Gui X, Xiao H. Diagnosis of tuberculosis pleurisy with adenosine deaminase (ADA): A systematic review and meta-analysis. Int J Clin Exp Med 2014; 7(10): 3126-5.
[29]
Mohamed T, Tahoun A. Evaluation of diagnostic value of adenosine deaminase in diagnosis of tuberculous pleural effusion. Med J Cairo Univ 2018; 86(1): 77-83.
[30]
Bañales 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(2): 355-7.
[http://dx.doi.org/10.1378/chest.99.2.355] [PMID: 1824928]
[http://dx.doi.org/10.1378/chest.99.2.355] [PMID: 1824928]
[31]
Maturu VN, Dhooria S, Bal A, et al. Role of medical thoracoscopy and closed-blind pleural biopsy in undiagnosed exudative pleural effusions: A single-center experience of 348 patients. J Bronchology Interv Pulmonol 2015; 22(2): 121-9.
[http://dx.doi.org/10.1097/LBR.0000000000000145] [PMID: 25887007]
[http://dx.doi.org/10.1097/LBR.0000000000000145] [PMID: 25887007]
[32]
Verma SK, Dubey AL, Singh PA, Tewerson SL, Sharma D. Adenosine deaminase (ADA) level in tubercular pleural effusion. Lung India 2008; 25(3): 109-10.
[http://dx.doi.org/10.4103/0970-2113.44121] [PMID: 20165661]
[http://dx.doi.org/10.4103/0970-2113.44121] [PMID: 20165661]
[33]
Kim HW, Kim KH, Shin AY, et al. Investigating the appropriate adenosine deaminase cutoff value for the diagnosis of tuberculous pleural effusion in a country with decreasing TB burden. Sci Rep 2022; 12(1): 7586.
[http://dx.doi.org/10.1038/s41598-022-11460-w] [PMID: 35534515]
[http://dx.doi.org/10.1038/s41598-022-11460-w] [PMID: 35534515]
[34]
Kim SB, Shin B, Lee JH, et al. Pleural fluid ADA activity in tuberculous pleurisy can be low in elderly, critically ill patients with multi-organ failure. BMC Pulm Med 2020; 20(1): 13.
[http://dx.doi.org/10.1186/s12890-020-1049-6] [PMID: 31937286]
[http://dx.doi.org/10.1186/s12890-020-1049-6] [PMID: 31937286]
[35]
Andreasyan NA, Hairapetyan HL, Sargisova YG, Mardanyan SS. ADA2 isoform of adenosine deaminase from pleural fluid. FEBS Lett 2005; 579(3): 643-7.
[http://dx.doi.org/10.1016/j.febslet.2004.11.109] [PMID: 15670822]
[http://dx.doi.org/10.1016/j.febslet.2004.11.109] [PMID: 15670822]
[36]
Shibagaki T, Hasegawa Y, Saito H, Yamori S, Shimokata K. Adenosine deaminase isozymes in tuberculous pleural effusion. J Lab Clin Med 1996; 127(4): 348-52.
[http://dx.doi.org/10.1016/S0022-2143(96)90182-1]
[http://dx.doi.org/10.1016/S0022-2143(96)90182-1]
[37]
Tianrui-Xue GC. Clinical investigation on diagnostic value of interferon-c, interleukin-12 and adenosine deaminase isoenzyme for tuberculous pleurisy. Chin Med J 2005; 118.
[38]
Zhang M, Li D, Hu ZD, Huang YL. The diagnostic utility of pleural markers for tuberculosis pleural effusion. Ann Transl Med 2020; 8(9): 607.
[http://dx.doi.org/10.21037/atm.2019.09.110] [PMID: 32566633]
[http://dx.doi.org/10.21037/atm.2019.09.110] [PMID: 32566633]
[39]
Keng LT, Shu CC, Chen JYP, et al. Evaluating pleural ADA, ADA2, IFN-γ and IGRA for diagnosing tuberculous pleurisy. J Infect 2013; 67(4): 294-302.
[http://dx.doi.org/10.1016/j.jinf.2013.05.009] [PMID: 23796864]
[http://dx.doi.org/10.1016/j.jinf.2013.05.009] [PMID: 23796864]
[40]
Xu HY, Li CY, Su SS, et al. Diagnosis of tuberculous pleurisy with combination of adenosine deaminase and interferon-γ immunospot assay in a tuberculosis-endemic population. Medicine 2017; 96(47): e8412.
[http://dx.doi.org/10.1097/MD.0000000000008412] [PMID: 29381918]
[http://dx.doi.org/10.1097/MD.0000000000008412] [PMID: 29381918]
[41]
Feng M, Sun F, Wang F, Cao G. The diagnostic effect of sequential detection of ADA screening and T-SPOT assay in pleural effusion patients. Artif Cells Nanomed Biotechnol 2019; 47(1): 3272-7.
[http://dx.doi.org/10.1080/21691401.2019.1647221] [PMID: 31379209]
[http://dx.doi.org/10.1080/21691401.2019.1647221] [PMID: 31379209]
[42]
Perlepe G, Varsamas C, Petinaki E, Antonopoulos D, Daniil Z, Gourgoulianis KI. Discrimination of exudative pleural effusions based on pleural adenosine deaminase (ADA)-C-Reactive Protein (CRP) levels, and their combination: An observational prospective study. J Pers Med 2021; 11(9): 864.
[http://dx.doi.org/10.3390/jpm11090864] [PMID: 34575641]
[http://dx.doi.org/10.3390/jpm11090864] [PMID: 34575641]
[43]
Vieira JL, Foschiera L, Ferreira ICS, Chakr VCBG. Performance of the quantification of adenosine deaminase and determination of the lactate dehydrogenase/adenosine deaminase ratio for the diagnosis of pleural tuberculosis in children and adolescents. J Bras Pneumol 2021; 47(2): e20200558.
[http://dx.doi.org/10.36416/1806-3756/e20200558] [PMID: 34008761]
[http://dx.doi.org/10.36416/1806-3756/e20200558] [PMID: 34008761]
[44]
Beukes A, Shaw JA, Diacon AH, Irusen EM, Koegelenberg CFN. The utility of pleural fluid lactate dehydrogenase to adenosine deaminase ratio in pleural tuberculosis. Respiration 2021; 100(1): 59-63.
[http://dx.doi.org/10.1159/000509555] [PMID: 33333531]
[http://dx.doi.org/10.1159/000509555] [PMID: 33333531]
[45]
Fenhua J, Daohui W, Hui L, Xiaodong X, Wen H. Diagnostic value of combined pleural interleukin-33, adenosine deaminase and peripheral blood tuberculosis T cell spot detection TB for tuberculous pleurisy. BMC Infect Dis 2021; 21(1): 861.
[http://dx.doi.org/10.1186/s12879-021-06575-w] [PMID: 34425761]
[http://dx.doi.org/10.1186/s12879-021-06575-w] [PMID: 34425761]
[46]
Yang X, Xu X, Song B, Zhou Q, Zheng Y. Misdiagnosis of primary pleural DLBCL as tuberculosis: A case report and literature review. Mol Clin Oncol 2018; 8(6): 729-32.
[http://dx.doi.org/10.3892/mco.2018.1601] [PMID: 29732155]
[http://dx.doi.org/10.3892/mco.2018.1601] [PMID: 29732155]
[47]
Lee J, Park JE, Choi SH, et al. Laboratory and radiological discrimination between tuberculous and malignant pleural effusions with high adenosine deaminase levels. Korean J Intern Med (Korean Assoc Intern Med) 2022; 37(1): 137-45.
[http://dx.doi.org/10.3904/kjim.2020.246] [PMID: 33045810]
[http://dx.doi.org/10.3904/kjim.2020.246] [PMID: 33045810]
[48]
Guisti G, Galanti B. Colorimetric method. In: Bergmeyer HU, Ed. Methods of enzymatic analysis. Weinheim: Verlag Chemie 1984; pp. 315-323.
[49]
Passing H, Bablok W. A new biometrical procedure for testing the equality of measurements from two different analytical methods. Application of linear regression procedures for method comparison studies in clinical chemistry, Part I. Clin Chem Lab Med 1983; 21(11): 709-20.
[http://dx.doi.org/10.1515/cclm.1983.21.11.709] [PMID: 6655447]
[http://dx.doi.org/10.1515/cclm.1983.21.11.709] [PMID: 6655447]
[50]
Feres MC, Martino MC, Maldijian S, Batista F, Gabriel Júnior A, Tufik S. Laboratorial validation of an automated assay for the determination of adenosine deaminase activity in pleural fluid and cerebrospinal fluid. J Bras Pneumol 2008; 34(12): 1033-9.
[http://dx.doi.org/10.1590/S1806-37132008001200008] [PMID: 19180338]
[http://dx.doi.org/10.1590/S1806-37132008001200008] [PMID: 19180338]
[51]
Technical Bulletin. Available from: https://www.sigmaaldrich.cn/deepweb/assets/sigmaaldrich/product/documents/377/155/epi023bul.pdf
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