Global Advanced Research Journal of Medicine and Medical Sciences (GARJMMS) ISSN: 2315-5159
October 2017 Vol. 6(10), pp. 249-256
Copyright © 2017 Global Advanced Research Journals


Full Length Research Paper 

Effects of the age and sex of an automated assay for  adenosine deaminase among a Brazilian population sample with pleural tuberculosis

Joeber Bernardo Soares de Souza1, Cyro Teixeira da Silva Junior2*, Jorge Luiz Barillo1, Patricia Siqueira Silva3, Salim Kanaan4, Elizabeth Giestal de Araujo4 and Analucia Rampazzo Xavier5

1MD, Physicians, Hospital Universitário Antônio Pedro, Fluminense Federal University, Niteroi, State of Rio de Janeiro, Brazil.
2PhD, MD, Associate Professor, Department of Clinics, School of Medicine, Fluminense Federal University, Niteroi, State of Rio de Janeiro, Brazil.
3Bsc, Biologist, Clinical Analysis Posgraduate Program, Fluminense Federal University, Niteroi, State of Rio de Janeiro, Brazil.
4PhD, MD, Associate Professor, Department of Neurobiology, Fluminense Federal University, Niteroi, State of Rio de Janeiro, Brazil.
5PhD, Associate Professor, Department of Clinical Pathology, School of Medicine, Fluminense Federal University, Niteroi, State of Rio de Janeiro, Brazil.

*Corresponding Author E-mail:

Accepted 26 October, 2017 


Adenosine deaminase (ADA) is a diagnostic biomarker assay for pleural tuberculosis (P-TB) using pleural fluid (P-ADA). Our aim was to establish a new reference value for P-ADA in consideration of the influence of age and sex on the cut-off value for pleural TB in a Brazilian population sample. Diagnostic accuracy study conducted in a Center for Teaching and Research in Pleurology at a hospital of a public university. An automated ADA assay was performed using a commercial kit. In the P-TB group (n=26), 11 patients were male (42%) and 15 patients were female (58%). The median ages of the patients in the P-TB, non-P-TB (n=95), and overall pleural effusion groups (n=121) were 46.0±18.98, 64.0±17.88, and 62.0±19.14 years, respectively.  A correlation of the P-ADA level with sex in patients with P-TB was not found to be significant (rho= -0.191, P=0.5739). However, when the P-ADA levels were dichotomized by the median age (62 years) the Spearman’s correlation was negative and non-significant in all patients (rs= -0.0061, P=0.9630), tuberculosis (rs=-0.0857, P=0.9194), and non-tuberculosis groups (rs= -0.2789, P=0.0813). For the diagnosis of pleural TB, the best cut-off value established according to the ROC curve for P-ADA was ≥31.5 IU/L (AUC=88.2, P=0.0001). Age and sex did not have a significant influence on the clinical decision limit for the diagnosis of TB pleural effusion using the ADA automated assay. For the diagnosis of pleural TB, the cut-off value established for P-ADA was ≥31.5 IU/L.

Keywords: Adenosine deaminase, reference values, pleural effusion, pleural tuberculosis, tuberculous pleurisy



Abrao FC,  Abreu IRLB, Miyaki DH,  Busico MAM,  Younes RN (2014).  Role of adenosine deaminase and the influence of age on the diagnosis of pleural tuberculosis. Int. J. Tuberc. Lung Dis. 18:1363-1369.

Behrsin RF, Silva Junior CT, Barillo JL, Souza JBS, Araujo EG (2015).  Combined evaluation of adenosine deaminase level and histopathological findings from pleural biopsy with Cope’s needle for the diagnosis of tuberculous pleurisy.  Int. J. Clin. Exp. Pathol. 8(6):7239-7246.

Bossuyt PM, Reitsma JB, Bruns DE, Gatsonis CA, Glasziou PP, Irwing JG, et al (2015). STARD 2015: An updated list of essential items for reporting diagnostic accuracy studies. Clin. Chem.  61(12):1446-5142.

Boyd JC (1997). Mathematical tools for demonstrating the clinical usefulness of biochemical markers. Scand. J. Clin. Lab. Invest. Suppl. 227:46-63.

Boyd JC (2010). Defining laboratory reference values and decision limits: populations, intervals, and interpretations. Asian J.  Androl. 12 (1):83-90.

Ceriotti F (2007). Prerequisites for use of common reference intervals. Clin. Biochem. Rev. 28:115-121.

Delacour H, Sauvanet C, Ceppa F, Burnat P (2010). Analytical performance of the Diazyme assay on the Cobas 6000 system. Clin. Biochem. 43 (18):1468-1471.

DeLong ERDeLong DMClarke-Pearson DL (1988). Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. Biometrics. 44 (3):837-845.

Eusebi P (2013). Diagnostic accuracy measures. Cerebrovasc. Dis. 36:267–272.

Feres MC, Martino MC, Maldijian S, Batista F, Gabriel Junior A, Tufik S (2008).  Laboratorial validation of an automated assay for the determination of adenosine deaminase activity in pleural fluid and cerebrospinal fluid. J. Bras. Pneumol. 34(12):1033-1039.

Friedrich SO, Groote-Bidlingmaier F, Diacon AH (2011). Xpert MTB/RIF assay for diagnosis of pleural tuberculosis. J. Clin. Microbiol. 49 (12):4341-4342.

Gasparini S, Bonifazi M (2017). Curr. Opin. Pum. Med. 23(3):269-274.

Giusti G,  Galanti B (1984).  Colorimetric method. In: Bergmeyer HU, editor. Methods of enzymatic analysis, 1 st ed.  Weinheim: Verlag Chemie. pp. 315-323.

Grubbs FE (1969).  Procedures for detecting outlying observations in samples. Technometrics. 11:1-21.

Haridas N, Suraj KP, Rajagopal TP, James PT, Chetambath R (2014). Medical thoracoscopy  vs.  closed pleural biopsy in pleural effusions: A randomizes controlled study. J. Clin. Diagn. Res. 8(5):MC01-MC04.

Harris EK, Boyd JC (1990). On dividing reference data into subgroups to produce separate reference ranges. Clin. Chem. 36 (2):265-270.

Henny J (2009). The IFCC recommendations for determining reference intervals: strengths and limitations. J. Lab. Med. 33 (2):45-51.

Henny J, Vassault A, Boursier G, Vukasovic I, Mesko Brguljan P, Lohmander M, et al (2016). Recommendation for the review of biological reference intervals in medical laboratories. Clin. Chem. Lab. Med. 54(12):1893-1900.

Hooper C, Gary Lee YC, Maskell N (2010). Investigation of a unilateral pleural effusion in adults: British Thoracic Society  pleural disease guideline 2010. Thorax. 65:ii4-ii17.

 Horowitz GL, Altaie S, Boyd JC, Ceriotti F, Garg U, Horn P, et al (2010). Defining, establishing, and verifying reference intervals in the clinical laboratory. Approved guideline. Clinical and Laboratory Standard Institute. 28(30):C28-A3c.

Kapisyzi P, Argjiri D, Aliko A, Beli J, Vakeflliu Y, Kore R, et al (2011). The use of different cutoff values of ADA liquid level in diagnosis of tuberculous pleurisy in countries with different incidence of tuberculosis. Chest. 140 (4):703A-703A.

Kawamatawong T, Panompong K, Kiatboonsri S, Khupulsup K (2008). The appropriate cutoff level of pleural fluid adenosine deaminase activity by Diazyme commercial kit for diagnosis pleural tuberculosis in Ramathibodi Hospital. Chest. 55001A-55001A.

Klimiuk J, Krenke R, Safianowska A, et al (2015). Diagnostic performance of different pleural fluid biomarkers in tuberculous pleurisy. Adv. Exp. Med. Biol. 852: 21-30.

Kumar R, Indrayan A (2011). Receiver operating characteristic (ROC) curve for medical researchers. Indian Ped. 48:277-287.

Lahti A, Petersen PH, Boyd JC, Rustad P, Laake P, Solberg HE (2004). Partitioning of nongaussian-distributed biochemical reference data into subgroups. Clin. Chem. 50 (5):891-900.

Lee SJ, Kim HS, Lee SH, Lee TW, Lee HR, Cho YJ, et al (2014). Factors influencing pleural adenosine deaminase level in patients with tuberculous pleurisy. Am. J. Med. Sci. 348 (5):362-365.

Maranhão BH, Silva Junior CT, Chibante MAS, Cardoso GP (2010). Determination of total proteins and lactate dehydrogenase for the diagnosis of pleural transudates and exudates: redefining the classical criterion with a new statistical approach. J. Bras. Pneumol. 36:468-474. 

Mehta AA, Gupta AS, Ahmed S, Rajesh V (2014). Diagnostic utility of adenosine deaminase in exsudative pleural effusions. Lung India. 31:142-144.

Moon JW, Han CH, Kang SM, Park SM, Hwang SY, Byun Mk, et al (2005). The relationship between age and pleural fluid adenosine deaminase activity in pleural tuberculosis. Tuberc. Respir. Dis. 58:459-464.

Morisson P,  Neves DD (2008). Evaluation of adenosine deaminase in the diagnosis of pleural tuberculosis: a Brazilian meta-analysis. J. Bras. Pneumol. 34:217-224.

Mukaka MM (2012). A guide to appropriate use of correlation coefficient in medical research. Malawi  Med. 24 (3):69-71.

Okeh UM, Ogbonna LN (2013). Statistical evaluation of indicators of diagnostic test performance. Am. J. Biosci. 1(4):63-73.

Purohit M, Mustafa T (2015). Laboratory diagnosis of extra-pulmonary tuberculosis (EPTB) in resource-constrained setting: State of the art, challenges and the need. J. Clin. Diagn. Res. 9(4):1-6.

Raslich MA,  Markert RJ,  Stutes SA (2007). Selecting and interpreting diagnostic tests. Biochem. Med. 17(2):151-161.

Riantawan P,  Chaowalit P, Wongsangiem M, Rojanaraweewong P (1999). Diagnostic value of pleural fluid adenosine deaminase in tuberculous pleuritis with reference to HIV coinfection and a Bayesian analysis. Chest. 116 (1):97-103.

Riccetto AGL, Zambom MP, Pereira ICMR, Morcillo AM (2003). Influence of social-economical and nutritional factors on the evolution to complications in children hospitalized with pneumonia. Rev. Assoc. Med. Bras. 49 (2):191-195.

São José BP, Camargos PAM, Cruz Filho AAS, Corrêa RA (2014). Diagnostic accuracy of respiratory diseases in primary health units. Rev. Assoc. Med. Bras. 60(6):599-512.

Seiscento M, Vargas F, Rujula MJP, Bombarda S, Uip DE, Galesi VMN (2009). Epidemiological as­pects of pleural tuberculosis in the state of São Paulo, Brazil (1998-2005). J. Bras. Pneumol.  35:548-554.

Sikaris KA (2014).  Physiology and its importance for reference intervals. Clin. Biochem. Rev. 35(1):3–14.

Silva Junior CT (2012). Diagnostic Approach to Tuberculosis in the Pleura, Lymph Nodes, Kidneys, and Central Nervous System. Pulmão RJ. 21:32-35.  

Song D (2010). Diazyme adenosine deaminase in the diagnosis of tuberculous pleural effusion: method evaluation and clinical experiences in a New Zealand population. NZ. J. Med. Lab. Sci. 64 (1):11-13.

Sunderman Junior FW (1975). Current concepts, of “normal values”, “reference values”, and “discrimation values” in clinical chemistry. Clin. Chem. 21:1873-1877.

Tay T R, Tee A (2013). Factors affecting pleural fluid adenosine deaminase level and the implication on the diagnosis of tuberculous pleural effusion: a retrospective cohort study. BMC Infect. Dis. 13:546–553.

Thiese  MS (2014). Observational and interventional study design types; an overview. Biochem. Med. 24:199-110.

Valdes L, Alvarez D, San Jose E, Juanetey JRG, Pose A, Valle JM, et al (1995). Value of adenosine deaminase in the diagnosis of tuberculous pleural effusions in young patients in a region of high prevalence of tuberculosis. Thorax. 50:600–603.

World Health Organization (2017). Global Tuberculosis Report: WHO report; 2016. Available from: (Last accessed on 2017 May 11).

Yeon KM, Kim CJ, Kim JS, Kim CH (2002). Influence of age on the adenosine deaminase activity in patients with exudative pleural effusion. Tuberc. Respir. Dis. 53 (5):530–541.

Yildiz PBYazar EE, Gorgun D, Secik F, Cakir G (2011). Predictive role of adenosine deaminase for differential diagnosis of tuberculosis and malignant pleural effusion in Turkey. Asian Pac. J. Cancer Prev. 12(2):419-423.

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