{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T09:08:03Z","timestamp":1788944883637,"version":"build-2803163510"},"reference-count":37,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:00:00Z","timestamp":1788912000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of Oradea"},{"id":[{"id":"https:\/\/ror.org\/00wzhv093","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diseases"],"abstract":"<jats:p>Background\/Objectives: The rapid diagnosis of tuberculous pleural effusion (TPE) presents significant challenges for clinicians due to its paucibacillary nature. Routine biochemical markers may complement microbiological and molecular tests, especially in resource-limited settings. The objective of this study was to evaluate the diagnostic performance of pleural fluid adenosine deaminase (ADA), lactate dehydrogenase (LDH), total protein (TP), and the ADA\/LDH and ADA\/TP ratios for tuberculous pleural effusion, using L\u00f6wenstein\u2013Jensen culture and Xpert MTB\/RIF as microbiological reference standards Methods: We conducted a retrospective study (2016\u20132024) including 325 consecutive patients investigated for suspected TPE in a tertiary hospital. ADA, TP and LDH were measured, and additional ratio-based indices (ADA\/TP, ADA\/LDH) were calculated for 325 pleural fluid (PF) samples. L\u00f6wenstein\u2013Jensen (LJ) culture (with MPT64 confirmation) and GeneXpert MTB\/RIF (Xpert MTB\/RIF) were used as separate microbiological reference standards. Sensitivity (Se), specificity (Sp), and areas under the ROC curve (AUC) were estimated, and optimal thresholds were determined using the Youden index. Results: Among 325 pleural fluid samples, 23 (7.1%) were culture-positive. Xpert MTB\/RIF was performed in 73\/325 patients (22.5%), with Mycobacterium tuberculosis detected in 19\/73 (26.0%) tested samples. In PF, ADA provided the best performance against culture, with Se of 100%. Correlation analysis in PF showed a moderate positive association between TP and LDH (p &lt; 0.0001). Conclusions: Among routine biochemical markers, PF ADA shows high NPV. Integrating these rapid, low-cost tests alongside LJ culture and Xpert MTB\/RIF may streamline the diagnostic pathway for TPE.<\/jats:p>","DOI":"10.3390\/diseases14090327","type":"journal-article","created":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T08:05:43Z","timestamp":1788941143000},"page":"327","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Biochemical Markers in Pleural Fluid for the Diagnosis of Tuberculous Pleural Effusion: A Retrospective Study"],"prefix":"10.3390","volume":"14","author":[{"given":"Natalia","family":"Zaporojan","sequence":"first","affiliation":[{"name":"Doctoral School of Biomedical Sciences, University of Oradea, University Street 1, 410087 Oradea, Romania"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7507-5072","authenticated-orcid":false,"given":"Ramona","family":"Hodi\u0219an","sequence":"additional","affiliation":[{"name":"Department of Preclinical Disciplines, Faculty of Medicine and Pharmacy, University of Oradea, 1 December Square 10, 410073 Oradea, Romania"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Claudiu","family":"Zaporojan","sequence":"additional","affiliation":[{"name":"Doctoral School of Biomedical Sciences, University of Oradea, University Street 1, 410087 Oradea, Romania"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"given":"Andreea Atena","family":"Zaha","sequence":"additional","affiliation":[{"name":"Doctoral School of Biomedical Sciences, University of Oradea, University Street 1, 410087 Oradea, Romania"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"}]},{"given":"Andrei Nicolae","family":"Csep","sequence":"additional","affiliation":[{"name":"Department of Psycho-Neurosciences and Recovery, Faculty of Medicine and Pharmacy, University of Oradea, 1 December Square 10, 410073 Oradea, Romania"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4021-4989","authenticated-orcid":false,"given":"Dana Carmen","family":"Zaha","sequence":"additional","affiliation":[{"name":"Doctoral School of Biomedical Sciences, University of Oradea, University Street 1, 410087 Oradea, Romania"},{"name":"Department of Preclinical Disciplines, Faculty of Medicine and Pharmacy, University of Oradea, 1 December Square 10, 410073 Oradea, Romania"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"107325","DOI":"10.1016\/j.ijid.2024.107325","article-title":"Insights from the 2024 WHO Global Tuberculosis Report\u2014More Comprehensive Action, Innovation, and Investments Required for Achieving WHO End TB Goals","volume":"150","author":"Goletti","year":"2025","journal-title":"Int. J. Infect. Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1080\/17476348.2021.1927718","article-title":"Extrapulmonary Tuberculosis","volume":"15","author":"Sharma","year":"2021","journal-title":"Expert Rev. Respir. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"47","DOI":"10.4046\/trd.2015.78.2.47","article-title":"Diagnosis and Treatment of Extrapulmonary Tuberculosis","volume":"78","author":"Lee","year":"2015","journal-title":"Tuberc. Respir. Dis."},{"key":"ref_4","unstructured":"(2025, August 01). Tuberculosis\u2014Annual Epidemiological Report for 2022. Available online: https:\/\/www.ecdc.europa.eu\/en\/publications-data\/tuberculosis-annual-epidemiological-report-2022."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"439","DOI":"10.2147\/TCRM.S347748","article-title":"Tuberculosis Surveillance in Romania Among Vulnerable Risk Groups Between 2015 and 2017","volume":"18","author":"Munteanu","year":"2022","journal-title":"Ther. Clin. Risk Manag."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Jimborean, G., Iano\u0219i, E.-S., Hu\u021banu, D., S\u00e1rk\u00f6zi, H.-K., Vultur, M.A., Ianosi, M.B., and Csipor-Fodor, A. (2024). Epidemiological Insights and Diagnostic Strategies of Extrarespiratory Tuberculosis: A Five-Year Retrospective Study in Clinic of Pneumology, T\u00e2rgu Mure\u0219. Appl. Sci., 14.","DOI":"10.3390\/app142311259"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"106607","DOI":"10.1016\/j.rmed.2021.106607","article-title":"Diagnosis of Tuberculous Pleural Effusions: A Review","volume":"188","author":"Kaul","year":"2021","journal-title":"Respir. Med."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Dodd, P.J., Osman, M., Cresswell, F.V., Stadelman, A.M., Lan, N.H., Thuong, N.T.T., Muzyamba, M., Glaser, L., Dlamini, S.S., and Seddon, J.A. (2021). The Global Burden of Tuberculous Meningitis in Adults: A Modelling Study. PLoS Glob. Public Health, 1.","DOI":"10.1371\/journal.pgph.0000069"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Aggarwal, A.N., Agarwal, R., Sehgal, I.S., and Dhooria, S. (2019). Adenosine Deaminase for Diagnosis of Tuberculous Pleural Effusion: A Systematic Review and Meta-Analysis. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0213728"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e00258-18","DOI":"10.1128\/JCM.00258-18","article-title":"Diagnostic Performance of Pleural Fluid Adenosine Deaminase for Tuberculous Pleural Effusion in a Low-Incidence Setting","volume":"56","author":"Blakiston","year":"2018","journal-title":"J. Clin. Microbiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e1111","DOI":"10.1016\/j.ijid.2013.06.003","article-title":"The Validity of Cerebrospinal Fluid Parameters for the Diagnosis of Tuberculous Meningitis","volume":"17","author":"Solari","year":"2013","journal-title":"Int. J. Infect. Dis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1753466618808660","DOI":"10.1177\/1753466618808660","article-title":"Biomarkers in the Diagnosis of Pleural Diseases: A 2018 Update","volume":"12","author":"Porcel","year":"2018","journal-title":"Ther. Adv. Respir. Dis."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Whitmore, K.V., and Gaspar, H.B. (2016). Adenosine Deaminase Deficiency\u2014More Than Just an Immunodeficiency. Front Immunol., 7.","DOI":"10.3389\/fimmu.2016.00314"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.arbres.2018.05.007","article-title":"Eficacia Diagn\u00f3stica de La Adenosina Desaminasa En L\u00edquido Pleural Para Diagnosticar Tuberculosis. Metaan\u00e1lisis de Estudios Espa\u00f1oles","volume":"55","author":"Palma","year":"2019","journal-title":"Arch. Bronconeumol."},{"key":"ref_15","first-page":"7078652","article-title":"The Value of Adenosine Deaminase 2 in the Detection of Tuberculous Pleural Effusion: A Meta-Analysis and Systematic Review","volume":"2022","author":"Zeng","year":"2022","journal-title":"Can. Respir. J."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2627","DOI":"10.21037\/jtd-23-383","article-title":"Differentiating between Tuberculous and Non-Tuberculous Pleural Effusions Using the Pleural Fluid Ratio of 10\u00d7 Adenosine Deaminase\/Lactate Dehydrogenase","volume":"15","author":"Li","year":"2023","journal-title":"J. Thorac. Dis."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Yan, Z., Wen, J.-X., Wang, H., Jiang, T.-W., Huang, J.-H., Chen, H., Yan, L., Hu, Z.-D., and Zheng, W.-Q. (2022). Diagnostic Accuracy of Pleural Fluid Lactate Dehydrogenase to Adenosine Deaminase Ratio for Tuberculous Pleural Effusion: An Analysis of Two Cohorts. BMC Pulm. Med., 22.","DOI":"10.1186\/s12890-022-02247-w"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e00614-19","DOI":"10.1128\/JCM.00614-19","article-title":"Same-Day Tools, Including Xpert Ultra and IRISA-TB, for Rapid Diagnosis of Pleural Tuberculosis: A Prospective Observational Study","volume":"57","author":"Meldau","year":"2019","journal-title":"J. Clin. Microbiol."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Aggarwal, A.N., Agarwal, R., Dhooria, S., Prasad, K.T., Sehgal, I.S., and Muthu, V. (2022). Xpert MTB\/RIF Ultra versus Xpert MTB\/RIF for Diagnosis of Tuberculous Pleural Effusion: A Systematic Review and Comparative Meta-Analysis. PLoS ONE, 17.","DOI":"10.1371\/journal.pone.0268483"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"506","DOI":"10.3923\/ajava.2014.506.512","article-title":"Identification of Mycobacterium Tuberculosis Complex by Culture and Duplex Polymerase Chain Reaction in Bovines","volume":"9","author":"Neeraja","year":"2014","journal-title":"Asian J. Anim. Vet. Adv."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Boggs, Z.H., Heysell, S., Eby, J., and Arnold, C. (2021). Adenosine Deaminase Negative Pleural Tuberculosis: A Case Report. BMC Infect. Dis., 21.","DOI":"10.1186\/s12879-021-06276-4"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Han, X.-F., Han, C., Jin, F., Wang, J.-L., and Wang, M.-S. (2021). Factors Associated with Negative Pleural Adenosine Deaminase Results in the Diagnosis of Childhood Pleural Tuberculosis. BMC Infect. Dis., 21.","DOI":"10.1186\/s12879-021-06209-1"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.1136\/thorax-2023-220304","article-title":"British Thoracic Society Guideline for Pleural Disease","volume":"78","author":"Roberts","year":"2023","journal-title":"Thorax"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Aggarwal, A.N., Agarwal, R., Dhooria, S., Prasad, K.T., Sehgal, I.S., and Muthu, V. (2021). Comparative Accuracy of Pleural Fluid Unstimulated Interferon-Gamma and Adenosine Deaminase for Diagnosing Pleural Tuberculosis: A Systematic Review and Meta-Analysis. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0253525"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"962","DOI":"10.1111\/resp.13673","article-title":"Tuberculous Pleural Effusion","volume":"24","author":"Shaw","year":"2019","journal-title":"Respirology"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Tay, T.R., and 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.","DOI":"10.1186\/1471-2334-13-546"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1111\/crj.13277","article-title":"Adenosine Deaminase Cutoff Value When Diagnosing Tuberculous Pleurisy in Patients Aged 40 Years and Older","volume":"15","author":"Satici","year":"2021","journal-title":"Clin. Respir. J."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Shimoda, M., Hirata, A., Tanaka, Y., Morimoto, K., Yoshiyama, T., Yoshimori, K., Saraya, T., Ishii, H., and Ohta, K. (2022). Characteristics of Pleural Effusion with a High Adenosine Deaminase Level: A Case\u2013Control Study. BMC Pulm. Med., 22.","DOI":"10.1186\/s12890-022-02150-4"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"282","DOI":"10.21037\/atm.2016.07.23","article-title":"Advances in the Diagnosis of Tuberculous Pleuritis","volume":"4","author":"Porcel","year":"2016","journal-title":"Ann. Transl. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"156019","DOI":"10.1016\/j.cyto.2022.156019","article-title":"Pleural Fluid Interleukins for Diagnosis of Tuberculous Pleural Effusion: A Systematic Review and Meta-Analysis","volume":"159","author":"Aggarwal","year":"2022","journal-title":"Cytokine"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Yang, W.-B., Liang, Q.-L., Ye, Z.-J., Niu, C.-M., Ma, W.-L., Xiong, X.-Z., Du, R.-H., Zhou, Q., Zhang, J.-C., and Shi, H.-Z. (2012). Cell Origins and Diagnostic Accuracy of Interleukin 27 in Pleural Effusions. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0040450"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1016\/j.rmed.2007.12.007","article-title":"Diagnostic Accuracy of Adenosine Deaminase in Tuberculous Pleurisy: A Meta-Analysis","volume":"102","author":"Liang","year":"2008","journal-title":"Respir. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"697","DOI":"10.5588\/ijtld.16.0803","article-title":"The Diagnostic Utility of Pleural Fluid Adenosine Deaminase for Tuberculosis in a Low Prevalence Area","volume":"21","author":"Sivakumar","year":"2017","journal-title":"Int. J. Tuberc. Lung Dis."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Garcia-Zamalloa, A., Vicente, D., Arnay, R., Arrospide, A., Taboada, J., Castilla-Rodr\u00edguez, I., Aguirre, U., M\u00fagica, N., Aldama, L., and Aguinagalde, B. (2021). Diagnostic Accuracy of Adenosine Deaminase for Pleural Tuberculosis in a Low Prevalence Setting: A Machine Learning Approach within a 7-Year Prospective Multi-Center Study. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0259203"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.arbres.2022.09.017","article-title":"Diagnosis and Treatment of Pleural Effusion. Recommendations of the Spanish Society of Pulmonology and Thoracic Surgery. Update 2022","volume":"59","author":"Porcel","year":"2023","journal-title":"Arch. Bronconeumol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"230143","DOI":"10.1183\/20734735.0143-2023","article-title":"The Tuberculous Pleural Effusion","volume":"19","author":"McNally","year":"2023","journal-title":"Breathe"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/s12931-023-02645-6","article-title":"Features Which Discriminate between Tuberculosis and Haematologic Malignancy as the Cause of Pleural Effusions with High Adenosine Deaminase","volume":"25","author":"Choe","year":"2024","journal-title":"Respir. Res."}],"container-title":["Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-9721\/14\/9\/327\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T08:32:30Z","timestamp":1788942750000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-9721\/14\/9\/327"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,9]]},"references-count":37,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["diseases14090327"],"URL":"https:\/\/doi.org\/10.3390\/diseases14090327","relation":{},"ISSN":["2079-9721"],"issn-type":[{"value":"2079-9721","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,9]]}}}