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      Pleural IFN-γ release assay combined with biomarkers distinguished effectively tuberculosis from malignant pleural effusion

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          Abstract

          Background

          Tuberculosis (TB) remains a major public health concern on a global scale, especially in developing nations. So far, no formal guidelines are available for the diagnosis and treatment of tuberculosis pleurisy. The diagnosis of TB is worsened by the immense difficulty in differential determination of tuberculosis pleural effusion (TPE) and malignant pleural effusion (MPE). The purpose of this investigation is to assess the differential diagnostic efficiencies of the pleural IFN-γ release assay (IGRA) and widely-used biochemical parameters in the distinction analysis of TPE and MPE.

          Methods

          A cohort of 222 patients with pleural effusion was examined, comprising of 143 TPE and 58 MPE patients. The patients were examined with IGRA, and the widely-used biomarkers in the pleural effusion and peripheral blood.

          Results

          Our results show that the TPE patients have significantly higher M. tuberculosis (Mtb) antigen-specific IFN-γ responses to ESAT-6 protein and peptide pool in the blood compared to MPE patients. TPE patients were also shown to have enriched Mtb antigen-specific IFN-γ responses in pleural effusion than in peripheral blood. Among the widely-used biomarkers, the adenosine deaminase (ADA) and carcinoembryonic antigen (CEA) in pleural effusion were better biomarkers with high sensitivity and specificity to discriminate TPE and MPE. In addition, pleural IGRA could not be affected by the pleural adhesion, and the applications of the pleural IGRA together with ADA and CEA provide a promising approach for the TPE and MPE differential identification.

          Conclusions

          Our study proposes that the integration of pleural IGRA and ADA, CEA detection could add to more effective diagnosis stratagems in the discernment between TPE and MPE.

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          Most cited references20

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          Etiology of pleural effusions: analysis of more than 3,000 consecutive thoracenteses.

          To investigate the etiology of pleural effusions (PE) in adults and the accuracy of pleural fluid (PF) cytology and cultures in malignant and infectious PE, respectively.
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            Tuberculous pleural effusions: advances and controversies.

            On a global scale, tuberculosis (TB) remains one of the most frequent causes of pleural effusions. Our understanding of the pathogenesis of the disease has evolved and what was once thought to be an effusion as a result of a pure delayed hypersensitivity reaction is now believed to be the consequence of direct infection of the pleural space with a cascade of events including an immunological response. Pulmonary involvement is more common than previously believed and induced sputum, which is grossly underutilised, can be diagnostic in approximately 50%. The gold standard for the diagnosis of tuberculous pleuritis remains the detection of Mycobacterium tuberculosis in pleural fluid, or pleural biopsy specimens, either by microscopy and/or culture, or the histological demonstration of caseating granulomas in the pleura along with acid fast bacilli (AFB). In high burden settings, however, the diagnosis is frequently inferred in patients who present with a lymphocytic predominant exudate and a high adenosine deaminase (ADA) level, which is a valuable adjunct in the diagnostic evaluation. ADA is generally readily accessible, and together with lymphocyte predominance justifies treatment initiation in patients with a high pre-test probability. Still, false-negative and false-positive results remain an issue. When adding closed pleural biopsy to ADA and lymphocyte count, diagnostic accuracy approaches that of thoracoscopy. The role of other biomarkers is less well described. Early pleural drainage may have a role in selected cases, but more research is required to validate its use and to define the subpopulation that may benefit from such interventions.
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              Tuberculous pleural effusion.

              Tuberculous pleural effusion is one of the most common forms of extrapulmonary tuberculosis (TB). The immediate cause of the effusion is a delayed hypersensitivity response to mycobacterial antigens in the pleural space. For this reason microbiological analyses are often negative and limited by the lengthy delay in obtaining results. In areas with high TB prevalence, pleural fluid adenosine deaminase (ADA) levels greater than 40 U/l argue strongly for TB; in contrast, low levels of pleural ADA have high negative predictive value in low-prevalence countries. The specificity of this enzyme increases if only lymphocytic exudates are considered. The shortcoming of the ADA test is its inability to provide culture and drug sensitivity information, which is paramount in countries with a high degree of resistance to anti-TB drugs. Sputum induction (in addition to pleural fluid) for acid-fast bacilli and culture is a recommended procedure in all patients with TB pleurisy. The microscopic-observation drug-susceptibility assay performed on pleural fluid or pleural tissue increases by two to three times the detection of TB over conventional cultures, and it allows for the identification of multidrug-resistant TB. A reasonable management strategy for pleural TB would be to initiate a four-drug regimen and perform a therapeutic thoracentesis in patients with large, symptomatic effusions.
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                Author and article information

                Contributors
                951655206@qq.com
                1747343658@qq.com
                randingchao@126.com
                hexing1130@foxmail.com
                1140680278@qq.com
                1369778599@qq.com
                13603038752@139.com
                373821547@qq.com
                cnyets@126.com
                renliliipb@163.com
                yingxialiu@hotmail.com
                szdsyy@aliyun.com
                Journal
                BMC Infect Dis
                BMC Infect. Dis
                BMC Infectious Diseases
                BioMed Central (London )
                1471-2334
                16 January 2019
                16 January 2019
                2019
                : 19
                : 55
                Affiliations
                [1 ]GRID grid.410741.7, Department of Tuberculosis, , Shenzhen Third People’s Hospital, University of South China, ; Shenzhen, 518112 China
                [2 ]ISNI 0000 0004 1760 3078, GRID grid.410560.6, Department of Laboratory Medicine, , Shenzhen Longhua District Central Hospital, Guangdong Medical University, ; Shenzhen, 518110 China
                [3 ]GRID grid.410741.7, Guangdong Key Laboratory of Emerging Infectious Diseases, , Shenzhen Third People’s Hospital, University of South China, ; Shenzhen, 518112 China
                [4 ]ISNI 0000 0000 9889 6335, GRID grid.413106.1, MOH Key Laboratory of Systems Biology of Pathogens and Christophe Mérieux Laboratory, IPB, CAMS-Fondation Mérieux, , Institute of Pathogen Biology (IPB), Chinese Academy of Medical Sciences & Peking Union Medical College, ; Beijing, 100730 China
                Author information
                http://orcid.org/0000-0002-3617-5449
                Article
                3654
                10.1186/s12879-018-3654-z
                6335673
                30651075
                4f62287e-f448-471c-ba11-de6a5067c0f6
                © The Author(s). 2019

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 6 September 2018
                : 21 December 2018
                Funding
                Funded by: Thirteenth-Fifth Mega-Scientific Projects
                Award ID: 2017ZX10103004
                Award Recipient :
                Funded by: Natural Science Foundation of China
                Award ID: 81501714
                Award Recipient :
                Funded by: Natural Science Foundation of China
                Award ID: 81873958
                Award Recipient :
                Funded by: Shenzhen Scientific and Technological Foundation
                Award ID: JCYJ20170412151620658
                Award ID: JCYJ20170307095003051
                Award Recipient :
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2019

                Infectious disease & Microbiology
                tuberculosis pleural effusion,malignant pleural effusion,ifn-γ release assay,adenosine deaminase,carcinoembryonic antigen

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