Diagnosis of tuberculous pleurisy with combination of adenosine deaminase and interferon-γ immunospot assay in a tuberculosis-endemic population

Xu, Hong; Li, Cheng-ye; Su, Shanshan; Li, Yang; Ye, Min; Ye, Junru; Ke, Pei-Pei; Chen, Chengshui; Xie, Yupeng; Li, Yuping

doi:10.1097/md.0000000000008412

Cited by 16 publications

(13 citation statements)

References 36 publications

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“…The combinatorial analysis of the biomarkers positivity showed an impressing good performance, in particular when IFN-γ plus ADA (25.8 IU/L) was analyzed. In the clinical practice, few studies used two or three assays in combination to improve their isolated diagnostic power for PlTB: QFT-GIT plus polymerase chain reaction [ 42 ]; ADA plus lymphocyte percentage on PF [ 43 ]; QFT-GIT on PB, ADA and carcinoembryonic antigen (CEA) on PF [ 2 ]; T-SPOT.TB on PB and PF combined with ADA on PF [ 44 ]. In all cases, the diagnostic yield enhanced when at least two assays were combined.…”

Section: Discussionmentioning

confidence: 99%

Application of Venn's diagram in the diagnosis of pleural tuberculosis using IFN-γ, IP-10 and adenosine deaminase

Santos¹,

Corrêa²,

Ribeiro-Alves³

et al. 2018

PLoS ONE

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BackgroundPleural tuberculosis (PlTB) is the most common extrapulmonary manifestation of this infectious disease which still presents high mortality rates worldwide. Conventional diagnostic tests for PlTB register multiple limitations, including the lack of sensitivity of microbiological methods on pleural specimens and the need of invasive procedures such as pleural biopsy performance. In this scenario, the search for biological markers on pleural fluid (PF) has been the target of several studies as a strategy to overcome the limitations of PlTB diagnosis. This study aims to evaluate the use either isolated or in combination with adenosine deaminase (ADA), interferon-gamma (IFN-γ), interferon-gamma inducible protein of 10-kD (IP-10) levels on PF in order to guide an accurate anti-TB treatment in microbiologically non-confirmed cases.Methods and findingsEighty patients presenting pleural effusion under investigation were enrolled in a cross-sectional study conducted at Pedro Ernesto University Hospital, Rio de Janeiro, RJ, Brazil. Peripheral blood (PB) and PF samples collected from all patients were applied to the commercial IFN-γ release assay, QuantiFERON-TB Gold In-Tube, and samples were analyzed for IFN-γ and IP-10 by immunoassays. ADA activity was determined on PF by the colorimetric method. Based on microbiological and histological criteria, patients were categorized as follow: confirmed PlTB (n = 16), non-confirmed PlTB (n = 17) and non-PlTB (n = 47). The Mycobacterium tuberculosis antigen-specific production of IFN-γ and IP-10 on PB or PF did not show significant differences. However, the basal levels of these biomarkers, as well as the ADA activity on PF, were significantly increased in confirmed PlTB in comparison to non-PlTB group. Receiver operating characteristics curves were performed and the best cut-off points of these three biomarkers were estimated. Their either isolated or combined performances (sensitivity [Se], specificity [Sp], positive predictive value [PPV], negative predictive value [NPV] and accuracy [Acc]) were determined and applied to Venn's diagrams among the groups. Based on the confirmed PlTB cases, IFN-γ showed the best performance of them at a cut-off point of 2.33 IU/mL (Se = 93.8% and Sp = 97.9%) followed by ADA at a cut-off of 25.80 IU/L (Se = 100% and Sp = 84.8%) and IP-10 (Cut-point = 4,361.90 pg/mL, Se = 75% and Sp = 82.6%). IFN-γ plus ADA (cut-point: 25.80 IU/L) represent the most accurate biomarker combination (98.4%), showing Se = 93.7%, Sp = 100%, PPV = 100% and NPV = 97.9%. When this analysis was applied in non-confirmed PlTB, 15/17 (88.2%) presented at least two positive biomarkers in combination.ConclusionIFN-γ, IP-10, and ADA in PlTB effusions are significantly higher than in non-PlTB cases. IFN-γ is an excellent rule-in and rule-out test compared to IP-10 and ADA. The combination of IFN-γ and ADA, in a reviewed cut-off point, showed to be particularly useful to clinicians as their positive results combined prompts immediate treatment for TB while both negative resu...

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Section: Discussionmentioning

confidence: 99%

Application of Venn's diagram in the diagnosis of pleural tuberculosis using IFN-γ, IP-10 and adenosine deaminase

Santos¹,

Corrêa²,

Ribeiro-Alves³

et al. 2018

PLoS ONE

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“…The incidence of MPE is higher than 200,000 cases/year in the United States [2] , with lung cancer (36%) and breast cancer (26%) accounting for the vast majority of cases due to metastasis to the pleura [ 3 , 4 ]. With regard to BPE, tuberculous pleurisy effusion (TPE) is the most common cause [5] and a prominent problem in developing countries, including China [6] . The prognosis for patients with MPE is extremely poor in clinical practice [ 7 , 8 ], and delaying treatment due to misdiagnosis will directly lead to an increase in mortality.…”

Section: Introductionmentioning

confidence: 99%

Development and validation of a novel scoring system developed from a nomogram to identify malignant pleural effusion

Wang

Tian

et al. 2020

EBioMedicine

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Background This study aimed to establish and validate a novel scoring system based on a nomogram for the differential diagnosis of malignant pleural effusion (MPE) and benign pleural effusion (BPE). Methods Patients with PE and confirmed aetiology who underwent diagnostic thoracentesis were included in this study. One retrospective set ( N = 1261) was used to develop and internally validate the predictive model. The clinical, radiological and laboratory features were collected and subjected to logistic regression analyses. The primary predictive model was displayed as a nomogram and then modified into a novel scoring system, which was externally validated in an independent set ( N = 172). Findings The novel scoring system was composed of fever (3 points), erythrocyte sedimentation rate (4 points), effusion adenosine deaminase (7 points), serum carcinoembryonic antigen (CEA) (4 points), effusion CEA (10 points) and effusion/serum CEA (8 points). With a cutoff value of 15 points, the area under the curve, specificity and sensitivity for identifying MPE were 0.913, 89.10%, and 82.63%, respectively, in the training set, 0.922, 93.48%, 81.51%, respectively, in the internal validation set and 0.912, 87.61%, 81.36%, respectively, in the external validation set. Moreover, this scoring system was exclusively applied to distinguish lung cancer with PE from tuberculous pleurisy and showed a favourable diagnostic performance in the training and validation sets. Interpretation This novel scoring system was developed from a retrospective study and externally validated in an independent set based on six easily accessible clinical variables, and it exhibited good diagnostic performance for identifying MPE. Funding grants (no. 81572942, no. 81800094).

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“…[26] Xu et al . [9] reported that the area under the receiver operating characteristic curve of the T-SPOT test for diagnosing tuberculous pleurisy in the pleural fluid is 0.918.…”

Section: Discussionmentioning

confidence: 99%

“…The diagnosis of tuberculous pleurisy remains a challenge. [9] The gold standard diagnostic is the detection of M. tuberculosis in pleural fluid or pleural biopsy specimens, either by smear, culture, or histopathology. Lymphocytic predominant exudate and high adenosine deaminase (ADA) levels represent a valuable adjunct in the diagnosis of tuberculous pleurisy, and these may be useful in settings with high TB burden.…”

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confidence: 99%

Medical thoracoscopy for tuberculous pleurisy: A retrospective analysis of 575 cases

Zhao

Song

et al. 2019

Ann Thorac Med

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OBJECTIVE: The objective of this retrospective study was to assess the efficacy of medical thoracoscopy in diagnosing of tuberculous pleurisy and characterize tuberculous pleurisy with medical thoracoscopy. METHODS: A total of 575 patients with tuberculous pleurisy who underwent medical thoracoscopy were included in the study. Demographic data, clinical manifestations, and routine and biochemical tests on pleural fluid, cultures of pleural fluid, sputum, and pleural biopsy for the detection of Mycobacterium tuberculosis and pathological findings were evaluated. RESULTS: Sputum, pleural fluid, and pleural biopsy cultures were positive for M. tuberculosis in 12.5%, 19.2%, and 41.9% of patients, respectively. Furthermore, there were significant differences in total positive tuberculosis (TB) tests in the pleural cavity according to patient's age (<18 years old, 50.0%; 18–34 years old, 50.2%; 35–59 years old, 34.8%; >60 years old, 18.6%; and all groups vs. >60 years old, P < 0.001). Patients with 18–34 years old were more likely to have granuloma in pleural biopsy specimens when compared to patients >60 years old (77.0% vs. 37.9%). The percentage of patients with high adenosine deaminase (ADA) levels in pleural fluid (>40 U/L), who were <18, 18–34, 35–59, and > 60 years old, was 83.3% (15/18), 72.8% (193/265), 51.2% (88/172), and 34.7% (17/49), respectively (all groups vs. >60 years old, P < 0.001). CONCLUSION: Medical thoracoscopy is effective for diagnosing tuberculous pleurisy. Younger patients with tuberculous pleurisy have a higher number of positive TB tests in the pleural cavity, are more likely to have granuloma in pleural biopsy specimens, and have higher ADA levels in the pleural fluid.

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Diagnosis of tuberculous pleurisy with combination of adenosine deaminase and interferon-γ immunospot assay in a tuberculosis-endemic population

Cited by 16 publications

References 36 publications

Application of Venn's diagram in the diagnosis of pleural tuberculosis using IFN-γ, IP-10 and adenosine deaminase

Application of Venn's diagram in the diagnosis of pleural tuberculosis using IFN-γ, IP-10 and adenosine deaminase

Development and validation of a novel scoring system developed from a nomogram to identify malignant pleural effusion

Medical thoracoscopy for tuberculous pleurisy: A retrospective analysis of 575 cases

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