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Objectives: The diagnosis of tuberculosis pleural effusion (TPE) remains challenging, traditional diagnostic tests have limited diagnostic efficacy. This study aimed to assess the diagnostic performance of pleural fluid (PF) lipoarabinomannan (LAM) in TPE. Methods: A diagnostic method for PF LAM (LAM-PF) was established using LEDBIO's AIMLAM kit. The diagnostic performance of LAM-PF was evaluated in 162 HIV-negative patients with suspected TPE. Results: The LAM-PF method established in this study exhibited good linearity and recovery rate, with a limit of detection (LOD) of 2.90 pg/mL. Using a cut-off value of 5.33 pg/mL, the sensitivity and specificity of LAM-PF in diagnosing TPE (n = 128) were 47.7% and 100.0%, respectively. The sensitivity in patients with probable TPE (n = 29) and definite TPE (n = 99) were 41.4% and 49.5%, respectively. LAM-PF displayed a significantly higher sensitivity in probable TPE compared to other tuberculosis detection methods. Combined testing of adenosine deaminase (ADA)and LAM increased the detection sensitivity of TPE to 68.0%, and the area under the curve was 0.84 (0.77–0.89). Conclusion: This study successfully established a method for detecting LAM in PF, which exhibited favorable diagnostic performance for TPE, particularly in challenging cases of probable TPE. Combined detection of LAM and ADA in PF significantly improves TPE diagnostic efficiency.

Background and aimsComplement activation is essential for tuberculosis pleural effusion. However, little is known about the value of complement regulatory protein (CD46, CD55, and CD59) in the differential diagnosis of tuberculosis.Materials and methodsNinety-nine patients with exudative pleural effusion admitted to Xiangya Hospital of Central South University from June 1, 2021to November 14, 2022 were enrolled. The expression levels of soluble CD46 (sCD46), soluble CD55 (sCD55), and soluble CD59 (sCD59) in pleural effusion were quantified by enzyme-linked immunosorbent assay, and the receiver operating characteristic (ROC) curves were plotted to evaluate the diagnostic and co-diagnostic values.ResultsThe ADA level is higher in TPE patients than non-TPE patients. It is well-found that TPE patients had lower levels of sCD46, sCD55, and sCD59 compared with non-TPE patients. Moreover, the expression of sCD46, sCD55, and sCD59 in pleural effusion was negatively correlated with ADA. In addition, the diagnostic efficacy of sCD46, sCD55 and sCD59 was comparable to that of ADA, with 0.896, 0.857, 0.858 and 0.893, respectively. Furthermore, combine detection of sCD46, sCD55, sCD59 and ADA could improve the diagnostic accuracy.ConclusionsComplement regulatory factors (CD46, CD55, and CD59) were validated by this project to be promising candidate biomarkers for the diagnosis of TPE with high accuracy. The combination of the CD46, CD55, and CD59 and ADA assay exist a better diagnostic value in TPE.

Abstract Background Tuberculosis pleural effusion (TPE) and malignant pleural effusion (MPE) are very common clinical complications. Considering the totally different prognosis and clinical treatment of TPE and MPE, the accurate and non-invasive diagnosis are very critical for patients with pleural effusion to initiate efficient management and treatment. However, effective clinical biomarkers were rarely explored to distinguish benign from MPE. The purpose of this study is to identify potential miRNAs which can probably be used to differentiate malignant pleural effusion from TPE. Results A total of 23 significantly differentially expressed miRNAs were identified in MPE, with 18 up-expressed and 5 down-expressed. And the target genes of the miRNAs mainly involved in the biology process of nervous system, cancer, immune system and metabolic process etc. Three high confident target genes, AGO4, FGF9 and LEF1 can be regulated by miR-195-5p, miR-182-5p and miR-34a-5p respectively. And these genes participate in the canonical pathway of regulation of the Epithelial-Mesenchymal and the biological functions of apoptosis, growth of tumor and cell proliferation of tumor cell lines. Further, RT-PCR validation results based on 64 collected individuals showed that the expression levels of the three miRNAs were 2–5 times higher in MPE samples, which were consistent with the microarray results. In addition, ROC curve analysis demonstrated that the combination of the three miRNAs can achieve higher AUC of 0.93 (p-value

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.

Background: Tuberculosis pleural effusion (TPE) and malignant pleural effusion (MPE) are very common clinical complications. Considering the totally different prognosis and clinical treatment of TPE and MPE, the accurate and non-invasive diagnosis are very critical for patients with pleural effusion to initiate efficient management and treatment. However, effective clinical biomarkers were rarely explored to distinguish benign from MPE. The purpose of this study is to identify potential miRNAs which can probably be used to differentiate malignant pleural effusion from TPE. Results: A total of 23 significantly differentially expressed miRNAs were identified in MPE, with 18 up-expressed and 5 down-expressed. And the target genes of the miRNAs mainly involved in the biology process of nervous system, cancer, immune system and metabolic process etc. Three high confident target genes, AGO4, FGF9 and LEF1 can be regulated by miR-195-5p, miR-182-5p and miR-34a-5p respectively. And these genes participate in the canonical pathway of regulation of the Epithelial-Mesenchymal and the biological functions of apoptosis, growth of tumor and cell proliferation of tumor cell lines. Further, RT-PCR validation results based on 64 collected individuals showed that the expression levels of the three miRNAs were 2–5 times higher in MPE samples, which were consistent with the microarray results. In addition, ROC curve analysis demonstrated that the combination of the three miRNAs can achieve higher AUC of 0.93 (p-value< 0.0001) to differentiate MPE from TPE. Conclusions: The identified miR-195-5p, miR-182-5p and miR-34a-5p can become potential diagnostic biomarkers for MPE with further evidences. [ABSTRACT FROM AUTHOR]

Abstract Objective Tuberculous pleural effusion remains difficult to diagnose despite numerous diagnostic tools. The aim of this study was to evaluate and compare the diagnostic efficiency of adenosine deaminase (ADA) analysis in the diagnosis of tuberculous pleural effusion when used alone or in combination with QuantiFERON-TB Gold (QFT-G) or Xpert MTB/RIF. Patients and methods Seventy-one patients with unknown bilateral or unilateral pleural effusion were subjected to pleural tapping, and pleural fluid samples were subjected to total ADA, QFT-G, and Xpert MTB/RIF. Pleural biopsies (thoracoscopic or closed) were performed for 41 patients, sent for histopathology of tuberculosis culture and Xpert MTB/ RIF, and they were differentiated into tuberculous (TB) and non-TB effusions by culture for Myobacterium tuberculosis and/or histopathology of pleural biopsy. ADA results were further analyzed using receiver operating characteristic curve to determine the cutoff values to achieve the optimum sensitivity and specificity. Results Forty-six patients had definite TB pleural effusion and 25 patients had non-TB pleural effusion. For ADA at a cutoff point of >40 IU/l, the sensitivity was 97.83% (n=45) [95% confidence interval (CI): 88.47–99.94%) and specificity was 76.00% (95% CI: 54.87–90.64%), but at a cutoff point of 70 U/l, the specificity was 96.00% (95% CI: 79.65–99.90%) and sensitivity was 84.78% (n=39) (95% CI: 71.13–93.66%). The sensitivity of QFT-G was 23.91% (95% CI: 12.59–38.77%) and specificity was 96.00% (95% CI: 79.65–99.90%). The sensitivity of Xpert MTB/RIF was 47.83% (95% CI: of 32.89–63.05%) and specificity was 100.00% (95% CI: 86.28–100.00%). Combined analysis of ADA at a cutoff value greater than 70 U/l with Xpert MTB/RIF showed a sensitivity of 85.64% (95% CI: 71.13–96.23%) and specificity of 98.50% (95% CI: 78.64–99.93%). ADA at a lower cutoff value greater than 40 U/l showed a sensitivity of 96.78% (95% CI: 77.13–99.66%) and specificity of 97.00% (95% CI: 79.65–99.90%). Conclusion ADA is a useful marker in the diagnosis of TB pleural effusion. ADA specificity with low cutoff value can be improved by combining with Xpert MTB/RIF, resulting in an accurate test to identify patients with suspected TB pleural effusion.

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. [ABSTRACT FROM AUTHOR]

To discuss the differences in protein expression among tuberculosis pleural effusion (TBPE), malignant pleural effusion (MPE) and transudative pleural effusion (TSPE). We recruited 50 patients with pleural effusion, including 20 TBPEs, 17 MPEs and 13 TSPEs. Using the two-dimensional electrophoresis (2-DE) and matrix-assisted laser desorption ionization-time of flight-mass spectrometry (MALDI-TOF-MS), we acquired the peptide mass finger printings (PMFs) of featured proteins. Then, we identified characteristic proteins by searching in the protein databank of the National Center of Biotechnology Information (NCBI) and assessed their diagnostic significance. We found five characteristic proteins: C1-inhibitor (C1-INH), transthyretin (TTR), human complement fragment 3b (C3b), human ceruloplasmin (CP), and Z34c protein fragment Fc (Z34c-Fc). C1-INH shows a high expression in TBPE and a low expression in MPE while TTR and C3 show low expression in TBPE and high expressions in MPE. Z34c-Fc and CP have a higher expression in TBPE than in TSPE. No common characteristic protein was found between MPE and TSPE. Statistic analysis consisted of paired t-tests and the difference between them is significance (P??0.05). C1-inhibitor (C1-INH), transthyretin (TTR), human Complement fragment 3b (C3b), human Ceruloplasmin (CP) and Z34c protein fragment Fc (Z34c-Fc) may provide an additional perspective in the differential diagnosis of PE. [ABSTRACT FROM AUTHOR]

Extrapulmonary involvement can occur in isolation or along with a pulmonary focus as in the case of patients with disseminated tuberculosis (TB). The recent human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS) pandemic has resulted in changing epidemiology and has once again brought extrapulmonary tuberculosis (EPTB) into focus. EPTB constitutes about 15 to 20 per cent of all cases of tuberculosis in immunocompetent patients and accounts for more than 50 per cent of the cases in HIV-positive individuals. Lymph nodes are the most common site of involvement followed by pleural effusion and virtually every site of the body can be affected. Since the clinical presentation of EPTB is atypical, tissue samples for the confirmation of diagnostic can sometimes be difficult to procure, and the conventional diagnostic methods have a poor yield, the diagnosis is often delayed. Availabiity of computerised tomographic scan, magnetic resosnance imaging laparoscopy, endoscopy have tremendously helped in anatomical localisation of EPTB. The disease usually responds to standard antituberculosis drug treatment. Biopsy and/or surgery is required to procure tissue samples for diagnosis and for managing complications. Further research is required for evolving the most suitable treatment regimens, optimal duration of treatment and safety when used with highly active antiretroviral treatmenrt (HAART). [ABSTRACT FROM AUTHOR]

A sarcoidosis associated pleural effusion (SAPE) is a pleural effusion caused by active granulomatous inflammation from sarcoidosis. We describe the epidemiology, clinical features, diagnostic approach, treatment strategies and outcome of this condition. SAPE occurs in approximately 1% of sarcoidosis patients. The condition most commonly occurs at the initial presentation of sarcoidosis or within the first year. Dyspnea is the most common presenting symptom. Although a definitive diagnosis of SAPE requires a pleural biopsy, the diagnosis may be established on the basis of clinical features alone provided that alternative conditions can be reliably excluded. Pleural fluid analysis is essential in establishing the clinical diagnosis of SAPE. Corticosteroids are the drugs of choice for SAPE, and they are usually rapidly effective with courses of therapy often lasting less than two months. SAPE tends to have a low rate of recurrence that appears be to lower than for many other forms of sarcoidosis., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Purpose: To identify potential protein biomarkers for distinguishing tuberculosis plural effusion (TBPE) from malignant plural effusion (MPE)., Experimental Design: Five independent samples from each group (TBPE and MPE) are enrolled for label-free quantitative proteomics analyses. The differentially expressed proteins are validated by western blot and ELISA. Logistic regression analysis is used to obtain the optimal diagnostic model., Results: In total, 14 proteins with significant difference are identified between TBPE and MPE. Seven differentially expressed proteins are validated using western blot, and the expression patterns of these seven proteins are similar with those in proteomics analysis. Statistically significant differences in four proteins (AGP1, ORM2, C9, and SERPING1) are noted between TBPE and MPE in the training set (n = 230). Logistic regression analysis shows the combination of AGP1-ORM2-C9 presents a sensitivity of 73.0% (92/126) and specificity of 89.4% (93/104) in discriminating TBPE from MPE. Additional validation is performed to evaluate the diagnostic model in an independent blind testing set (n = 80), and yielded a sensitivity of 74.4% (32/43) and specificity of 91.9% (34/37) in discriminating TBPE from MPE., Conclusion: The study uncovers the proteomic profiles of TBPE and MPE, and provides new potential diagnostic biomarkers for distinguishing TBPE from MPE., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

This systematic review and meta-analysis was performed to determine accuracy and usefulness of adenosine deaminase (ADA) in diagnosis of tuberculosis pleurisy. Medline, Google scholar and Web of Science databases were searched to identify related studies until 2014. Two reviewers independently assessed quality of studies included according to standard Quality Assessment of Diagnosis Accuracy Studies (QUADAS) criteria. The sensitivity, specificity, diagnostic odds ratio and other parameters of ADA in diagnosis of tuberculosis pleurisy were analyzed with Meta-DiSC1.4 software, and pooled using the random effects model. Twelve studies including 865 tuberculosis pleurisy patients and 1379 non-tuberculosis pleurisy subjects were identified from 110 studies for this meta-analysis. The sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR) and diagnosis odds ratio (DOR) of ADA in the diagnosis of tuberculosis pleurisy were 45.25 (95% CI 27.63-74.08), 0.86 (95% CI 0.84-0.88), 0.88 (95% CI 0.86-0.90), 6.32 (95% CI 4.83-8.26) and 0.15 (95% 0.11-0.22), respectively. The area under the summary receiver operating characteristic curve (SROC) was 0.9340. Our results demonstrate that the sensitivity and specificity of ADA are high in the diagnosis of tuberculosis pleurisy especially when ADA≥50 (U/L). Thus, ADA is a relatively sensitive and specific marker for tuberculosis pleurisy diagnosis. However, it is cautious to apply these results due to the heterogeneity in study design of these studies. Further studies are required to confirm the optimal cut-off value of ADA.