Diagnosis Of Tuberculous Pleural Effusion Research Articles

The Impact Profile and Adenosine Deaminase of Age and Female Sex on Its Level in Patients with Pleural Effusion Syndrome

Background: Pleural fluid analysis and closed pleural biopsy are integral parts in the investigative work up of an exudative pleural effusion. For diagnosis of tuberculous pleural effusion (TPE), the yield of pleural fluid culture for mycobacteria is low at about 36%. Objective: To evaluate the levels of adenosine deaminase (ADA) in the pleural fluids (P-ADA) of untreated and non-surgically manipulated female and male adult patients with several confirmed causes of PES. Methods: This was an observational study conducted at dept. of Internal Medicine, 250 Bedded Mohammad Ali Hospital, Bogura, Bangladesh from January to June 2023. 100 pleural fluid samples from 100 patients with proven causes of PES. The sample size was appropriate according to the study design. Written consent was obtained from all patients. It was precise enough to calculate descriptive and inferential statistics on type I and II errors, effect size, standard deviation, and was not influenced by administrative issues and costs. Results: 100 patients summarize the prevalence of the causes of PES and the demographic characteristics. TB was the most prevalent cause of PES (28/100, 28%). Most prevalent male sex was in the lymphoma group (4/0, 100%). None of the five patients with lymphoma were female. When the frequencies were compared for males and females, only adenocarcinoma and lymphoma were significant (chi- square tests, p=0.0021 and p=0.0003, respectively). The causes, prevalence, and median P-ADA (n/%/U/L) were tuberculosis (28/28.0/42.0), adenocarcinoma (24/24.0/9.75), transudate (21/21.0/6.85), simple parapneumonic pleural effusions (PPE; 10/10.0/9.38), complicated PPE/empyema (5/5.0/32.9), lymphoma (4/4.0/401.2), squamous cell carcinoma (4/4.0/13.11), and others (4/4/15.2). For P-ADA, Dunn's post hoc test revealed significance for tuberculosis vs. transudates, vs. simple PPE, and vs. adenocarcinoma (all P<0.05), and not significant for CPPE/empyema, lymphoma, SCC, and others (all P>0.05). For age, Dunn’s post hoc test revealed significance for tuberculosis vs. transudates, vs. simple PPE, and vs. adenocarcinomas (all P<0.05). Sex was not significant in the overall PES group (Chi=0.062, P=0.8028). Kendall's correlation of the relationship between P-ADA and age for pleural tuberculosis (n=26) was significant after 1000 iterations with bootstrap for 95% CI (Tau=-0.213, 95% CI - 0.449-0.0833, P=0.0490). A negative LOESS regression was evident between P-ADA and age >40 years. Conclusions: Evaluation of pleural ADA levels is useful for diagnosing pleural tuberculosis, while sex is not. A negative and significant relationship between P- ADA level and age >40 years was evident.

Gamma interferon as a superior diagnostic marker in tuberculous pleural effusion: A comparative analysis with adenosine deaminase

Background: The diagnosis of tuberculous pleural effusion (TPE) poses a massive problem during tuberculosis (TB) control worldwide. This study set out to find the role of Interferon Gamma (IFN-γ) and Adenosine Deaminase (ADA) in pleural fluid as markers for early diagnosis of TPE to improve the accuracy and, hence, the opportunity for early and effective intervention for patients. Aims and Objectives: (i) The aims and objectives of the study are to compare the levels of IFN-γ and ADA in pleural fluid samples from patients with tuberculous and non-TPEs; (ii) to determine the diagnostic accuracy of these biomarkers in differentiating TPE from other causes; and (iii) to analyze the correlation of IFN-γ and ADA levels with other routine diagnostic parameters for TB. Materials and Methods: The study adopted a forwardlooking, case–control methodology to compare outcomes across groups. One hundred individuals presenting with pleural effusion were selected for participation. This cohort was divided evenly, with 50 individuals identified with TPE and 50 showing non-tuberculous types of effusion, including those caused by parapneumonic and cancerous processes. Eligible participants were aged between 20 and 60 years and tested negative for the human immunodeficiency virus. Exclusion criteria included pleural effusion arising from viral infections, pregnancy or breastfeeding status, adverse drug reactions affecting the skin, or empyema. Thoracocentesis was performed to collect pleural fluid following participants’ informed consent under sterile conditions. The analysis of pleural fluid encompassed measurements of IFN-γ through enzyme-linked immunosorbent assay techniques and ADA levels through an ADA assay kit. In addition, venous blood was drawn to conduct routine hematological and biochemical tests, including evaluating serum lactate dehydrogenase, total protein, albumin, and cholesterol levels. Results: It was found that the mean level of IFN-γ was significantly (P < 0.00001) higher in patients with TPE, 186.66 ± 134.46 pg/mL, as compared to the level in non-tuberculous effusion 47.53 ± 68.94 pg/mL. Similarly, the difference in ADA level was also significant (P = 0.016) between the two groups. The mean level of ADA was significantly (P = 0.016) higher in TPE, 135.93 ± 239 U/L, compared to the level in non-tuberculous effusion, 58.86 ± 87.83 U/L. Conclusion: The significant elevation in IFN-γ and ADA levels in TPE patients re-emphasizes their potential as specific markers in this clinical condition and suggests considering IFN-γ in combination with ADA as valuable parameters in the differentiation of tuberculous from non-tuberculous effusions and thereby, this advancement in the realm of quick markers of diagnosis would play a crucial role in the refinement of diagnosis strategy in TB which would be of immense help in improving the patients’ outcome.

Diagnostic and comparative performance for the prediction of tuberculous pleural effusion using machine learning algorithms

ObjectiveEarly diagnosis and differential diagnosis of tuberculous pleural effusion (TPE) remains challenging and is critical to the patients’ prognosis. The present study aimed to develop nine machine learning (ML) algorithms for early diagnosis of TPE and compare their performance. MethodsA total of 1435 untreated patients with pleural effusions (PEs) were retrospectively included and divided into the training set (80%) and the test set (20%). The demographic and laboratory variables were collected, preprocessed, and analyzed to select features, which were fed into nine ML algorithms to develop an optimal diagnostic model for TPE. The proposed model was validated by an independently external data. The decision curve analysis (DCA) and the SHapley Additive exPlanations (SHAP) were also applied. ResultsSupport vector machine (SVM) was the best model in discriminating TPE from non-TPE, with a balanced accuracy of 87.7%, precision of 85.3%, area under the curve (AUC) of 0.914, sensitivity of 94.7%, specificity of 80.7%, and F1-score of 86.0% among the nine ML algorithms. The excellent diagnostic performance was also validated by the external data (a balanced accuracy of 87.7%, precision of 85.2%, and AUC of 0.898). Neural network (NN) and K-nearest neighbor (KNN) had better net benefits in clinical usefulness. Besides, PE adenosine deaminase (ADA), PE carcinoembryonic antigen (CEA), and serum CYFRA21-1 were identified as the top three important features for diagnosing TPE. ConclusionsThis study developed and validated a SVM model for the early diagnosis of TPE, which might help clinicians provide better diagnosis and treatment for TPE patients.

Pleural fluid soluble Fas ligand and tuberculous pleural effusion: a prospective diagnostic test accuracy study.

The diagnosis of tuberculous pleural effusion (TPE) is challenging for pulmonologists. Adenosine deaminase (ADA), interferon-gamma (IFN-γ), and interleukin-27 (IL-27) have some limitations for diagnosing TPE. Soluble Fas ligand (sFasL) had a high diagnostic value for TPE. However, it remains unknown: (I) whether sFasL has an additional diagnostic value to the traditional markers (e.g., ADA); (II) whether sFasL provides a net benefit in patients with undiagnosed pleural effusion; (III) factors affecting the diagnostic accuracy of sFasL for TPE. This study aimed to evaluate the additional diagnostic value and benefit of pleural fluid sFasL for TPE. We prospectively enrolled 211 patients with undiagnosed pleural effusion. The concentration of sFasL in pleural fluid was measured by an enzyme-linked immunosorbent assay (ELISA). The diagnostic accuracy and net benefit of sFasL and ADA for TPE were analyzed by a receiver operating characteristic (ROC) curve, decision curve analysis (DCA), net reclassification improvement (NRI), and integrated discriminant improvement (IDI). The area under the ROC curves (AUCs) of sFasL and ADA were 0.74 (95% CI: 0.65-0.83) and 0.80 (95% CI: 0.71-0.90), respectively. The decision curve of sFasL revealed net benefit. The continuous NRI and IDI of sFasL were 0.36 (0.00-0.72, P=0.05) and 0.02 (-0.01-0.06, P=0.18), respectively. Pleural fluid sFasL has moderate diagnostic accuracy for TPE.

Role of Adenosine Deaminase and Lymphocyte/Neutrophil Ratio in the Diagnosis of Tuberculous Pleural Effusion in Patients with Exudative Pleural Effusion

Role of Adenosine Deaminase and Lymphocyte/Neutrophil Ratio in the Diagnosis of Tuberculous Pleural Effusion in Patients with Exudative Pleural Effusion

Biomarkers for distinguishing tuberculous pleural effusion from non-tuberculosis effusion: a retrospective study

BackgroundPleural effusion (PE) is a common clinical feature that presents a diagnostic challenge for clinicians. In this retrospective study, we aimed to assess the biomarkers, ratios, and multiple indicators in serum and Pleural effusion for the differential diagnosis of tuberculous pleural effusion (TPE) from non-tuberculosis effusion (non-TPE).MethodsThe participants, who were divided into two groups: TPE and non-TPE (MPE and PPE), from Ningbo First Hospital, were incorporated in this study. The clinical and laboratory features were collected and analyzed using logistic regression analysis. Twelve biomarkers and their ratios in serum and PE were investigated for TPE versus non-TPE. Additionally, the value of multiple indicators for joint diagnosis was estimated.ResultsBiomarkers and ratios showed good diagnostic performance. The five variables including Serum ADA, IGRA, Effusion ADA, Effusion ADA/Serum ADA and Effusion LDH/Effusion ADA were identified as valuable parameters for differential diagnosis of TPE from non-TPE. The combined diagnosis of the five indexes yielded the highest diagnostic accuracy for TPE with an AUC (0.919), sensitivity (90.30%), and specificity (94.50%).ConclusionsThe biomarkers and ratios demonstrated strong diagnostic performance, and the utilization of multiple indicators for joint diagnosis can improve the diagnostic efficacy of tuberculous pleurisy.

Evaluation of Adenosine Deaminase as a Diagnostic Marker in Tuberculous Pleural Effusion

Abstract: Tuberculous pleural effusion (TPE) is a common medical condition more frequently encountered in poor countries. It is the second most common form of extra-pulmonary tuberculosis. The diagnosis of TPE is problematic because the clinical features are non-specific, and most laboratory tests are not diagnostic. An accurate diagnosis requires the detection of TB bacilli in the pleural fluid or tissue sample from the pleura, which is not an easy task due to the scarcity of bacilli in the pleural fluid and the need for invasive maneuvers to get pleural tissue for histopathological, bacteriological or molecular confirmation for the TB bacilli. : Different markers in pleural fluid have been evaluated to aid in diagnosing TPE. Among those biomarkers, Adenosine deaminase (ADA) was the most studied marker. It is an enzyme predominantly produced by T-lymphocytes and catalyzes the conversion of adenosine to inosine and deoxyadenosine. It is a hallmark of active cellular immunity. A high level of ADA can be found in exudative effusion of different etiologies such as parapneumonic, tuberculous and malignant effusions. : Although there is still a debate over the diagnostic accuracy of ADA as a marker for TPE, many studies recommend its use. A correct diagnosis is crucial for the start of treatment for TPE. Therefore, it is crucial to assess the diagnostic value of adenosine deaminase in diagnosing tuberculous pleural effusion. The ADA optimal cutoff value is still under investigation.

Application of Adenosine Deaminase and γ-Interferon Release Assay in Pleural Fluid for the Diagnosis of Tuberculous Pleural Effusion in Patients Over 40 Years Old.

In patients with tuberculous pleural effusion (TPE) of various ages, the diagnostic accuracy of pleural biomarkers varies, and there are insufficient studies specifically in different age groups. Therefore, we investigated the adenosine deaminase cut-off value and its combination with the gamma interferon release assay for the diagnosis of TPE among patients aged ≥40 years. A retrospective analysis of 198 patients who underwent medical thoracoscopy and were admitted to the hospital between 2015 and 2020 with exudative pleural effusion and either fever, night sweats, fatigue, cough, or other clinical manifestations was performed. The medical thoracoscopy, ADA, and T-SPOT results were analysed in the pleural fluid. The patients were divided into groups based on age: 18-39, 40-59, and 60-87. The best cut-off values of ADA were 29.5, 31.5 and 19.5 U/L, respectively, for the aged 18-39, aged 40-87 and aged 60-87 groups. The accuracy of 31.5 U/L was higher than 40 U/L for aged ≥40 years (86 vs 83%). The ADA diagnostic accuracy was higher than that of people under 40 years (83 vs 77%) when cut-off value of ADA was 40 U/L, but the IGRA accuracy was lower than that of people under 40 (87 vs 91%). The sensitivity of ADA or IGRA detection in patients over 40 years was 99%, and the specificity was 78%. The ADA specificity combined with IGRA for TPE was the highest (100%) in the ≥40 age group, and the sensitivity was 69%. Our study revealed the best cut-off values of ADA for TBE in different age groups. Combining ADA and IGRA in pleural fluid improves the detection rate of TPE in patients over 40 years of age with exudative pleural effusion. ADA combined with IGRA increases specificity, and ADA or IGRA increases sensitivity substantially.

Hepatocyte growth factor combined with adenosine deaminase as biomarker for diagnosis of tuberculous pleural effusion.

The simple, rapid, and accurate diagnosis of tuberculous pleural effusion (TPE) remains difficult. This study aimed to determine the accuracy of hepatocyte growth factor (HGF) in the diagnosis of TPE. We quantified the expression of HGF, adenosine deaminase (ADA), and interferon gamma (IFN-γ) in pleural effusion (PE) in 97 TPE subjects and 116 non-TPE subjects using an enzyme-linked immunosorbent assay (ELISA) or a fully automatic biochemical analyzer. The diagnostic performance of these three biomarkers was evaluated using a receiver operating characteristic (ROC) curve of subjects by age and gender. We discovered that the TPE group had much higher levels of HGF than the non-TPE group, regardless of age or gender, and that there was no statistically significant difference between the two groups' levels of HGF expression in peripheral plasma. In female TPE patients aged ≤65 years, the AUCs of TPE and non-TPE diagnosed by HGF, ADA or IFN-γ were 0.988, 0.964, and 0.827, respectively. HGF plus ADA had the highest diagnostic efficacy in female TPE patients aged ≤65 years. With HGF plus ADA having a cut-off value of 0.219 for distinguishing TPE from non-TPE, the area under the curve (AUC), sensitivity (SEN), specificity (SPE), positive predictive value (PPV), and negative predictive value (NPV) were, respectively, 0.998 (95% confidence interval [CI], 0.993-1.000), 100 (95% CI, 89.997-100.000), 96.667 (95% CI, 82.783-99.916), 97.222 (95% CI, 83.594-99.586), and 100. This study confirmed that HGF plus ADA has high diagnostic efficacy in younger female TPE patients and has the potential to be an excellent biomarker.

Diagnosis of tuberculous pleural effusion in a tertiary care hospital of central India: The role of xpert Mycobacterium tuberculosis/rifampicin.

In India, 15%-20% of tuberculosis (TB) cases are categorized as extra-pulmonary TB, and tuberculous pleural effusion (TPE) is the second-most common type after tuberculous lymphadenitis. However, the paucibacillary nature of TPE makes its diagnosis challenging. As a result, relying on empirical anti-TB treatment (ATT) based on clinical diagnosis becomes necessary for achieving the best possible diagnostic outcome. The study aims to determine the diagnostic utility of Xpert Mycobacterium tuberculosis/rifampicin (MTB/RIF) for the detection of TB in TPE in high incidence setting of Central India. The study enrolled 321 patients who had exudative pleural effusion detected through radiological testing and were suspected of having TB. The medical procedure of thoracentesis was conducted to collect the pleural fluid, which was then subjected to both the Ziehl-Neelsen staining and Xpert MTB/RIF test. The patients who showed improvement after receiving anti-tuberculosis treatment (ATT) were considered the composite reference standard. The sensitivity of smear microscopy was found to be 10.19%, while that of the Xpert MTB/RIF method was 25.93% when compared to the composite reference standard. The accuracy of clinical diagnosis was measured using receiver operating characteristics based on clinical symptoms, and it was found to be 0.858 (area under the curve). The study shows that Xpert MTB/RIF has significant value in diagnosing TPE, despite its low sensitivity of 25.93%. Clinical diagnosis based on symptoms was relatively accurate, but relying on symptoms alone is not enough. Using multiple diagnostic tools, including Xpert MTB/RIF, is crucial for accurate diagnosis. Xpert MTB/RIF has excellent specificity and can detect RIF resistance. Its quick results make it useful in situations where a rapid diagnosis is necessary. While it should not be the only diagnostic tool, it has a valuable role in diagnosing TPE.

Pleural fluid interleukins for diagnosis of tuberculous pleural effusion: A systematic review and meta-analysis.

The diagnostic performance of pleural fluid interleukins as potential biomarkers for tuberculous pleural effusion (TPE) remains unclear. We assessed the diagnostic accuracy of various interleukins in the pleural fluid for TPE and evaluated their ability to differentiate TPE from other effusions. We queried the PubMed and Embase databases for studies indexed till October 2021. We included studies that (a) provided information regarding sensitivity and specificity of pleural fluid interleukins for diagnosing TPE, or (b) compared pleural fluid interleukin levels between TPE and malignant or parapneumonic effusions. We used hierarchical summary receiver operating characteristic plots to model summary sensitivity and specificity. Random effects modeling was employed to pool standardized mean differences (SMD) across descriptive studies comparing TPE and other effusions. We included 80 publications in our review; most were small and of poor quality. All interleukins except interleukin-27 (interleukins 1-beta, 2, 4, 6, 8, 10, 12, 12p40, 13, 18, 33) showed poor diagnostic accuracy and inconsistent discrimination of TPE from other effusions. The summary estimates for sensitivity, specificity, and diagnostic odds ratio were 0.94 (95% CI 0.85-0.98), 0.97 (95% CI 0.93-0.99), and 507.13 (95% CI 130.66-1968.34) respectively for pleural fluid interleukin-27. Mean pleural fluid interleukin-27 levels in TPE were significantly higher than malignant (summary SMD 3.72, 95% CI 2.81-4.63) or parapneumonic (summary SMD 2.45, 95% CI -1.80-3.09) effusions. Pleural fluid interleukins are poor diagnostic biomarkers for TPE. Only pleural fluid interleukin-27 exhibited good accuracy in diagnosing TPE and needs further evaluation.

Activated partial thromboplastin time as a potential biomarker for the diagnosis of tuberculous pleural effusion

BackgroundThe aim of this study was to explore the difference in activated partial thromboplastin time (APTT) levels in patients with tuberculous and non-tuberculous pleural effusion (TPE and non-TPE) and its possible mechanism to provide a new direction for the diagnosis of pleural effusion (PE). MethodsA total of 61 patients diagnosed with tuberculous pleurisy with pleural effusion at Shunde Hospital of Southern Medical University from July 2013 to September 2020 were selected as the observation group (tuberculosis group). Another 89 patients (45 with malignant pleural effusion (MPE) and 44 with parapneumonic pleural effusion (PPE) composed the control group. The adenosine deaminase (ADA) level in pleural fluid and plasma APTT level were measured in the two groups. ResultsThe levels of APTT and ADA in the TPE group were significantly higher than the control group, and were 40.03 (37.00, 42.60) (s) and 55.00 (47.00, 69.25) (U/L) for TPE, 29.50 (25.45, 34.20) (s) and 11.90 (9.15, 19.05) (U/L) for malignant pleural effusion (MPE) and 31.35 (27.43, 35.76) (s) and 15.15 (7.40, 35.00) (U/L) for parapneumonic pleural effusion (PPE), respectively. ConclusionsThe level of plasma APTT has certain significance in differentiating tuberculous pleural effusion from nontuberculous pleural effusion.

The Level of Expression and Diagnostic Value of Biomarkers in Tuberculous Pleurisy

Objective: Observe and analyze the clinical significance of the differences in the expression levels of sCD163, haptoglobin and cytokines. Methods: 120 patients with tuberculous pleural effusion diagnosed in our hospital from January 2019 to December 2021 were randomly selected as the experimental group. On the other hand, 40 patients with non-tuberculous pleural effusion admitted in the same period were selected as the control group. The expression levels of sCD163, haptoglobin and cytokines were observed and analyzed. Results: The expression levels of sCD163 (?g/mL), haptoglobin (g/L), IL-6 (pg/mL) and IL-12 (pg/mL) of the control group were 31.26 ± 14.12, 32.14 ± 18.79, 401.23 ± 24.36 and 1.32 ± 0.14, respectively. As for the experimental group, the expression levels of sCD163 (?g/mL), haptoglobin (g/L), IL-6 (pg/mL) and IL-12 (pg/mL) were 74.12 ± 14.78, 113.25 ± 19.45, 612.12 ± 36.98 and 4.12 ± 0.56 respectively, and p < 0.05 which shows that the data was statistically significant. Conclusion: The level of inflammatory cytokines in the pleural fluid of tuberculous pleural effusion patients are higher, which can be used for the diagnosis of auxiliary tuberculous pleurisy. Tuberculous pleural effusion patients has a significantly increased expression levels of sCD163 and haptoglobin in the pleural fluid. The combination of sCD163 and haptoglobin in the diagnosis of tuberculous pleural effusion has higher clinical diagnostic value, and sCD163 and haptoglobin are not interfered by inflammatory factors in the diagnosis of tuberculous pleural effusion

A scoring model for diagnosis of tuberculous pleural effusion

BackgroundDue to the low efficiency of a single clinical feature or laboratory variable in the diagnosis of tuberculous pleural effusion (TBPE), the diagnosis of TBPE is still challenging. This study aimed to build a scoring diagnostic model based on laboratory variables and clinical features to differentiate TBPE from non-tuberculous pleural effusion (non-TBPE).MethodsA retrospective study of 125 patients (63 with TBPE; 62 with non-TBPE) was undertaken. Univariate analysis was used to select the laboratory and clinical variables relevant to the model composition. The statistically different variables were selected to undergo binary logistic regression. Variables B coefficients were used to define a numerical score to calculate a scoring model. A receiver operating characteristic (ROC) curve was used to calculate the best cut-off value and evaluate the performance of the model. Finally, we add a validation cohort to verify the model.ResultsSix variables were selected in the scoring model: Age ≤ 46 years old (4.96 points), Male (2.44 points), No cancer (3.19 points), Positive T-cell Spot (T-SPOT) results (4.69 points), Adenosine Deaminase (ADA) ≥ 24.5U/L (2.48 point), C-reactive Protein (CRP) ≥ 52.8 mg/L (1.84 points). With a cut-off value of a total score of 11.038 points, the scoring model’s sensitivity, specificity, and accuracy were 93.7%, 96.8%, and 99.2%, respectively. And the validation cohort confirms the model with the sensitivity, specificity, and accuracy of 92.9%, 93.3%, and 93.1%, respectively.ConclusionThe scoring model can be used in differentiating TBPE from non-TBPE.

The value of interleukin-27 for differentiating tuberculous pleural effusion from Mycoplasma pneumoniae pneumonic effusion in children.

ObjectivesThe early diagnosis of tuberculous pleural effusion (TPE) is challenging due to the difficulty of isolating Mycobacterium tuberculosis, and pleural biomarkers are an optional choice. Recent studies showed that interleukin-27 (IL-27) appears to be a new accurate biomarker for TPE in adults and no related studies were reported in children. In this study, we aimed to evaluate the potential value of IL-27 in pediatric tuberculous pleurisy by detecting its levels in pleural fluid and serum.MethodsA total of 48 children with TPE and 64 children with severe Mycoplasma pneumoniae (MP) pneumonic effusion (SMPPE) were enrolled in this study. IL-27 concentrations were measured in serum and pleural fluid. The diagnostic yield of IL-27 was evaluated using receiver operating characteristic (ROC) curves.ResultsThe level of p-IL-27 in TPE showed statistically no significant difference when compared with SMPPE (p > 0.05). However, pleural fluid IL-27 (p-IL-27) / serum IL-27 (s-IL-27) ratio in TPE were significantly much higher than those in SMPPE (p < 0.05). By the analysis of the ROC curves, the diagnostic sensitivity and specificity of the p-IL-27/s-IL-27 ratio were 100% and 48.44%, respectively (cutoff value of 1.0280). The area under the ROC curve for p-IL-27/s-IL-27 was 0.7295.ConclusionPleural fluid IL-27 alone was not accurate in distinguishing pediatric TPE from SMPPE, which was different from the diagnostic value of IL-27 in adult studies due to the different disease spectra between children and adults. Our results implied that the p-IL-27/s-IL-27 ratio had a potential value in distinguishing TPE from SMPPE. However, the specificity of IL-27 was relatively lower and it is necessary to find a more specific marker in tuberculous pleurisy of children.

Interleukin 32 as a Potential Marker for Diagnosis of Tuberculous Pleural Effusion.

ABSTRACTAccurate differential diagnosis is the key to choosing the correct treatment for pleural effusion. The present study aimed to assess whether interleukin 32 (IL-32) could be a new biomarker of tuberculous pleural effusion (TPE) and to explore the biological role of IL-32 in TPE. IL-32 levels were evaluated in the pleural effusions of 131 patients with undetermined pleural effusion from Wuhan and Beijing cohorts using an enzyme-linked immunosorbent assay method. Macrophages from TPE patients were transfected with IL-32-specific small interfering RNA (siRNA), and adenosine deaminase (ADA) expression was determined by real-time PCR and colorimetric methods. With a cutoff value of 247.9 ng/mL, the area under the curve of the receiver operating characteristic (ROC) curve for IL-32 was 0.933 for TPE, and the sensitivity and specificity were 88.4% and 93.4%, respectively. A multivariate logistic regression model with relatively good diagnostic performance was established. IL-32-specific siRNA downregulated ADA expression in macrophages, and IL-32γ treatment significantly induced ADA expression. Our results indicate that IL-32 in pleural effusion may be a novel biomarker for identifying patients with TPE. In addition, our multivariate model is acceptable to rule in or rule out TPE across diverse prevalence settings. Furthermore, IL-32 may modulate ADA expression in the tuberculosis microenvironment. (This study has been registered at ChiCTR under registration number ChiCTR2100051112 [https://www.chictr.org.cn/index.aspx].)IMPORTANCE Tuberculous pleural effusion (TPE) is a common form of extrapulmonary tuberculosis, with manifestations ranging from benign effusion with spontaneous absorption to effusion with pleural thickening, empyema, and even fibrosis, which can lead to a lasting impairment of lung function. Therefore, it is of great significance to find a rapid method to establish early diagnosis and apply antituberculosis therapy in the early stage. This study indicates that interleukin 32 (IL-32) in pleural effusion is a new high-potency marker to distinguish TPE from pleural effusions with other etiologies. A multivariate model combining age, adenosine deaminase (ADA), lactic dehydrogenase, and IL-32 may reliably rule in TPE in intermediate- or high-prevalence areas. Additionally, we observed that IL-32 might regulate ADA expression in macrophages in the tuberculosis microenvironment. Therefore, this study provides new insights into the role of IL-32 in the tuberculosis microenvironment.

Is GeneXpert MTB/RIF assay reliable for the diagnosis of pleural tuberculosis?

Introduction: Tuberculosis is the most common cause of infectious diseases related mortality globally. Tuberculous pleural effusion is a common presentation of extra pulmonary tuberculosis and a diagnostic challenge most of the time. The rapid diagnosis of tuberculous pleural effusion is essential for early treatment. GeneXpert is a new tool for rapid diagnosis but the ability to correctly diagnose of GeneXpert is a vital concern in the diagnosis of extra pulmonary tuberculosis.&#x0D; Objective: To determine the accurate ability of diagnosing the pleural fluid GeneXpert MTB/RIF assessment in the suspected pleural tuberculosis patients considering as gold standard to the pleural biopsy.&#x0D; Methods: This study was a validational cross sectional survey and it was conducted in pulmonology department of Pakistan Institute of Medical Sciences, Islamabad from 1st July to 31st December 2018 after approval of IRB. Participants with suspected pathology ≥ 18 year with exudative pleural effusion were included in the study. By implementing the process of standard technique, closed needle pleural biopsy was executed by means of ABRAM’S needle. The collected samples of patients were sent to the pathology department of Pakistan Institute of Medical Sciences for histopathology. Pleural fluid was referred to National Institute of Health Islamabad for GeneXpert MTB/RIF assessment on the alike day and reports were assembled. All findings were entered in a structured Proforma. Data was entered in SPSS version 20 and analyzed.&#x0D; Results: Total 180 patients were included; 65.6% patients were male. When the sensitivity of pleural fluid GeneXpert MTB/RIF examination was calculated it was 10.4% whereas, the calculated specificity was 72.8%. While +ve predictive value of GeneXpert was 22.2% and -ve predictive value was 52.1%. Likelihood ratio was 8.25 and ROC curve also showed similar values. &#x0D; Conclusion: The sensitivity of pleural fluid GeneXpert MTB/RIF assay is very low and specificity is moderate for diagnosis of pleural tuberculosis when compared with pleural biopsy.

Comparison of Ziehl Neelsen Stain, Auramine Rhodamine Stain and Culture Sensitivity of AFB in Routine and Concentrated Pleural Fluid

Background: Nearly one third of the global population is infected with mycobacterial tuberculosis. Pleural tuberculosis accounts for 20% of extrapulmonary tuberculosis. The diagnosis of tuberculous pleural effusion is difficult because of the low detection rate of different diagnostic tests like microscopy and culture. Current study aimed to compare the detection rate of different tests in non-concentrated and concentrated pleural fluid.&#x0D; Methods: A hospital based prospective cross sectional study was carried out over one year duration in the Medicine Department of Bir Hospital. A total of 52 cases were enrolled. Detailed history taking and physical examination; radiological, hematological and serum biochemical investigations were performed. Thoracocentesis was performed in all the patients; 20 ml pleural fluid was sent for microscopy with ZN and AR staining as well as for AFB culture. Up to 500ml of pleural fluid was heparinized and kept on cylindrical jar for two hours and 50 ml of sediment was also sent for microscopy and culture within one hour. The results obtained were documented and analysis was done.&#x0D; Results: A total of 52 patients, 31 (59.6%) males and 21 (40.4%) females were included. Their mean age of study participants was 38.67 ± 17.71 (range 16-82 years). Common presentations were fever (94.2%), cough (92.3%), breathlessness (84.6%), chest pain (65.4%) and significant weight loss (59.6%). Haemoptysis was present in 13.5%, anemia in 48.1%, enlarged cervical lymph nodes in 5.8% of the patients. The detection rates of ZN stain, AR stain and AFB culture in non-concentrated pleural fluid were 3.8%, 9.6% and 11.5% respectively. The detection rates for the same tests using concentrated pleural fluid of the same patients were 7.7%, 25% and 17.3% respectively. Differences in detection rate with AR stain and AFB culture for non- concentrated and concentrated pleural fluid were statistically significant (p value &lt;0.01).&#x0D; Conclusion: The detection of AFB using microscopy with ZN and AR staining as well as culture in solid media is low. The detection rate was significantly increased by using concentrated pleural fluid sample for microscopy and culture.

Investigating the appropriate adenosine deaminase cutoff value for the diagnosis of tuberculous pleural effusion in a country with decreasing TB burden

As the burden of tuberculosis (TB) in South Korea decreases while that of malignancy increases with an aging society, the composition of etiology for pleural effusion is changing. The aim of this study was to investigate the diagnostic value of adenosine deaminase (ADA) for diagnosis of tuberculous pleural effusion (TPE) in this circumstance. Medical records of patients who underwent medical thoracoscopy from May 2015 to September 2020 in Incheon St. Mary Hospital, Korea were retrospectively reviewed. TPE was diagnosed if one of the following criteria was met: (1) granuloma in pleura, (2) positive TB polymerase chain reaction or culture in pleural fluid or tissue with non-specific pathologic findings in pleura, or (3) bacteriologically confirmed pulmonary TB with non-specific pathologic findings in pleura. A total of 292 patients, including 156 with malignant pleural effusion (MPE), 52 with TPE, and 84 with other benign effusion, were analyzed. Among 206 patients with lymphocyte dominant pleural effusion, the area under receiver characteristic curve of ADA for diagnosis of TPE was 0.971. The sensitivity and specificity of a current cutoff value of 40 IU/L were 1.00 and 0.61, respectively, whereas those of a raised cutoff value of 70 IU/L were 0.93 and 0.93, respectively. Among 54 patients with ADA levels of 40–70 IU/L, 30 (55.6%) patients were diagnosed as MPE, 21 (38.9%) as other benign effusion, and only 3 (5.6%) as TPE. Caution is needed in clinical diagnosis of TPE with current ADA cutoff value in countries with decreasing TB incidence, due to many false positive cases.

Clinical diagnostic algorithm in defining tuberculous unilateral pleural effusion in high tuberculosis burden areas short of diagnostic tools.

BackgroundEmpirical treatment was introduced when pathological or microbiological results of tuberculosis (TB) were not available. This report was designed to evaluate an algorithm based on empirical treatment in defining tuberculous pleural effusion (TPE) in high burden areas but short of diagnostic tools.MethodsIn this retrospective study, a total of 924 eligible patients were enrolled and 203 (22.0%) were primarily diagnosed as TPE by our diagnostic algorithm based on effusion characteristics [adenosine deaminase (ADA) and exudate] and immunoassays [purified protein derivative (PPD), M. tuberculosis antibody (TB-Ab) and interferon-gamma release assay (IGRA)]. All diagnosed cases received World Health Organization (WHO) standard anti-TB treatment and 187 of them had at least one year of follow-up. The final diagnosis and prognosis of these patients were traced and recorded.ResultsA total of 177 (94.65%) cases benefited from standard treatment, 5 (2.67%) failed due to early termination or drug resistance, and 5 (2.67%) were finally confirmed as misdiagnosis. Regarding diagnostic efficacy, 72 (30.13%) patients received four TB tests, and the combination of the four tests could increase the diagnosis of TPE. Besides, receiving operating characteristics curve (ROC) analysis revealed that our algorithm was the best method to differentiate TPE from malignant pleural effusion (MPE) with higher sensitivity and specificity than other serum markers.ConclusionsThis clinical diagnostic algorithm was an efficient and available method for the diagnosis of TPE. This diagnostic algorithm should be implemented in regions with high TB prevalence but short of diagnostic tools.