Tuberculous Pleural Effusion Patients Research Articles

Enhanced differential evolution algorithm for feature selection in tuberculous pleural effusion clinical characteristics analysis

Tuberculous pleural effusion poses a significant threat to human health due to its potential for severe disease and mortality. Without timely treatment, it may lead to fatal consequences. Therefore, early identification and prompt treatment are crucial for preventing problems such as chronic lung disease, respiratory failure, and death. This study proposes an enhanced differential evolution algorithm based on colony predation and dispersed foraging strategies. A series of experiments conducted on the IEEE CEC 2017 competition dataset validated the global optimization capability of the method. Additionally, a binary version of the algorithm is introduced to assess the algorithm's ability to address feature selection problems. Comprehensive comparisons of the effectiveness of the proposed algorithm with 8 similar algorithms were conducted using public datasets with feature sizes ranging from 10 to 10,000. Experimental results demonstrate that the proposed method is an effective feature selection approach. Furthermore, a predictive model for tuberculous pleural effusion is established by integrating the proposed algorithm with support vector machines. The performance of the proposed model is validated using clinical records collected from 140 tuberculous pleural effusion patients, totaling 10,780 instances. Experimental results indicate that the proposed model can identify key correlated indicators such as pleural effusion adenosine deaminase, temperature, white blood cell count, and pleural effusion color, aiding in the clinical feature analysis of tuberculous pleural effusion and providing early warning for its treatment and prediction.

Pleural Mesothelial Cells-Induced Monocytes to the Pleural Cavity through the Effect of C3 Lytic Products in Tuberculous Pleural Effusion

Background. The activation of complement is involved in monocyte recruitment in tuberculous pleural effusion (TPE), while the role of the cleavage product of complement C3 in this process needs further research. Methods. The expression of complement components in pleural biopsy specimens of TPE patients was measured. The concentration of cleavage products of complement was tested in TPE by ELISA. Moreover, the colocalizations of C3b and CR1, C3d and CR3, and CXCL12 and CXCR4 in monocytes and pleural mesothelial cells (PMCs) isolated from TPE were determined by an immunofluorescent assay. Monocyte chemotaxis assay was analyzed via transwell chambers. Results. Three pathways of the complement system were activated in tuberculous pleurisy. In patients with TPE, C3 lysis was more active than peripheral blood in pleural cavity. Tuberculous protein Mpt64 and anaphylatoxin C3a could significantly promote CXCL12 production in human PMCs isolated from TPE. C3b-CR1, C3d-CR3, and CXCL12-CXCR4 were colocalized in PMCs and monocytes from TPE. The recruitment of monocytes into TPE mediated by PMCs could be inhibited by anti-CR1, anti-CR3, and anti-CXCL12 monoclonal antibodies (mAbs). Conclusions. Complement activates strongly in TPE, and PMCs induced monocytes to the pleural cavity through C3a, C3b, and C3d.

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.

Diagnostic scoring systems for tuberculous pleural effusion in patients with lymphocyte-predominant exudative pleural profile: A development study

BackgroundDiagnosing tuberculous pleural effusion (TPE) in patients presenting with Lymphocyte-Predominant Exudative pleural effusion (LPE) is challenging, due to the poor clinical utility of TB culture. Adenosine deaminase (ADA) has been recommended for diagnosis, but its high cost and limited availability hinder its clinical utility. We aim to develop diagnostic prediction tools for Thai patients with LPE in scenarios where pleural fluid ADA is available but yields negative results and in situations where pleural fluid ADA is not available. MethodsTwo diagnostic prediction tools were developed using retrospective data from patients with LPE at Surin Hospital. Model 1 is for ADA-negative results, and Model 2 is for situations where pleural fluid ADA testing is unavailable. The models were derived using multivariable logistic regression and presented as two clinical scoring systems: round-up and count scoring. The score cut-point that achieves a positive predictive value (PPV) comparable to the post-test probability of a pleural fluid ADA at a cut-point of 40 U/L was used as a threshold for initiating anti-TB treatment. ResultsA total of 359 patients were eligible for analysis, with 166 diagnosed with TPE and 193 diagnosed with non-TPE. Age <40 years, fever, pleural fluid protein ≥5 g/dL, male gender, pleural fluid color, and pleural fluid ADA ≥20 U/L were identified as final predictors. Both models demonstrated excellent discriminative ability (AuROC: 0.85 to 0.89). The round-up scoring demonstrated PPV above 90% at cut-off points of 4 and 4.5, while the count scoring achieved cut-off points of 3 and 4 for Model 1 (Lex-2P2A) and Model 2 (Lex-2P-MAC), respectively. ConclusionThese diagnostic tools offer valuable assistance in differentiating between TPE and non-TPE in LPE patients with negative pleural fluid ADA (Lex-2P2A) and in settings where pleural fluid ADA testing is not available (Lex-2P-MAC). Implementing these diagnostic scores may have the potential to improve TPE diagnosis and facilitate prompt initiation of treatment.

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

Development and validation of a prediction model to assess the probability of tuberculous pleural effusion in patients with unexplained pleural effusion

Differentiating tuberculous pleural effusion (TPE) from non-tuberculosis pleural effusion remains a challenge in clinical practice. This study aimed to develop and externally validate a novel prediction model using the peripheral blood tuberculous infection of T cells spot test (T-SPOT.TB) to assess the probability of TPE in patients with unexplained pleural effusion. Patients with pleural effusion and confirmed etiology were included in this study. A retrospective derivation population was used to develop and internally validate the predictive model. Clinical, radiological, and laboratory features were collected, and important predictors were selected using the least absolute shrinkage and selection operator. The prediction model, presented as a web calculator, was developed using multivariable logistic regression. The predictive performance of the model was evaluated for discrimination and calibration and verified in an independent validation population. The developed prediction model included age, positive T-SPOT.TB result, logarithm of the ratio of mononuclear cells to multiple nuclear cells in pleural effusion (lnRMMPE), and adenosine deaminase in pleural effusion ≥ 40 U/L. The model demonstrated good discrimination [with area under the curve of 0.837 and 0.903, respectively] and calibration (with a Brier score of 0.159 and 0.119, respectively) in both the derivation population and the validation population. Using a cutoff value of 60%, the sensitivity and specificity for identifying TPE were 70% and 88%, respectively, in the derivation population, and 77% and 92%, respectively, in the validation population. A novel predictive model based on T-SPOT.TB was developed and externally validated, demonstrating good diagnostic performance in identifying TPE.

Differentiating between tuberculous and non-tuberculous pleural effusions using the pleural fluid ratio of 10× adenosine deaminase/lactate dehydrogenase.

Adenosine deaminase (ADA) is a sensitive marker of tuberculous pleural effusion (TBPE). However, in pleural effusion (PE), the detection of ADA alone cannot be used to determine whether the increase in the ADA level is caused by the rising proportion of macrophages and lymphocytes in the cell components or by the increase in the total cell number. The diagnostic precision of ADA is probably restricted due to the false positive and negative results. Thus, we explored the clinical value of the ratio of PE ADA to lactate dehydrogenase (LDH) in differentiating between TBPE and non-TBPE. Patients hospitalized with PEs between January 2018 and December 2021 were retrospectively recruited for this study. We analyzed the values of ADA, LDH, and 10× ADA/LDH in the patients with TBPE and non-TBPE. We also determined the sensitivity, specificity, Youden index, and area under the curve for 10× ADA/LDH at different ADA levels and evaluated its diagnostic accuracy. In total, 382 patients with PEs were included in the study. Among whom, 144 were diagnosed with TBPE, this supposes a "pre-test probability" >40%. It is quite high, 134 with malignant PEs, 19 with parapneumonic PEs, 43 with empyema, 24 with transudate PEs, and 18 with other types of PE of a known etiology. The ADA levels were positively correlated with the LDH levels in TBPE. LDH levels usually increase in response to cell damage or cell death. The 10× ADA/LDH level was significantly increased in the TBPE patients. In addition, the 10× ADA/LDH level increased as the ADA level increased in TBPE. To differentiate between TBPE and non-TBPE, the optimal cut-off value of 10× ADA/LDH at different ADA levels was assessed using receiver operating curves. At an ADA level >20 U/L, 10× ADA/LDH showed the best diagnostic performance, and had a specificity and sensitivity of 0.94 (95% CI: 0.84-0.98) and 0.95 (95% CI: 0.88-0.98), respectively. The 10× ADA/LDH dependent diagnostic index can be used to distinguish TBPE from non-TBPE and could be used to guide future clinical decisions.

Different characteristics of pleural abnormalities on computed tomography between tuberculous and malignant pleural effusions

BackgroundComputed tomography (CT) is the mainstay imaging modality for suspected pleural malignancy. Tuberculous pleural effusion (TPE) can present with various pleural abnormalities. However, few studies have evaluated the different characteristics of pleural abnormalities on chest CT between TPE and malignant pleural effusion (MPE). MethodsPleural abnormalities on contrast-enhanced CT in 277 and 289 patients with confirmed TPE and MPE diagnoses, respectively, were retrospectively assessed and compared between the two groups. Discriminating factors and diagnostic performance for MPE were evaluated using multivariate analysis and receiver operating characteristic curves. ResultsFocal pleural thickening was present in 44 (16%) cases of TPEs and 202 (70%) of MPEs. Further characterization of focal pleural thickening showed that MPEs had a significantly greater number, larger maximal thickness, and more nodular contour form, compared to TPEs. On the other hand, diffuse and circumferential pleural thickening were significantly more common in TPEs. In multivariate analysis, independent predictors for MPE included focally thickened pleurae ≥7, maximum thickness ≥6 mm, nodular contour pattern, and the absence of diffuse pleural thickening. Out of all the individual or combined predictors for MPE, the presence of any one of the three sub-parameters of focal pleural thickening provided the best diagnostic yield with 66% sensitivity and 92% specificity. ConclusionAlthough focal pleural thickening in TPE mimics that in MPE, the features of MPE are significantly different from those of TPE in terms of size, number, and contour. These different characteristics may help differentiate MPE from TPE in patients with suspected MPE.

An Observational Study on Clinical Profiles of Tuberculous Pleural Effusion Patients in A Tertiary Care Teaching Hospital, Dhanmondi, Dhaka, Bangladesh

Background: Mycobacterium tuberculosis has infected around 1.7 billion people around the world so far and has been categorized as one of the top 10 causes of mortality globally. The rate of infection is increasing every year mainly 30 high TB burden countries. Due to high density of population every year the number of Tuberculosis (TB) patients are increasing in Bangladesh. Objective: To analyze the clinical profiles and radiological features of the pleural fluid (PF) among tuberculous pleural effusion (TPE) patients attending Bangladesh Medical College, Dhanmondi, Dhaka, Bangladesh. Methods: This is a hospital-record based cross sectional observational study executed in a tertiary care teaching hospital, Dhanmondi, Dhaka. The study group comprises 182 diagnosed tuberculous pleural effusion patients enrolled in our Bangladesh Medical College Hospital from July 2020 to June 2022. Analysis of data was done by using SPSS 15 software. Results: In our observational study we found that tuberculous pleural effusion was predominant in the male gender (62%) with predominant age group of 31-40 years (36.26%). Among various clinical manifestations the predominant features were fever (89.56%), chest pain (63.19%) and night sweats (51.09%). Duration of TPE patients was 16-30 days (69.78%) when they presented to us. During BMI measurements we found that 56.59% of our patients were within normal BMI range and only 7.14% were undernourished indicating the assumption that low BMI or undernutrition is not a vulnerability factor anymore. 72% of our TPE patients belonged from urban locality. During radiological analysis of pleural fluid through chest x ray we have observed that 60.98% cases were right sided small (65.38%) pleural effusion and 36.81% had loculated pleural effusion. 59.89% of our patients got cured with anti TB medications but we lost follow ups to some of our study populations 15.93%. There were no mortality records during our study period. Conclusion: Most common manifestations of tuberculous pleural effusion were low grade fever and chest pain. TPE was predominant among young adults in our study which we need to be more attentive during our diagnosis and treating patients with pleural effusion.

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.

Tuberculous pleural effusion prediction using ant colony optimizer with grade-based search assisted support vector machine.

Although tuberculous pleural effusion (TBPE) is simply an inflammatory response of the pleura caused by tuberculosis infection, it can lead to pleural adhesions and cause sequelae of pleural thickening, which may severely affect the mobility of the chest cavity. In this study, we propose bGACO-SVM, a model with good diagnostic power, for the adjunctive diagnosis of TBPE. The model is based on an enhanced continuous ant colony optimization (ACOR) with grade-based search technique (GACO) and support vector machine (SVM) for wrapped feature selection. In GACO, grade-based search greatly improves the convergence performance of the algorithm and the ability to avoid getting trapped in local optimization, which improves the classification capability of bGACO-SVM. To test the performance of GACO, this work conducts comparative experiments between GACO and nine basic algorithms and nine state-of-the-art variants as well. Although the proposed GACO does not offer much advantage in terms of time complexity, the experimental results strongly demonstrate the core advantages of GACO. The accuracy of bGACO-predictive SVM was evaluated using existing datasets from the UCI and TBPE datasets. In the TBPE dataset trial, 147 TBPE patients were evaluated using the created bGACO-SVM model, showing that the bGACO-SVM method is an effective technique for accurately predicting TBPE.

A novel biomarker for pleural effusion diagnosis: Interleukin‐36γ in pleural fluid

Numerous studies have described the critical importance of interleukin (IL) -36γ in host defense against lung infections, but it is unknown whether it plays a role in infectious pleural effusion (IPE). This study aimed to examine the levels of IL-36γ in pleural effusions of different etiologies and evaluate the diagnostic accuracy of IL-36γ in the differential diagnosis of IPE. A total of 112 individuals was enrolled in this research. IL-36γ levels in pleural fluids of all 112 patients were measured by enzyme-linked immunosorbent assay (ELISA). We also characterized these markers' diagnostic values across various groups. Patients with tuberculous pleural effusion (TPE) and parapneumonic effusion (PPE) had exhibited markedly higher IL-36γ levels in their pleural fluid than the malignant pleural effusion (MPE) and transudative effusion patients. Furthermore, the IL-36γ concentrations in TPE patients were evidently higher than in uncomplicated parapneumonic effusion (UPPE) patients but significantly lower than in complicated parapneumonic effusion (CPPE)/empyema patients. Pleural fluid IL-36γ is a useful marker to differentiate TPE from UPPE, at a cut-off value for 657.5pg/ml (area under the curve=0.904, p < 0.0001) with 70.0% sensitivity and 95.7% specificity. The elevated IL-36γ in pleural effusion may be used as a novel biomarker for infectious pleural effusion diagnosis, particularly in patients with CPPE/empyema, and is a potentially promising biomarker to differentiate between TPE and UPPE.

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 &lt; 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

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.

Monocytes subtypes from pleural effusion reveal biomarker candidates for the diagnosis of tuberculosis and malignancy.

BackgroundPleural effusion is a common clinical condition caused by several respiratory diseases, including tuberculosis and malignancy. However, rapid and accurate diagnoses of tuberculous pleural effusion (TPE) and malignant pleural effusion (MPE) remain challenging. Although monocytes have been confirmed as an important immune cell in tuberculosis and malignancy, little is known about the role of monocytes subpopulations in the diagnosis of pleural effusion.MethodsPleural effusion samples and peripheral blood samples were collected from 40 TPE patients, 40 MPE patients, and 24 transudate pleural effusion patients, respectively. Chemokines (CCL2, CCL7, and CX3CL1) and cytokines (IL‐1β, IL‐17, IL‐27, and IFN‐γ) were measured by ELISA. The monocytes phenotypes were analyzed by flow cytometry. The chemokines receptors (CCR2 and CX3CR1) and cytokines above in different monocytes subsets were analyzed by real‐time PCR. Receiver operating characteristic curve analysis was performed for displaying differentiating power of intermediate and nonclassical subsets between tuberculous and malignant pleural effusions.ResultsCCL7 and CX3CL1 levels in TPE were significantly elevated in TPE compared with MPE and transudate pleural effusion. Cytokines, such as IL‐1β, IL‐17, IL‐27, and IFN‐γ, in TPE were much higher than in other pleural effusions. Moreover, CD14+CD16++ nonclassical subset frequency in TPE was remarkably higher than that in MPE, while CD14++CD16+ intermediate subset proportion in MPE was found elevated. Furthermore, CX3CL1‐CX3CR1 axis‐mediated infiltration of nonclassical monocytes in TPE was related to CX3CL1 and IFN‐γ expression in TPE. Higher expression of cytokines (IL‐1β, IL‐17, IL‐27, and IFN‐γ) were found in nonclassical monocytes compared with other subsets. Additionally, the proportions of intermediate and nonclassical monocytes in pleural effusion have the power in discriminating tuberculosis from malignant pleural effusion.ConclusionsCD14 and CD16 markers on monocytes could be potentially used as novel diagnostic markers for diagnosing TPE and MPE.

Use of Platelet Parameters in the Differential Diagnosis of Lung Adenocarcinoma-Associated Malignant Pleural Effusion and Tuberculous Pleural Effusion.

Background Both malignant pleural effusion (MPE) and tuberculous pleural effusion (TPE) are common etiologies of pleural effusion; the present study was conducted to establish the diagnostic value of platelet parameters in the differential diagnosis of MPE and TPE. Methods This retrospective study enrolled patients with lung adenocarcinoma-associated MPE and TPE. Platelet parameter data, including platelet count (PLT), mean platelet volume (MPV), plateletcrit (PCT), platelet distribution width (PDW), and platelet-larger cell ratio (P-LCR), were collected. Principal component analysis and multiple logistic regression modelling were carried out to assess the diagnostic value of these platelet parameters. Results The MPE group and the TPE group enrolled 270 and 433 patients, respectively. Demographic characteristics of patients were more female and higher age in the MPE group. MPV, PDW, and P-LCR were significantly higher in MPE patients, while PLT and PCT were significantly higher in TPE patients. Principal component analysis generated two principal components (PCs) based on above platelet parameters. After adjusting for confounding factors including gender and age, multiple logistic regression showed positive association between PC1 and MPE. Conclusion Platelet parameters were potential biomarkers in distinguishing lung adenocarcinoma-associated MPE from TPE. A patient with lower PLT and PCT and higher MPV, PDW, and P-LCR was more likely to be diagnosed as the former. Principal component analysis and multiple logistic regression performed well in improving multicollinearity, adjusting confounding factors, and identifying important risk factors for MPE.

Single-cell immune profiling reveals functional diversity of T cells in tuberculous pleural effusion.

Orchestration of an effective T lymphocyte response at infection sites is critical for protection against Mycobacterium tuberculosis (Mtb) infection. However, the local T cell immunity landscape in human tuberculosis is poorly defined. Tuberculous pleural effusion (TPE), caused by Mtb, is characterized by an influx of leukocytes to the pleural space, providing a platform suitable for delineating complex tissue responses to Mtb infection. Using single-cell transcriptomics and T cell receptor sequencing, we analyzed mononuclear cell populations in paired pleural fluid and peripheral blood of TPE patients. While all major cell clusters were present in both tissues, their relative proportions varied significantly by anatomic location. Lineage tracking analysis revealed subsets of CD8 and CD4 T cell populations with distinct effector functions specifically expanded at pleural sites. Granzyme K-expressing CD8 T cells were preferentially enriched and clonally expanded in pleural fluid from TPE, suggesting that they are involved in the pathogenesis of the disease. The findings collectively reveal the landscape of local T cell immunity in tuberculosis.

Development and Validation of a Clinical Prediction Model to Assess the Probability of Tuberculous Pleural Effusion in Patients with Unexplained Pleural Effusion: Diagnostic Study

Development and Validation of a Clinical Prediction Model to Assess the Probability of Tuberculous Pleural Effusion in Patients with Unexplained Pleural Effusion: Diagnostic Study