Non-tuberculous Pleural Effusion Research Articles

Differentiating between tuberculous and non-tuberculous pleural effusion: The role of biochemical analysis

Differentiating between tuberculous and non-tuberculous pleural effusion: The role of biochemical analysis

The regulation and potential role of interleukin-32 in tuberculous pleural effusion.

The possible protective effect of interleukin-32 (IL-32) in Mycobacterium tuberculosis (Mtb) infection has been indicated. However, few studies have been focused on IL-32 in tuberculosis patients. Additionally, the regulation of IL-32 production has rarely been reported. In the present study, the production, regulation, and role of IL-32 in tuberculous pleurisy (TBP) were investigated. We found that the content of IL-32 in tuberculous pleural effusion (TPE) was higher than the level in the malignant pleural effusion and transudative pleural effusion. The level of IL-32 mRNA in pleural fluid mononuclear cells (PFMCs) was higher than that in peripheral blood mononuclear cells (PBMCs) of patients with TBP, and this difference was mainly reflected in the splice variants of IL-32α, IL-32β, and IL-32γ. Compared with the PBMCs, PFMCs featured higher IL-32β/IL-32γ and IL-32α/IL-32γ ratios. In addition, lipopolysaccharide (LPS), Bacillus Calmette-Guérin (BCG), and H37Ra stimulation could induce IL-32 production in the PFMCs. IL-32 production was positively correlated with the TNF-α, IFN-γ, and IL-1Ra levels in TPE, whereas IFN-γ, but not TNF-α or IL-1Ra, could induce the production of IL-32 in PFMCs. Furthermore, IL-32γ could induce the TNF-α production in PFMCs. Monocytes and macrophages were the main sources of IL-32 in PFMCs. Nevertheless, direct cell-cell contact between lymphocytes and monocytes/macrophages plays an important role in enhancing IL-32 production by monocyte/macrophage cells. Finally, compared with the non-tuberculous pleural effusion, the purified CD4+ and CD8+ T cells in TPE expressed higher levels of intracellular IL-32. Our results suggested that, as a potential biomarker, IL-32 may play an essential role in the protection against Mtb infection in patients with TBP. However, further studies need to be carried out to clarify the functions and mechanisms of the IFN-γ/IL-32/TNF-α axis in patients with TBP.

Diagnostic accuracy and microbial profiles of tuberculous pleurisy: a comparative study of metagenomic next generation sequencing and GeneXpert Mycobacterium tuberculosis.

There is a clinical challenge in diagnosing tuberculous pleurisy accurately and promptly, highlighting the urgent need for a rapid and sensitive diagnostic method. This study aimed to evaluate the diagnostic accuracy of metagenomic next-generation sequencing (mNGS) and GeneXpert Mycobacterium tuberculosis (MTB) for identifying tuberculous pleurisy and analyzing the microbial profiles of both tuberculous and non-tuberculous pleural effusions. The study enrolled 31 patients with suspected tuberculous pleurisy, of which 15 were confirmed to have tuberculous pleurisy and subsequently allocated to the tuberculous pleurisy group (TP group), while the remaining 16 individuals were assigned to the non-tuberculous pleurisy group (NTP group). mNGS and GeneXpert MTB were performed on pleural effusion samples, and the diagnostic accuracy of both tests was compared. We employed established formulas to compute crucial indicators, including sensitivity, specificity, missed diagnosis rate, misdiagnosed rate, positive predictive value (PPV), and negative predictive value (NPV). The results showed that both tests had high specificity (100%) and positive predictive value (100%) for detecting tuberculous pleurisy, along with comparable sensitivity (46.67% for mNGS and 40.0% for GeneXpert MTB). Further analysis of the combined efficacy of mNGS and GeneXpert MTB showed that the combined test had a sensitivity of 66.67% and a specificity of 100%. mNGS analysis revealed that MTB was detected in 7 out of 15 patients with tuberculous pleural effusions, while non-tuberculous pleural effusions were associated with a diverse range of microbial genera and species. The most frequently detected genera at the microbial genus level in the NTP group were Microbacterium spp. (6/16), Prevotella spp. (5/16), and Campylobacter spp. (5/16). These findings suggest that mNGS and GeneXpert MTB are useful diagnostic tools for identifying patients with tuberculous pleurisy, and mNGS can provide valuable insights into the microbial profiles of both tuberculous and non-tuberculous pleural effusions.

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.

Enzymes of purine metabolism — biomarkers for the diagnostics of tuberculous pleurisy in patients with HIV infection

The objective of the study was to evaluate the information content of determining the activity of adenosine deaminase and adenosine deaminase-2 in the diagnosis of tuberculous pleurisy in patients with HIV infection.Materials and methods. A total of 378 patients with pleural effusion were retrospectively examined. In 215 cases, tuberculous pleurisy was detected (TP); and 163 patients had non-tuberculous pleural effusion (non-TP). As much as 27 patients in the TP group were HIV co-infected (TP/HIV+), the remaining 188 patients were HIV — negative (TP/HIV–). In all the patients, the activity of total adenosine deaminase (ADA) and its isoenzymes (ADA-1 and ADA-2) in the pleural fluid was determined.Results and discussion. In the TP group, the activity of total ADA (95.5 [67.7; 115.4] versus 82.0 [59.6; 100.0] U/L, p=0.1), ADA-1 (14.2 [5.8; 20.5] versus 12.1 [6.1; 23.7] U/L, p=0.9) and ADA-2 (78,1 [38.1; 93.1] versus 62.4 [35.4; 82.2] U/L, p=0,1) did not depend on HIV status. The activity of these indicators was determined above the threshold level — total ADA in 96.3% and 95.2%, ADA-1 in 25.9% and 30.8% and ADA-2 in 92.6% and 83.3% of cases in the «TP/HIV+» and «TP/HIV–» groups, respectively. A negative correlation between ADA-1 activity and HIV viral load in the group of patients with tuberculous pleurisy and HIV infection (r=–0.45; p=0.008), as well as in the subgroup of TP/HIV+ patients who received (r=–0.9; p=0.008) and in those who didn’t receive ART (r=–0.47; p=0.04) was obtained. Our results show that a total ADA activity increase in the patients with tuberculous pleurisy, regardless of patients’ HIV status, occur due to ADA-2. Thus, the increase in activity of total ADA and ADA-2 in our study was caused by active tuberculosis, not by the presence or absence of HIV co-infection. Also, the ADA-2 activity in HIV-infected patients is likely consistent with ADA-2 important role in cellular immune responses.Conclusion. Our data indicate the participation of purine metabolism enzymes in the pathogenesis of HIV infection. At the same time, adenosine deaminase activity is not a specific biomarker of individual changes characteristic of HIV infection. The study results suggest that the total adenosine deaminase and adenosine deaminase-2 activity increase is a valuable and diagnostically significant marker of tuberculous pleurisy in HIV-infected patients. The value of adenosine deaminase and adenosine deaminase-2 activity remains high even in the patients having severe immunosuppression, which allows them to be actively used for rapid diagnostics and hence, early TB therapy initiation.

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.

Diagnostic Value of Model-Based Iterative Algorithm in Tuberculous Pleural Effusion.

Although there are several diagnostic modalities for tuberculous pleurisy, there is still a lack of easy, cost-effective, and rapid methods for confirming the diagnosis. In order to facilitate clinicians to diagnose patients with tuberculous pleurisy at an early stage, help patients to obtain treatment early, and reduce lung damage, it is hoped that new techniques will be available in the future to help diagnose tuberculous pleurisy rapidly in the clinic. To this end, this paper investigates the problem of bidirectional consistency based on event-triggered iterative learning. Firstly, a dynamic linearized data model of TB pleurisy intelligent system is established using compact-form dynamic linearization method, and a parameter estimation algorithm of TB pleurisy data model is proposed; then, based on this data model, an output observer and a dead zone controller are designed, and an event-triggered distributed model-free iterative learning bidirectional consistency control strategy is constructed by combining with signal graph theory. In this paper, 112 patients with pleural effusion were collected, including 76 patients with confirmed or clinically diagnosed tuberculous pleural effusion and 36 patients with nontuberculous pleural effusion. Pleural effusion T-SPOT.TB, blood T-SPOT.TB, pleural effusion Xpert MTB/RIF, and pleural effusion adenosine deaminase (ADA) tests were performed before treatment in the included patients. The sensitivity of pleural effusion T-SPOT.TB was higher than that of peripheral blood T-SPOT.TB (76.32%, 58/76), pleural effusion Xpert MTB/RIF (65.79%, 50/76), and pleural effusion ADA (28.95%, 22/76); the differences were statistically significant (x2 = 14.74, 25.22, and 76.45, P < 0.01). The specificity of the Xpert MTB/RIF test for pleural effusion (100%, 36/36) was higher than that for pleural effusion T-SPOT.TB (77.78%, 28/36), peripheral blood T-SPOT.TB, and pleural effusion T-SPOT.TB. The sensitivity of the combined Xpert MTB/RIF test (64.47%, 49/76) was lower than that of the pleural effusion T-SPOT.TB alone (97.37%, 74/76).

T Helper Cell Subsets in the Pleural Fluid of Tuberculous Patients Differentiate Patients With Non-Tuberculous Pleural Effusions.

BackgroundTuberculous pleural effusion (TPE) is one of the most common forms of extrapulmonary tuberculosis (Tb). Patients with TPE or malignant pleural effusions (MPE) frequently have a similar lymphocytic pleural fluid profile. Since the etiology of PE in various diseases is different, identifying the cellular components may provide diagnostic clues for understanding the pathogenesis.ObjectiveWe determined the frequency of T helper (Th) subtypes in the PEs for differentiation of Tb and non-Tb patients.MethodsThirty patients with TPE, 30 patients with MPE, 14 patients with empyema (EMP), and 14 patients with parapneumonic effusion (PPE) were enrolled between December 2018 and December 2019. Five-milliliter fresh PE in tubes containing heparin as an anticoagulant was obtained from patients. The frequencies of CD4+IL-9+, CD4+IL-22+, CD+IL-17+, and regulatory T-cells CD4+CD25+ FOXP3+ (Treg) were determined by flow cytometry.ResultsTreg cells have a lower frequency in TPE patients [4.2 (0.362–17.24)] compared with non-TPE patients [26.3 (3.349–76.93, p < 0.0001)]. The frequency of CD4+IL-9+ cells was significantly lower in TPE patients [3.67 (0.87–47.83)] compared with non-TPE groups [13.05 (1.67–61.45), p < 0.0001]. On the contrary, there was no significant difference in the frequency of CD4+IL-17+ and CD4+IL-22+ cells between TPE and non-TPE patients (p = 0.906 and p = 0.2188). Receiver-operator curve (ROC) analysis demonstrated that CD4+CD25+FOXP3+ T cells [optimal cutoff value = 13.6 (%), sensitivity 90%, specificity 75.86%] could be considered as predictor for TPE. However, adenosine deaminase [cutoff value 27.5 (IU/l), sensitivity 90%, specificity 96.5%] levels had an even greater predictive capacity.ConclusionADA, Treg cells, and CD4+IL-9+ cells may differentiate TPE from non-TPE patients. However, these results need validation in an independent large cohort.

Complement Component C1q as an Emerging Biomarker for the Diagnosis of Tuberculous Pleural Effusion.

Background and Objective: The accurate differential diagnosis of tuberculous pleural effusion (TPE) from other exudative pleural effusions is often challenging. We aimed to validate the accuracy of complement component C1q in pleural fluid (PF) in diagnosing TPE.Methods: The level of C1q protein in the PF from 49 patients with TPE and 61 patients with non-tuberculous pleural effusion (non-TPE) was quantified by enzyme-linked immunosorbent assay, and the diagnostic performance was assessed by receiver operating characteristic (ROC) curves based on the age and gender of the patients.Results: The statistics showed that C1q could accurately diagnose TPE. Regardless of age and gender, with a cutoff of 6,883.9 ng/mL, the area under the curve (AUC), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of C1q for discriminating TPE were 0.898 (95% confidence interval: 0.825–0.947), 91.8 (80.4–97.7), 80.3 (68.2–89.4), 78.9 (69.2–86.2), and 92.5 (82.6–96.9), respectively. In subgroup analysis, the greatest diagnostic accuracy was achieved in the younger group (≤ 50 years of age) with an AUC of 0.981 (95% confidence interval: 0.899–0.999) at the cutoff of 6,098.0 ng/mL. The sensitivity, specificity, PLR, NLR, PPV, and NPV of C1q were 95.0 (83.1–99.4), 92.3 (64.0–99.8), 97.4 (85.2–99.6), and 85.7 (60.6–95.9), respectively.Conclusion: Complement component C1q protein was validated by this study to be a promising biomarker for diagnosing TPE with high diagnostic accuracy, especially among younger patients.

Diagnostic Accuracy of Adenosine deaminase enzyme (ADA) in the diagnosis of tuberculous pleural effusion

Objective: To study the diagnostic accuracy of Adenosine deaminase enzyme (ADA) in the diagnosis of tuberculous pleural effusion (TPE).Material and Methods: It was a cross-sectional descriptive study conducted in the Pulmonology departments of Lady Reading and Khyber Teaching Hospital Peshawar and department of Pathology, Khyber Medical College, Peshawar from April 2015 to Jan 2016. A total of 210 tuberculous and non-tuberculous pleural effusion patients were selected through consecutive non-probability sampling techniques. After physical and systemic examination, 3cc of pleural fluid was taken. ADA was estimated by Non-Guisti and Galanti method through the simple colorimetric method. All the data was entered in a specially designed proforma and SPSS v16 was used for statistical analysis.Results: Out of 210 tuberculous and non-tuberculous pleural effusions, the commonest cause of pleural effusion was tuberculosis followed by malignancy. In our study, Pleural fluid ADA levels have sensitivity, specificity, positive predictive value( PPV), and negative predictive value (NPV) of 95.5%, 92.3%, 92.4%, and 96% respectively in differentiating tuberculous pleural effusions from non-tuberculous lymphocytes predominant pleural effusions. Conclusion: Tuberculosis is the commonest infectious disease worldwide. A pleural fluid ADA level of ≥ 35 U/L in lymphocyte-predominant effusions makes mycobacterium tuberculosis most likely etiology. This test is not only very sensitive and specific but also it is very cheap, quick, and easy to perform by routine colorimetric method.&#x0D;

Diagnostic Accuracy of Pleural Fluid Adenosine Deaminase Level Test in Tuberculous Pleural Effusion

Background: Tuberculous pleural effusion is a paucibacillary manifestation of tuberculosis, so isolation of Mycobacterium tuberculosis is difficult, biomarkers being an alternative for diagnosis. Adenosine deaminase has the potential to optimize the diagnostic approach of tuberculous pleural effusion.&#x0D; Methods: This study is a diagnostic test observational (cross-sectional), which included 35 inpatient samples that meet inclusion and exclusion criteria from H. Adam Malik Medan General Hospital. Research began on February 1st until July 31st 2016 to examine 10 cc of pleural fluid specimens for the levels of Adenosine deaminase.&#x0D; Results: There are significant differences in the levels of adenosine deaminase from tuberculous and non-tuberculous pleural effusion (P=0.001). In the cut-off point 36.55 IU/L, level of sensitivity 95.8%, specificity 90.99%, positive predictive value 95.8%, negative predictive value 90.99%, and accuracy 94.2% of pleural fluid adenosine deaminase level test in tuberculous pleural effusion. &#x0D; Conclusion: Adenosine deaminase pleural fluid can be a diagnostic modality that is easy, fast, relatively affordable and applicable in the diagnosis of tuberculous pleural effusion. (J Respir Indo. 2017; 37(4): 278-82)

Pleural Fluid Adenosine Deaminase Values in Diagnosis of Tuberculous Pleural Effusion in South Khorasan Province

Background: Due to variability of pleural fluid ADA measures in pleural tuberculosis, researchers have recommended the necessity of regional studies for determination of specific regional values. Objectives: The purpose of the present study was to evaluate the values of pleural fluid ADA in diagnosis of Tuberculous pleural effusion in South Khorasan province. Methods: A cross-sectional study was conducted on patients > 12 years old with exudative pleural effusion in South Khorasan province (east of Iran). Light criteria were used to define exudative effusion. Total ADA was determined calorimetrically by Diazyme ADA assay. The data were analyzed using t test, ANOVA and χ2 tests through Spss 16 version software. Results: We studied 255 cases including 139 (54.5%) males and 116 (45.5%) females with mean age of 63.8 ± 18 years. There were 36 (14.1%) cases with Tuberculous pleural effusion and 219 (85.9%) cases of non-Tuberculous pleural effusion. Malignant and acute bacterial infection comprise 106 (41.6%) and 29 cases (11.4%), respectively. The mean levels and optimal cut off point of ADA in Tuberculous pleural effusion were40.2 ± 24.7 and 30 IU/L respectively. ADA in Tuberculous pleural effusion showed negative correlation with age (r = -0.40, p = 0.01), but weak positive correlation with fluid protein(r = 0.44, P = 0.007) and LDH (r = 0.32, P = 05). Conclusions: Mean and cut off point of ADA was relatively low in patients with Tuberculous pleural effusion in South Khorasan province. The age of patients and fluid levels of protein, and LDH must be considered in interpretation of pleural fluid ADA levels.

Utility of adenosine deaminase (ADA), PCR & thoracoscopy in differentiating tuberculous & non-tuberculous pleural effusion complicating chronic kidney disease

Utility of adenosine deaminase (ADA), PCR & thoracoscopy in differentiating tuberculous & non-tuberculous pleural effusion complicating chronic kidney disease

A study of pleural effusion with reference to different diagnostic modalaties

Background: Aim of current study was to determine the different etiologies of pleural effusion and efficacy of diagnostic methods. Methods: 100 patients of pleural effusion of both sexes were taken randomly coming to our institution either indoor or OPD. Inclusion criteria: 100 patients of pleural effusion of any age and of either sex in whom thoracentesis can yield minimum amount of pleural fluid for diagnostic purposes. Exclusion criteria: Patients of pleural effusion in whom fluid could not be aspirated were excluded from the study. Results: In this study 70% of the patients were male and 30% were female. Most of the patients were between 21-30 years of age. 92% of the pleural effusion was exudative and 8% was transudative. Tuberculosis is the most common (44%) cause of pleural effusion followed by malignancy (23%), 5% of the patients remains undiagnosed. Sensitivity, specificity, NPV, PPV of Light’s criteria is 100% to differentiate between transudates and exudates. Among parameters of Light's criteria pleural LDH has highest specificity (100) and sensitivity (100) and NPV (80%). Sensitivity, specificity, NPV, PPV of ADA to differentiate between tuberculous and non tuberculous pleural effusion is 100%, 95%, 100%, 96.77% respectively. Pleural biopsy was positive in 80% of the tuberculous patients while in malignancy it was positive only in 20% of the patients. Conclusions: Tuberculosis remains to be main cause of pleural effusion in India. Light’s criteria is most specific & sensitive to diagnose between exudative & transudative pleural fluid. ADA is highly sensitive & specific to differentiate between tuberculous & nontuberculous pleural effusion. In centres where thorascopy is not available for undiagnostic cases of pleural effusion, pleural biopsy can be helpful in fair no. of cases for diagnosis.

Utility of adenosine deaminase (ADA), PCR & thoracoscopy in differentiating tuberculous & non-tuberculous pleural effusion complicating chronic kidney disease.

Pleural effusion is a common occurrence in patients with late-stage chronic kidney disease (CKD). In developing countries, many effusions remain undiagnosed after pleural fluid analysis (PFA) and patients are empirically treated with antitubercular therapy. The aim of this study was to evaluate the role of adenosine deaminase (ADA), nucleic acid amplification tests (NAAT) and medical thoracoscopy in distinguishing tubercular and non-tubercular aetiologies in exudative pleural effusions complicating CKD. Consecutive stage 4 and 5 CKD patients with pleural effusions underwent PFA including ADA and PCR [65 kDa gene; multiplex (IS6110, protein antigen b, MPB64)]. Patients with exudative pleural effusion undiagnosed after PFA underwent medical thoracoscopy. All 107 patients underwent thoracocentesis with 45 and 62 patients diagnosed as transudative and exudative pleural effusions, respectively. Twenty six of the 62 patients underwent medical thoracoscopy. Tuberculous pleurisy was diagnosed in six while uraemic pleuritis was diagnosed in 20 subjects. The sensitivity and specificity of pleural fluid ADA, 65 kDa gene PCR, and multiplex PCR were 66.7 and 90 per cent, 100 and 50 per cent, and 100 and 100 per cent, respectively. Thoracoscopy was associated with five complications in three patients. Uraemia remains the most common cause of pleural effusion in CKD even in high TB prevalence country. Multiplex PCR and thoracoscopy are useful investigations in the diagnostic work-up of pleural effusions complicating CKD while the sensitivity and/or specificity of ADA and 65 kDa gene PCR is poor.

Evaluation of pleural effusion sCD26 and DPP-IV as diagnostic biomarkers in lung disease

In this study, we measured ADA and DPP-IV enzymatic activity and sCD26 concentration in 150 pleural effusion (PE) samples and tested for correlations between these and other cellular and biochemical measures. We found that DPP-IV in particular might improve the specificity (but not the sensitivity) of the ADA test for diagnosis of pulmonary tuberculosis, since half of the false ADA positive results in non-tuberculous PE were also DPP-IV positive. A percentage of patients with malignant PE were sCD26 or DPP-IV positive; however, some patients with benign PE also tested positive. As a pattern associated with DPP-IV (but not the CD26 protein) was observed in PE, we searched for a finding that might increase the value of these biomarkers for diagnosis of malignancy. The observed pattern was related to the presence of leukocytes, as indicated by correlations with the cell count, and to a band of 180 kDa, detected by immunoblotting.

High pleural fluid adenosine deaminase levels: a valuable tool for rapid diagnosis of pleural TB in a middle-income country with a high TB/HIV burden.

South Africa has the highest burden of tuberculosis (TB) in the World Health Organization (WHO) African region. Using traditional TB diagnostic tools, the diagnosis of pleural TB (PTB) is highly unrewarding. Elevated levels of pleural fluid adenosine deaminase (FADA) have been shown to be useful in the diagnosis of PTB; however, similar levels may be found in some other medical conditions leading to misdiagnosis. Following queries from clinicians concerning the likely high false-positive (FP) rate of FADA from our laboratory, we performed a retrospective audit of all high FADA results generated over a 12-month period. To determine the positive predictive value (PPV) of FADA, the frequent causes of FPs in our laboratory and the demographic characteristics of tuberculous pleural effusions (TPEs) and non-tuberculous pleural effusions (NTPEs). High FADA results generated in the past year were extracted with corresponding TB culture results, fluid cell count, cytology/ histology results, radiology reports and HIV results. Hospital records were reviewed for the final diagnosis in each case. Diagnosis of PTB was based on the WHO case definition of TB. A total of 159 results were reviewed: 133 (83.6%) were TPE, hence FADA had a PPV of 83.6%. Neoplasm was the most common cause of an FP in 13/26 (50%) NTPEs. While TPE was more common than NTPE in younger people, both groups had an equal gender distribution. FADA had a high PPV for PTB in our laboratory. We recommend its continued use as a rapid and reliable diagnostic tool for PTB.

Diagnostic performance of different pleural fluid biomarkers in tuberculous pleurisy.

Due to the paucibacillary nature of tuberculous pleural effusion the diagnosis of pleural tuberculosis is challenging. This prospective study was undertaken to evaluate the diagnostic performance of ten different pleural fluid biomarkers in the differentiation between tuberculous and non-tuberculous pleural effusions. Two hundred and three patients with pleural effusion (117 men and 86 women, median age 65 years) were enrolled. Routine diagnostic work-up, including thoracentesis and pleural fluid analysis, was performed to determine the cause of pleural effusion. The following biomarkers were measured in pleural fluid: adenosine deaminase (ADA), interferon gamma (IFN-γ), interleukin 2 soluble receptor (IL-2sRα), sub-unit p40 of interleukin 12b (IL-12p40), interleukin 18 (IL-18), interleukin 23 (IL-23), IFN-γ induced protein 10 kDa (IP-10), Fas-ligand, human macrophage-derived chemokine (MDC) and tumor necrosis factor alfa (TNF-α). There were 44 (21.7%) patients with tuberculous pleural effusion, 88 (43.3%) patients with malignant pleural effusion, 35 (17.2%) with parapneumonic effusion/pleural empyema, 30 (14.8%) with pleural transudates, and 6 (3%) with miscellaneous underlying diseases. Pleural fluid IFN-γ was found the most accurate marker differentiating tuberculous from non-tuberculous pleural effusion, with sensitivity, specificity, PPV, NPV, and AUC 97%, 98%, 95.5%, 99.4%, and 0.99, respectively. Two other biomarkers (IP-10 and Fas ligand) also showed very high diagnostic accuracy with AUC≥0.95. AUC for ADA was 0.92. We conclude that IFN-γ, IP-10, and Fas-ligand in pleural fluid are highly accurate biomarkers differentiating tuberculous from non-tuberculous pleural effusion.