Tuberculous Pleural Effusion Research Articles

Optimising the utility of pleural fluid adenosine deaminase for the diagnosis of tuberculous pleural effusion

Introduction: Pleural fluid adenosine deaminase (pfADA) is a simple, rapid and inexpensive surrogate marker for tuberculous pleural effusion (TPE). A nationwide cut-off of 40 U/L is currently used based on overseas data. There is a need to optimise the diagnostic utility of pfADA by establishing a local cut-off value. In this study, we aimed to describe the demographics and clinical characteristics of patients with TPE and non-TPE; determine the sensitivity and specificity of current pfADA of 40 U/L; and establish a new local pfADA cut-off for TPE. Methods: We conducted a single-centre, observational, prospective study of patients with exudative pleural effusion and pfADA measured from 1 October 2019 to 30 April 2020 at Queen Elizabeth Hospital, Malaysia. Results: The diagnosis of analysed patients ( n = 93) included TPE ( n = 41), malignancy ( n = 28), parapneumonic effusion ( n = 12) and other causes ( n = 12). The mean pfADA was 51.15 U/L (standard deviation (SD) = 13.77) among TPE group and 18.86 U/L (SD = 12.33) among non-TPE. When analysis was restricted to TPE patients, the local pfADA cut-off is 29.6 U/L, with a sensitivity of 97.6% and specificity of 90.4%. The current pfADA of 40 U/L has a sensitivity of 87.8% and specificity of 92.3%. Conclusion: We established a local pfADA cut-off of 29.6 U/L for TPE. Optimising the utility of pfADA helps to enhance clinicians’ treatment confidence of TPE when initial work-up is inconclusive.

Accumulation of TNFR2-expressing regulatory T cells in malignant pleural effusion of lung cancer patients is associated with poor prognosis.

BackgroundRegulatory T cells (Tregs) may represent a major cellular mechanism in immune suppression by dampening the anti-tumor response in malignant pleural effusion (MPE). Tumor necrosis factor receptor type II (TNFR2) has emerged as a novel identification for the maximally suppressive subset of Tregs in the tumor environment. At present, the significance of TNFR2 expression on Tregs in MPE remains unclear.MethodsThe distribution of TNFR2+cells in Tregs and effector T cells (Teffs) in MPE, peripheral blood (PB), and tuberculosis pleural effusion (TPE) were determined. The associations between TNFR2+Tregs frequencies present in MPE and the clinical and laboratorial characteristics of patients with lung cancer were investigated. The immunosuppressive phenotype of TNFR2+Tregs in MPE was analyzed. The effects of the TNF-TNFR2 interaction on the immunosuppressive function of Tregs was explored. The efficacy of targeting TNFR2 for MPE therapy was examined. The source of TNF in MPE was identified.ResultsWe observed that markedly higher levels of TNFR2 were expressed in MPE Tregs compared with the levels expressed in MPE Teffs, PB Tregs, or in TPE Tregs. The frequencies of TNFR2+Tregs were positively correlated with the number of tumor cells in MPE, as well as the volume of MPE. High frequencies of TNFR2+Tregs in MPE indicated short survival time and poor performance status for MPE patients. Compared to TNFR2-Tregs, TNFR2+Tregs expressed higher levels of immunosuppressive molecules cytotoxic T lymphocyte-associated protein 4 (CTLA-4), programmed cell death-ligand 1 (PD-L1), and replicating marker Ki-67. Consequently, the proportions of interferon gamma (IFN-γ)-producing cytotoxic T lymphocytes (CTLs) were significantly increased after TNFR2 blockade. Furthermore, tumor necrosis factor (TNF), through interaction with TNFR2, enhanced the suppressive capacity of Tregs by up-regulating CTLA-4 and PD-L1 expression. Interestingly, T helper 1 (Th1) and T helper 17 (Th17) cells are the major source of TNF in MPE, suggesting that MPE Teffs may paradoxically promote tumor growth by boosting MPE Treg activity via the TNF-TNFR2 pathway.ConclusionsOur data expanded the immunosuppressive mechanism present in MPE induced by Tregs, and provides novel insight for the diagnosis, disease evaluation, and treatment of MPE patients.

Host-Derived Lipids from Tuberculous Pleurisy Impair Macrophage Microbicidal-Associated Metabolic Activity

Mycobacterium tuberculosis (Mtb) regulates the macrophage metabolic state to thrive in the host, yet the responsible mechanisms remain elusive. Macrophage activation toward the microbicidal (M1) program depends on the HIF-1α-mediated metabolic shift from oxidative phosphorylation (OXPHOS) toward glycolysis. Here, we ask whether a tuberculosis (TB) microenvironment changes the M1 macrophage metabolic state. We expose M1 macrophages to the acellular fraction of tuberculous pleural effusions (TB-PEs) and find lower glycolytic activity, accompanied by elevated levels of OXPHOS and bacillary load, compared to controls. The eicosanoid fraction of TB-PE drives these metabolic alterations. HIF-1α stabilization reverts the effect of TB-PE by restoring M1 metabolism. Furthermore, Mtb-infected mice with stabilized HIF-1α display lower bacillary loads and a pronounced M1-like metabolic profile in alveolar macrophages (AMs). Collectively, we demonstrate that lipids from a TB-associated microenvironment alter the M1 macrophage metabolic reprogramming by hampering HIF-1α functions, thereby impairing control of Mtb infection.

Diagnostic Value of Soluble Form of Mer Tyrosine Kinase (sMerTK) in Tuberculous Pleural Effusion and Malignant Pleural Effusion

Objectives. With the development of proteomics, it has been indicated that differentially expressed proteins are biological markers for the diagnosis of different types of pleural effusion (PE). The aim of our study was to explore the value of sMerTK (soluble form of Mer tyrosine kinase) in the differential diagnosis of tuberculous pleural effusion (TPE) and malignant pleural effusion (MPE). In addition, we also wanted to explore whether MerTK was associated with IL-1β and TNF-α, which are inflammatory factors related to pleural effusion. Methods. We screened all patients who underwent thoracoscopy and had a definite diagnosis. In total, 136 patients were enrolled in this study and classified into two groups, with 64 patients in the TPE group and 72 patients in the MPE group. The concentrations of sMerTK in the TPE and MPE groups were detected by ELISA. The diagnostic accuracy was determined by generating receiver operating characteristic (ROC) curves and calculating the area under the curve (AUC). Correlations between the expression level of sMerTK and those of the inflammatory factors interleukin 1 beta (IL-1β) and tumor necrosis factor alpha (TNF-α) were also studied using Pearson’s linear correlation analysis. Results. The concentrations of sMerTK were 5,278.77 ± 2,479.98 ng / L and 859.91 ± 540.45 ng / L in the TPE and MPE groups, respectively. The concentration of sMerTK in TPE was shown to be significantly higher than that in MPE ( P < 0.05 ). The area under the ROC curve for sMerTK in distinguishing TPE from MPE was 0.958, with a cutoff value of 2,122 ng/L. The sensitivity and specificity for sMerTK were 98.61% and 90.63% ( P < 0.05 ). The expression levels of sMerTK in these two groups were not correlated with those of the inflammatory factors IL-1β and TNF-α ( P > 0.05 ). Conclusions. The expression level of sMerTK in PE could be a potential biomarker for common use in the diagnosis of TPE and MPE.

Imprint Cytology of Thoracoscopic Pleural Biopsy Tissue for Early Etiological Diagnosis of Pleural Effusion: A Pilot Study From India.

Thoracoscopic pleural biopsy provides the highest diagnostic yield in both malignant and tubercular pleural effusions. However histopathologic report takes 3 to 5 days to provide the diagnosis, resulting in a delay of further management plans like pleurodesis or chest tube removal. Imprint cytology of biopsy tissue can provide early information about the etiological diagnosis. Thus, we conducted this pilot study in 66 patients of exudative pleural effusions undergoing medical thoracoscopy. One or 2 biopsy pieces obtained during medical thoracoscopy from pleural nodules were used to prepare imprint cytology slides in the thoracoscopy suite. In comparison to thoracoscopic pleural biopsy, the diagnostic yield of imprint cytology of pleural tissue was 92% (49 of 53 cases) in cases of malignant pleural effusion and 75% (9 of 12 cases) in cases of tuberculosis pleural effusions. Imprint cytology provided a definite idea about the type of diagnosis, about 2.5 days before the histopathology results. By providing early etiological diagnosis, it may also decrease the duration of hospital stay and health care expenditure. A large prospective trial has been planned in our center to confirm this hypothesis.

Easy-to-Use Scoring System Based on CT Pleural Fluid and Blood Features for Discriminating Malignant Pleural Effusions from Tuberculous Pleural Effusions: A Retrospective and Prospective Validation Study

Background: Distinguishing malignant pleural effusion (MPE) from tuberculous pleural effusion (TPE) is a challenge when symptom is atypical. Computed tomography (CT) scans and biochemical indicators are the most commonly used methods to evaluate pulmonary and pleural diseases, and the role of CT features (especially pleural and pleural fluid features) in the diagnosis of MPE or TPE is poorly described. Therefore, this study aims to establish and verify diagnostic models based on the characteristics of pleural and pleural effusion for the differential diagnosis of MPE and TPE. Methods: In this study, a first batch of 986 patients from Wuhan union hospital and Wuhan Jinyintan Hospital in the training set was used to develop differential diagnosis models. The CT features (including maximum pleural thickness at the non-mass/nodule, density of the pleural effusion, pleural mass/nodule, mediastinal pleural involvement, pleural wrap, pleural calcifications) and biochemical markers (including serum carcinoembryonic antigen (CEA), and adenosine deaminase (ADA) in the pleural fluid) were collected and subjected to logistic regression analyses. Then, two models were constructed: a model based on CT features (Model 1) and a model based on pleural fluid markers with or without blood biochemical markers (Models 2a/2b). The differential diagnostic model was displayed in the form of nomograms, which were validated by an independent prospective cohort (N=422). Findings: In the training set, eight variables were selected as significant risk factors for distinguishing MPE from TPE after multivariable regression analyses, i.e. age, sex, maximum pleural thickness at the non-nodule/mass, pleural fluid density, pleural nodule/mass, serum CEA, effusion CEA and effusion ADA. In Model 1, the area under the Receiver Operating Characteristic Curve (AUROC) was 0.970, yielding a sensitivity and specificity of 91.07% and 89.86% respectively in the training set, and AUROC = 0.968, sensitivity and specificity was 93.85% and 87.73% respectively in the validation set. In Model 2a, the AUROC, sensitivity and specificity for distinguishing MPE from TPE were 0.976, 92.73% and 93.66% in the training set, respectively, and 0.959, 93.50% and 87.84% in the validation set, respectively. In Model 2b, the AUROC, sensitivity and specificity for distinguishing MPE from TPE were 0.970, 94.87% and 90.87% in the training set, respectively, and 0.962, 96.77% and 80.25% in the validation set, respectively. There were no significant differences between the three models. Interpretation: CT features of pleura and pleural fluid could effectively help physicians differentiate between MPE and TPE, which were readily acquired and could be used as a non-invasive and convenient diagnostic tool in clinical practice. Trial Registration: This study was registered on the Clinical Trials website (No. NCT03997669). Funding Statement: This research was supported by the National Natural Science Foundation of China (No. 81770096; No. 81800094), the National Science and Technology Key Project (No. 2019ZX09301001). Declaration of Interests: The authors declare no competing non-financial/financial interests. Ethics Approval Statement: This study was approved by the Institutional Review Board of the Tongji Medical College, Huazhong University of Science and Technology, and supported by the Wuhan Clinical Research Center for Pleural Diseases

A Prospective Study for comparison of diagnostic utility of Gene XPERT MTB/RIF Assay, adenosine deaminase and cytology in Tuberculous Pleural Effusion

Introduction: Tubercular pleural effusion is the second most common extrapulmonary form of tuberculosis in India. It poses several health challenges in a developing country like India which has limited resources, for developing appropriate methods to diagnose. Aim: The objective of the study was to determine the role of cartridge-based nucleic acid amplification test (CBNAAT) in the diagnosis of tubercular pleural effusion (TPE) and compare it with the diagnostic utility of Adenosine Deaminase (ADA) and lymphocyte counts in pleural fluid. Methods: Total 100 patients were selected from July 2019 to December 2019. Pleural fluid was collected in sterile container. Gene/xpert, Adenosine deaminase, total leukocytes count and lymphocytes percentage were evaluated. Results: It was found that high leukocytes count and lymphocyte predominance was present in >80% of the patient. Mean ADA was 68.7 U/L 13.2 (SD). CBNAAT was positive in 30 patients. Acid fast bacilli stain was negative in the entire patient. Conclusion: The usefulness of Xpert MTB/RIF to diagnose pleural TB is limited by its poor sensitivity. A high ADA40 U/L in combination with Light’s criteria to define exudates, with lymphocyte predominance is sufficient evidence to diagnose tuberculous pleural effusion and initiate anti-tubercular therapy, thereby deferring the need to perform an invasive pleural biopsy. Keywords: Tuberculosis, Xpert MTB/RIF, Adenosine deaminase, Lymphocytes, Pleural fluid.

Laboratory and radiological discrimination between tuberculous and malignant pleural effusions with high adenosine deaminase levels.

Background/AimsPleural fluid adenosine deaminase (ADA) levels are useful in discriminating tuberculous pleural effusions (TPEs) from malignant pleural effusions (MPEs). However, some patients with MPE exhibit high-ADA levels, which may mimic TPEs. There is limited data regarding the differential diagnosis between high-ADA MPE and high-ADA TPE. This study aimed to identify the predictors for distinguishing high-ADA MPEs from high-ADA TPEs.MethodsPatients with TPE and MPE with pleural fluid ADA levels ≥ 40 IU/L were included in this study. Clinical, laboratory, and radiological data were compared between the two groups. Independent predictors and their diagnostic performance for high-ADA MPEs were evaluated using multivariate logistic regression analysis and receiver operating characteristic curve.ResultsA total of 200 patients (high-ADA MPE, n = 30, and high-ADA TPE, n = 170) were retrospectively included. In the multivariate analysis, pleural fluid ADA, pleural fluid carcinoembryonic antigen (CEA), and pleural nodularity were independent discriminators between high-ADA MPE and high-ADA TPE groups. Using pleural ADA level of 40 to 56 IU/L (3 points), pleural CEA level ≥ 6 ng/mL (6 points), and presence of pleural nodularity (3 points) for predicting high-ADA MPEs, a sum score ≥ 6 points yielded a sensitivity of 90%, specificity of 96%, positive predictive value of 82%, negative predictive value of 98%, and area under the receiver operating characteristic curve of 0.965.ConclusionsA scoring system using three parameters may be helpful in guiding the differential diagnosis between high-ADA MPEs and high-ADA TPEs.

Levels of YKL-40 in pleural effusion and blood from patients with pleuritis.

In recent years, there have been a significant increase in the tests and biomarkers available for pleural fluid analysis. YKL-40 is one of the inflammatory biomarkers that is used for this purpose. The aim of our study is to assess the levels and diagnostic values of YKL-40 in patients with different types of pleural effusions (PE). This was a prospective, observational and crosssectional study. Pleural and serum YKL-40 levels were measured using enzyme-linked immunosorbent assay in 119 patients with PEs, including 23 transudates PE, 47 malignant PE, 26 parapneumonic PE (PPPE), 17 paramalignant PE (PME) and 6 tuberculous PE (TBPE). Median pleural YKL-40 level was higher in exudates (390.3 ng/mL) than in transudates (369.5 ng/mL) (p<0.02). For a cut-off level of 378 ng/mL, it was found to predict exudates with 70% sensitivity and 64% specificity. [area under the curve (AUC)= 0.660, p= 0.01]. Median pleural YKL-40 level was highest in PMEs (407.1 ng/mL) and the lowest in transudates (369.5 ng/ mL) and high levels, with a cut-off value of 396 ng/mL, differentiated PMEs from other subgroups with 65% sensitivity and 68% specificity. (AUC= 0.680, p= 0.02). Median serum YKL-40 level was the highest in PPPEs (351.4 ng/mL) and the lowest in TBPEs (114.2 ng/mL) (p= 0.01). For a cut-off level of 284 ng/mL, it differentiated PPPEs from TBPEs with 61% sensitivity and 100% specificity (AUC= 0.830, p= 0.01). In TBPEs, pleural/serum YKL-40 ratio was strongly related with pleural ADA (r= 1, p= 0.04). Pleural YKL-40 may be useful for differentiating exudates and detecting PMEs. Serum YKL-40 may be good diagnostic biomarker for differentiating PPPEs and TBPEs. Additionally, measuring serum and pleural YKL-40 and pleural ADA may be reliable way to diagnose TBPEs.

Detection of Klebsiella pneumoniae cfDNA in pleural fluid and its clinical value

Klebsiella pneumoniae (KP) is an important opportunistic pathogen that can easily cause pneumonia and pleural effusion when body resistance is reduced. However, the positive rate of KP detected from clinical pleural effusion by traditional methods, including bacterial culture, is meager. Therefore, new detection methods are urgently needed to improve the positive detection rate of KP and other bacteria in pleural effusion. Simulated pleural fluid of KP infection was first set up. Then circulating cell-free DNA (cfDNA) was extracted from cultured hydrothorax and detected by fluorescence polymerase chain reaction (PCR) to verify KP cfDNA in the pleural fluid. The specificity, sensitivity, and repeatability of this method are verified by detecting the cfDNAs in pleural effusion, samples of malignant pleural effusion, tuberculous pleural effusion, and other common microbial infections. Finally, this method was compared with three traditional methods, pleural effusion, precipitation DNA, sputum culture, and pleural effusion culture to explore the clinical diagnostic value of this method. KP cfDNA was positive by fluorescence PCR from the simulated KP infected pleural effusion, which confirmed KP cfDNA in pleural effusion. KP cfDNA was positive by fluorescence PCR from the pleural effusion of KP infected patients, while with the same detection method, KP cfDNA in clinical carcinomatous hydrothorax, tuberculosis hydrothorax, and other standard microbial infection samples was negative, which confirmed the method had high specificity, high sensitivity, and reproducibility. Compared with the three traditional methods, this method has a higher positive rate. Compared with the gold standard, sputum bacterial culture, the sensitivity, specificity, positive predictive value, and negative predictive value of this method were 91.67%, 95.45%, 91.7%, and 95.5%, respectively. The detection of cfDNA by fluorescence PCR is possible. Moreover, the positive rate of this method in clinical pleural effusions is high.

Molecular diagnostics for verification of pleural tuberculosis in Morocco

Pleural tuberculosis (pTB) is a very common form of extrapulmonary tuberculosis (TB). pTB diagnostics represents a major burning challenge worldwide due to the limitations of available conventional diagnostic tools. These latter include microscopic examination of the pleural fluid for acid-fast bacilli, mycobacterial culture of pleural fluid in solid or liquid media, sputum or pleural tissue, and histopathological examination of pleural tissue; these tests have recognized limitations for clinical use. Hence, to overcome these limitations, attention has been devoted to new nucleic acid amplification (NAA) diagnostic tests such as the polymerase chain reaction (PCR) and real-time PCR (RT-PCR), owing to their accuracy, rapidity, high sensitivity and specificity. Within this context, this prospective study was conducted to evaluate the performance of molecular diagnosis methods for differentiation between tuberculosis and non-tuberculosis pleural effusions. Fifty patients with pleural effusion were enrolled in this prospective study in Rabat, Morocco. The efficacy of conventional polymerase chain reaction (PCR) in the diagnostics of tuberculous pleurisy by targeting IS6110 and mycobacterial internal transcribed spacer (MYITS) was evaluated compared to histopathologic examination and culture data. Our results showed that IS6110 PCR could “rule in” pTB, the sensitivity and specificity being 41.6% and 85.7%, respectively. Therefore, the findings confirmed that molecular tests exert a relatively high specificity in EPTB but lower sensitivity, thus a positive test is considered as a pTB case whereas negative one cannot exclude the disease. Although the study was limited by a small sample size, it adds to the body of evidence of usefulness of molecular testing as adjuncts to histopathologic examination for accurate diagnosis of pTB, to treat timely and to avoid the emergence and spread of drug resistant pTB. However, further efforts should be made to increase the sensitivity of NAA methods and to identify the best molecular targets to be useful in clinical practice.

Utility of MTP40 nested PCR in diagnosis of tubercular pleural effusion

Extra pulmonary TB is present in 15% of all TB cases. This incidence is higher about 50% in HIV affected patients. Tuberculous pleural effusion accounts for 4% of all TB cases. Though we have lot of diagnostic methods to diagnose pulmonary TB, we are lacking of a good diagnostic method to identify tubercular pleural effusion.In this issue we have studied the utility of Nested PCR (MTP40) in diagnosis of tubercular pleural effusion. We have included 200 pleural effusion patients. The sensitivity of Nested PCR test is 19% and specificity 100%, Diagnostic Accuracy 59.5%.This study conducted from May 2017 to June 2019. This is a cross sectional study done in a tertiary care center in Varanasi included 200 patients of pleural effusion.

Serum Creatinine as a Potential Biomarker for the Diagnosis of Tuberculous Pleural Effusion

BackgroundPrevious studies have revealed the disadvantages of traditional methods for the diagnosis of tuberculous pleural effusions (TPEs) and have created interest in exploring other effective biomarkers. Many studies have focused on the correlation between pulmonary diseases and serum creatinine (Cr), a representative biomarker of renal function, but little is known about the direct relationship between Cr and TPE. Our study aimed to explore whether Cr can act as a biomarker for the diagnosis of TPE and to evaluate the correlation between Cr and TPE. Materials and MethodsPatients with pleural effusions (PEs) were enrolled in this study. By comparing the concentrations of Cr and adenosine deaminase (ADA) in patients with TPEs and non-TPEs, we determined the sensitivity, specificity, Youden index, and area under the curve for these biomarkers. We generated receiver operating characteristic curves and quantifications to evaluate the diagnostic accuracy. ResultsIn total, 86 patients (44 with TPE, 25 with malignant pleural effusion (MPE) and 17 with non-tuberculosis infectious PE (NTIPE)) were enrolled in the study. The concentrations of Cr in TPE were significantly higher than those in non-TPE. However, a similar trend was not observed for NTIPE and MPE. The levels of ADA in TPE were significantly higher than those in NTIPE and MPE. ConclusionCr has the potential for the diagnosis of TPE to some extent though its accuracy is not as good as that of ADA. Further studies are necessary for Cr to be applied in clinical practice for the diagnosis of TPE.

Mycobacterial antigens in pleural fluid mononuclear cells to diagnose pleural tuberculosis in HIV co-infected patients

BackgroundExtra pulmonary manifestation of tuberculosis (TB) accounts for approximately one-half of TB cases in HIV-infected individuals with pleural TB as the second most common location. Even though mycobacteria are cleared, mycobacterial antigens may persist in infected tissues, causing sustained inflammation and chronicity of the disease. The aim of this study was to explore various mycobacterial antigens in pleural effusions, the impact of HIV infection and CD4+ T-cell depletion on the presence of antigens, and the diagnostic potential of antigens for improved and rapid diagnosis of pleural TB.MethodsPleural fluid specimens were collected from patients presenting with clinically suspected pleural TB, and processed routinely for culture, cytology, and adenosine deaminase activity analysis. HIV status and CD4+ T-cell counts were recorded. Pleural fluid mononuclear cells (PFMC) were isolated, and cell smears were stained with acid-fast staining and immunocytochemistry for various mycobacterial antigens. Real-time and nested-PCR were performed. Patients were categorized as pleural TB or non-TB cases using a composite reference standard. Performance of the mycobacterial antigens as diagnostic test was assessed.ResultsA total of 41 patients were enrolled, of which 32 were classified as pleural TB and 9 as non-TB. Thirteen patients had culture confirmed pleural TB, 26 (81%) were HIV-TB co-infected, and 64% had < 100 CD4+ T-cells/microL. Both secreted and cell-wall mycobacterial antigens were detected in PFMC. Lipoarabinomannan (LAM) was the most frequently detected antigen. There was no direct correlation between positive culture and antigens. Cases with low CD4+ T-cell counts had higher bacterial and antigen burden. By combining detection of secreted antigen or LAM, the sensitivity and specificity to diagnose pleural TB was 56 and 78%, respectively, as compared to 41 and 100% for culture, 53 and 89% for nested PCR, and 6 and 100% for real-time PCR.ConclusionMycobacterial antigens were detectable in PFMC from tuberculous pleural effusions, even in cases where viable mycobacteria or bacterial DNA were not always detected. Thus, a combination of secreted antigen and LAM detection by immunocytochemistry may be a complement to acid-fast staining and contribute to rapid and accurate diagnosis of pleural TB.

Diagnostic Accuracy of Sonographic Septations in Tuberculous and Malignant Pleural Effusions

Background: Discrimination between tuberculous (TB) and malignant pleural effusions is a real practical challenge because both exist as exudative lymphocytic type. Transthoracic ultrasonography not only identifies and quantifies pleural effusion but also displays sonographic septations, which are frequently seen in TB pleural effusions and can help in differentiation between tuberculosis and malignancy successfully, without any invasive procedure. We designed this study to determine the diagnostic usefulness of these septations for tuberculous and malignant pleural effusions.&#x0D; Material and Methods: This prospective study was conducted in the OPD of Gulab Devi Chest Hospital Lahore, Pakistan, a 1500 bedded tertiary care hospital, from November 2016 to February 2018. Total of 339 consecutive cases, aged 14-83 years with radiological evidence of pleural effusion were included in the study. After detailed history, thorough physical examination, radiological, haematological and biochemical findings were recorded. Pleural fluid macroscopic, cytological, microbiologic and biochemical analysis results were also recorded. Ultrasonography was done, septated and non-septated pleural effusions identified and findings were noted. SPSS-16 was used for statistical evaluation. Fisher Exact test was utilized for comparison between TB and malignant cases with P-value &lt; 0.05 taken as significant. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), diagnostic accuracy and positive likelihood ratio were calculated.&#x0D; Results: Out of total 339 cases, 49 (14.45%) were malignant and 290 (85.55%) were non-malignant. In the malignant group, only 03 cases (6.12%) showed sonographic septations. In the non-malignant group, 259/290 (89.31%) cases showed tuberculous etiology and 187/259 (72.20%) of these cases displayed sonographic septations. By considering septations as predictor of TB, statistical analysis revealed a sensitivity of 79.23%, specificity of 92.85%, PPV of 98.42%, NPV of 44.31% and diagnostic accuracy of 81.29%, respectively.&#x0D; Conclusions: Sonographic septations can be a valuable predictor of tuberculosis, in a population with high prevalence of the disease. We found it to be a useful feature in differentiating between a malignant and tuberculous etiology, in exudative lymphocytic pleural effusions. It can be used with confidence in patients who are unfit for interventional procedures.

Relations between serum and pleural fluid biomarkers: a new look of an old concept

BackgroundAlthough cytological examination of pleural fluid samples can simply diagnose malignant pleural effusion (MPE), this test has many limitations. There are no established biomarkers for accurate diagnosis of MPE. This study investigated the association of serum lactate dehydrogenase (LDH)/pleural fluid adenosine deaminase (ADA) which is the cancer ratio with MPE together with assessment of the utility of combining pleural lymphocyte counts “cancer ratio plus” in diagnosing MPE and to evaluate the ability of these markers in differentiating MPE from tuberculous pleural effusion (TPE).ResultsThis prospective study included 150 individuals who were divided into 3 groups including malignant (n = 94), tuberculous (n = 31), and parapneumonic (n = 25) effusions. It was done during the period from January 2018 to July 2019 to assess the utility of cancer ratio and cancer ratio plus in discrimination between MPE and non-MPE. Serum LDH, cancer ratio, and cancer ratio plus were significantly associated with MPE. Also, age, cancer ratio, and serum LDH to pleural fluid lymphocyte count ratio were positive predictors of MPE. A cutoff level of > 16.02 for the cancer ratio showed sensitivity and specificity of 61% (95% CI 0.5002–0.7056) and 96% (95% CI 0.8769–0.9956) respectively. At this cutoff, the positive likelihood ratio was 16.99, while the negative likelihood ratio was 0.41.ConclusionCancer ratio was found to be more accurate than cancer ratio plus and serum LDH to pleural fluid lymphocyte count ratio in identifying MPE especially in patients with negative pleural fluid cytology.

Influence of age on the diagnostic accuracy of soluble biomarkers for tuberculous pleural effusion: a post hoc analysis

BackgroundAccurately diagnosing pleural effusion is a frequent and significant problem in clinical practice. Combining pleural biomarkers with patients’ age may be a valuable method for diagnosing TPE. We sought to evaluate the influence of age on diagnostic values of pleural adenosine deaminase (ADA), interferon-gamma (IFN-γ), and interleukin 27 (IL-27) for tuberculous pleural effusion (TPE).MethodsTwo hundred seventy-four consecutive adult patients with pleural effusion were selected from Beijing and Wuhan between January 1, 2014 and June 30, 2015, and their pleural fluid concentrations of ADA, IFN-γ, and IL-27 were tested. Biomarker performance was analyzed by standard receiver operating characteristic (ROC) curves according to different ages.ResultsData from the Beijing cohort showed that ADA, IFN-γ, and IL-27 could all accurately diagnose TPE in young patients (≤ 40 years of age). With a cutoff of 21.4 U/L, the area under the curve (AUC), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of ADA for diagnosing TPE were 1.000 (95% confidence interval: 0.884–1.000), 100.0, 100.0%, 100.0, and 100.0, respectively. In older patients (> 40 years of age), IL-27 and IFN-γ were excellent biomarkers for discriminating TPE versus non-TPE cases. With a cutoff of 591.4 ng/L, the AUC, sensitivity, specificity, PPV, and NPV of IL-27 for diagnosing TPE were 0.976 (95% confidence interval: 0.932–0.995), 96.3, 99.0%, 96.3, and 99.0, respectively. Similar diagnostic accuracy among the three pleural biomarkers was validated in the Wuhan cohort.ConclusionsAmong young patients, ADA is reliable for diagnosing TPE. Conversely, in older patients, IL-27 and IFN-γ are excellent biomarkers to differentiate TPE versus non-TPE cases.

FluoroType® MTB en líquido pleural para el diagnóstico de tuberculosis

ObjectivesThis work aims to investigate the diagnostic accuracy of a nucleic acid amplification test (FluoroType MTB®) in pleural fluid (PF) and sputum to diagnose tuberculous pleural effusion (TPE). We also analyzed the increase in diagnostic accuracy of a second FluoroType MTB® test on a second thoracentesis sample when the first was negative. MethodsWe conducted a prospective single-center study that included 207 patients with pleural effusion (31 tuberculous and 176 due to other causes). Of the 31 cases of TPE, 21 (68%) were confirmed histologically or microbiologically; the other cases were considered probable. ResultsThe operational characteristics of FluoroType MTB® in PF for identifying tuberculosis were a sensitivity of 13%, a specificity of 99%, a positive likelihood ratio of 11, and a negative likelihood ratio of 0.9. The diagnostic efficacy data for sputum samples were 21%, 91%, 2.4, and 0.9, respectively. PF and sputum cultures in solid and liquid media had greater sensitivity (36% and 31%, respectively). A second FluoroType MTB® test in PF was negative for 24 patients who had TPE and for whom the first FluoroType MTB® test was also negative. Only two (6.5%) patients with TPE had a confirmed diagnosis based exclusively on the positive results of the FluoroType MTB® in PF. ConclusionDue to its low sensitivity, the FluoroType MTB® test in PF has a limited role in diagnosing tuberculous pleurisy.

Investigating causes of undiagnosed exudative pleural effusion by medical Pleuroscopy and close biopsy

Introduction: Pleural effusion may develop during various acute or chronic medical conditions. Despite different diagnostic workups, some cases of pleural effusion may remain undiagnosed. Pleuroscopy and closed biopsy are common diagnostic approaches used for the diagnosis of undiagnosed cases. The present research aimed to evaluate the diagnostic yield of medical pleuroscopy and closed biopsy in Iran. Materials and methods: The present cross-sectional study was performed within 2016-2018, in the North-East of Iran. Patients who had undiagnosed lymphocytic predominance exudative pleural effusion were included in the present research. Every patient underwent medical pleuroscopy or closed pleural biopsy by an Abrams needle. The collected data were analyzed in SPSS software (version 12).Ap-valuelessthan0.05 was considered statistically significant. Results:A total of 108 patients with the mean age of 58.73±18.13 years enrolled in the present study. Around 50 patients underwent needle biopsy,while the other 58 patients went through medical pleuroscopy. Chronic pleuritis, malignant pleural effusion, negative results, and tuberculosis were the common results. When pleuritis is regarded as negative results and malignant and tuberculosis pleural effusion as positive results, medical thoracoscopy provides more significant positive results and fewer negative results (P=0.024). No patient developed complications after the procedures. Conclusion: In contrast to other studies, both of these techniques had low diagnostic yield for the diagnosis of undiagnosed pleural effusion. Therefore, performing other diagnostic workups (e.g., imaging techniques) may decrease the rate of undiagnosed pleural effusion.

The clinical utility of joined detection of cancer ratio, cancer ratio plus, Interferon gamma (IFN-\u03d2) & Carcinoembryonic antigen (CEA) in differentiating lymphocytic pleural effusions

BackgroundThe differentiation between malignant (MPE) and tuberculous (TPE) pleural effusions should be considered in any patient with an exudative lymphocytic pleural effusion. A rapid precise diagnosis is valuable as the treatment and prognosis are totally different. The histopathological proof may shorten the time to differential diagnosis. But it may be invasive and costly. The aim of this study is to validate the clinical reliability of joined detection of cancer ratio (serum LDH to pleural ADA), cancer ratio plus (cancer ratio to percentage of pleural fluid lymphocytic count), pleural interferon gamma (pIFN-ϒ), and pleural carcinoembryonic antigen (pCEA) values to differentiate between lymphocytic pleural effusions.ResultsSeventy-eight patients were included with mean age ± SD 53.09 ± 9.56 years old, 49 males and 29 females, diagnosed as 47 MPE, 24 TPE, and 7 others. Cancer ratio at cutoff value of ≥ 22 and cancer ration plus at cutoff value of ≥ 41 can discriminate MPE from any other cause with sensitivity (91.5%, 93.6%), specificity (87.5%, 91.7%), and diagnostic accuracy (90.1%, 92.9%) respectively. When the levels of pCEA and pIFN-ϒ were combined with cutoff value of cancer ratio, there were powerful diagnostic differentiating results.ConclusionsCancer ratio and cancer ratio plus offered valid, efficient, non-invasive, and easy measuring diagnostic tools. On diagnostic uncertainty, the add-on of pCEA in cases of suspected MPE, and pIFN-ϒ in cases of suspected TPE has a trustable diagnostic efficacy with no need for further investigations.