non-TB Pleural Effusions Research Articles

Adenosine deaminase activity in serum and pleural fluid of patients with tuberculosis and those without tuberculosis

Background Adenosine deaminase (ADA) has been considered as a marker for cell-mediated immunity. The purpose of this study is to evaluate the usefulness of ADA as a biomarker in diagnosis of pleural effusion in tuberculosis (TB). Patients and methods Forty patients from Abbasia Chest Hospital who were suspected to have exudative pleural effusion and prepared for pleural biopsy were enrolled in the study. ADA in pleural fluid and serum was measured for all of them, and then data were reported and analyzed. Results Of the 40 patients included in the study, most of the 20 patients with TB pleurisy were diagnosed mainly by thoracoscope (16/20), whereas the rest four cases were diagnosed by sonar-guided biopsy. The other 20 patients, diagnosed as non-TB pleural effusion (6/20), mesothelioma (8/20), pneumonia, and adenocarcinoma (6/20). There were significant statistical difference between both groups regarding age, total leukocyte count, erythrocyte sedimentation rate, and tuberculin skin test, whereas no significant association regarding sex, clinical presentation, and radiological finding within any groups. ADA in effusion, serum, and index had a significant statistical difference between the two groups, with cutoff point value in effusion and serum of ∼31.4 and 29.5 U/l, respectively, and 1.1 for the index, with sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of ∼100, 90, 90, 100, and 95%, respectively, for ADA in effusion and serum, whereas for the index of ∼80, 65, 69, 76, and 73%, respectively. Conclusion Serum and pleural fluid ADA level significantly increases in patients with TB pleural effusion than non-TB pleural effusion with higher sensitivity, specificity, positive predictive value, negative predictive value, and accuracy in prediction.

Novel biomarkers for Diagnosis of Pulmonary Tuberculosis and Tuberculous Pleural Effusion

Background: The present study aimed to evaluate the importance of serum, pleural adenosine deaminase (ADA), and Gene Xpert in Diagnosis of TB and TB Pleural Effusion (TB-PLE.).Material & Methods:The study was done with 75 TB cases, 50 cases of them were diagnosed as Pulmonary TB and 25 cases as TB pleural effusion, collecting also 50 non-TB pleural effusion, Malignant and acute bacterial infection comprise 21 and 29 cases respectively. Cases with transudative pleural effusion were excluded from the study. Finally, 75 were healthy control group.Results:There was a highly significant difference between the mean age of TB-PE Patients and Patients non-TB-PLE (P-value <0.001), while there was a non-significant difference with patients with P-TB (P-value >0.05). Mean of Serum ADA level were highest 53.16 U/L in TB-PE cases, shown to be statistically significant when compared to 43.2 U/L in P-TB and 25.4 U/L in non TBpleural effusion. With p-value of 0.02 and 0.001respectively.Conclusions:We concluded that GeneXpert can be a useful diagnostic method in patients with suspected pulmonary tuberculosis. Serum and pleural fluid ADA level is a very helpful test to rule out a TB and can help differentiate tubercular etiology from non-tubercular.

Diagnostic Accuracy of Pleural Effusion Mononuclear Cells/Leukocyte Ratio in Tuberculous Pleurisy.

Background: Tuberculous pleurisy (TBP) is a common clinical type of tuberculosis (TB) in China. TBP is difficult to diagnose. Whether the mononuclear cell/leukocyte (MNC/LEU) ratio in pleural effusion can contribute to accurate TBP diagnosis remains yet unclear.Objective: To explore the diagnostic value of MNC/LEU ratio in pleural effusion for TBP in China.Methods: This study was a retrospective case-control study involving 406 patients with pleural effusion of unknown cause who were hospitalized at the Henan Provincial People's Hospital. Using histopathological examination of thoracoscopic pleural biopsy as the gold standard for TBP diagnosis, a final total of 215 subjects were included in this study including 91 cases of TBP and 124 cases of non-TBP. The receiver operating characteristic (ROC) curve of pleural effusion MNC/LEU ratio for TBP diagnosis was plotted and the area under curve (AUC) and the optimal cutoff value were determined. In addition, the sensitivity, specificity and accuracy of the MNC/LEU ratio at the optimal cutoff value for TBP diagnosis were also evaluated.Results: The MNC/LEU ratio was significantly higher in TB pleural effusion [95.9% (89.7–98.0%)] than in non-TB pleural effusion [77.8% (39.3–93.2%)] (P < 0.001). The AUC was 0.776 (95% CI, 0.714–0.830), and the sensitivity, specificity and accuracy for TBP diagnosis at the 93.7% cutoff value were 64.83%, 79.03%, and 0.730, respectively.Conclusion: The pleural effusion MNC/LEU ratio may be a new and valuable laboratory indicator for the diagnosis of tuberculous pleurisy in China.

The comparison of pleural fluid TNF-α levels in tuberculous and nontuberculous pleural effusion

BackgroundTuberculous pleural effusion is the manifestation of Mycobacterium tuberculosis infection in pleura. With existing means, it is difficult to establish the diagnosis of tuberculosis (TB) and non-TB pleural effusions; thus, establishing the diagnosis of TB pleural effusion and non-TB pleural effusion is still a clinical problem. Tumour necrosis factor alpha (TNFα) is a potent inflammatory cytokine that plays an important role in immunity to Mycobacterium tuberculosis infections, this level of cytokine increases in pleural effusion due to tuberculosis. ObjectiveTo compare the TNF-α level of pleural fluid in TB and non-TB pleural effusion. MethodsThe samples in this study that fulfilled the inclusion criteria were patients with non-TB pleural tuberculosis effusion in the inpatient ward in Pulmonology Unit Dr. Soetomo General Hospital Surabaya, male and female, aged between 15 and 60 years. The data is divided into two: primary data and secondary data of patients who fulfilled inclusion and exclusion criteria. The data with normal distribution was analyzed using independent t2 test and if the data distribution is abnormal, it was analyzed using Fisher's exact test. ResultsThere were 22 subjects divided into 2 groups that were 11 patients with TB pleural effusion and 11 patients with non-TB pleural effusion. The TNF-α level of pleural fluid in TB pleural effusion was 25.43±13.55pg/mL. The TNF-α level of pleural fluid in non-TB was 5.98±1.89pg/mL. The serum TNF-α level in TB pleural effusion was 83.22±88.15pg/mL. The serum TNF-α level in non-TB was 68.54±57.88pg/mL. There was higher level of TNF-α pleural fluid in TB pleural effusion than in non-TB pleural effusion (25.43±13.55pg/mL vs 5.98±1.89pg/mL, p value <0.05). The serum TNF-α level in patients with TB pleural effusion was higher than TNF-α serum level of non-TB pleural effusion. There was no significant difference between TNF-α level of pleural fluid and serum TNF-α levels in the TB pleural effusion group (p value >0.05). ConclusionThe TNF-α level of pleural fluid in TB pleural effusion was higher than non-TB pleural effusions and there was no significant difference between serum TNF-α levels in the TB pleural effusion group and in the non-TB pleural effusion group.

Diagnostic utility of QuantiFERON-TB Gold and Xpert MTB/RIF combined with adenosine deaminase in tuberculous pleural effusion: a prospective study

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

A clinical study of diagnostic efficacy of adenosine deaminase levels in tubercular pleural effusion

Background: Tuberculosis is a common cause of pleural effusion in countries like India where it is highly endemic. However, the organism mycobacterium tuberculosis is seldom detectable in pleural fluid. The diagnosis of pleural tuberculosis has been greatly improved by the use of biochemical markers. The pleural fluid activity of adenosine deaminase (ADA) is one of the best providing reliable bases for a treatment decision, particularly in excluding the diagnosis of tuberculosis, due to its high sensitivity. The present study was aimed to evaluate the diagnostic efficacy of ADA levels in tubercular pleural effusion. Methods: The study is a clinical, prospective and observational study of 50 Patients of pleural effusion consecutively admitted in Government Medical College and Hospital, Kannouj from Dec 2008 to Dec 2009. Macroscopic findings, cytological, microbiological and biochemical analysis of pleural fluid were performed, including ADA levels in all patients. Results: Mean age group was 31 years and common in men. In our study, out of 30 patients with tuberculosis pleural fluid ADA was done in them and 28 (93.33%) of them had a level more than 40IU/L. Using a cut off of greater 40IU/L we got a sensitivity and specificity of 93.3% and 90% respectively and positive predictive value 93.3% and Negative predictive value 90%. Conclusions: All patients with TB pleural effusion had elevated ADA levels and there was a statistical significant association (p value <0.05) of ADA levels in differentiating TB pleural effusion from Non-TB pleural effusion.

IP-10 and MIG are compartmentalized at the site of disease during pleural and meningeal tuberculosis and are decreased after antituberculosis treatment.

The diagnosis of active tuberculosis (TB) disease remains a challenge, especially in high-burden settings. Cytokines and chemokines are important in the pathogenesis of TB. Here we investigate the usefulness of circulating and compartmentalized cytokines/chemokines for diagnosis of TB. The levels of multiple cytokines/chemokines in plasma, pleural fluid (PF), and cerebrospinal fluid (CSF) were determined by Luminex liquid array-based multiplexed immunoassays. Three of 26 cytokines/chemokines in plasma were significantly different between TB and latent tuberculosis infection (LTBI). Among them, IP-10 and MIG had the highest diagnostic values, with an area under the receiver operating characteristic curve (ROC AUC) of 0.92 for IP-10 and 0.86 for MIG for distinguishing TB from LTBI. However, IP-10 and MIG levels in plasma were not different between TB and non-TB lung disease. In contrast, compartmentalized IP-10 and MIG in the PF and CSF showed promising diagnostic values in discriminating TB and non-TB pleural effusion (AUC = 0.87 for IP-10 and 0.93 for MIG), as well as TB meningitis and non-TB meningitis (AUC = 0.9 for IP-10 and 0.95 for MIG). A longitudinal study showed that the plasma levels of IP-10, MIG, granulocyte colony-stimulating factor (G-CSF), and gamma interferon (IFN-γ) decreased, while the levels of MCP-1/CCL2 and eotaxin-1/CCL11 increased, after successful treatment of TB. Our findings provide a practical methodology for discriminating active TB from LTBI by sequential IFN-γ release assays (IGRAs) and plasma IP-10 testing, while increased IP-10 and MIG at the site of infection (PF or CSF) can be used as a marker for distinguishing pleural effusion and meningitis caused by TB from those of non-TB origins.

Challenges in the Development of an Immunochromatographic Interferon-Gamma Test for Diagnosis of Pleural Tuberculosis

Existing diagnostic tests for pleural tuberculosis (TB) have inadequate accuracy and/or turnaround time. Interferon-gamma (IFNg) has been identified in many studies as a biomarker for pleural TB. Our objective was to develop a lateral flow, immunochromatographic test (ICT) based on this biomarker and to evaluate the test in a clinical cohort. Because IFNg is commonly present in non-TB pleural effusions in low amounts, a diagnostic IFNg-threshold was first defined with an enzyme-linked immunosorbent assay (ELISA) for IFNg in samples from 38 patients with a confirmed clinical diagnosis (cut-off of 300pg/ml; 94% sensitivity and 93% specificity). The ICT was then designed; however, its achievable limit of detection (5000pg/ml) was over 10-fold higher than that of the ELISA. After several iterations in development, the prototype ICT assay for IFNg had a sensitivity of 69% (95% confidence interval (CI): 50-83) and a specificity of 94% (95% CI: 81-99%) compared to ELISA on frozen samples. Evaluation of the prototype in a prospective clinical cohort (72 patients) on fresh pleural fluid samples, in comparison to a composite reference standard (including histopathological and microbiologic test results), showed that the prototype had 65% sensitivity (95% CI: 44-83) and 89% specificity (95% CI: 74-97). Discordant results were observed in 15% of samples if testing was repeated after one freezing and thawing step. Inter-rater variability was limited (3%; 1out of 32). In conclusion, despite an iterative development and optimization process, the performance of the IFNg ICT remained lower than what could be expected from the published literature on IFNg as a biomarker in pleural fluid. Further improvements in the limit of detection of an ICT for IFNg, and possibly combination of IFNg with other biomarkers such as adenosine deaminase, are necessary for such a test to be of value in the evaluation of pleural tuberculosis.

Predictive Models for Tuberculous Pleural Effusions in a High Tuberculosis Prevalence Region

Patients with pleural effusions who reside in geographic areas with a high prevalence of tuberculosis frequently have similar clinical manifestations of other diseases. The aim of our study was to develop a simple but accurate clinical score for differential diagnosis of tuberculosis pleural effusion (TPE) from non-TB pleural effusion (NTPE). This was an unblinded, prospective study of Turkish patients 18 years of age or older with pleural effusion of indeterminate etiology conducted from June 2003 to June 2005. Unconditional logistic regression models were used to discriminate TPE cases from NTPE cases. Standard errors for the area under the curve (AUC) were calculated using the Mann-Whitney method. Data were statistically significance if two-tailed P < 0.05. A total of 63.3% (157/248) of the patients had TPE while 36.7% (91/248) of the patients had other etiologies for pleural effusions. We were able to provide a predictive model of TPE that included age <47 years and either pleural fluid adenosine deaminase enzyme (PADA) >35 U/l or pleural serum protein ratio >0.710. However, only the combination of age <47 and PADA >35 U/l was significant (odds ratio [OR]: 7.46; 95% confidence interval [CI]: 3.99-13.96). The generated summary score (range = 0-6) was significantly predictive of TPE (OR: 2.91; 95% CI: 2.18-3.89) and with high AUC (0.79). We propose an affordable model that includes age <47 years and PADA >35 U/l for timely diagnosis of TPE in geographical regions with a high prevalence of TB.

Differential cytokine/chemokines and KL-6 profiles in patients with different forms of tuberculosis

Cytokines are involved in the mediation and regulation of immunity, inflammation, and haematopoiesis. Secretion patterns may reflect the pathology or etiology of different diseases. In an attempt to increase our understanding of immunopathology during different forms of tuberculosis, and identify potential biological markers that may differentiate between forms of tuberculosis, we investigated the levels of 29 cytokines and KL-6 in the plasma of HIV uninfected patients with active pulmonary tuberculosis (TB) without pleural effusions and in pleural TB with and without HIV-co-infection. Healthy individuals with latent Mycobacterium tuberculosis infection and patients with non-TB pleural effusions were used as controls, We showed that pleural TB patients had increased levels of markers associated with systemic inflammation compared to pulmonary TB (EGF, G-CSF, IL-1β IL-6, IL-8, IL-10, MCP-1, MIP-1α, MIP-1β, TNF-α and VEGF), whereas pulmonary TB patients without effusions had higher levels of factors involved in cell-mediated immunity (IL-12p40 and sCD40L). Plasma levels of cytokines may therefore contribute to biosignatures of diseases like TB but the data also highlight systemic differences between pulmonary TB, pleural TB and other form of pleural effusion diseases.

Pleural fluid interferon‐γ and adenosine deaminase levels in tuberculosis pleural effusion: a cost‐effectiveness analysis

Pleural fluid levels of interferon-gamma (IFN-gamma) and adenosine deaminase (ADA) have been found to be high in patients with tuberculosis (TB). The present study was carried out to compare the diagnostic utility of these two markers and to carry out a cost-effectiveness analysis of performing IFN-gamma estimation in comparison to ADA. A total of 52 patients with pleural effusion, 35 of which were found to have TB etiology, were prospectively included for estimation of ADA and IFN-gamma levels. The difference in the cost of performing the two diagnostic tests was compared with the cost of the treatment for a patient with TB. Pleural fluid IFN-gamma (median [range]: 2,100 [70-14,000] vs. 3 [0-160]; P<0.001) as well as ADA levels (mean [SD]: 93.1 [62.3] vs 15.4 [8.7]; P<0.001) were significantly higher in patients with TB effusion. Even though IFN-gamma estimation was more sensitive (97.1 vs. 91.4%), the extra cost of IFN-gamma estimation for detecting one patient with TB was found to be equivalent to the cost of a complete course of antituberculosis treatment for six patients. In developing countries, where TB is rampant and cost is a major concern, pleural fluid IFN-gamma estimation does not seem to be a cost-effective investigation method for differentiating TB from non-TB pleural effusion.