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Background: Accurately 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)., Methods: Two 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., Results: Data 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., Conclusions: Among 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.

Introduction: Tubercular pleural effusion is the second most common extrapulmonary form of tuberculosis in India. Developing nations like India face several health challenges and with limited resources, appropriate planning and channelization of the same is the need of the hour., Material and Methods: 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 also to study if any association exists between CBNAAT and pleural fluid adenosine deaminase (ADA) and lymphocyte counts. Clinically suspected TPE, lymphocyte predominant (≥ 70%) exudates (according to the Lights criteria) with ADA ≥ 40 U/L and microbiologically confirmed pulmonary tuberculosis patients with aco-existent pleural effusion were included. Pleural fluid CBNAAT was performed on all the samples., Results: Out of atotal of 75 patients, 57 were males and 18 were females. Alymphocyte predominance of ≥ 70% was seen in 73 subjects (97%). Mean ADA was 61.7 U/L ± 16.2 (SD). Pleural fluid CBNAAT was positive for Mycobacterium tuberculosis (MTB) in 24 patients (32%). Out of these patients, rifampicin resistance was detected in 2 individuals (8.3%). Sputum smear for acid fast bacilli (AFB) was positive in 3 (4%) patients, whereas in sputum CBNAAT MTB was detected in 8 (10.6%) persons. Association between pleural fluid ADA, lymphocyte count and CBNAAT positivity was evaluated by Student T-test. There was asignificant association between higher ADA levels and CBNAAT (p value = 0.001)., Conclusions: Pleural fluid CBNAAT, owing to its low sensitivity, should not be included in the diagnostic protocol of TPE in high prevalence areas. Ahigh ADA ≥ 40 U/L in combination with Light's criteria to define exudates, with lymphocyte predominance is sufficient evidence to diagnose TPE and initiate anti-tubercular therapy, thereby deferring the need to perform an invasive pleural biopsy.

Adenosine deaminase (ADA) activity measurement in pleural fluid is a relevant test to diagnose pleural tuberculosis (pTB) in high tuberculosis prevalence settings. We investigated the diagnostic utility of pleural ADA using a retrospective analysis of patients admitted with newly diagnosed pleural effusion without identified etiology between 2001 and 2008 in Paris suburb, a low to medium tuberculosis prevalence area. 104 adults (mean age 55 years; 34 with pTB, 70 with other diagnoses) were analyzed. Median follow-up was 15.6 months. Mean [interquartile range] pleural ADA was 119 U/L [IQR: 83-143] in pTB and 24 U/L [IQR: 15-31] in non-tuberculous effusions (P<0.001). With an optimal pleural ADA cut-off value of 41.5 U/L for pTB diagnosis, sensitivity and specificity were 97.1% and 92.9%, while positive and negative predictive values were 86.8% and 98.5%, respectively. We conclude that pleural ADA activity could be integrated in the diagnostic procedures of pTB in low to medium tuberculosis prevalence settings., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Introduction: The aim of the present study was to evaluate and compare the diagnostic accuracy of pleura levels of adenosine deaminase (ADA) and neopterin for the differential diagnosis of pleural tuberculosis (TP)., Patients and Methods: The study included 50 patients with TB, 27 patients with malignancies, and 24 patients with pleural effusion of non-tuberculous and non-malignant origin as controls. ADA and neopterin levels in pleural fluid were measured by spectrofotometric and ELISA method, respectively., Result: Pleural neopterin levels were significantly higher in patients with pleural TB than patients with malignancy (p< 0.001). Pleural ADA levels were significantly higher in patients with pleural TB than patients with malignancy (p< 0.001) and patients with benign non-tuberculosis effusions (p< 0.001). The mean levels of ADA and neopterin in pleural effusion were evaluated according to their underlying diseases for the diagnostic accuracy. As for pleural TB receiving operating characteristic curves identified the following results; The best cut-off value for pleural neopterin was 4.7 U/L and yielded a sensitivity and specificity of 86% and 72.55%, respectively. Taking a cut-off value of 42 U/L for pleural ADA, the sensitivity and the specificity were found to be 88% and 68.63%, respectively., Conclusions: In the diagnosis of pleural TB pleural neopterin level has a comparable sensitivity to pleural ADA activity. Both markers may find a place as a routine investigation in the coming days for early detection of TB. However, these tests should not be considered an alternative to biopsy and culture.

The yield for using a pleural fluid culture to diagnose tuberculous pleural effusion (TPE) is low. Adenosine deaminase activity (ADA) has been shown to have good diagnostic value for TPE. The ADA cutoff point for the diagnosis of TPE is unclear. We attempted to determine the ADA level cutoff point for diagnosing of TPE in Thailand, where tuberculosis is endemic. We reviewed the medical records of patients with newly diagnosed pleural effusion aged >15 years who had a pleural fluid ADAlevel and who underwent a pleural biopsy. The study period was from March 1, 2010 to January 31, 2011. The diagnoses of TPE and malignant pleural effusion (MPE) were based on pathological findings. The diagnostic cutoff level for using ADA to diagnose TPE was determined. Forty-eight patients met study criteria. Of those, 18 patients (37.5%) were diagnosed with TPE. The mean ADA level was significantly higher among patients in the TPE group than in the MPE group (38.2 vs 14.8 U/l, p < 0.001). The cutoff level of 17.5 U/l gave sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio of 88.9%, 73.3%, 3.33, and 0.15, respectively. An ADA level >17.5 U/l had good diagnostic values among TPE patients in our study.

Background: Previous studies reported interleukin-27 (IL-27), interferon-γ (IFN-γ), or adenosine deaminase (ADA) alone plays a helpful role in diagnosing tuberculous pleural effusion (TPE). The present study aims at comparing the diagnostic accuracy of pleural IL-27, IFN-γ, and ADA, and investigate the diagnostic accuracy of the combination of IL-27, IFN-γ, or/and ADA for differentiating TPE from pleural effusions with the other etiologies., Methods: The concentrations of IL-27, IFN-γ and ADA were simultaneously determined in pleural fluids and sera from 40 patients with TPE; 26 with malignant pleural effusion, seven with infectious pleural effusion, and eight with transudative pleural effusion by enzyme linked immunosorbent assay and colorimetric method. The corresponding biochemical indexs were also simultaneously determined., Results: The concentrations of pleural IL-27 and IFN-γ in the tuberculous group were significantly higher than those in the malignant, infectious, and transudative groups. The concentrations of ADA in TPE were significantly higher than those in MPE or transudative effusions, while much lower than those in infectious effusions. Among these three biomarkers, IL-27 was the most effective for TPE diagnosis, with the cut off value of 900.8 ng/L. IL-27 had a high sensitivity of 95% and specificity of 97.6% for differential diagnosis of TPE from non-TPEs. Combinations of IL-27, IFN-γ and ADA measurements further increased the sensitivity or specificity up to 100%., Conclusions: Compared to non-TPEs, IL-27, IFN-γ and ADA all simultaneously increased in TPE; and among these three rapid detection methods, IL-27 appeared to be the best for distinguishing tuberculous from non-TPEs, especially from MPE. Combinations of the three markers (IL-27, IFN-γ and ADA) yielded the highest sensitivity and specificity. These findings suggest that the applications of a new biomarker, IL-27, alone or with IFN-γ and ADA, may contribute to more efficient diagnosis strategies in the management of tuberculous pleurisy.

Background and Objective: The aim of this study was to determine whether high levels of pleural adenosine deaminase (pADA) are predictive for tuberculosis when pleural effusions do not satisfy the criteria for lymphocytic effusions or show neutrophil predominance., Methods: This was a retrospective observational study of 147 consecutive patients with exudative pleural effusions that were diagnosed by analysis of fluid samples during a 3-year period from 1 April 2007 to 31 March 2010. Multiple linear correlation tests were used to assess clinical variables as possible predictors of high pADA levels., Results: High pleural LDH (pLDH) and pleural potassium (pK) levels were associated with high pADA levels (P < 0.0001). Although there was a linear correlation between pLDH and pADA levels in patients with parapneumonic effusions (PPE) (n = 75), tubercular effusions (n = 21), malignant effusions (n = 41) and miscellaneous effusions (n = 10), a significant linear correlation between pK and pADA levels was observed only in patients with PPE (ρ = 0.525, P < 0.0001). When the cut-off value for pK was set at 5.0 mEq/L, pADA levels were >50 IU/L and pK levels were >5.0 mEq/L in only one patient (5%) in the tuberculosis group (n = 21) and 15 patients (12%, all with PPE) in the non-tuberculosis group (n = 126)., Conclusions: When pK levels exceed 5.0 mEq/L, high pADA levels do not necessarily indicate the presence of tuberculous pleuritis., (© 2011 The Authors. Respirology © 2011 Asian Pacific Society of Respirology.)

Objective: Current tools for the diagnosis of tuberculous pleural effusions are suboptimal. The study was undertaken to evaluate the accuracy of pleural fluid adenosine deaminase (ADA), interferon (IFN)-γ, interferon-γ-induced protein of 10 kDa (IP-10), and dipeptidyl peptidase (DPP) 4 levels in differentiating tuberculous pleural effusion (TPE) and non-TPE., Methods: A total of 122 samples of pleural effusion were studied. Pleural fluid ADA activity was measured with the colorimetric method, and IP-10, IFN-γ, and DPP4 levels were measured with enzyme-linked immunosorbent assay., Results: ADA activity and IP-10, IFN-γ, and DPP4 levels were significantly higher in TPE than in non-TPE (88.9 ± 62.7 U/L vs 18.1 ± 16.2 U/L, P < .05; 147.5 ± 117.3 ng/L vs 24.9 ± 19.7 ng/L, P < .05; 627.2 ± 345.3 ng/L vs 152.6 ± 71.4 ng/L, P < .05; and 560.6 ± 451.2 vs 56.8 ± 57.7, P < .05, respectively). The diagnostic sensitivity and specificity of ADA activity (cutoff value of 40 U/L) were 93.6% and 90.9%, respectively, and higher than those of IFN-γ (91.0% and 88.6% at the cutoff value of 225 ng/L, respectively), DPP4 (88.5% and 81.8% at the cutoff value of 75 ng/L, respectively), and IP-10 (83.3% and 86.4% at the cutoff value of 44 ng/L, respectively)., Conclusion: The roles of ADA and IFN-γ in the differential diagnosis of tuberculous pleurisy are pivotal. ADA or IFN-γ in combination with DPP4 or IP-10 can aid in differentiation between TPE and non-TPE with improved specificity and diagnostic efficiency., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objective: Pleural tuberculosis (TB) is a diagnostic challenge because of its non-specific clinical presentation and paucibacillary nature. Conventional diagnosis methods have limitations. We evaluated the real-time polymerase chain reaction (PCR), interferon-gamma (IFN-γ), adenosine deaminase (ADA), and immunoglobulin A (IgA)., Methods: We assessed 204 cases: 50 were confirmed pleural TB, 104 were probable pleural TB, and 50 formed the non-TB group. IFN-γ and IgA were measured by enzyme-linked immunosorbent assay and ADA was measured by colorimetric assay. Real-time PCR was carried out using the 16S rRNA sequence, pleural biopsy specimens were submitted to histopathologic examination, pleural fluid culture was undertaken using Lowenstein-Jensen and MGIT-BACTEC, and pleural fluid smears were stained with auramine O., Results: For confirmed and probable pleural TB cases, the area under the curve (AUC) of the receiver operating characteristic (ROC) curve was highest for IFN-γ (0.994 and 0.963, respectively), followed by ADA (0.989 and 0.945, respectively), real-time PCR (0.898 and 0.784, respectively), and IgA (0.817 and 0.784, respectively). For confirmed and probable pleural TB cases, IFN-γ showed the highest sensitivity (98% and 76.9%, respectively), followed by ADA (92% and 73%, respectively), real-time PCR (80% and 57.7%, respectively), and IgA (70% and 57.7%, respectively). With regard to combined positivity, the combination of 'either real-time PCR or IFN-γ' showed the highest sensitivity: 100% in confirmed pleural TB and 96.2% in probable pleural TB., Conclusions: IFN-γ showed the highest sensitivity as an individual diagnostic test. When a combination of tests was used, positivity of 'either IFN-γ or real-time PCR' appeared valuable for the diagnosis of pleural TB., (Copyright © 2010 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Accurately differentiating tuberculous pleurisy from lung cancer is important for disease management but difficult using conventional laboratory methods. This study assessed the value of adenosine deaminase (ADA) and interferon gamma (IFN-γ) for differentiating the two conditions in a region of Taiwan with a high prevalence of tuberculosis. The study population comprised patients with lymphocytic exudative pleural effusions: tuberculous (n=24) and malignant (n=42). Mean levels of ADA and IFN-γ in pleural fluid, measured with commercial standardized kits, were significantly higher for tuberculous than for malignant pleurisy (p<0.001 for both). For differentiating the two effusions, results for ADA versus IFN-γ were: sensitivity, 70.8% versus 91.7%; specificity, 95.2% versus 97.6%; positive predictive value, 89.5% versus 96.7%; and negative predictive value, 85.1% versus 95.3%. IFN-γ allows precise diagnosis of pleural tuberculosis, but ADA is easier to use, has a low cost, and results are quickly available. Our study confirms previous studies and extends the usefulness of these diagnostic methods to a wider group of clinical laboratories by showing the reliability of standardized relatively inexpensive commercial kits. We recommend that initial ADA screening be used in conjunction with IFN-γ measurements for differential diagnosis of tuberculous pleurisy., (Copyright © 2011. Published by Elsevier B.V.)

Objective: To determine the diagnostic utility of adenosine deaminase (ADA) in a large series of pleural effusions of different etiologies., Methods: A retrospective study of 2104 consecutive patients presenting with pleural effusion was carried out at a Spanish university hospital. ADA levels in pleural fluid were determined using a non-Giusti automatic kinetic assay, and a receiver operating characteristics curve analysis was applied to estimate their discriminative properties., Results: Pleural tuberculosis (TB) accounted for 221 (10.5%) effusions. Pleural fluid ADA >35U/L yielded 93% sensitivity, 90% specificity, a positive likelihood ratio (LR) of 10.05 and a negative LR of 0.07 for the diagnosis of TB among lymphocytic exudates. The ADA activity was significantly higher in neutrophil- (111.6U/L) than in lymphocyte-rich (62.4U/L; p=0.002) TB effusions. Overall, more than 40% of parapneumonics and half of lymphomatous effusions exceeded the cutoff set for TB. These were the only causes of ADA activity above 250U/L. When the prevalence of TB as a cause of exudative effusions is low (e.g., 1%), the estimated positive predictive value of the ADA test may be as low as 7%, although the negative predictive value remains high (99.9%)., Conclusion: Where available, pleural ADA should be routinely used to rule TB in or out in areas with moderate to high or low TB prevalence, respectively. A high ADA level is a characteristic not only of lymphocytic, but also of neutrophilic TB effusions. An extremely high ADA activity should raise suspicion of empyema or lymphoma., (Copyright (c) 2010 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Background: Tuberculous pleural effusions (TPE) are common. The diagnosis is often problematic. As the determination of ADA is often unavailable in some countries, the aim of this study was to evaluate the diagnostic usefulness of other data from pleural fluid analysis, in young patients from populations with high prevalence of tuberculosis (TB)., Methods: We analysed 218 patients with pleural effusion (165 tuberculous, 21 infectious, 11 neoplastic, 16 miscellaneous, 3 idiopathic). We performed two regression models; one included pleural fluid ADA values (model 1), and the other without ADA (model 2)., Results: Model 1 selected two variables (ADA >35U/L) and lymphocytes (>31.5%) and correctly classified 216/218 effusions (1 false negative, 1 false positive). Model 2 (without ADA) selected three variables: lymphocytes (>31.5%), fever and cough, and correctly classified 207/218 effusions (8 false negatives, 3 false positives). The sensitivity of models 1 and 2 was 99.4% and 95.2%, specificity 98.1% and 94.3% and accuracy 99% and 95%., Conclusions: In geographic areas with high prevalence of TB and a low prevalence of HIV, in young patients (

Several biological markers have been proposed to improve the efficacy of diagnosing tuberculous pleurisy. The study was undertaken to evaluate the accuracy of pleural fluid adenosine deaminase (ADA) activity and interferon-gamma (IFN-gamma) concentration in differentiating tuberculous pleural effusion (TPE) and nontuberculous pleural effusion (non-TPE). Ninety four patients (50 M and 44 F, mean age 60+/-18, range 18-95 years) with pleural effusion (PE) were studied. TPE was diagnosed in patients with: (i) positive pleural fluid or pleural biopsy culture or (ii) granulomas in the pleural biopsy specimen, after exclusion of other granulomatous diseases. Pleural fluid ADA activity was measured with the colorimetric method of Giusti, while IFN-gamma level was measured with ELISA. TPE was diagnosed in 28 patients. The non-TPE group consisted of 35 patients with malignant PE, 20 patients with parapneumonic effusion/pleural empyema, 5 with pleural transudate, and 6 with miscellaneous PE. The ADA activity and IFN-gamma concentration were significantly higher in TPE than in non-TPE (614.1+/-324.5 vs. 15.1+/-36.0 pg/ml, P<0.0001 and 75.1+/-39.1 vs. 11.0+/-16.6 U/l respectively, P<0.0001). The diagnostic sensitivity and specificity of IFN-gamma measurement (cut-off value of 75.0 pg/ml) were 100% and 98.5% respectively and were similar to those of ADA (100% and 93.9% at the cut-off value of 40.3 U/L). We conclude that pleural fluid ADA activity and IFN-gamma concentration are highly sensitive and specific markers of tuberculous pleurisy.

The assessment of the adenosine deaminase activity (ADA) in the pleural effusion is used for the diagnosis of tuberculous pleural effusion (TPE). To examine whether the procedure can be applied to immunocompromised patients, we analyzed the ADA activity in the pleural fluid of renal transplant recipients. We studied 23 renal transplant patients with TPE (21 men and 2 women; the mean age, 33 years). They were treated at the Yonsei University Hospital between January 1985 and December 2001. Patients with granuloma in the pleural biopsy specimen or positive for Mycobacterium tuberculosis in the pleural fluid culture were recruited. The ADA activity in the pleural effusion of 23 renal transplant patients with TPE was compared with 23 immunocompetent patients with TPE. The mean ADA activity was 69.5 +/- 4.6 in renal transplant patients and 65.0 +/- 4.9 U/L in immunocompetent patients. Applying the 40 U/L cut-off point, the positivity of ADA was 91.3% in renal transplant patients, and 86.9% in immunocompetent patients. We thus concluded that the measurement of ADA in the pleural fluid is a useful means in the diagnosis of TPE in renal transplant patients.

Background: Pleural effusion (PE) is a common problem in medical practice. Transudative effusions usually do not present difficulty in diagnosis, in most populations. Exudative PE however, require careful differential diagnosis that include necessarily tuberculosis and metastatic cancer., Methods: We have conducted a cross-sectional study of 221 patients with persistent PE, in order to evaluate accuracy of determining adenosine deaminase activity (ADA) for diagnosis of tuberculosis pleuritis. This group of patients, taken mostly from the State Hospital for pulmonary diseases, consecutively, was constituted as follows: 1) Tuberculosis (confirmed, n = 150; likely, n = 9); 2) Cancer (confirmed, n = 21; likely, n = 16; Lymphoma = 3); and 3) Miscellaneous (n = 22). All individuals were submitted to clinical examination, chest X-ray, blood tests, and underwent thoracocentesis with pleural biopsy. Pleural fluids were analyzed by routine tests plus determination of ADA activity using Giusti's Method., Results: In agreement with previous reports we have found 40 U/L to be the best cutoff point according to a Receiver Operating Curve (ROC) analysis of our data. Sensitivity of ADA activity < or = 40 U/L was 93.3% and specificity 93.5%, resulting in a positive predictive value of 97.2% and a negative predictive value of 85.3%, in this specific population of patients, when taking into account only the individuals with confirmed tuberculosis by histopathology or culture. Three out of the 4 patients with elevated ADA without tuberculosis had lymphoma., Conclusion: ADA determination in pleural fluids, a quick and inexpensive technique, is shown to be an accurate method for identifying tuberculosis pleuritis. Our findings are comparable to reports from other series, and stress how useful it is to incorporate this test to the routine evaluation of pleural effusions in areas of high incidence of tuberculosis.

Adenosine deaminase (ADA) activity and tuberculostearic acid (TSA) levels in pleural effusions were measured in 18 patients with active tuberculous pleuritis, 16 patients suspected of having tuberculous pleuritis, 14 patients with carcinomatous pleuritis, and 19 patients suffering from pleuritis of non-malignant and non-tuberculous etiology. In the patients with active tuberculous pleuritis, ADA was elevated in 56% and TSA was positive in 78%. In 83% of these patients, either ADA was elevated or TSA was positive. ADA was elevated together with a positive TSA in 50%. In contrast, TSA was positive in only 6% and ADA was elevated in 24% of the patients with non-tuberculous pleuritis, and none of these patients showed the combination of an elevation of ADA and a positive TSA. These results suggest that simultaneous measurements of both ADA and TSA in pleural effusions are useful for the diagnosis of tuberculous pleuritis.