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Background: Adenosine deaminase (ADA) activity is typically elevated in patients with tuberculous pleural effusion (TPE), but low ADA has occasionally been reported in patients with TPE. The characteristics of these patients are not well-known, and erroneous exclusion of the possibility of TPE can result in a delayed diagnosis. This study investigated the characteristics of patients with TPE who had low ADA activity., Methods: We retrospectively reviewed patients with microbiologically or pathologically confirmed TPE between 2012 to 2018 in a tertiary hospital in South Korea. Patients were categorised into two groups: high ADA (≥40 IU/L) and low ADA (< 40 IU/L). Clinical characteristics and Sequential Organ Failure Assessment (SOFA) scores were compared between groups., Results: A total of 192 patients with TPE were included; 36 (18.8%) had ADA < 40 IU/L with a mean ADA activity level of 20.9 (±9.2) IU/L. Patients with low ADA were older (75.3 vs. 62.0 years, p < 0.001) and had a lower mean lymphocyte percentage (47.6% vs. 69.9%, p < 0.001) than patients with high ADA. Patients in the low ADA group had a significantly higher mean SOFA score (2.31 vs. 0.68, p < 0.001), and patients with organ dysfunction were significantly more common in the low ADA group (p < 0.001). Patients with 2 or ≥ 3 organ dysfunctions constituted 19.4 and 13.9% of the patients in the low ADA group, whereas they constituted 7.1 and 1.3% of the patients in the high ADA group (p < 0.001). Multivariate logistic regression analyses showed that older age (odds ratio = 1.030, 95% confidence interval 1.002-1.060, p = 0.038) and a higher SOFA score (odds ratio = 1.598, 95% confidence interval 1.239-2.060, p < 0.001) were significantly associated with low ADA activity in patients with TPE., Conclusions: ADA activity can be low in patients with TPE who are elderly, critically ill, and exhibit multiorgan failure. Low ADA activity cannot completely exclude the diagnosis of TPE, and physicians should exercise caution when interpreting pleural fluid exams.

Objective: Immunoglobulin G4-related disease (IgG4-RD) is a recently described systemic disorder. Pleural effusion is considered an uncommon manifestation of the disease. We describe a case series of patients with IgG4-RD and clinically significant pleural effusions., Methods: A retrospective analysis of patients with histologically proven IgG4-RD treated for pleural effusion in our clinic., Results: We identified 4 male patients with pleural effusion caused by IgG4-RD. The effusions were lymphocytic exudates, with especially high protein concentrations. All patients had hyperglobulinemia, elevated serum immunoglobulin G (IgG) levels and elevated levels subclasses IgG1 and IgG4. In two patients, levels of adenosine deaminase (ADA) were measured in the effusion and were elevated (309 and 108 IU/L). Tuberculosis was excluded in both cases by pleural biopsy. Involvement of other organs by IgG4-RD was the rule, especially thoracic lymphadenopathy which was prominent in all patients. In all cases, effusion responded to corticosteroids therapy. One patient developed radiological findings compatible with rounded atelectasis during remission., Conclusions: IgG4-RD may cause an ADA-positive, lymphocytic exudate with a high protein concentration, characteristics resembling tuberculous effusion. Thoracic lymphadenopathy, hyperglobulinemia, and an increased total IgG, IgG1, IgG4 may suggest the diagnosis. Not previously described, IgG4-RD pleural inflammation may result in rounded atelectasis. (Sarcoidosis Vasc Diffuse Lung Dis 2020; 37 (2): 225-230) ., Competing Interests: The authors report no conflict of interest regarding this manuscript. The study was self-funded by the Pulmonary Institute of Rabin Medical Center., (Copyright: © 2020 SARCOIDOSIS VASCULITIS AND DIFFUSE LUNG DISEASES.)

Background: In China, tuberculous pleural effusion is the most common cause for pleural effusion. Elevated ADH and positive tuberculin test usually are characteristic of tuberculous pleural effusion. We reported a 71-year-old male patient with elevated ADH and positive tuberculin test firstly misdiagnosed as tuberculous pleural effusion finally proven as pleural mesothelial sarcoma by thoracoscopic pathology., Methods: Appropriate laboratory tests and thoracentesis were carried out. Thoracoscopy and pathological biopsy were performed to differentiate tuberculous pleural effusion., Results: Chest CT showed right pleural effusion. ADH in pleural effusion was over 45 U/L and PPD test was positive. No abnormal cells were found in pleural effusion pathology. Pathology of thoracoscopic biopsy proved pleural mesothelioma., Conclusions: Elevated ADH and positive tuberculin test are not a specific index for tuberculosis and thoracoscopic biopsy pathology is crucial for differential diagnosis.

Objective: Thymidine kinase 1 (TK1) is a key enzyme in the pyrimidine salvage pathway. Increased TK1 concentration correlates with cell division. TK1 is an emerging biomarker in cancer diagnosis; however, its effectiveness in diagnosis and management for malignant pleural effusion (MPE) is unclear. We evaluated the diagnostic efficiency and prognostic value of pleural effusion TK1 (pTK1) concentration for MPE., Methods: From 2013 to 2017, 210 pleural effusion samples were collected from 160 patients diagnosed with MPE and 50 patients diagnosed with benign pleural effusion (BPE). TK1 concentrations in pleural effusion were measured by chemiluminescence dot blot assays. The median follow-up was 12 months. We constructed a receiver-operating characteristic (ROC) curve to find the optimal cutoff value for MPE diagnosis. The hazard ratios were estimated using a multivariable Cox proportional hazard model. A nomogram was drawn to illustrate the prognostic characteristics of MPE., Results: The TK1 concentration in pleural effusion was significantly higher in MPE than BPE (P < 0.001), and patients with MPE could be distinguished by an optimal cutoff value of 3.10 pmol/L with a sensitivity of 0.894 and a specificity of 0.800. The multivariate analysis suggested that pTK1 concentration was an independent predictor of survival in patients with MPE., Conclusions: The diagnostic and prognostic prediction of MPE may be improved by measuring pTK1 concentration and utilizing a multivariate nomogram., (© 2019 The Authors. Journal of Clinical Laboratory Analysis Published by Wiley Periodicals, Inc.)

Objective: Pleural fluid adenosine deaminase (ADA) is a useful diagnostic test for tuberculous pleural effusion (TPE), but its exact threshold and accuracy in clinical decision-making is unclear. We aimed to assess diagnostic performance of ADA in TPE and to clarify its optimal diagnostic threshold., Methods: We searched PubMed, Embase, and Cochrane Library databases for articles indexed up to October 2018. We included English language studies that provided both sensitivity and specificity of ADA in TPE diagnosis. Summary estimates for sensitivity and specificity were obtained through bivariate random effects model, both overall and at prespecified threshold ranges of <36, 40±4, 45-65 and >65 IU/L., Results: We retrieved 2162 citations, and included 174 publications with 27009 patients. All studies showed high risk of bias. Summary sensitivity, specificity and diagnostic odds ratio estimates were 0.92 (95% CI 0.90-0.93), 0.90 (95% CI 0.88-0.91) and 97.42 (95% CI 74.90-126.72) respectively. 65 studies with ADA threshold of 40±4 IU/L showed summary sensitivity and specificity of 0.93 (95% CI 0.90-0.95) and 0.90 (95% CI 0.87-0.91) respectively. Four studies with ADA threshold >65 IU/L showed summary sensitivity and specificity of 0.86 (95% CI 0.61-0.96) and 0.94 (95% CI 0.80-0.99) respectively., Conclusion: ADA levels in pleural fluid show good diagnostic accuracy in diagnosis of TPE; however, all included studies showed high risk of bias. It was not possible to derive any firm inference on relative clinical utility of different diagnostic thresholds., Competing Interests: The authors have declared that no competing interests exist.

Introduction In contrast to tuberculous pleurisy (TP), no accurate and commonly accepted biochemical marker of malignant pleural effusion (MPE) has been established. Objectives We aimed to evaluate the ability of a previously reported cancer ratio (CR) to discriminate between MPEs and non-MPEs; to test whether age may have additional value in differentiating MPEs from non-MPEs; and if so, to combine lactate dehydrogenase (LDH) and age with other TP biomarkers in search of an index useful in the identification of MPEs. Patients and methods A retrospective analysis of data from 140 patients with malignant (n = 74), tuberculous (n = 37), and parapneumonic (n = 29) pleural effusions was performed. The diagnostic performance of a test to discriminate between MPEs and non-MPEs was evaluated using the receiver operating characteristic curve analysis. Results Three ratios showed the largest area under the curve (AUC): serum LDH to pleural fluid soluble Fas ligand, age to pleural fluid adenosine deaminase (ADA), and serum LDH to pleural fluid interleukin 18; moreover, the ratios were characterized by high sensitivity (95%, 93.2%, and 92.9%, respectively) and fair specificity (64.8%, 71.2%, and 58.5%, respectively) for differentiating MPEs from non-MPEs. The AUC for CR was lower and showed a sensitivity of 94.6% and a specificity of 68.2%. Conclusions Our study showed a lower specificity of the CR for discriminating between MPEs and non-MPEs than previously reported. We demonstrated that the combinations of serum LDH with other pleural fluid biomarkers of TP have a similar diagnostic performance. We also found that age might be an important factor differentiating between MPEs and non-MPEs and proposed a new age to pleural fluid ADA ratio which has a discriminative potential similar to that of the CR.

Background: A follow-up thoracentesis is proposed in suspected atypical tuberculosis cases. The study aimed to define the variability of pleural ADA values across repeated thoracenteses in different types of pleural effusions (PEs) and to evaluate whether ADA variance, in regard to the cutoff value of 40 U/L, affected final diagnosis., Methods: A total of 131 patients with PEs of various etiologies underwent three repeated thoracenteses. ADA values were subsequently estimated., Results: 82% and 55% of patients had greater than 10% and 20% deviation from the highest ADA value, respectively. From those patients who had a variance of 20%, 36% had only increasing ADA values, while 19% had only decreasing values. Considering the cutoff value of 40 U/L, only in two cases, ADA decreased below this threshold, which concerned a man with tuberculous pleurisy and a woman with lymphoma both in the course of treatment. Furthermore, only in two cases with rising values, ADA finally exceeded the cutoff limit, which concerned a man with rheumatoid pleurisy and a man with tuberculous pleurisy. Surprisingly, malignant PEs (MPEs) showed a higher percentage of increasing values compared to all other exudates that did not, however, exceed the threshold., Conclusion: The determination of pleural ADA levels is a reproducible method for rapid tuberculosis diagnosis. The detected measurement deviations do not appear to affect final diagnosis. In specific situations, repeated ADA measurements may be valuable in directing further diagnostic evaluation. More investigation is needed to elucidate the possible prognostic significance of the increasing trend in ADA values in MPEs., (© 2017 Wiley Periodicals, Inc.)

Purpose: We studied the diagnostic value of cytokines, including vascular endothelial growth factor (VEGF), transforming growth factor-β (TGF-β), and interleukin-8 (IL-8), and the ratio of lactate dehydrogenase (LDH) to adenosine deaminase (ADA) in pleural fluid., Methods: Prospective analysis of 44 inpatients or outpatients with pleural fluid, from December 2016 to March 2017 was conducted., Results: We enrolled patients with malignant pleural effusion (MPE, N = 15), empyema (N = 11), parapneumonic effusion (PPE, N = 7), chronic renal failure (CRF)/chronic heart failure (CHF) (N = 7), and tuberculous pleural effusion (TBPE, N = 4). The pleural fluid values of IL-8 and VEGF were significantly higher in empyema patients than in CRF/CHF or PPE patients. In all patients, the pleural fluid VEGF and IL-8 values were significantly positively correlated (r = 0.405, p = 0.006; r = 0.474, p = 0.047, respectively). TGF-β was elevated in patients with empyema, PPE, TBPE, and MPE. The pleural LDH-to-ADA ratio in patients with MPE or empyema/PPE was significantly higher than in patients with CRF/CHF or TBPE. LDH and ADA levels correlated significantly only in patients with MPE (r = 0.648, p = 0.009) and empyema/PPE (r = 0.978, p < 0.001)., Conclusions: VEGF and IL-8 production in the pleural cavity appear to accelerate the progression of PPE to empyema, by enhancing vascular permeability associated with inflammation. Sequential sampling would be needed to confirm this. The pleural LDH/ADA ratio may be a useful diagnostic tool for discriminating between various pleural effusion etiologies.

Background: Although pleural fluid lactate dehydrogenase (LDH) and adenosine deaminase (ADA) levels are often used to distinguish between tuberculous pleural effusion (TPE) and parapneumonic pleural effusion (PPE), this can be challenging as the LDH level may vary from normal to severely increased in PPE and a significantly elevated ADA is frequently measured in both conditions. In this study, we evaluated use of the pleural fluid LDH/ADA ratio as a new parameter to discriminate TPE from PPE., Methods: A retrospective study was conducted in patients with pathologically-confirmed TPE (n = 72) and PPE (n = 47) to compare pleural fluid LDH and ADA levels and LDH/ADA ratios between the 2 groups. A receiver operating characteristic (ROC) curve was constructed for identifying TPE., Results: The median pleural fluid LDH and ADA levels and LDH/ADA ratios in the TPE and PPE groups were: 364.5 U/L vs 4037 U/L (P < .001), 33.5 U/L vs 43.3 U/L (P = .249), and 10.88 vs 66.91 (P < .0001), respectively. An area under the ROC curve of 0.9663 was obtained using the LDH/ADA ratio as the indicator for TPE identification, and the sensitivity, specificity, positive likelihood ratio (PLR), and negative likelihood ratio (NLR) were, respectively, 93.62%, 93.06%, 13.48, and 0.068 at a cut-off level of 16.20., Conclusions: The pleural fluid LDH/ADA ratio, which can be determined from routine biochemical analysis, is highly predictive of TPE at a cut-off level of 16.20. Measurement of this parameter may be helpful for clinicians in distinguishing between TPE and PPE.

Background: Diagnosis of tuberculous (TB) pleurisy remains challenging due to the paucibacillary nature of the disease. We prospectively assessed the diagnostic usefulness of the T-cell based ELISPOT assay, and created a clinical algorithm for differentiating TB pleurisy from other diagnoses., Methods: All adult patients with suspicion for TB pleurisy were enrolled in a tertiary hospital in Seoul, South Korea, over a 7-year period. ELISPOT assays were performed using mononuclear cells from peripheral blood and pleural effusion., Results: Seventy-seven patients with suspected TB pleurisy were enrolled. Of these, 33 (43%) patients, comprising 27 confirmed and 6 probable TB pleurisy, were classified as TB pleurisy, and 36 (47%) were classified as not TB. The remaining 8 with possible TB pleurisy were excluded from the final analysis. The sensitivities and specificities, respectively, of the diagnostic methods were as follows: pleural fluid adenosine deaminase (ADA) level 32 U/L, 81% and 79%; peripheral blood mononuclear cells (PBMC) ELISPOT assay, 82% and 73%; pleural effusion-mononuclear cells (PE-MC) ELISPOT assay, 58% and 87%. When the diagnostic algorithm was applied, PBMC ELISPOT ≥6 spots or ADA ≥32 U/L' as a rule-out test safely excluded 46% (12/26) of the not TB patients, and 'PE-MC ≥6 spots' as a rule-in test accurately classified 23% (7/31) of the patients with TB pleurisy., Conclusions: A diagnostic algorithm combining ELISPOT assays and ADA levels in pleural fluid appears to be a promising and non-invasive approach for patients with suspected TB pleurisy.

The differential diagnosis of tuberculous pleural effusion (TPE) and malignant pleural effusion (MPE) remains difficult despite the availability of numerous diagnostic tools. The current study aimed to evaluate the performance of the whole blood QuantiFERON-TB Gold In-Tube (QFT-GIT) assay and conventional laboratory biomarkers in differential diagnosis of TPE and MPE in high tuberculosis prevalence areas. A total of 117 patients with pleural effusions were recruited, including 91 with TPE and 26 with MPE. All of the patients were tested with QFT-GIT, and the conventional biomarkers in both blood and pleural effusion were detected. The level of antigen-stimulated QFT-GIT in the whole blood of TPE patients was significantly higher than that of MPE (2.89 vs 0.33 IU/mL, P<0.0001). The sensitivity and specificity of QFT-GIT for the diagnosis of TPE were 93.0% and 60.0%, respectively. Among the biomarkers in blood and pleural effusion, pleural adenosine deaminase (ADA) was the most prominent biomarker, with a cutoff value of 15.35 IU/L. The sensitivity and specificity for the diagnosis of TPE were 93.4% and 96.2%, respectively. The diagnostic classification tree from the combination of these two biomarkers was 97.8% sensitive and 92.3% specific. Ultimately, the combination of whole blood QFT-GIT with pleural ADA improved both the specificity and positive predictive value to 100%. Thus, QFT-GIT is not superior to pleural ADA in the differential diagnosis of TPE and MPE. Combined whole blood QFT-GIT and pleural ADA detection can improve the diagnosis of TPE.

Purpose of Review: This article summarizes current data regarding the accuracy of pleural fluid tests assisting the diagnosis of tuberculous pleuritis (TBP)., Recent Findings: No pleural fluid test reliably rules-in TBP in settings with low TBP prevalence. Interferon-γ) alone or in combination with adenosine deaminase (ADA) is more reliable than ADA for this purpose in nonlow prevalences. ADA can reliably rule-out TBP in prevalences of less than 40% although in higher prevalences the product of interleukin-27 and ADA is the most accurate rule-out test., Summary: The definite diagnosis of TBP requires the isolation of Mycobacterium tuberculosis from pleural fluid or biopsies. Because of the low sensitivity of pleural fluid cultures and the invasiveness of pleural biopsy techniques, the concept of a pleural fluid test that accurately establishes or excludes TBP diagnosis has been proposed. Numerous pleural fluid tests have been evaluated for this purpose with ADA being the most widely accepted one. During the last years, it has been demonstrated that the ability of ADA to rule-in or rule-out TBP is affected by the prevalence of TBP in the setting where the test is used. The complementary use of interferon-γ or interleukin-27 increases the ability of ADA to rule-in or rule-out the disease, respectively.

Aim: To assess the relationship between imaging features of pulmonary tuberculosis at computed tomography (CT) and adenosine deaminase (ADA) values via pleural fluid analysis in patients with pleural tuberculosis., Materials and Methods: This retrospective study enrolled 60 patients who underwent fluid analysis for ADA and chest CT and were diagnosed with tuberculosis by culture or polymerase chain reaction of pleural fluid and sputum. The presence of centrilobular nodules, consolidation, cavitation, and mediastinal lymphadenopathy at CT were evaluated. The relationship between ADA values and the pattern of pulmonary involvement of tuberculosis was analysed., Results: Pulmonary involvement was seen in 42 of the 60 patients. A centrilobular nodular pattern was seen in 37 and consolidation in 22. In 17 patients, both findings were identified. A centrilobular nodular pattern was more common than consolidation or cavitary lesions. When ADA values were high, pulmonary involvement was more frequent (p=0.002). Comparing low and high ADA groups using an obtained cut-off value of 80 IU/l, the high group had more frequent pulmonary involvement (p<0.001)., Conclusion: Patients with tuberculous pleurisy who had high ADA values had a higher probability of manifesting pulmonary tuberculosis. High ADA values may help predict contagious pleuroparenchymal tuberculosis. The most common pulmonary involvement of tuberculous pleurisy showed a centrilobular nodular pattern., (Copyright © 2016 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Objectives: Delay in the treatment of pleural infection may contribute to its high mortality. In this retrospective study, we aimed to evaluate the diagnostic accuracy of pleural adenosine deaminase in discrimination between Gram-negative and Gram-positive bacterial infections of the pleural space prior to selecting antibiotics., Methods: A total of 76 patients were enrolled and grouped into subgroups according to Gram staining: 1) patients with Gram-negative bacterial infections, aged 53.2±18.6 years old, of whom 44.7% had empyemas and 2) patients with Gram-positive bacterial infections, aged 53.5±21.5 years old, of whom 63.1% had empyemas. The pleural effusion was sampled by thoracocentesis and then sent for adenosine deaminase testing, biochemical testing and microbiological culture. The Mann-Whitney U test was used to examine the differences in adenosine deaminase levels between the groups. Correlations between adenosine deaminase and specified variables were also quantified using Spearman's correlation coefficient. Moreover, receiver operator characteristic analysis was performed to evaluate the diagnostic accuracy of pleural effusion adenosine deaminase., Results: Mean pleural adenosine deaminase levels differed significantly between Gram-negative and Gram-positive bacterial infections of the pleural space (191.8±32.1 U/L vs 81.0±16.9 U/L, p<0.01). The area under the receiver operator characteristic curve was 0.689 (95% confidence interval: 0.570, 0.792, p<0.01) at the cutoff value of 86 U/L. Additionally, pleural adenosine deaminase had a sensitivity of 63.2% (46.0-78.2%); a specificity of 73.7% (56.9-86.6%); positive and negative likelihood ratios of 2.18 and 0.50, respectively; and positive and negative predictive values of 70.6% and 66.7%, respectively., Conclusions: Pleural effusion adenosine deaminase is a helpful alternative biomarker for early and quick discrimination of Gram-negative from Gram-positive bacterial infections of the pleural space, which is useful for the selection of antibiotics.

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.)

Background and Objective: Carbonic anhydrase IX (CAIX) is widely expressed in a variety of malignant tumors, including-lung cancer. Our previous study has shown that the serum level of soluble form of carbonic anhydrase IX (s-CAIX) was significantly higher in patients with lung cancer than that in the healthy group. The aim of this study is to detect the s-CAIX level in the pleural effusion and its sediment, and to evaluate the significance of CAIX detection in the diagnosis of lung cancer., Methods: The s-CAIX level in pleural effusion of 29 lung cancer patients and 27 patients with tuberculosis was detected by ELISA. The expression of CAIX in the pleural effusion sediment of 21 lung cancer patients with malignant pleural effusion and 6 patients with benign pleural effusion was examined by immunohistochemistry. With pathological diagnosis as the gold standard, receiver operating characteristic (ROC) curve of pleural effusion s-CAIX was established for the diagnosis of lung cancer with malignant pleural effusion., Results: The s-CAIX level in the malignant pleural effusion was significantly higher than that in the tuberculosis group (P<0.05). The AUC of pleural effusion s-CAIX level was 0.761. At a threshold level of 109.135 pg/mL, sensitivity and specificity were 92.3% and 58.3%, respectively. The CAIX expression in all samples of the benign pleural effusion sediment was negative. The positive rate of CAIX expression in malignant pleural effusion sediment was 66.67%., Conclusions: Detection of CAIX in the pleural effusion and its sediment exhibits high sensitivity and specificity, and is helpful in diagnosis of lung cancer with malignant pleural effusion.

Though pulmonary tuberculosis is the common presentation of Mycobacterium tuberculosis infection, extra-pulmonary tuberculosis is also a growing problem worldwide. Tuberculous pleural effusion is the second frequent form of extra-pulmonary presentation after tuberculous lymphadenitis and if untreated up to 65% of patients with tubercular pleural effusions will eventually develop active TB. Traditional diagnostic methods are very useful for the diagnosis of pulmonary TB but have a low yield when applied to pleural fluid. So,the aim of this study was to evaluate the diagnostic value of ADA level in plural fluid and other conventional methods for diagnosis of tubercular plural effusion. This was a cross sectional study. This study was carried out in 64 Patients suffering from plural effusion and were consecutively selected and divided into two groups: tuberculous (n=40) and non tuberculous (n=24), depending upon etiology. Details clinical history, physical examination, routine and other relevant investigations including ADA estimation was measured. The mean value of ADA in the tuberculous group was 64.11 ± 19.50 U/L which was significantly higher (p<0.05). Cut off value of ADA was ≥ 40 U/L with 97% sensitivity and 93%specificity. In this study, sensitivity, specificity, PPV and NPV of ADA level in pleural effusion were more significant than other conventional parameters.

High serum lactate dehydrogenase (LDH) level, immunologic defects, enlarged mediastinal lymph nodes, and frequent hydration and diuresis in lymphoma patients may affect the development of pleural effusion (PE). The study was to assess the clinical utility of "Light criteria" and the "recommended algorithm for investigating PEs" in patients with lymphoma.The characteristics of 126 PEs of lymphoma patients who underwent diagnostic thoracentesis between January 1, 2003, and April 30, 2012, were reviewed. Using Light criteria, 29 (23%) PEs were incorrectly classified. The sensitivity for exudates in Light criteria was 88% and the specificity was only 44%. In 32 transudates, PE LDH correlated with blood LDH concentration (P < 0.001, r = 0.66). Nine transudates were misclassified as exudates (50%; 9/18) just due to PE LDH more than two-thirds the upper limits. Among the 56 bilateral PEs, 33 (59%) were exudates. Ten (63%) polymorphonuclear (PMN)-predominant exudative PEs were malignant. Infective PEs were often mononuclear (67%) rather than PMN predominant.When a patient has lymphoma with either unilateral or bilateral PE, thoracentesis for microbiological testing and cytology is imperative. Carefully clinical correlation in addition to the result from Light criteria and differential cell count is essential for prompt management.

Introduction: Previous studies have assessed the diagnostic ability of pleural fluid adenosine deaminase (pfADA) in detecting tuberculous pleural effusions, with good specificity and sensitivity reported. However, in North Western Europe pfADA is not routinely used in the investigation of a patient with an undiagnosed pleural effusion, mainly due to a lack of evidence as to its utility in populations with low mycobacterium tuberculosis (mTB) incidence., Methods: Patients presenting with an undiagnosed pleural effusion to a tertiary pleural centre in South-West England over a 3 year period, were prospectively recruited to a pleural biomarker study. Pleural fluid from consecutive patients with robust 12-month follow up data and confirmed diagnosis were sent for pfADA analysis., Results: Of 338 patients enrolled, 7 had confirmed tuberculous pleural effusion (2%). All mTB effusions were lymphocyte predominant with a median pfADA of 72.0 IU/L (range- 26.7 to 91.5) compared to a population median of 12.0 IU/L (range- 0.3 to 568.4). The optimal pfADA cut off was 35 IU/L, which had a negative predictive value (NPV) of 99.7% (95% CI; 98.2-99.9%) for the exclusion of mTB, and sensitivity of 85.7% (95% CI; 42.2-97.6%) with an area under the curve of 0.88 (95% CI; 0.732-1.000)., Discussion: This is the first study examining the diagnostic utility of pfADA in a low mTB incidence area. The chance of an effusion with a pfADA under 35 IU/L being of tuberculous aetiology was negligible. A pfADA of over 35 IU/L in lymphocyte-predominant pleural fluid gives a strong suspicion of mTB.

Purpose: Tuberculous pleural effusion (TPE) is characterized by lymphocytic predominance and high adenosine deaminase (ADA) levels. However, TPEs sometimes present non-lymphocytic predominance, and parapneumonic effusion (PPE) often exceeds the cutoff value of ADA for TPE. Thus, the differential diagnosis of cases with pleural fluid (PF) showing non-lymphocytic predominance and high ADA levels is challenging. However, limited data concerning the clinical differences in these patients are available., Methods: A retrospective study was conducted on TPE and PPE patients with PF showing non-lymphocytic predominance and ADA levels ≥40 U/L in 2009-2013 in a South Korean tertiary referral hospital. The clinical, laboratory, and computed tomography (CT) findings between the groups were analyzed using multivariate logistic regression to develop a prediction model with independent factors for TPE., Results: Among 353 patients with TPE, 24 (6.8 %) showed PF with non-lymphocytic predominance and ADA levels of ≥40 U/L. Twenty-eight PPE patients who presented PF findings comparable with those of TPE patients were included in the control group. In the final analysis, PF ADA levels >58 U/L and nodular lung lesions on CT were independent positive predictors, while loculated effusion was an independent negative predictor for TPE. Using the prediction model, a score ≥ +3 provided a sensitivity of 88 %, specificity of 93 %, positive predictive value of 91 %, and negative predictive value of 90 % for TPE., Conclusion: PF ADA levels, nodular lung lesions, and loculated pleural effusion may help differentiate TPE from PPE in patients with PF showing non-lymphocytic predominance and ADA levels ≥40 U/L.

Objective: Pleural effusion (PE) adenosine deaminase (ADA) has good performance in detection of tuberculous pleural effusion (TPE). However, few study was conducted for its value in pediatric patients. To evaluate PE ADA in diagnosis of pediatric TPE, a retrospective study was performed., Patients and Methods: 204 pediatric PE patients were enrolled, and then were grouped into TPE group (77 cases, aged 11.51 ± 0.40 years) and non-TPE group (127 cases, aged 6.39 ± 0.35 years). Man-Whitney U test was used to compare difference in pleural ADA between the two groups. The correlation between age and ADA activity was analyzed by Spearman's correlation coefficient analysis., Results: In our study, there was no difference in pleural ADA between TPE (62.1 ± 4.2 U/L) and non-TPE patients (87.7 ± 10.0 U/L). Compared with empyema patients (183.8 ± 30.0 U/L), pleural ADA was lower in parapneumonic effusion (PPE) patients (63.4 ± 3.8, p < 0.01), or TPE patients (p <0.01). Correlation analysis showed that there were no correlation between age and pleural ADA within TPE, PPE or both patients (all p > 0.05). Meanwhile, there was no significant difference in PE ADA level between genders., Conclusions: Considering the fact that the majority of pediatric PEs is TPE and PPE, our study suggests that PE ADA isn't accurate in detection of pediatric TPE. Meanwhile, an extremely high ADA activity should raise suspicion of empyema or lymphoma.

Background and Aim: The purpose of this study was to assess the relationship of pleural adenosine deaminase (P-ADA) and non-Hodgkin's lymphoma (NHL)., Design and Methods: We retrospectively analysed 63 NHL patients with pleural effusions who accepted a diagnostic thoracentesis and who had P-ADA available at the China Medical University Hospital (Taichung, Taiwan) between January 2003 and April 2012., Results: There were 46 exudates [40 malignant pleural effusions (MPE), 5 complicated para-pneumonic effusions and 1 undiagnosed effusion] and 17 transudates. The P-ADA activity was significantly different between the two groups (P < 0.005). Among 40 MPE cases, 29 were due to B-cell and 11 due to T-cell NHL. There was no pleural transudative effusion with P-ADA value higher than 26 U/l in our study, but simultaneously 48% (22/46) of exudative pleural effusions showed a P-ADA value under that cut-off point. The P-ADA level reached the diagnostic cut-off for tuberculosis (40 IU/l) in 11 cases of MPE (11/40 = 27.5%): 9 B-cell NHL (9/29 = 31%) and 2 T-cell NHL (2/11 = 18%). The median levels (25th, 75th percentiles) of P-ADA were 28 IU/l (14-50) in the MPE of B-cell NHL and 26 IU/l (14-28) in the T-cell NHL (P = 0.693)., Conclusions: The use of P-ADA in NHL effusion could aid the separation of transudates from exudates. Around one-quarter MPE of NHL had abnormal P-ADA ( > 40 IU/l). There was no difference in the P-ADA activity in T-cell and B-cell NHL., (© Crown copyright 2014.)

Background: Adenosine deaminase (ADA) activity is useful for diagnosing tuberculous (TB) pleurisy in regions with a high prevalence of tuberculosis. However, some cases of TB pleural effusion show decreased ADA activity. Therefore, we evaluated factors influencing pleural ADA levels in patients with TB pleurisy., Methods: We retrospectively evaluated 182 patients with TB pleural effusion who were admitted to Gyeongsang National University Hospital from January 2004 to September 2008. Patients were dichotomized into 2 groups: a low-ADA (<40 IU/L) group (n = 22) and a high-ADA (≥40 IU/L) group (n = 160). Age, sex, ADA level of pleural effusion, smoking status, history of tuberculosis and comorbid diseases were evaluated in each group., Results: The median age of the patients was 50.5 years, with a male to female ratio of 1.72:1. Patients with a low-ADA level were significantly older than those with a high ADA level (66.9 ± 12.0 versus 49.4 ± 21.2 years, P < 0.001). A history of tuberculosis and hypertension was more common in the low-ADA group than in the high-ADA group (31.8% versus 15.0%, P = 0.049 and 36.4% versus 16.9%, P = 0.03, respectively). A multivariate analysis revealed that older age and current smoking were predictive of TB pleurisy with a low ADA level (odds ratios, 1.053 and 4.848; P = 0.002 and 0.028, respectively)., Conclusions: Physicians should be careful when interpreting pleural ADA levels in elderly patients and/or current smokers for the diagnosis of TB pleurisy.

Objective: 1) To determine factors affecting adenosine deaminase (ADA) levels in pleural fluid (PF), and 2) to establish the optimal ADA cut-off level for a Brazilian population., Design: ADA levels in PF of 309 patients were analysed to investigate pleural effusion. All patients were evaluated for age, sex and presence of tuberculosis (TB) based on a positive pleural biopsy. Differences in ADA levels between groups were analysed using Kruskal-Wallis one-way analysis of variance. Logistic regression analysis was also carried out to predict the occurrence of TB. ADA cut-off levels were selected using the receiver operating characteristic (ROC) curve., Results: The mean PF ADA level was significantly higher in the tuberculous pleural group than in non-tuberculous pleural patients (63.3 ± 29 IU/l vs. 19 ± 31 IU/l, P < 0.001). There was a significant correlation between PF ADA levels and age: for patients aged ⩾45 years, the ROC curve for ADA had an area under the curve of 0.91. An ADA level of 29 IU/l resulted in a sensitivity of 88.6% and specificity of 91.5%., Conclusions: There is a significant negative correlation between PF ADA level and age. The use of a lower ADA cut-off reduces the number of false-negative results.

Background: 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., Objectives: 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)., Methods: 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., Results: 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., Conclusion: FADA had a high PPV for PTB in our laboratory. We recommend its continued use as a rapid and reliable diagnostic tool for PTB.

The diagnosis of pleural tuberculosis (TB) continues to be a challenge in clinical practice. Traditional diagnostic methods are very useful for the diagnosis of pulmonary TB but have a low yield when applied to pleural fluid. It is produced during the inflammatory process triggered by the M. tuberculosis. Usefulness of adenosine deaminase (ADA) estimation in pleural fluid has been shown as a reliable chemical bio-marker specially when there is suspicion of tuberculosis in endemic areas. ADA level was determined in the pleural fluid of 100 patients present with pleural effusion admitted at Mymensingh Medical College Hospital during the period of March 2012 to September 2012. ADA level was >40IU/L among the 52 tubercular pleural effusion patients with sensitivity & specificity is 100% and 66% respectively. Thus is evident that ADA level can be used along with conventional methods for diagnosis of pleural TB.

Background: Adenosine deaminase (ADA) is useful in the diagnosis of tuberculous pleural effusion (TPE). This study aims to determine the factors affecting pleural fluid ADA levels and to establish the optimal ADA levels for diagnosis of TPE for different age groups., Methods: This was a retrospective study from January 2007 to October 2011. One hundred and sixty patients who had pleural fluid ADA performed for investigation of pleural effusion were analyzed. Variables examined included demographics, pleural fluid characteristics and peripheral blood counts. The ADA cut-offs according to age were selected using the receiver operating characteristic (ROC) curve., Results: The mean pleural fluid ADA was significantly higher in the TPE group (100 ± 35 IU/L) compared to non TPE patients (30 ± 37 IU/L). There was significant correlation between pleural fluid ADA and age, pleural fluid protein, LDH, and fluid absolute lymphocyte count. The strongest correlation was seen with age (r = -0.621). For patients ≤ 55 years old the ROC for ADA had area under curve (AUC) of 0.887. A pleural fluid ADA of 72 IU/L had sensitivity of 95.1%, specificity of 87.5%, positive predictive value (PPV) of 95.1% and negative predictive value (NPV) of 87.5% for the diagnosis of TPE. For patients > 55 years old the AUC is 0.959. ADA of 26 IU/L had a sensitivity of 94.7%, specificity of 80.4%, PPV of 62% and NPV of 97.8%., Conclusions: There is a significant negative correlation between pleural fluid ADA and age. For older patients, a lower ADA cut-off should be used to exclude TPE.

Background: Pleural fluid is a frequent manifestation in pulmonary diseases, such as lung cancer and infectious diseases, including pulmonary tuberculosis (TB). The enzyme indoleamine 2,3-dioxygenase (IDO) catalyses tryptophan through the kynurenine pathway, and is considered a crucial immunoregulatory molecule mediating immune tolerance. Recent studies have shown IDO activity to be a novel prognostic factor not only in cancer patients but also in those with infectious diseases, including pneumonia and pulmonary TB. However, no studies have measured and determined the clinical significance of IDO activity in pleural fluid., Methods: We enrolled 92 patients, including 34 with tuberculous pleurisy (TBP), 36 with malignant pleuritis and 15 with parapneumonic effusions. IDO activity was evaluated using liquid chromatography/electrospray ionisation tandem mass spectrometry, and was estimated by calculating kynurenine-to-tryptophan ratio., Results: Pleural fluid from patients with TBP had significantly higher kynurenine concentrations and significantly lower tryptophan concentrations, resulting in significantly higher IDO activity compared with pleural effusion or serum from non-tuberculous pleuritis (all P < 0.001). Pleural tissue from TBP showed enhanced IDO expression in epithelioid granuloma regions by immunohistochemistry., Conclusions: These results suggest that IDO is strongly involved in the pathogenesis of TBP.

We report a case of tuberculous pleurisy that required differentiation from pleurisy caused by Mycoplasma infection. A 28-year-old woman presented to a clinic with fever and pain on the left side of her chest. A chest radiograph revealed pleural effusion in the left thorax, and the condition was diagnosed as bacterial pleurisy. The patient was referred to our hospital because of an increase in the pleural effusion despite antibiotic treatment. Mycoplasma infection was suspected because the patient was young, the white blood cell count was not elevated, and the result of the ImmunoCard Mycoplasma test (IC) for Mycoplasma pneumoniae-specific IgM antibodies was positive. However, the fever persisted even after treatment with azithromycin and pazufloxacin. The left pleural effusion was exudative, with lymphocytosis and high adenosine deaminase (ADA) levels. The results of the QuantiFERON test were positive. Therefore, tuberculous pleurisy was diagnosed, and the effusion subsided after treatment with standard anti-tuberculosis chemotherapy. Although detection of Mycoplasma infection using the IC is rapid and simple, the accuracy of this test is poor. The patient was first diagnosed with pleurisy of Mycoplasma origin because of a single high-particle agglutination titer of 1: 320 and because of the presence of exudative pleural effusion with lymphocytosis and elevated ADA levels, which has been reported in patients with Mycoplasma infection. The results of the IC test and the ADA level of the pleural effusion might not be reliable when distinguishing between tuberculous pleurisy and pleurisy caused by Mycoplasma infection.

Objectives: Our aim was to determine the diagnostic value of the matrix metalloproteinase-9/vascular endothelial grow factor receptor-1 pathway in differentiating pleural effusions (PE) of varying origin., Methods: In the last two years, 55 consecutive patients with exudative PE have been enrolled. In all patients, we measured PE levels of vascular endothelial grow factor receptor-1 (VEGFR-1) in soluble form, through enzyme-linked immunosorbent assay (ELISA) (results expressed in pg/ml) and western blot, and of matrix metalloproteinase-9 (MMP-9), through ELISA (results expressed in ng/ml). The values recorded were then statistically compared with the etiologic diagnosis of the PEs., Results: Between the PEs analysed, 40 were found to be malignant and 15 to be benign. VEGFR-1 in soluble form (sVEGFR-1) was significantly higher in malignant than in benign effusions (P < 0.0001), using ELISA; the same was shown by the western blot analysis method. MMP-9 levels results also indicated significantly more malignant than benign effusions (P < 0.0001). VEGFR-1 in soluble form showed a sensitivity and specificity of 92% and 93%, respectively, (cut-off value >852; AUC: 0.9) in predicting the malignant nature of a PE. Sensitivity and specificity of MMP-9 in predicting the malignant nature of a PE were, respectively, 95% and 73% (cut-off value >639; AUC: 0.8). In the pleural fluids, the values of the two markers were significantly related to each other (r = 0.5; P < 0.0001). Eighteen patients with malignancies, diagnosed by pleural biopsy, had negative cytological findings. Of these patients, sixteen (89%) presented elevated levels of both markers., Conclusions: Our data suggest that the VEGFR-1/MMP-9 pathway is significantly increased in malignant-rather than in benign-pleural effusions; thus, the measurement of their levels in the pleural effusion could be useful, throughout the diagnostic work-up, to select which cases would warrant a pleural biopsy.

Aims: Activating mutations in the gene encoding epidermal growth factor receptor (EGFR) can confer sensitivity to EGFR tyrosine kinase inhibitors such as gefitinib in patients with advanced non-small-cell lung cancer. Testing for mutations in EGFR is therefore an important step in the treatment-decision pathway. We reviewed reported methods for EGFR mutation testing in patients with lung cancer, initially focusing on studies involving standard tumour tissue samples. We also evaluated data on the use of cytology samples in order to determine their suitability for EGFR mutation analysis., Methods: We searched the MEDLINE database for studies reporting on EGFR mutation testing methods in patients with lung cancer., Results: Various methods have been investigated as potential alternatives to the historical standard for EGFR mutation testing, direct DNA sequencing. Many of these are targeted methods that specifically detect the most common EGFR mutations. The development of targeted mutation testing methods and commercially available test kits has enabled sensitive, rapid and robust analysis of clinical samples. The use of screening methods, subsequent to sample micro dissection, has also ensured that identification of more rare, uncommon mutations is now feasible. Cytology samples including fine needle aspirate and pleural effusion can be used successfully to determine EGFR mutation status provided that sensitive testing methods are employed., Conclusions: Several different testing methods offer a more sensitive alternative to direct sequencing for the detection of common EGFR mutations. Evidence published to date suggests cytology samples are viable alternatives for mutation testing when tumour tissue samples are not available.

Objective: To assess the practical utility of pleural fluid carbonic anhydrase XII (CAXII) quantification for differential diagnosis of effusions., Materials and Methods: Fluid was collected prospectively from fifty patients presenting with lymphocytic pleural effusions for investigation and CAXII was quantified by ELISA., Results: Pleural fluid CAXII concentrations were significantly higher in lung cancer patients (n=30) than in tuberculous controls (n=20). The sensitivity and specificity of this biomarker were 60%and 75%, respectively. CAXII measurement was not inferior to cytological examination in the diagnosis and exclusion of pleural effusions from lung cancer patients (sensitivity 60% vs. 57%; specificity 75% vs. 100%; positive predictive value 77%; negative predictive value 54%). In patients with negative cytology, it offered a sensitivity of 54%., Conclusions: Pleural fluid CAXII is elevated in pleural effusions from lung cancer patients. Measurement of CAXII may be used in the future as a valuable adjunct to cytology in the diagnostic assessment of patients with pleural effusions related to lung cancer, especially when cytological examination is inconclusive.

Tuberculosis (TB) is one of the most common infectious diseases in developing countries including Nepal. Delay in diagnosis and treatment of tuberculosis results in poor prognosis of the disease. This study was conducted to estimate diagnostic cut off values of Adenosine Deaminase (ADA) in cerebrospinal fluid (CSF) and pleural fluid and to evaluate the sensitivity, specificity, positive and negative predictive values ofADA in pleural fluid and CSF from patients with tuberculous and non-tuberculous disease. A total of 98 body fluid (CSF: 24, Pleural fluid: 74) specimens were received for the estimation of ADA. ADA activity was measured at 37 degrees C by spectrophotometric method of Guisti and Galanti, 1984 at 625nm wavelength. Among the patients enrolled for the study subjects for which CSF were received (n = 24) included 8 tuberculous meningitis (TBM), and 16 non-tubercular meningitis (NTM). Pleural fluid samples (n = 74) were received from 19 pulmonary TB with pleural effusion, 17 PTB without pleural effusion and 37 of non-tuberculous disease patients. CSF ADA activity were (11. 1 +/- 2.03 IU/L) and (5.3 +/- +1.89 IU/L) (p <00001) in TM and non-NTM groups and Pleural fluid ADA activity were (10 +/- 22.18 IU/L) and (23.79 +/- 11.62 IU/L) (p < 0.001) in PTB and non-TB groups respectively. ADA test in body fluids, which is simple, cost-effective and sensitive, specific for the tubercular disease is recommended to perform before forwarding the cumbersome and expensive procedures like culture and PCR for TB diagnosis.

Tuberculosis (TB) is a major public health problem in developing countries including Nepal. One of the common presentations of TB is pleural effusion. The diagnosis of tubercular pleural effusion can be difficult because of the low rate of detecting tubercule bacilli by direct stain and culture of pleural fluid for acid-fast bacilli (AFB). Pleural biopsy can be useful but is invasive and requires experts. In this context, pleural fluid Adenosine Deaminase (ADA) level has been proposed as easy, cheap and highly sensitive test for diagnosis of TB pleural effusion. The present study was undertaken to define the role ofpleural fluid ADA value in accurate diagnosis of TB pleural effusion. A Prospective analysis of 100 patients admitted in Nepal Medical College and teaching Hospital with pleural effusion was done. Pleural fluid ADA level was evaluated in all patients, and significance of pleural fluid ADA level in TB pleural effusion was studied. It was found that mean ADA level in pleural fluid was 105.8 +/- 67.23 U/L in cases of TB, as compared to 16.83 +/- 8.91 U/L in malignancy, 44.53 +/- 32.84 U/L in parapneumonic effusion and 15.94 +/- 4.88 U/L in patients with miscellaneous diagnosis. For a cut-off value of 42.19 U/L for diagnosis of TB pleural effusion, sensitivity was found to be 90.8% and specificity 82.8%. Almost all patients diagnosed to have TB pleural effusion responded completely to anti-tubercular treatment. So, we concluded that pleural fluid ADA analysis could be easy, cheap and highly sensitive and specific test for diagnosis of TB pleural effusion.

The ubiquitin-conjugating enzyme (UbcH10) plays important roles in the regulation of cell cycle progression. Recently, UbcH10 expression has been demonstrated in several human and experimental tumors, and proteasome inhibitors have been tested in trials for pulmonary neoplasms; however, the underlying mechanisms as well as the clinicopathological relevance of UbcH10 in the genesis and progression of lung cancer remain largely unknown. Therefore, the authors evaluated the expression of UbcH10 in human lung cancer and evaluated its possible diagnostic and prognostic use. They found that most cases of lung adenocarcinoma, squamous cell carcinoma, and large cell and small cell carcinoma were positive for UbcH10. The expression levels of UbcH10 progressively increased with decreasing degree of tumor differentiation. There was a statistically significant difference of UbcH10 positivity between grade I/III of lung adenocarcinoma (p=0.013) and squamous cell carcinoma (p=0.002). No significant differences were found between histological types (p=0.072). In the case of cell blocks prepared from pleural effusions, inflammatory and reactive mesothelial elements did not show appreciable UbcH10 expression, whereas neoplastic cells exhibited clear UbcH10 positivity. The results suggest that UbcH10 might represent a new and promising diagnostic and prognostic marker in both histologic and cytologic specimens of lung cancer.

Objective: To evaluate the application of traditional cytomorphology, telomerase activity analysis and immunocytochemistry in cytopathologic diagnosis of pleural effusion and bronchoalveolar lavage samples., Methods: A total of 123 agar-paraffin double-embedded pleural effusion and bronchoalveolar lavage fluid samples were enrolled into study. The cytomorphologic features were reviewed and correlated with immunocytochemical findings and telomerase activity., Results: Telomerase activity was detected in 53 specimens using the real-time telomeric repeat amplification protocol. Amongst the cases studied, 39 samples (31.7%) contained overtly malignant cells while 20 cases (16.0%) were equivocal by conventional cytology. After verification by immunocytochemistry and clinical follow-up data, the diagnostic accuracy of telomerase activity and cytology was 87.0% and 82.1%, respectively. The sensitivity (97.6%) and specificity (100.0%) of cytology examination, when combined with telomerase activity analysis, were greater than those of cytology examination or telomerase activity analysis alone., Conclusions: Telomerase activity analysis can be used as an adjunctive investigative tool in cytology assessment of pleural effusion and bronchoalveolar lavage samples. The diagnostic accuracy can be further improved with the application of immunocytochemistry on agar-paraffin double-embedded cell block tissues.

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.)

Pulmonary tuberculosis is the India's biggest health problem especially in rural areas. A quick and dependable investigation is absolutely essential. Adenosine deaminase was estimated from the biological fluids (ascitic/pleural/CSF) with the help of the kit obtained from Tulip India Pvt Ltd. The method is based on the principle of Galati & Giusti colorimetric method. The method is simple, inexpensive and results are also reproducible. Elevation of adenosine deaminase has shown high specificity in all biological fluids. As the estimation principle is based on synthesis of ammonia so there is limitation of the procedure when the site is kidney. Similarly if the site is skin, as fluid cannot be collected from the site, adenosine deaminase estimation is also not possible.

A 74-year-old man was referred to our hospital with complaint of dyspnea and left pleural effusion. The pleural effusion was exudative and lymphocytic with elevation of adenosine deaminase (ADA). Antitubercular agents were administered on a diagnosis of tuberculous pleuritis, but the pleural effusion did not improve. After he had been followed up with diuretic agents during about 2 years, he suffered cardiac tamponade and right pleural effusion. We diagnosed primary effusion lymphoma based on the cytology findings of the pleural effusion. The measurement of ADA activity in pleural effusions was useful for diagnosis of tuberculous pleuritis, but not only tuberuculous pleuritis but also lymphoma or other diseases can show elevation of ADA activity in pleural effusions.

The objective of this study was to evaluate the utility of the determination of adenosine deaminase (ADA) level in pleural fluid for the differential diagnosis between tuberculous pleural effusion (TPE) and malignant pleural effusion (MPE) in Japan, a country with intermediate incidence of tuberculosis (TB). We retrospectively reviewed the clinical records of 435 patients with pleural effusion and investigated their pleural ADA levels as determined by an auto analyzer. ROC analysis was also performed. The study included patients with MPE (n＝188), TPE (n＝124), benign nontuberculous pleural effusion (n＝94), and pleural effusion of unknown etiology (n＝29). The median ADA level in the TPE group was 70.8U/L, which was significantly higher than that in any other groups (p＜0.05). The area under the curve (AUC) in ROC analysis was 0.895. With a cut-off level for ADA of 36U/L, the sensitivity, specificity, positive predictive value, and negative predictive value were 85.5%, 86.5%, 69.7%, and 93.6%, respectively. As many as 9% of patients with lung cancer and 15% of those with mesothelioma were false-positive with this ADA cutoff setting. Although the ADA activity in pleural fluid can help in the diagnosis of TPE, it should be noted that some cases of lung cancer or mesothelioma show high ADA activity in geographical regions with intermediate incidence of TB, in contrast to high prevalence areas.

Pancreaticopleural fistula is a condition in which pancreatitic enzymes drain into the pleural cavity. It is a complication of pancreatic disease and usually presents with thoracic rather than abdominal symptoms. Although unusual, it should be included in the differential diagnosis to substantial and persistent unilateral pleural effusion. We report the case of a 71-year-old man who presented with dyspnoea. During two months, the patient underwent pulmonary evaluation before the pancreas was identified as the site of primary pathology. The key to the diagnosis was an elevated level of pleural fluid amylase.

Objective: To evaluate the analytical performance of the Diazyme ADA assay on the Cobas® 6000 system for pleural fluid samples analysis., Design and Methods: Imprecision, linearity, calibration curve stability, interference, and correlation studies were completed., Results: The Diazyme ADA assay demonstrated excellent precision (CV<4%) over the analytical measurement range (0.5-117 U/L). Bilirubin above 50 μmol/L and haemoglobin above 177 μmol/L interfered with the test, inducing a negative and a positive interference respectively. The Diazyme ADA assay correlated well with the Giusti method (r(2)=0.93) but exhibited a negative bias (~ -30%)., Conclusions: The Diazyme ADA assay on the Cobas® 6000 system represents a rapid, accurate, precise and reliable method for determination of ADA activity in pleural fluid samples., (Copyright © 2010 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

The investigation of pleural effusion has been greatly assisted by advancements in pleural fluid analysis. In the case of tuberculous pleural effusion, diagnosis traditionally requires the demonstration of acid fast bacilli in the pleural space using microbiological or histological techniques. In recent years, there has been progress in pleural fluid analysis in suspected tuberculous effusions, with particular interest in adenosine deaminase and interferon-γ. These individual tests are quite sensitive and specific; however, data are sparse on the benefits that multiple-parameter testing may have when analysed in combination. We reviewed the literature to investigate the evidence for multiple-parameter testing, both biochemical and clinical, in the evaluation of tuberculous effusion.

We describe a case of exudative pleural effusion in a patient with mucinous pulmonary adenocarcinoma. Pleural fluid examination showed markedly raised amylase with normal serum amylase concentration. There was no clinical or radiological evidence of oesophageal rupture or pancreatitis. The case illustrates the importance of considering pulmonary malignancy in the context of amylase-rich pleural effusion. Causes of amylase-rich pleural effusion and the significance of isoenzyme analysis are discussed.

Objective: To investigate the clinical value of pleural fluid adenosine deaminase (ADA) activity in differentiating tuberculous pleural effusions (TPE) from malignant effusions., Methods: The serum and pleural adenosine deaminase activity of 91 cases confirmed by pleural biopsy through medical thoracoscopy were retrospectively analyzed. TPE was confirmed in 49 cases and malignant effusion in 42 cases. The optimal cutoff for TPE was determined by using the ROC curve., Results: The mean pleural ADA was significantly (t = 7.383, P < 0.01) higher in PTE (46 +/- 26) U/L as compared to malignancy (16 +/- 8) U/L, so was the pleural fluid/serum ADA ratio (4.1 +/- 4.0 vs 1.76 +/- 1.2, t = 3.852, P < 0.01), but there was no statistically significant difference between malignant and tuberculous effusion in serum ADA activity [(13 +/- 5) U/L vs (12 +/- 6) U/L, t = 1.582, P > 0.05]. The cutoff value of pleural ADA for PTE was 28.7 U/L, with a sensitivity of 75.5% and a specificity of 95.2%., Conclusions: Pleural fluid, but not serum, ADA activity, can be used for the differentiation between tuberculous and malignant pleural effusions.

Background and Objective: It has been proven that telomerase activation correlates with the carcinogenesis, aggressiveness and turnover of lung cancer. Telomerase is one of the improtant molecular biomarkers for diagnosis and targeting therapy in lung cancer. The aim of this study is to investigate the diagnostic value of the combined determination of telomerase activity in induced sputum, pleural effusion and fiberobronchoscopic biopsy in lung cancer patients., Methods: The technique of TRAP (telomeric repeat amplification protocal)-PCR-ELISA was employed to detect telomease levels of induced sputum, pleural effusion and fiberobronchoscopic biopsy in 80 lung cancer patients with pleural effusion and 50 benign pulmonary disease patients with pleural effusion., Results: Telomemse levels of induced sputum, pleural effusion and fiberobronchoscopic biopsy were all significantly higher in patients with lung cancer than those with benign pulmonary disease (P < 0.001). There was no significant difference in the level of telomerase activity between different pathologic types (P > 0.05). The sensitivity of induced sputum, pleural effusion and fiberobronchoscopic biopsy were 62.5% (50/80), 46.3% (37/80) and 60.0% (48/80), respectively. The specificity were 72.0% (36/50), 66.0% (33/50) and 70.0% (35/50), respectively. The overall accuracy were 66.2% (86/130), 53.8% (70/130) and 63.8% (83/130), respectively. The sensitivity, specificity and overall accuracy of combined induced sputum, pleural effusion and fiberobronchoscopic biopsy were 85.0% (68/80), 78.0% (39/50) and 82.3% (107/130), respectively. The sensitivity of telomease level in combined detection for diagnosis of lung cancer was much higher than that in single sample detection (P < 0.01)., Conclusion: The sensitivity of telomease activity in combined three samples was the highest. It can further improve the accuracy for the diagnosis of lung cancer with pleural effusion.

Generation of oxidative stress induced by reactive oxygen species (ROS) and nitrogen (RNS) is believed to be a primary factor in the etiology of various inflammatory diseases. Although, the process of generation of oxygen species is a physiological event, in the inflammatory process this event is increased and produces large amounts of reactive species that leads to lipid peroxidation and to cell death. Mycophenolate mofetil (MMF) is a drug effective in protecting against chronic allograft failure and recently was introduced as an alternative for the treatment of various inflammatory diseases such as glomerulopathies, systemic lupus erythematosus and systemic vasculitis. Based on studies of the anti-inflammatory effect of MMF the aim of this study was to evaluate the effects of MMF on the inhibition of leukocytes and exudation, as well as myeloperoxidase and some antioxidant enzyme activities using carrageenan-induced pleurisy in mice. Our results showed that MMF significantly decreased leukocyte influx (P<0.01), exudation (P<0.01), superoxide dismutase (P<0.05), catalase (P<0.05), glutathione peroxidase (P<0.01), glutathione S-transferase (P<0.01) activities, levels of lipid peroxidation (P<0.05), as well as myeloperoxidase activity (P<0.05) on both phases (4h and 48h) of the inflammatory response induced by carrageenan into the mice pleural cavity. In conclusion, the anti-inflammatory effect of MMF may be, at least in part, via inhibition of ROS and/or NRS overgeneration, and consequently, attenuating the related oxidative stress.

Measurement of pleural fluid adenosine deaminase (ADA) levels aids diagnosing tuberculous pleural effusion (TPE). Dipeptidyl peptidase IV (DPP) enzyme is closely related to ADA. Our aim was to determine the value of concurrent measurement of these T-cell-associated enzymes, ADA and DPP levels in the diagnosis of TPE. Patients with pleural effusion were grouped as TPE, parapneumonic, malignant, congestive heart failure related, and miscellaneous pleural effusions. Pleural and serum ADA and DPP levels were measured. Pleural and serum levels of ADA and pleural DPP were higher in TPE group than the rest. In 7 patients, pleural biopsy revealed granulomatous pleuritis. All of these patients had TPE and had elevated serum and pleural ADA levels. Serum and pleural ADA or DPP levels and pleural ADA and DPP levels correlated with each other. Selecting cutoff values of 40 and 27 IU/L for pleural ADA and DPP, respectively, the sensitivity of concurrent measurement of both enzymes was 77%, specificity 94%, and diagnostic efficiency 91%. ADA and DPP play an important role in tuberculous immunopathogenesis. The utility of DPP in the diagnosis of TPE has never been determined before. Concurrent measurement of ADA-DPP can aid in diagnosing TPE with higher specificity, sensitivity, and efficiency.

Purpose: To investigate diagnostic values of pleural fluid matrix metalloproteinase-2 (MMP-2), MMP-9, tissue inhibitors of metalloproteinase-1 (TIMP-1) and TIMP-2 measurements in tuberculous pleurisy(TP) and malignat pleurisy (MP)., Methods: The study included 24 patients with TP, 22 patients with MP and 15 patients with pleural effusion of non-tuberculous and non-malignant origin as controls. MMP-2,-9 and TIMP-1,-2 levels in pleural fluid were measured by ELISA method., Results: Pleural fluid MMP-2 and MMP-9 levels were higher (P < 0.001, P < 0.001, respectively) in TP than in MP and controls. MP patients have higher pleural fluid MMP-2 and MMP-9 levels (P < 0.01, P < 0.05, respectively) than controls. Pleural fluid TIMP-2 levels were higher (P < 0.01 and P < 0.001, respectively) in MP than in TP and controls. Pleural fluid MMP-9 levels were negatively correlated with pleural fluid TIMP-2 levels (r: 0.464, P=0.029) in patients with MP., Conclusions: Determination of TIMP-2 in pleural fluid may contribute to differentiate TP from MP. These results suggest that overproduction of MMP-9 and TIMP-2 is associated with accumulation of the pleural effusion in malignancy. Further studies with a greater number of patients are needed to confirm this hypothesis.