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Purpose of the article: The indication of pleural drainage in parapneumonic pleural effusion (PPE) is still controversial. Pleural fluid's (PF) pH is widely used as an indicator of the need for pleural drainage. We hypothesized that PF's lactate will have a high concordance with pH, and thus, may be a valuable tool to determine the need for pleural drainage in pediatric PPE.We performed a descriptive, prospective study sequentially enrolling those pediatric patients admitted to a tertiary University Hospital with a PPE between 2008 and 2018. Patients were classified in two groups: drainable PPE (pH 7) and non-drainable PPE (pH 7). Correlation with the pH, the area under the curve (AUC), and the sensitivity and specificity values for lactate and other parameters (glucose, and LDH) were analysed too.72 patients with a median age of 4 years (interquartile range 2.25-6) were included. Both groups were homogeneous. Lactate levels were higher in the drainable PPE group (p 0.001), and a strong inverse correlation between pH and lactate was found (r: -0.7; p 0.001). A lactate cut-off value of 60.5 mmol/L, exhibit an AUC of 0.86 with a sensitivity of 70% and a high specificity (97.9%) to predict a pH 7.Our data indicates that lactate in PF presents a strong correlation with pH and could potentially serve as a highly specific biomarker of the need for pleural drainage.

To measure the accuracy of pleural fluid cell-free DNA (cfDNA) concentration for diagnosis of parapneumonic pleural effusions (PPE).We studied pleural fluids obtained by thoracocentesis in patients with pleural effusion. DNA was automatically extracted from pleural fluid using the MagNa Pure Compact instrument (Roche Diagnostics), and was measured by a real-time quantitative PCR assay for the β-globin gene using a Light-Cycler 480 Real-Time PCR instrument (Roche Diagnostics). Patients were classified into two groups according to the etiology of pleural effusion: PPE and NOT PPE. The diagnostic accuracy was determined using receiver operating characteristic (ROC) techniques by analyzing the area under the ROC curve (AUC).We studied 78 patients with ages between 1 and 86 years old (median=64). Sixteen patients were PPE and 62 were NOT PPE (24 transudative, 30 malignant and 8 other etiology). Pleural fluid cfDNA concentration was higher in patients with PPE (median=46,240 ng/mL) than in those with NOT PPE (median=224 ng/mL). The AUC value was 0.907 (p0.0001) and the optimal cut-off value was 6740 ng/mL exhibiting 87.5% sensitivity and 80.6% specificity. Also, there were significant differences between transudative and exudative effusions according to pleural fluid cfDNA concentration (p0.0001). The AUC value was 0.994 and the optimal cut-off value was 162ng/mL exhibiting 100% sensitivity and 96.3% specificity.Pleural fluid cfDNA concentration showed high accuracy for diagnosis of PPE and to discriminate between transudative and exudative effusions.

Background: Diagnosis of tuberculous pleuritis is difficult because of its nonspecific clinical presentation and decreased efficiency of traditional diagnostic methods. We investigated the use of procalcitonin (PCT) concentration in tuberculous pleuritis diagnosis. Methods: A prospective clinical study was performed with two different patient groups. A total of 28 patients were included: 18 with tuberculosis and 10 with nontuberculous pleurisy. Serum and pleural fluid PCT concentrations were evaluated before treatment. Results: Serum and pleural fluid PCT concentrations were statistically different between tuberculous and nontuberculous pleurisy groups ( P = 0.012 and P = 0.004, respectively), even though they were not elevated in relation to the cut-off level of 0.5 ng/mL. A positive and significant correlation was detected between serum and pleural fluid PCT levels ( r = 0.49, P = 0.008). Diagnostic specificity and sensitivity values for serum and pleural fluid PCT in discriminating tuberculous from nontuberculous pleurisy were 80% and 72.2%, and 90% and 66.7% at the 0.081 and 0.113 ng/mL cut-off values, respectively. Conclusion: Relative to the current cut-off level of 0.5 ng/mL, PCT concentration is not a useful parameter for the diagnosis of tuberculous pleurisy. Because there were PCT levels in patients with tuberculous pleurisy that were below the current cut-off level but were significantly different from those of the nontuberculous group, the use of PCT should be further investigated.

Objectives: To investigate whether pleural levels of the soluble oncoprotein 185 HER-2 (sp185HER-2), individually or in combination with CEA and CA 15-3, were useful for the diagnosis of malignant effusions. Design and methods: Levels of CEA, CA 15-3, and sp185HER-2 were measured in the pleural fluid from 135 malignant and 103 benign effusions. Thresholds of these tumor markers were chosen for a diagnostic specificity of ≥99%. Results: Pleural sp185HER-2 levels greater than 25 ng/mL were observed in 20% of breast and 10% of lung adenocarcinomas, and predicted a malignant effusion with a sensitivity of 7% and a likelihood ratio of 7.6. Combination of CEA and CA 15-3 resulted in 50% sensitivity, while adding sp185HER-2 to this panel nonsignificantly increased sensitivity by 5% (P = 0.45). Only 1 patient with breast adenocarcinoma among 45 cytology-negative malignant effusions had sp185HER-2 above the diagnostic cutoff point. Conclusion: Measurement of pleural fluid sp185HER-2 has poor diagnostic performance in patients with malignant effusions.

The performance of three point of care methods for pleural fluid pH analysis was compared to a currently validated blood gas analyzer.An ABL 725 (Radiometer America, Westlake, OH) was used as the reference method to evaluate three cartridge-based assays: ABL 90 FLEX (Radiometer), and i-STAT 1 (Abbott Point of Care, Abbott Park, IL) CG4+ and G3+ cartridges for pleural fluid pH analysis. Pooled residual pleural fluid samples and quality control material were analyzed to determine intra- and inter-assay precision. Method comparison was performed with spiked (n=40) and clinically-ordered (n=10) pleural fluid samples across the analytical measuring range.All methods demonstrated inter-assay CVs0.1% at pH values of 7.1 and 7.6, and intra-assay CVs0.3% at pH values of 7.2 and 7.7. Bland-Altman plots demonstrated clinically significant bias between ABL 725 and each cartridge-based method only at pH7.6. For samples with pH7.6 mean bias vs. ABL 725 was -0.01 for ABL 90 FLEX and 0.03 for i-STAT 1 CG4+ and G3+ cartridges. Clinical concordance using a decision limit of pH7.2 was 96-98% for the three methods.Analytical and clinical performance of the three cartridge-based methods was comparable to a validated blood gas analyzer for pleural fluid pH analysis. Cartridge-based pH methods offer the advantage of easier troubleshooting for clots and clogs as they use disposable electrodes. However cartridge-based methods are not currently FDA-approved for pleural fluid samples, such that additional validation would be required for this specimen type.

To evaluate the analytical performance of the Diazyme ADA assay on the Cobas® 6000 system for pleural fluid samples analysis.Imprecision, linearity, calibration curve stability, interference, and correlation studies were completed.The Diazyme ADA assay demonstrated excellent precision (CV4%) 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%).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.

Neopterin is produced by stimulated macrophages under the influence of gamma interferon of lymphocyte origin. It is regarded as a biochemical marker of cell-mediated immune response. This study was designed to assess the diagnostic value of pleural fluid neopterin levels in tuberculous pleurisy in comparison with adenosine deaminase activity.Pleural fluid adenosine deaminase (ADA) activity and neopterin levels were measured in 16 patients with tuberculous pleurisy (TP) and 19 patients with malignant pleurisy (MP). ADA activity was determined by a colorimetric method, whereas neopterin levels were determined by a reversed-phase liquid chromatography technique. All values were given as median (min-max).The mean age was 45.43+/-20.39 years in the TP group and 60.42+/-11.02 years in the MP group (p=0.026). The median pleural fluid ADA activity was 51.75 U/L (3.50-62.40 U/L) in the TP group and was 2.30 U/L (1-8.20 U/L) in the MP group. The difference was statistically significant (p0.001). The median pleural fluid neopterin levels were 13.15 nmol/L (1.86-59.50 nmol/L) and 2.44 nmol/L (0.92-27.60 nmol/L) in the TP group and the MP group, respectively (p=0.021). In order to evaluate the diagnostic value of pleural fluid neopterin concentrations, receiver-operating-characteristic curve analysis was performed.Pleural fluid neopterin concentration is significantly higher in TP when compared to MP, however when compared, its clinical use as a diagnostic marker is not valuable as ADA.

The purpose of this study was to evaluate the usefulness of a new parameter, pleural adenosine deaminase (PADA), for separating transudative pleural effusion from exudative pleural effusion, and to compare the results with other tests (albumin gradient and protein gradient).From November 2001 to January 2003, 359 consecutive patients with pleural effusion who underwent a diagnostic thoracentesis were included in the study. Effusions were individually classified as transudates or exudates after the careful evaluation of all clinical data and biochemical parameters of pleural fluid and serum of patients on the basis of Light's criteria. The means and standard deviations of PADA, pleural/serum ADA (P/S ADA) ratio, albumin gradient and protein gradient were evaluated for transudative and exudative effusions. The best cut-off values for each test were identified by using the receiver operating characteristic (ROC) curve. The optimum cut-off level was determined by selecting points of test values that provided the greatest sum of sensitivity and specificity.There were 113 transudates and 246 exudates. For each test, differences in mean value between the transudate group and the exudate group were statistically significant (t test, P0.001). The optimum cut-off levels for PADA and P/S ADA were 15.3 U/L and 0.66 U/L, respectively. ROC analysis confirmed previous recommendations for albumin gradient (12 g/L) and protein gradient (31 g/L). For detecting exudates, the PADA test yielded a sensitivity and specificity of 85.8% and 82.3%, respectively. Sensitivity and specificity of the albumin gradient were found to be 88.5% and 79.3%, and of the protein gradient 85% and 83.2%, respectively. The areas under the curve (AUC) data and accuracy demonstrated similar discriminative properties in the examined tests.The measurement of PADA is suggested as a reliable test in the separation of pleural exudates from transudates with accuracy similar to that of the albumin gradient and protein gradient.

Objectives: To examine the diagnostic utility of pleural adenosine deaminase (PADA), pleural lactate dehydrogenase (PLDH), and several other biochemical tests in bronchogenic carcinoma and malignant mesothelioma, and to compare biochemical characteristics of their fluid with nonmalignant pleural effusions. Design and methods: This study consisted of 226 patients diagnosed with malignant (75), tuberculous (65), and parapneumonic pleural effusions (86). We examined the following biochemical parameters in the pleural fluid and serum: adenosine deaminase, lactate dehydrogenase, glucose level, protein level, pleural fluid/serum ADA ratio (P/S ADA), P/S LDH ratio, and P/S protein ratio. Results: Parapneumonic pleural effusions had a significantly higher level of PLDH and of P/S LDH than malignant and tuberculous pleural effusions ( P = 0.000), and malignant pleural effusions had a higher level of PLDH than tuberculous pleural effusions. Tuberculous and parapneumonic effusions had significantly higher levels of PADA than those of malignant effusions ( P = 0.000). When the 54 patients having bronchogenic carcinoma were compared to the remaining 21 mesothelioma patients, the former had a lower median level of PADA ( P = 0.001) with a higher level of PLDH ( P = 0.05). Conclusion: Our results show that high pleural LDH and low PADA levels are suggestive of pleural effusion due to bronchogenic carcinoma, whereas high levels of PADA alone can be indicative of tuberculous pleural effusion and high levels of both markers can show complicated parapneumonic effusions or empyema.