Search

Objective: To evaluate the usefulness of pleural fluid adenosine deaminase (ADA) for diagnosing tuberculous pleural effusions in the Spanish population, according to laboratory technique and cut-off point, and to compare the results with other populations., Methods: Meta-analysis of diagnostic studies on pleural fluid ADA in the Spanish population, extracted from the PubMed and Embase databases from inception until July 2017, with no language restrictions. The overall diagnostic accuracy of ADA and that of each of the measurement techniques (Giusti, manual and automated kinetic methods) and selected cut-offs were analyzed. The QUADAS-2 tool was used to evaluate the quality of studies. A bivariate random effects model was used. Results were compared with those obtained from previous meta-analyses in non-Spanish populations., Results: Sixteen studies in a total of 4,147 patients, 1,172 of whom had tuberculous pleural effusions, were included. ADA had 93% sensitivity, 92% specificity, positive likelihood ratio of 12, negative likelihood ratio of 0.08, and an area-under-the-curve of 0.968 for identifying tuberculosis. There were no differences in diagnostic accuracy between the techniques used for ADA measurement or the selected cut-offs. In 73 studies from non-Spanish populations a trend toward lower ADA sensitivity (88%, 95% CI:86%-90%) and specificity (88%, 95% CI: 86%-90%) was noted, but differences did not reach statistical significance., Conclusions: Pleural fluid ADA in the Spanish population shows good diagnostic accuracy (regardless of the measurement technique or cut-off), similar to that reported in non-Spanish populations., (Copyright © 2018 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.)

Objectives: To analyze the clinical and radiological characteristics and features of pleural fluid (PF) in patients with tuberculous pleural effusion (TPE)., Methods: Retrospective analysis of TPEs treated in our clinic over the last 23years., Results: We included 320 patients with TPE (70% men; median age 33years). Mycobacterium tuberculosis was identified in the sputum or PF of 36% of the patients by microscopic examination, solid and liquid media cultures, or nucleic acid amplification tests. The greatest percentage of positive microbiological findings were associated with human immunodeficiency virus (HIV) co-infection (OR: 3.27), and with the presence in PF of proteins <4g/dL (OR: 3.53), neutrophils >60% (OR: 3.23), and glucose <40mg/dL (OR: 3.17). Pleural adenosine deaminase <35U/L was associated with TPEs that occupied less than half of the hemithorax (OR: 6.36) and with PF lactate dehydrogenase levels <500U/L (OR: 8.09). Radiological pulmonary opacities (30%) were more common in TPE occupying less than half of the hemithorax (OR: 2.73), in bilateral TPE (OR: 4.48), and in older patients (OR: 1.02). Factors predicting mortality were: HIV co-infection (OR: 24), proteins in PF <5g/dL (OR: 10), and greater age (OR: 1.05)., Conclusions: Patients with TPE and HIV co-infection and those with lower concentrations of proteins in PF had higher rates of positive microbiological results and death. Moreover, older patients had more pulmonary opacities and a higher incidence of death., (Copyright © 2018 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.)

Analysis of pleural fluid can have, on its own, a high diagnostic value. In addition to thoracocentesis, a diagnostic hypothesis based on medical history, physical examination, blood analysis and imaging tests, the diagnostic effectiveness will significantly increase in order to establish a definite or high probable diagnosis in a substantial number of patients. Differentiating transudates from exudates by the classical Light's criteria helps knowing the pathogenic mechanism resulting in pleural effusion, and it is also useful for differential diagnosis purposes. An increased N-terminal pro-brain natriuretic peptide, both in the fluid and in blood, in a due clinical context, is highly suggestive of heart failure. The presence of an increased inflammatory marker, such as C-reactive protein, together with the presence of over 50% of neutrophils is highly suggestive of parapneumonic pleural effusion. If, in these cases, the pH is<7.20, then the likelihood of complicated pleural effusion is high. There remains to be demonstrated the usefulness of other markers to differentiate complicated from uncomplicated effusions. An adenosine deaminase > 45 U/L and>50% lymphocytes is suggestive of tuberculosis. If a malignant effusion is suspected but the cytological result is negative, increased concentrations of some markers in the pleural fluid can yield high specificity values. Increased levels of mesothelin and fibruline-3 are suggestive of mesothelioma. Immunohistochemical studies can be useful to differentiate reactive mesothelial cells, mesothelioma and metastatic adenocarcinoma. An inadequate use of the information provided by the analysis of pleural fluid would results in a high rate of undiagnosed effusions, which is unacceptable in current clinical practice., (Copyright © 2014 Elsevier España, S.L.U. All rights reserved.)

Chylous ascites is an accumulation of lymph in the abdominal cavity. The diagnosis is established when the concentration of triglycerides in plasma is greater than in ascitic fluid over a level of 200 mg/dl. The clinical and biochemical characteristics of 22 patients with chylous ascites (11 cirrhotics and 11 non cirrhotics) were studied in order to assess differences between patients with and without hepatic cirrhosis. The cirrhotic patients with chylous ascites showed lower protein (1.3 +/- 0.74 mg/dl, p = 0.002) and cholesterol concentration (46.0 +/- 45.2 mg/dl, p = 0.02) in ascitic fluid than non cirrhotic patients (3.1 +/- 1.09 mg/dl, and 100.85 +/- 41.7 mg/dl, respectively). In addition, the cellularity in the ascitic fluid was also lower in cirrhotic patients (209.09 +/- 113.96 cel/mm3) versus (831.8 +/- 945.08 cel/mm3; p < 0.05). Four patients (18.18%) presented high adenosine deaminase levels (ADA) in the ascitic fluid in the absence of tuberculous peritonitis. The authors conclude that the biochemical differences observed in the ascitic fluid of the cirrhotic patients with chylous ascites may be explained by a dilutional mechanism due to the combination of "clear" ascites secondary to portal hypertension and chylous ascites. Furthermore, chylous ascites could be the cause of an elevation in ADA in the absence of tuberculous peritonitis.

Background: To analyze the adenosine deaminase (ADA) pleural levels and the possibility of a typical pattern of tuberculous pleuritis (TP) in relation to these values., Patients and Methods: We analyzed 90 consecutive cases of TP dividend into two groups on the basis of the pleural ADA measurements: group 1 (less than 43 U/I) and group 2 (equal or higher than 43 U/I). We compared: age, sex, tuberculous risk factors, clinic onset and duration, PPD, chest roentgenogram, biochemical (LDH, glucose and proteins) and cytological examination of the pleural fluid, microbiologic studies on sputum, pleural fluid and biopsies, histologic findings of the biopsies, evolution and sequelae after the treatment., Results: 36 patients in the group 1 (40%) and 54 in the group 2 (60%) (p = 0.01). All the parameters were similar in both groups excluding LDH pleural levels, that were higher in group 2. In 20 cases of the group 1, we obtained a second analysis of pleural ADA and we observed in 11 cases (55%) an ADA value above 43 U/I., Conclusions: We confirmed that ADA pleural level is increased in the majority of our patients with a low initial sensibility of 60%, that can increase with a second determination (72%). ADA activity below 43 U/I cannot exclude the tuberculous aetiology of an effusion and can persist negative in other analyses. The results suggest a response of different chronology without any relation to initial ADA pleural level.

In order to better understand the immunological mechanisms involved in host protection against Mycobacterium tuberculosis infection, we studied soluble interleukin 2 receptor (sIL-2R) concentration in tuberculous pleural exudates as well as in pleural fluids of non-mycobacterial etiology. We collected pleural fluid from 40 patients: 10 with tuberculous bacterial pneumonia and 10 with trasudate. Soluble IL-2R was measured in the stored specimens using a standard ELISA technique. In patients with tuberculosis, sIL-2R in pleural fluid was 14,666 +/- 5,634 U/ml, significantly higher than was detected in any other group, being 4,341 +/- 2,655 U/ml in pneumonic exudates, 5,542 +/- 3,682 U/ml in neoplastic exudates and 1,377 +/- 125 in trasudates (p < 0.001). Also, an excellent correlation was demonstrated between adenosine-desaminase (ADA) and sIL-2R in tuberculous pleural fluids, with p < 0.001 and r = 0.805. In pleuropulmonary tuberculosis, compartmentalization of the immune response in the pleural space is responsible for the significantly higher levels of sIL-2R that were found in tuberculous pleural liquids compared with the ones detected in other diseases. This observation, as well as the demonstration of a good correlation between sIL-2R and ADA, suggest the possible usefulness of this molecule as an additional marker in the differential diagnosis of pleural effusions, though in the present study it appears to be less reliable than ADA.

Clinical and analytic data of 64 patients with firm etiologic diagnosis of pleural effusion with adenosine deaminase (ADA) present, were analyzed retrospectively. The patients had entered our hospital over a 40-month period. ADA activity in pleural fluid was analyzed by the Blake and Berman kinetic method. Mean ADA activity of the total sample was 32 U/l (SD:23.9). In patients with tuberculous pleural effusion ADA activity was higher than in the remaining patients (47.7, SD:21.4, versus 15.5 SD: 13.2; p < 0.0001). In the group of patients with tuberculous pleuritis diagnosed by pleural biopsy (22 cases) the presence of necrotizing granulomas was associated with slightly higher ADA activity although the difference was not statistically significant (49.2 SD 10.1 versus 41.3 SD 8.9; p = 0.07). Among only patients with tuberculous pleuritis or neoplasia with lymphocytic exudate, a cut off point greater than 23 U for ADA predicted a diagnosis of tuberculous pleuritis with a sensitivity of 0.96, specificity of 1, positive predictive value of 1, negative predictive value of 0.94, and a confidence limit of 0.97. In conclusion, ADA activity greater than 23 U determined by the kinetic method in pleural fluid with signs of lymphocytic exudate is strongly suggestive of pleural tuberculosis based on our sample of patients with pleural effusion.

The concentration of gamma interferon (IFN gamma) and adenosine deaminase (ADA) activity were measured in the pleural fluid of 162 patients to compare their diagnostic significance and to establish a possible correlation between both tests. The IFN gamma levels in tuberculous pleural effusions were quite variable, with a mean of 93 U/ml and a median of 48 U/ml. They were higher than 2 U/ml in all cases, whereas no case of nontuberculous effusion showed higher values. ADA activity was higher than 43 U/l in all tuberculous effusions, with a mean value of 80 U/l, higher than in any other group except lymphoma. In three pleural effusions associated with lymphoma, one with mesothelioma, one with adenocarcinoma and four with empyema, ADA activity was higher than 43 U/l. In these patients, IFN gamma levels were low. There was no correlation in the whole series or in any group between IFN and ADA. Both parameters can be very useful for the diagnosis of tuberculous pleuritis. The measurement of IFN gamma is more specific, although the experience with this test is more limited than with ADA. It has the additional shortcoming of a high cost and it requires facilities for radionuclide use. Therefore, we think that ADA measurement should be considered as a routine test while IFN gamma measurement should be reserved for reference institutions.

In this paper we present the results of a study about the diagnostic utility of Adenosine Deaminase (ADA) determination for diagnosing the tuberculous pleural effusion. We carried out this study in 71 patients who came to our Hospital and were diagnosed for pleural effusion. The ADA determination was made in sera and pleural effusion of all these patients. Also we determined how much of this ADA activity was linked to microsomes or not (soluble ADA), by ultracentrifugation as a separative method. Taking as a base the data obtained and using 43 U/l as cutoff point, the Diagnostic Sensitivity of ADA determined in pleural liquid calculated was 1. This means that all patients with tuberculous pleural effusions had ADA activities higher than 43 U/l in their pleural liquid. On the other hand, Diagnostic Specificity was of 0.83. This was due to the existence of 10 false positives: 2 malignancies, 3 empyemas, 1 postpneumonia, 1 secondary to thromboembolic pulmonary disease, 1 secondary to rheumatoid arthritis and 2 of unknown origin. Results obtained show the utility, with some limitations, of ADA determination in pleural liquid in order to diagnose tuberculous pleural effusions. Neither ADA determination in sera nor quantity of ADA linked to microsomes or solubles ADA in pleural liquid seem to have great clinical interest.