Non-tuberculous, adenosine deaminase-positive lymphocytic pleural effusion: Consider immunoglobulin G4-related disease.

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).

Pleural fluid ADA activity in tuberculous pleurisy can be low in elderly, critically ill patients with multi-organ failure.

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.

Elevated Adenosine Dehydrogenase (ADH) and Positive Tuberculin Test Firstly Misdiagnosed as Tuberculous Pleural Effusion Finally Proved as Pleural Mesothelial Sarcoma by Thoracoscopic Biopsy Pathology: a Case Report and Literature Review.

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.

Thymidine kinase 1 concentration in pleural effusion is a diagnostic marker and survival predictor for malignant pleural effusion.

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.

Adenosine deaminase for diagnosis of tuberculous pleural effusion: A systematic review and meta-analysis.

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.

Eficacia diagnóstica de la adenosina desaminasa en líquido pleural para diagnosticar tuberculosis. Metaanálisis de estudios españoles / Diagnostic Accuracy of Pleural Fluid Adenosine Deaminase for Diagnosing Tuberculosis. Meta-analysis of Spanish Studies

Objetivo: Determinar la utilidad de la adenosina desaminasa (ADA) pleural para diagnosticar derrame pleural tuberculoso en población española, según la técnica de medición y punto de corte utilizados, y compararla con la descrita para otras poblaciones. Métodos: Metaanálisis de estudios diagnósticos sobre ADA pleural en población española, extraídos de PubMed y Embase desde sus comienzos hasta julio de 2017, sin restricciones de lenguaje. Se analizó la eficacia diagnóstica global de la ADA, según sus técnicas de medición (Giusti, métodos cinéticos manuales y métodos cinéticos automatizados) y el punto de corte seleccionado. La herramienta QUADAS-2 evaluó la calidad de los estudios. Se utilizó un método bivariante de efectos aleatorios. Se compararon los resultados con los descritos en metaanálisis previos sobre población no española. Resultados: Se incluyeron 16 estudios, con 4.147 pacientes, de los que 1.172 tenían derrame pleural tuberculoso. La ADA tuvo una sensibilidad del 93%, especificidad del 92%, likelihood ratio positiva de 12, likelihood ratio negativa de 0,08, y área bajo la curva de 0,968 para identificar tuberculosis. No hubo diferencias de eficacia diagnóstica entre las técnicas de medición de ADA o el punto de corte escogido. En 73 estudios de población no española se observó una tendencia hacia una menor sensibilidad (88%, IC95%: 86-90%) y especificidad (88%, IC95% 86-90%) de la ADA, pero las diferencias no alcanzaron significación estadística. Conclusiones: La ADA pleural en población española tiene una buena precisión diagnóstica (independientemente de la técnica de medición o punto de corte empleados), similar a la reportada en población no española

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

Cancer ratio and other new parameters for differentiation between malignant and nonmalignant pleural effusions.

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.

Diagnostic Value of Vascular Endothelial Growth Factor, Transforming Growth Factor-ß, Interleukin-8, and the Ratio of Lactate Dehydrogenase to Adenosine Deaminase in Pleural Effusion.

PURPOSE: We studied the diagnostic value of cytokines, including vascular endothelial growth factor (VEGF), transforming growth factor-ß (TGF-ß), 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-ß 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.

Tuberculosis pleural en paciente pediátrico: reporte de un caso y revisión de la literatura / Pleural tuberculosis in a pediatric patient: case report and review

Tuberculosis (TB) is a common cause of pleural effusion in young people from endemic areas. Among the forms of extrapulmonary TB in people with immunodeficiencies, the most frequent localization is the pleura. The use of immunological and molecular biology tests for the diagnosis of TB in pleural fluid and other locations with high sensitivity and specificity is highlighted. We present a clinical case with the objective of giving an overview of the treatment of the patient with suspected pleural tuberculosis

La Tuberculosis (TB) es una causa común de derrame pleural en jóvenes en zonas endémicas. Dentro de las formas de TB extrapulmonar en personas que cursan con inmunodeficiencias, la localización más frecuente es la TB pleural. Se destaca el uso de las pruebas inmunológicas y de biología molecular para el diagnóstico de TB en líquido pleural y de otras localizaciones con una elevada sensibilidad y especificidad. Se presenta un caso clínico con el objetivo de describir una visión general del abordaje del paciente con sospecha de tuberculosis pleural

Repeatability of pleural adenosine deaminase measurements in diagnostic evaluation of pleural effusions.

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.

The pleural fluid lactate dehydrogenase/adenosine deaminase ratio differentiates between tuberculous and parapneumonic pleural effusions.

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.

A combination of the QuantiFERON-TB Gold In-Tube assay and the detection of adenosine deaminase improves the diagnosis of tuberculous pleural effusion.

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.

Pleural effusion adenosine deaminase: a candidate biomarker to discriminate between Gram-negative and Gram-positive bacterial infections of the pleural space.

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.

A diagnostic algorithm for tuberculous pleurisy using the ELISPOT assay on peripheral blood and pleural effusion.

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.

Pleural effusion adenosine deaminase: a candidate biomarker to discriminate between Gram-negative and Gram-positive bacterial infections of the pleural space

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.

Pleural fluid tests to diagnose tuberculous pleuritis.

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.

Can pleural adenosine deaminase (ADA) levels in pleural tuberculosis predict the presence of pulmonary tuberculosis? A CT analysis.

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.

Adenosine deaminase is a useful biomarker to diagnose pleural tuberculosis in low to medium prevalence settings.

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.

[Value of Detection of CAIX in the Pleural Effusion and Its Sediment in the Diagnosis of Lung Cancer].

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.

Comparative Study of Adenosine Deaminase and Other Conventional Diagnostic Parameters in Diagnosis of Tuberculous 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.