Pleural Fluid Adenosine Deaminase Research Articles

Diagnostic value of IFN-gamma in tuberculous pleural effusion

BackgroundSimple, rapid, and accurate diagnosis of tuberculous pleural effusion (TPE) remains challenging. This study aimed to determine the accuracy of IFN-γ in diagnosing TPE. MethodsWe quantified the expression of interferon-gamma (IFN-γ) in blood (B), adenosine deaminase (ADA), and IFN-γ in pleural effusions (PE) from 25 TPE patients and 31 non-TPE patients using a combination of immunological assays and flow cytometric analysis. The diagnostic performance of these three biomarkers was evaluated using receiver operating characteristic (ROC) curves. ResultsWe found that IFN-γ levels in blood and pleural fluid were higher in the TPE group than in the non-TPE group. The mean concentration of IFN-γ in pleural fluid of the TPE group was 3140.90 (1817.94, 6611.05) pg/mL, while that of the non-TPE group was 4.91 (0.69, 8.6) pg/mL), and the difference was statistically significant (z = 6.39, P < 0.001). The mean blood IFN-γ was 40.19 (16.45, 59.08) pg/mL in the TPE group and 2.76 (1.96, 6.02) pg/mL in the non-TPE group, which was statistically different (z = 5.12, P < 0.001). The area under the ROC curve (AUC) for pleural fluid IFN-γ, blood IFN-γ, and ADA were 0.999 (95 % CI: 0.994–1.00), 0.901 (95 % CI: 0.798–1.00) and 0.996 (95 % CI: 0.987–1.00), respectively. ConclusionThis study confirms that IFN-γ has high diagnostic validity in patients with TPE and can potentially be an excellent biomarker.

Diagnosis of pleural tuberculosis in the era of thoracoscopic surgery

Background Before thoracoscopic surgery, diagnosing tuberculous (TB) pleurisy was a medical challenge. Thoracoscopy is the most accurate but expensive method for TB pleurisy diagnosis. TB is common in low-income countries, where financial limitations prevent the use of thoracoscopy, motivating the search for a cheaper alternative. Patients and methods A prospective study was done from January 2019 to January 2023 to evaluate diagnostic methods for patients with exudative pleural effusions (PE) of unknown etiologies. The demographic, radiological, procedural, and histological data of exudative PE patients were analyzed. All patients were examined for adenosine deaminase (ADA) and lymphocyte/neutrophil ratio in pleural fluid. Ultrasound-guided Abrams needle biopsy and video-assisted thoracoscopic surgery pleural biopsies were obtained, and histopathological results were assessed. Results Of 250 patients with PE, 161 (64%) had TB PE, 72 (28.8%) had malignant PE, and 17 (6.8%) had idiopathic PE. Sensitivity of ADA (≥40 U/l) was 88%, lymphocyte/neutrophil ratio (≥0.75) was 86.1%, and their overall sensitivity was 91%. They had 93.2, 86.3, and 100% specificity, respectively. For ultrasound-guided Abrams needle biopsy, the sensitivity of histopathology, culture, and combined histopathology/culture was 66, 46.5, and 78.4%, respectively. All were 100% specific. For thoracoscopic biopsy, the sensitivity of histopathology, culture, and combined histopathology/culture was 100, 86.6, and 100%, respectively. All were 100% specific. The assay sensitivity of pleural fluid and tissue Xpert Mycobacterium tuberculosis/rifampin resistance was 12.5 and 49.7%, respectively. Both were 100% specific. Combining ADA more than or equal to 40 U/l, lymphocyte/neutrophil ratio more than or equal to 0.75, and an ultrasound-guided Abrams needle biopsy yielded 92.4% sensitivity and 100% specificity. Conclusion Combining pleural fluid ADA more than or equal to 40 U/l, lymphocyte/neutrophil ratio more than or equal to 0.75, and ultrasound-guided Abrams needle biopsy can accurately detect TB PE in high-TB populations. It may be an affordable alternative to thoracoscopy in countries with limited resources.

Utility of the Ratio of Adenosine Deaminase and Serum C-reactive Protein in Differentiating Parapneumonic, Tuberculous, and Malignant Pleural Effusions.

Introduction Pleural effusion is a challenging diagnosis at times, especially due to the overlap of symptoms in effusions of various etiologies. In this study, we aimed to identify if pleural fluid adenosine deaminase (ADA) or serum C-reactive protein (CRP) can be used as an additional novel biomarker for ADA in diagnosing tubercular, parapneumonic, and malignant pleural effusions. Materials and methods A prospective, observational, cross-sectional study was conducted on 79 patients diagnosed with tubercular, parapneumonic, or malignant pleural effusion from August 2022 to April 2024 at the Department of Respiratory Medicine at Dr.D. Y. Patil Medical College,Hospital&Research Centre, Pimpri, Pune. The pleural fluid ADA/serum CRP ratio was identified in each group, and analysis was done to compare the ratio in each group. The correlation with pleural fluid ADA was also identified. Results A total of 79 patients were enrolled in this study. Out of these patients, 53 (67.1%) were identified as having tubercular pleural effusion, 10 (12.7%) patients had parapneumonic effusion, and 16 (20.3%) had malignant pleural effusion. For malignant effusions, the area under the curve (AUC) using the receiver operating characteristic (ROC) for the ADA/CRP ratio was observed to be 0.862. Sensitivity was 87.50%and specificity was 82.54% at a cut-off value of ≤0.5. The positive predictive value was found to be 56%, and the negative predictive value was found to be 96.3%. For parapneumonic effusions, the AUC using the ROC for the ADA/CRP ratio was observed to be 0.880. Sensitivity was 100%and specificity was 69.57% at a cut-off value of ≤0.67. The positive predictive value was found to be 32.3%, and the negative predictive value was found to be 100%. For tubercular effusions, the AUC using the ROC for the ADA/CRP ratio was observed to be 0.955. Sensitivity was 92.45%and specificity was 88.46% at a cut-off value of >0.54. The positive predictive value was found to be 94.2%, and the negative predictive value was found to be 85.2%. The Pearson correlation coefficient (r) of 0.633 indicates a moderately strong positive linear relationship between ADA and ADA/CRP levels. Conclusion The pleural fluid ADA-to-serum CRP ratio can be used as a useful diagnostic tool for differentiating between tubercular, parapneumonic, and malignant pleural effusions. ADA/CRP ratio has added diagnostic value over ADA. In clinically puzzling scenarios, the ADA/CRP ratio can be a cost-effective tool before opting for a more expensive and invasive procedure, which is also often difficult to obtain in resource-limited healthcare settings. More research with a larger sample size is indicated to incorporate the ADA/CRP ratio as an added diagnostic tool along with ADA.

Evaluation of polymerase chain reaction and adenosine deaminase levels for rapid diagnosis of clinically suspected tuberculous pleural effusion

ABSTRACT Background: Tuberculosis (TB) often leads to pleural effusion, particularly prevalent in developing nations such as India. There has been a global rise in TB cases. Although lymphocytic predominant fluid is commonly associated with tubercular pleural effusion, it is essential to note that not all lymphocytic predominant fluids indicate TB. The diagnosis of pleural TB has benefited significantly from the use of biochemical markers. Conventional bacteriological methods are not very useful in diagnosing tubercular effusion and rarely identify Mycobacterium tuberculosis in pleural fluid. Owing to diagnostic difficulties, newer investigations, such as TB polymerase chain reaction (TB-PCR), adenosine deaminase (ADA) and culture, are amongst the most recent techniques currently used due to the challenges associated with diagnosis. Aims: This study aimed to measure the sensitivity and specificity of TB-PCR and compare them with those of ADA and TB cultures for suspected TB pleural effusion. Methods: This study included 50 patients diagnosed with pleural effusion who underwent pleural fluid analysis. Patients exhibiting exudative effusion with lymphocyte predominance also underwent a pleural biopsy. Pleural fluid ADA levels were also measured, and TB-PCR tests were conducted. Results: Eighteen patients were confirmed to have TB by biopsy. ADA was both sensitive and specific at 67% and 62.5%, respectively. However, PCR showed a sensitivity of 16.6% and a specificity of 100%. Conclusion: This study found a statistically significant association (P &lt; 0.05) between ADA levels and distinguishing pleural effusion, which is tubercular in origin, from non-tubercular effusion. Therefore, the pleural ADA estimate appears to have the potential to be a reliable test for diagnosing TB pleural effusion. It has sufficient sensitivity and specificity while being cost-effective and easily executable compared to pleural biopsy. Our study also compared the sensitivity of PCR with pleural biopsy and discovered that PCR was more specific and less sensitive.

Role of Pleural Fluid Lactate Dehydrogenase to Adenosine Deaminase Ratio in the Etiological Differentiation of Exudative Pleural Effusion

Abstract Background: Although pleural fluid adenosine deaminase (ADA) level &gt;70 U/L suggestive tuberculous pleural effusion (TPE). High ADA levels can also be seen in pneumonia, empyema, lymphoma, malignancy, and rheumatoid pleuritis. Elevated pleural fluid lactate dehydrogenase (LDH) is seen in tubercular pleural effusion (TPE), parapneumonic pleural effusion (PPE), and malignant pleural effusion (MPE). Therefore, it is challenging distinguish between TPE, PPE, and MPE based on elevated pleural fluid ADA and LDH levels. In this study, we evaluated the use of pleural fluid LDH/ADA ratio as a new parameter for etiological differentiation of exudative pleural effusions. Materials and Methods: A retrospective hospital-based observational study conducted in GHCCD, Visakhapatnam. A total of 52 patients (TPE – 19, PPE – 16, and MPE – 17) with exudative pleural effusion who fulfilled inclusion criteria were taken into study. Qualitative variables have been described in the form of frequency and percentages. Median and interquartile ranges were used for nonnormal distribution values. Receiver operating curve (ROC) curves with area under the curve (AUC) were calculated. P ≤ 0.05 was considered statistically significant. Results: The mean ADA value for TPE was 75.4 U/L (25–195 U/L), PPE was 59.1 U/L (13–180 U/L), and for MPE was 35.52 U/L (10–75 U/L). The mean LDH value for TPE was 887.8 U/L (139–2213 U/L), PPE was 1128 U/L (334–3110 U/L), and for MPE was 1470 U/L (234–4285 U/L). On ROC analysis, pleural LDH/ADA ratio ≤20.81 diagnose TPE with (sensitivity – 84.2%, specificity – 63.6%) with AUC of 0.758 (95% confidence interval [CI]: 0.619–0.866) (P = 0.0001) whereas LDH/ADA ratio in the diagnosis of PPE was found to be &gt;23.39 (sensitivity – 50%, specificity – 66.7%) with AUC of 0.535 (95% CI: 0.391–0.674) (P = 0.689) and the cutoff LDH/ADA ratio in the diagnosis of MPE was found to be &gt;20.86 (sensitivity – 70.6%, specificity – 68.6%) with AUC of 0.724 (95% CI: 0.583–0.839) (P = 0.007). The cutoff value of the LDH/ADA ratio in PPE does not reach the statistical significant value. Conclusion: Pleural fluid LDH/ADA ratio ≤20.81 U/L is predictive of TPE, and &gt;20.86 U/L is predictive of MPE and the cutoff value of 20.8 U/L can be used for etiological differentiation of pleural effusion.

Gamma interferon as a superior diagnostic marker in tuberculous pleural effusion: A comparative analysis with adenosine deaminase

Background: The diagnosis of tuberculous pleural effusion (TPE) poses a massive problem during tuberculosis (TB) control worldwide. This study set out to find the role of Interferon Gamma (IFN-γ) and Adenosine Deaminase (ADA) in pleural fluid as markers for early diagnosis of TPE to improve the accuracy and, hence, the opportunity for early and effective intervention for patients. Aims and Objectives: (i) The aims and objectives of the study are to compare the levels of IFN-γ and ADA in pleural fluid samples from patients with tuberculous and non-TPEs; (ii) to determine the diagnostic accuracy of these biomarkers in differentiating TPE from other causes; and (iii) to analyze the correlation of IFN-γ and ADA levels with other routine diagnostic parameters for TB. Materials and Methods: The study adopted a forwardlooking, case–control methodology to compare outcomes across groups. One hundred individuals presenting with pleural effusion were selected for participation. This cohort was divided evenly, with 50 individuals identified with TPE and 50 showing non-tuberculous types of effusion, including those caused by parapneumonic and cancerous processes. Eligible participants were aged between 20 and 60 years and tested negative for the human immunodeficiency virus. Exclusion criteria included pleural effusion arising from viral infections, pregnancy or breastfeeding status, adverse drug reactions affecting the skin, or empyema. Thoracocentesis was performed to collect pleural fluid following participants’ informed consent under sterile conditions. The analysis of pleural fluid encompassed measurements of IFN-γ through enzyme-linked immunosorbent assay techniques and ADA levels through an ADA assay kit. In addition, venous blood was drawn to conduct routine hematological and biochemical tests, including evaluating serum lactate dehydrogenase, total protein, albumin, and cholesterol levels. Results: It was found that the mean level of IFN-γ was significantly (P &lt; 0.00001) higher in patients with TPE, 186.66 ± 134.46 pg/mL, as compared to the level in non-tuberculous effusion 47.53 ± 68.94 pg/mL. Similarly, the difference in ADA level was also significant (P = 0.016) between the two groups. The mean level of ADA was significantly (P = 0.016) higher in TPE, 135.93 ± 239 U/L, compared to the level in non-tuberculous effusion, 58.86 ± 87.83 U/L. Conclusion: The significant elevation in IFN-γ and ADA levels in TPE patients re-emphasizes their potential as specific markers in this clinical condition and suggests considering IFN-γ in combination with ADA as valuable parameters in the differentiation of tuberculous from non-tuberculous effusions and thereby, this advancement in the realm of quick markers of diagnosis would play a crucial role in the refinement of diagnosis strategy in TB which would be of immense help in improving the patients’ outcome.

A Study of Tuberculous Pleural Effusion in Province 2, Southern Nepal

Introduction: Tuberculosis (TB) is a major public health problem in developing countries. Tuberculous pleural effusion is the second most common form of extrapulmonary tuberculosis (TB) (after lymphatic involvement) and is the most common cause of pleural effusion in areas where TB is endemic. The aim of this study is to depict the pattern of the Tuberculous Pleural Effusion (TPE) with its clinical presentation and diagnosis along with the different laboratory parameters of the TB patients at a tertiary care center of the Southern Nepal. Materials and Methods: A prospective hospital based cross-sectional study enrolling 107 subjects diagnosed as TBPE presenting to the Department of Internal Medicine, National Medical College was carried out from 15th March, 2023 to 14th October, 2023 (7 months). The different data collected were put in Excel Sheet and analyzed using SPSS version 26. The formal written and verbal consent was taken from the participants and ethical clearance was taken from Institutional Review Committee (IRC), National Medical College, Birgunj (Ref. F-NMC/633/079-080).Results: A total of 107 subjects diagnosed with TBPE showed 67.3 % (n=72) male and 32.7% (n=35) female participants. Majority of the participants (88.8%) presented with fever, and approximately 59% of the participants had chest pain. Almost 65% of them had dyspnea and 77% presented with frank cough. Majority of the participants had right sided effusion. Pleural ,fluid examination showed increased total leukocyte count (mean 3191 cells/cu mm) and with lymphocytic predominance and increased protein content (5.07±0.91 g/dL). Pleural fluid Adenosine Deaminase (ADA)was found to be elevated (86.5±26.4 U/L).Conclusion: The common presentation of the Tuberculous pleural effusion is deranged laboratory parameters of pleural fluid with increased fluid total leukocyte count having lymphocytic predominance and increased protein content along with high ADA levels.

Diagnostic scoring systems for tuberculous pleural effusion in patients with lymphocyte-predominant exudative pleural profile: A development study

BackgroundDiagnosing tuberculous pleural effusion (TPE) in patients presenting with Lymphocyte-Predominant Exudative pleural effusion (LPE) is challenging, due to the poor clinical utility of TB culture. Adenosine deaminase (ADA) has been recommended for diagnosis, but its high cost and limited availability hinder its clinical utility. We aim to develop diagnostic prediction tools for Thai patients with LPE in scenarios where pleural fluid ADA is available but yields negative results and in situations where pleural fluid ADA is not available. MethodsTwo diagnostic prediction tools were developed using retrospective data from patients with LPE at Surin Hospital. Model 1 is for ADA-negative results, and Model 2 is for situations where pleural fluid ADA testing is unavailable. The models were derived using multivariable logistic regression and presented as two clinical scoring systems: round-up and count scoring. The score cut-point that achieves a positive predictive value (PPV) comparable to the post-test probability of a pleural fluid ADA at a cut-point of 40 U/L was used as a threshold for initiating anti-TB treatment. ResultsA total of 359 patients were eligible for analysis, with 166 diagnosed with TPE and 193 diagnosed with non-TPE. Age <40 years, fever, pleural fluid protein ≥5 g/dL, male gender, pleural fluid color, and pleural fluid ADA ≥20 U/L were identified as final predictors. Both models demonstrated excellent discriminative ability (AuROC: 0.85 to 0.89). The round-up scoring demonstrated PPV above 90% at cut-off points of 4 and 4.5, while the count scoring achieved cut-off points of 3 and 4 for Model 1 (Lex-2P2A) and Model 2 (Lex-2P-MAC), respectively. ConclusionThese diagnostic tools offer valuable assistance in differentiating between TPE and non-TPE in LPE patients with negative pleural fluid ADA (Lex-2P2A) and in settings where pleural fluid ADA testing is not available (Lex-2P-MAC). Implementing these diagnostic scores may have the potential to improve TPE diagnosis and facilitate prompt initiation of treatment.

Assessment of pleural fluid adenosine deaminase and alkaline phosphatase in tubercular and non-tubercular effusions

Background: Many studies have showed that adenosine deaminase (ADA) and alkaline phosphatase (ALP) values were highly supportive in the diagnosis of tuberculosis but comparison between ADA and ALP has not been much documented in pleural fluid (PF) in eastern India. Hence, the main aim of the study was to identify the relation between ADA and ALP in diagnosis of tuberculosis if any. Aims and Objectives: This study was conducted to estimate and compare the levels of ADA and ALP of PF in tubercular and non-tubercular diseases. Materials and Methods: This study was hospital-based, cross-sectional, and observational study during the period of 1 year. A total of 90 patients have been analyzed among them after excluding few outliers, 82 patients had been taken whose ADA and ALP were measured in PFs. Results: Kolmogorov–Smirnov and Shapiro–Wilk tests for statistical analysis were used to determine whether continuous variables were normally distributed or not. In the comparison of tubercular and non-tubercular effusion groups, P-value for ADA in independent t-test was 0.000, and P-value for ADA and ALP in Mann–Whitney U-test was 0.000 and 0.000, respectively. Receiver operating characteristic (ROC) curve showed area under the curve (AUC) of 0.965 and 0.751 in ADA and ALP for diagnosing tuberculosis. Cutoff values of 31.87 IU/L for ADA were determined by ROC curve analysis with 100% of sensitivity and 82.3% of specificity and cutoff values of 40.5 IU/L for ALP were also determined by ROC curve analysis with 75.6% of sensitivity and 68.3% of specificity for diagnosis of tuberculosis. Conclusion: Although ADA is the best parameter for diagnosing tubercular pleural effusions, analysis of ALP is cost-effective.

LDH/ADA ratio in pleural fluid for the diagnosis of infectious pleurisy.

Pleural effusion (PE) is a common medical concern, often requiring thoracentesis for a definitive diagnosis. An elevated pleural fluid adenosine deaminase (ADA) may indicate tuberculosis, but this is not always the case. This study aimed to evaluate the accuracy of biomarkers determined in pleural fluid and propose a new diagnostic strategy for PE in patients with high levels of ADA in pleural fluid. This retrospective analysis studied patients with PE who received thoracentesis for the first time with an ADA level of > 33 U/L in the pleural fluid analysis at two tertiary hospitals from March 2019 to March 2023. Demographic and clinical data, as well as pleural fluid biomarkers and their ratios, were studied and compared between different PE groups, and a decision tree was developed. During the study period, 259 patients were enrolled, with four different types of PE: parapneumonic (PPE) 155, tuberculosis (TPE) 41, malignant (MPE) 50, and miscellaneous 13. Biomarkers and their ratios performed well in the differential diagnosis of PE, with the LDH/ADA ratio distinguishing between PPE and non-PPE with sensitivity and specificity of 98.06% and 98.08%, respectively. The combination of LDH/ADA ratio, ADA, and mononuclear cell percentage was identified as important factors for creating a decision tree with an overall accuracy of 89.96%. The pleural fluid LDH/ADA ratio was a useful diagnostic for distinguishing PPE from non-PPE, and a decision tree with an accuracy of 89.96% was created to differentiate the four forms of PE in clinical situations.

Pleural fluid adenosine deaminase to serum C-reactive protein ratio for diagnosing tuberculous pleural effusion

BackgroundTuberculous pleural effusion (TPE) and malignant pleural effusion (MPE) may occasionally show similar cytological and biochemical picture including ADA. In such cases, differentiating TPE and MPE is challenging and needs histopathology of pleural tissue which may involve invasive procedures. The present study aims to evaluate the diagnostic accuracy of pleural fluid ADA to serum CRP (ADA/CRP) ratio to discriminate between tuberculous and malignant pleural effusion. In addition, we investigated whether the ratio ADA/CRP adds diagnostic value to ADA.MethodsThis cross-sectional study was conducted in the National Institute of Diseases of the Chest and Hospital (NIDCH), Mohakhali, Dhaka, from July 2021 to February 2022 on diagnosed patients of TPE and malignant pleural effusion MPE. A receiver operating characteristic curve (ROC) was constructed for identifying TPE. The added value of the ADA/CRP ratio to ADA was evaluated using the net reclassification improvement (NRI) and integrated discrimination improvement (IDI). A value of p < 0.05 was considered statistically significant for all tests.ResultsFifty-nine patients were enrolled in this study, of which 31 had TPE, and 28 had MPE. Pleural fluid ADA to serum CRP ratio and pleural fluid ADA level was significantly higher in patients with TPE, but there was no significant difference in serum CRP levels between patients with TPE and MPE. At cut off value of > 1.25, pleural fluid ADA to serum CRP ratio had a sensitivity of 93.8%, specificity of 85.2%, and positive and negative predictive values were 88.2% and 92% respectively, in the diagnosis of TPE and area under ROC curve (AUC) was 0.94. The NRI and IDI analyses revealed added diagnostic value of ADA/CRP to ADA.ConclusionThis study shows that the ADA/CRP ratio improves the diagnostic usefulness of ADA for TPE.

DIAGNOSTIC YIELD OF ADA IN TUBERCULAR PLEURAL EFFUSION

Objective: Tuberculosis (TB) is one of the most common causes of pleural effusion in developing countries like India encountered by medical professionals globally. The present study was carried out to evaluate the diagnostic yield of pleural fluid adenosine deaminase (ADA) in tubercular pleural effusion. Methods: This descriptive study was conducted in the Department of Medicine and Pulmonary Medicine, Saheed Laxman Naik Medical College and Hospital from January 1, 2019, to March 31, 2020. All patients &gt;15 years of age with lymphocytic exudative pleural effusion and pleural effusion associated with smear/CBNAAT-positive pulmonary TB patients, who attended the department during the study period, were included in the study. A case was taken as tuberculous employing defined criteria. Patients with transudative effusions, post-traumatic effusions, pregnant and lactating women, and persons on drugs that affect ADA activity like interferon alpha, deoxycoformycin, ribavirin, and viramidine were excluded from the study. Results: The mean ADA value was 93.93±44.63 IU/L among the cases with tuberculous effusion and 56.36±62.81 IU/L in the non-tuberculous effusion group. At a cutoff value of 50.7 IU/L, pleural fluid ADA showed a sensitivity of 87% and a specificity of 74% in diagnosing TB etiology. Conclusion: The mean ADA values were significantly higher in tuberculous pleural effusions when compared to the non-tuberculous group. When this was combined with pleural fluid lymphocyte dominancy, the specificity increased to 96%. Pleural fluid ADA values have a strong association with age. ADA estimation is a simple, cost-efficient, and diagnostically helpful investigation with high reliability.

Developing a method to detect lipoarabinomannan in pleural fluid and assessing its diagnostic efficacy for tuberculous pleural effusion

ObjectivesThe diagnosis of tuberculosis pleural effusion (TPE) remains challenging, traditional diagnostic tests have limited diagnostic efficacy. This study aimed to assess the diagnostic performance of pleural fluid (PF) lipoarabinomannan (LAM) in TPE. MethodsA diagnostic method for PF LAM (LAM-PF) was established using LDEBIO's AIMLAM kit. The diagnostic performance of LAM-PF was evaluated in 162 HIV-negative patients with suspected TPE. ResultsThe LAM-PF method established in this study exhibited good linearity and recovery rate, with a limit of detection (LOD) of 2.90 pg/mL. Using a cut-off value of 5.33 pg/mL, the sensitivity and specificity of LAM-PF in diagnosing TPE (n = 128) were 47.7% and 100.0%, respectively. The sensitivity in patients with probable TPE (n = 29) and definite TPE (n = 99) were 41.4% and 49.5%, respectively. LAM-PF displayed a significantly higher sensitivity in probable TPE compared to other tuberculosis detection methods. Combined testing of adenosine deaminase (ADA)and LAM increased the detection sensitivity of TPE to 68.0%, and the area under the curve was 0.84 (0.77–0.89). ConclusionThis study successfully established a method for detecting LAM in PF, which exhibited favorable diagnostic performance for TPE, particularly in challenging cases of probable TPE. Combined detection of LAM and ADA in PF significantly improves TPE diagnostic efficiency.

Role of thoracoscopy in diagnosis of tubercular pleural effusion in low ADA setting- A prospective, observational study

BackgroundTubercular Pleural effusion (TBPE) is one of most common extrapulmonary tuberculosis. It can be difficult to diagnose due to low sensitivity of pleural fluid smear, culture and CBNAAT. Diagnosis of TBPE is then dependent on the level of pleural fluid Adenosine Deaminase (ADA). Thoracoscopic pleural biopsy gives definite diagnosis specially in Low Pleural fluid ADA setting. Aims and objectiveThis study was planned to find out the prevalence of tubercular etiology in patients of exudative pleural effusion with low ADA (ADA <40 IU/L). Material and methodsA Prospective, observational study was carried out in a tertiary teaching institute in north India. Total 142 patients of pleural effusion with low ADA were enrolled. All patients underwent rigid thoracoscopy for confirmation of their diagnosis. ResultsOut of 142 patients, male were 78 (55%) and female were 64 (45%). Mean age of patients were 57.4 years. Tuberculosis was diagnosed as a cause of effusion in 22 (15.5%) out of 142 patients. Majority of TBPE patients had pleural thickening as thoracoscopic finding. Mean ADA level in TBPE was 27.36 ± 11.6 as compared to 18.55 ± 9.02 in non tubercular pleural effusion patients and this difference was significant statistically (P- 0.002). ConclusionThe diagnosis of patients having exudative, low ADA pleural effusion can be very easily confirmed by thoracoscopy guided pleural biopsy which has a very high diagnostic yield.

Age affects the diagnostic accuracy of the cancer ratio for malignant pleural effusion

Background and objectiveCancer ratio (CR), which is defined as serum lactate dehydrogenase (LDH) to pleural fluid adenosine deaminase (ADA) ratio, has been reported to be a useful diagnostic marker for malignant pleural effusion (MPE). Whether its diagnostic accuracy is affected by age remains unknown. This study aimed to investigate the effects of age on the diagnostic accuracy of CR.MethodsThe participants in this study were from a prospective cohort (SIMPLE cohort, n = 199) and a retrospective cohort (BUFF cohort, n = 158). All participants were patients with undiagnosed pleural effusion (PE). We used receiver operating characteristic (ROC) curves to evaluate the diagnostic accuracy of CR. The effect of age on the diagnostic accuracy of CR was investigated by adjusting the upper limit of age for participant enrolment.ResultsEighty-eight MPE patients were verified in the SIMPLE cohort, and thirty-five MPE patients were verified in the BUFF cohort. The AUCs of CR in the SIMPLE and BUFF cohorts were 0.60 (95% CI: 0.52–0.68) and 0.63 (95% CI: 0.54–0.71), respectively. In both cohorts, the AUCs of CR decreased with the advancement of age.ConclusionAge can affect the diagnostic accuracy of CR for MPE. CR has limited diagnostic value in older patients.Key messageCancer ratio is a promising diagnostic marker for malignant pleural effusion.This study revealed that its diagnostic accuracy decreased in older patients.Its diagnostic accuracy is overestimated by previous studies using tuberculosis and pneumonia patients as controls.

Validity of Adenosine Deaminase (ADA) Level in Pleural Fluid for the Diagnosis of Tuberculosis

Introduction: 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. Despite wide variations in the reported sensitivity and specificity of pleural fluid ADA level, it can be used as a surrogate for pleural biopsy when the latter is not feasible. Adenosine deaminase (ADA) is the most cost-effective pleural fluid marker and is routinely used in high prevalence settings, whereas its value is questioned in areas with low prevalence. The lymphocyte proportion (LP) is known to increase the specificity of ADA for this diagnosis. Objectives: To determine the diagnostic accuracy of ADA level in pleural fluid for the diagnosis of TB as compared to other conventional methods available like gene expert. Materials &amp; Methods: The design of this study was a cross sectional study design. This study was conducted in Medicine Unit III, S.P.H. Quetta and the duration of this study was from 23rd October 2019 to 22nd April 2020. A total of 423 patients with pulmonary TB between the ages of 25 years to 45 years, having developed pleural effusion were included. Patients with pleural effusion due to causes other than TB, having extra pulmonary TB and those with other respiratory infections were excluded. Tests done specifically for TB in our setup include sputum AFB, CXR, and genexpert. These patients’ pleural fluid ADA were then sent. Results: Adenosine deaminase (ADA) found that 217 were True Positive and 13 were False Positive. Among 193, adenosine deaminase (ADA) negative patients, 12 (False Negative) had TB on gene expert whereas 181 (True Negative) had no TB on gene expert (p=0.0001). Overall sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy of ADA level in pleural fluid for the diagnosis of TB as compared to other conventional methods available like gene expert was 94.76%, 93.30%, 94.35%, 93.78% and 94.09% respectively. Practical Implication: This study was conducted to determine the validity of ADA levels for the diagnosis of TB and the results of this study if favorable will decrease the need for other laboratory tests usually done which take longer time, thus helping to decrease the need for multiple tests, early availability of report and timely management of the disease. This will further help to reduce the contact rate of TB and the risk of developing MDR TB by starting early treatment. Conclusion: This study concluded that diagnostic accuracy of ADA level in pleural fluid for the diagnosis of TB is quite high. Keywords: Pulmonary Tuberculosis, Pleural Fluid, Adenosine Deaminase, Biochemical, Mycobacterium .

Correlation of TB LAM Ag (Tuberculosis Lipoarabinomannan Antigen) Results from Urine with Adenosine Deaminase Levels from Pleural Fluid Patients with Pulmonary TB Accompanied by Pleural Effusion

Background: One of the newest testing methods for active TB uses TB LAM Antigen, in which lipoarabinomannan (LAM) as the examined substance serves as the main component of the cell wall of M. tuberculosis (MTB) and the degradation product of MTB by macrophages in the human body. Patients with active TB with or without HIV infection may experience a decreased antibody response, which causes LAM not to bind to antibodies so that it can pass through the normal glomerular basement membrane and can be detected in the urine. Lateral flow urine lipoarabinomannan assay (LF-LAM) can detect this material with urine samples from active TB patients. Another TB screening method uses the measurement of adenosine deaminase (ADA) activity. ADA has a very important function for the proliferation and differentiation of lymphoid cells, especially T cells, and assists in the maturation of monocytes into macrophages. Objective: This study aims to qualitatively prove the correlation between the pleural fluid ADA levels of pulmonary TB patients with pleural effusion using the LF-LAM test results and examine the potential of TB LAM Ag, which correlates with increased pleural fluid ADA levels, as a diagnostic tool for diagnosing pulmonary TB. Method: It is an observational analytic study with a crosssectional design. Materials for this study included temporary urine from active TB patients at Dr. Soetomo Regional Public Hospital collected in May-August 2022. The descriptive analysis was conducted using SPSS 25.0. The data were tested for normal distribution and with the homogeneity test of Shapiro-Wilk's data. The statistical analysis was performed using the Mann-Whitney test, while the kappa suitability test was carried out to determine the correlation and level of concordance between the ADA cut-off value of pleural fluid and the TB LAM Ag test results. Results: This study involved 50 subjects consisting of 22 (44%) subjects with ADA test results between 40-100 IU/L compared to 28 subjects (56%) with ADA test results below 40 IU/L. There were 14 (28%) subjects with positive TB LAM Ag test results, consisting of 10 (45%) active TB subjects with a high ADA test cut-off of 40-100 IU/L and 4 (14%) active TB subjects with a low ADA test cut-off below 40 IU/L, with a p-value = 0.012. Conclusions: There is a correlation between TB Lipoarabinomannan antigen test results of TB patients with pleural effusion. TB LAM Ag can be detected positive on ADA test results of < 40 IU/L and more positive in active TB patients with high ADA test results of > 40-100 IU/L. Therefore, the TB LAM Ag test is more sensitive than the ADA test. The cut-off value of the ADA test reached 76.4 U/L, and a positive TB LAM was found.

The laboratory investigation of pleural fluids: An update based on the available evidence.

Selecting appropriate laboratory tests based on available evidence is central to improve clinical effectiveness and impacting on patient outcome. Although long studied, there is no mutual agreement upon pleural fluid (PF) management in the laboratory context. Given the experienced confusion about the real contribution of laboratory investigations to guide clinical interpretation, in this update, we tried to identify useful tests for the PF analysis, aiming to unravel critical points and to define a common line in requesting modalities and practical management. We performed a careful literature review and a deepened study on available guidelines to finalize an evidence-based test selection, intended for clinicians' use to streamline PF management. The following tests depicted the basic PF profile routinely needed: (1) abbreviated Light's criteria (PF/serum total protein ratio and PF/serum lactate dehydrogenase ratio) and (2) cell count with differential analysis of haematological cells. This profile fulfils the primary goal to determine the PF nature and discriminate between exudative and transudative effusions. In specific circumstances, clinicians may consider additional tests as follows: the albumin serum to PF gradient, which reduces exudate misclassification rate by Light's criteria in patients with cardiac failure assuming diuretics; PF triglycerides, in differentiating chylothorax from pseudochylothorax; PF glucose, for identification of parapneumonic effusions and other causes of effusion, such as rheumatoid arthritis and malignancy; PF pH, in suspected infectious pleuritis and to give indications for pleural drainage; and PF adenosine deaminase, for a rapid detection of tuberculous effusion.

Application of Adenosine Deaminase and γ-Interferon Release Assay in Pleural Fluid for the Diagnosis of Tuberculous Pleural Effusion in Patients Over 40 Years Old.

In patients with tuberculous pleural effusion (TPE) of various ages, the diagnostic accuracy of pleural biomarkers varies, and there are insufficient studies specifically in different age groups. Therefore, we investigated the adenosine deaminase cut-off value and its combination with the gamma interferon release assay for the diagnosis of TPE among patients aged ≥40 years. A retrospective analysis of 198 patients who underwent medical thoracoscopy and were admitted to the hospital between 2015 and 2020 with exudative pleural effusion and either fever, night sweats, fatigue, cough, or other clinical manifestations was performed. The medical thoracoscopy, ADA, and T-SPOT results were analysed in the pleural fluid. The patients were divided into groups based on age: 18-39, 40-59, and 60-87. The best cut-off values of ADA were 29.5, 31.5 and 19.5 U/L, respectively, for the aged 18-39, aged 40-87 and aged 60-87 groups. The accuracy of 31.5 U/L was higher than 40 U/L for aged ≥40 years (86 vs 83%). The ADA diagnostic accuracy was higher than that of people under 40 years (83 vs 77%) when cut-off value of ADA was 40 U/L, but the IGRA accuracy was lower than that of people under 40 (87 vs 91%). The sensitivity of ADA or IGRA detection in patients over 40 years was 99%, and the specificity was 78%. The ADA specificity combined with IGRA for TPE was the highest (100%) in the ≥40 age group, and the sensitivity was 69%. Our study revealed the best cut-off values of ADA for TBE in different age groups. Combining ADA and IGRA in pleural fluid improves the detection rate of TPE in patients over 40 years of age with exudative pleural effusion. ADA combined with IGRA increases specificity, and ADA or IGRA increases sensitivity substantially.

Evaluating the efficacy of adenosine deaminase in pleural fluid as an early indicator for tuberculous pleural effusion

Background: Tuberculous pleural effusion (TPE) is a prominent clinical manifestation of extrapulmonary tuberculosis (TB). Traditional diagnostic markers often face challenges in sensitivity or specificity, necessitating the exploration of newer, more effective biomarkers. Aims and Objectives: This study aimed to evaluate the diagnostic potential of adenosine deaminase (ADA) in pleural fluid as an early indicator for TPE and to analyze its correlation with interferongamma (IFNγ) levels. Materials and Methods: We conducted a case–control study involving 100 patients: 50 diagnosed with TPE (cases) and 50 with non-TPE (controls). Pleural fluid samples from these patients were subjected to ADA and IFNγ level assessments using standardized protocols. Routine TB markers were concurrently examined. Results: The findings indicated significantly heightened ADA levels compared to controls in cases. IFNγ levels were similarly elevated in patients versus controls. A weak positive correlation was established between ADA and IFNγ in cases with an R-value of 0.1016. Conclusion: Our study underscores the potential of ADA in pleural fluid as a promising early diagnostic marker for TPE. Although the correlation with IFNγ is weak, it reinforces the proposition of combining multiple biomarkers to enhance diagnostic precision.