Diagnosis Of Tuberculous Pleuritis Research Articles

ADA kao glavni biohemijski marker kod bolesnika sa tuberkuloznim izlivom

Tuberculous pleuritis (TP) is one of the most common extra-pulmonary tuberculosis form. Because of tuberculous pleurisy is hard to diagnose due to slow course of disease and lack of specificity in symptoms and diagnostic methods. In that reason, we need multidisciplinary approach and efficient biomarkers. Acid-fast bacilli (AFB) staining, cultures and pathophysiological biopsy finding from the majority of patients are positive only in less than 10%. Löwenstein culture results need time about 6-8 weeks what delays diagnosis. Adenosine deaminase (ADA) is biomarker with high sensitivity and specificity (more than 90%) and considered as gold standard of biomarkers in the diagnosis of TP. It is very hard to distinguish malignant from TP with lymphocyte predomination, but in patient with malignant pleural effusion the level of ADA is decreased, opposite from TP. ADA in pleural punctate is a fast, simple, efficient and economical way for clarification the etiology of the pleural effusion as tuberculous pleurisy. Also, many studies have proved the role of ADA in the response to treatment for tuberculosis at follow up period.

Diagnostic value of Xpert MTB/RIF assay on pleural tissue obtained via closed pleural biopsy among persons with presumptive tuberculous pleuritis.

Background Tuberculous pleuritis (TBP) is a common extrapulmonary tuberculosis that contributes to the tuberculosis burden. Xpert MTB/RIF assay is a promising method for rapid diagnosis of TBP. The diagnostic value of Xpert MTB/RIF assay in pleural tissue obtained via closed pleural biopsy among sputum acid-fast bacilli (AFB) smear-negative persons is not well studied. Objectives To evaluate the diagnostic value of Xpert MTB/RIF assay on diagnosis of TB in pleural tissue obtained via blind closed pleural biopsy. Methods Closed pleural biopsy using Cope needle was performed on adult patients who presented with lymphocyte predominant exudative pleural effusion. Xpert MTB/RIF assay was performed in parallel to pathology and mycobacterial culture of the pleural tissue specimen to determine its sensitivity and specificity. Final clinical diagnosis of TBP was determined by improvement in 2-months follow-up of anti-tuberculous treatment. Results A total of 33 patients were included in the study. The median (interquartile range (IQR)) age was 27 (25 - 42) years. The sensitivity and specificity of Xpert MTB/RIF assay was 30% and 100% compared with Mycobacterium tuberculosis culture as the gold standard, and 20% and 95.7% compared with histopathology as the gold standard. Conclusion Xpert MTB/RIF assay in pleural tissue obtained by closed pleural biopsy did not increase diagnostic yield, but it shortens time for diagnosis compared with conventional methods.

Tuberkulozni pleuralni izliv kod prethodno zdravog pacijenta - prikaz slučaja i pregled literature

Introduction: Although pleural effusion is a common clinical manifestation, the differential diagnosis of the cause of the pleural effusion is often challenging, especially in the early differentiation of tuberculous pleurisy (TP) from other pleural effusion. Case report: We present a previously healthy man who had no contagious or TB contact but developed massive tuberculous pleural effusion which eventually was unexpected tuberculous. He started with therapy per protocol and feeling well. The purpose of this case and review of literature was to remind the physicians that tuberculosis is not a sickening illness, but on the contrary, it is in the expansion. Discussion: When a patient presents with new pleural effusion, the diagnosis of tuberculous pleuritis should be considered. The patient is at great risk for developing pulmonary or extra pulmonary TB if the diagnosis is not made properly. Between 3% and 25% of patients with TB will have TB pleuritic or more in immunocompromised patients. The treatment for TB pleuritis is the same as that for pulmonary TB. Conclusion: The gold standard for the diagnosis of tuberculous pleural effusion remains the detection of Mycobacterium tuberculosis in pleural fluid, or pleural biopsy specimens, either by microscopy and/or culture, or the histological demonstration of caseating granulomas in the pleura along with acid fast bacilli.

Imaging manifestations of B-mode ultrasound combined with CT in tuberculous pleuritis patients and the diagnostic value.

Clinical diagnostic values of B-mode ultrasound and computed tomography (CT) for tuberculous pleuritis were investigated. A total of 685 patients clinically diagnosed with tuberculous pleuritis in Yantaishan Hospital from January 2012 to August 2016 were selected as study subjects. The patients were examined by B-mode ultrasound and CT. The accuracy of B-mode ultrasound and CT in the diagnosis of tuberculous pleuritis was evaluated and the benefit-cost ratios of the two auxiliary diagnostic methods were compared. According to the imaging diagnostic results of 685 tuberculous pleuritis patients, B-mode ultrasound examinations identified 415 cases with tuberculous pleuritis and the accuracy rate was 60.15%. CT examinations identified 501 cases with the tuberculous pleuritis and the accuracy rate was 70.07%. The combined use of these two methods identified 546 cases with the tuberculous pleuritis and the accuracy rate was significantly increased to 85.99%. B-mode ultrasound imaging findings showed that the lesions of tuberculous pleuritis were localized on the right pleural cavities and the majority of images presented the free type; multiple anechoic areas were seen in the effusion. CT findings indicated obvious free effusion in the pleural cavities, local thickening of the pleural cavities, encapsulated pleural effusion and extensive pleural adhesion, thickening and calcification. Both B-mode ultrasound and CT examinations can be used to accurately diagnose tuberculous pleuritis and the combined diagnosis can significantly improve the accuracy.

Color Doppler Twinkling Artifact in Diagnosis of Tuberculous Pleuritis: A Comparison with Gray-Scale Ultrasonography and Computed Tomography

The aim of this study was to determine whether twinkling artifact (TA) detected on color Doppler ultrasonography can effectively determine the presence of pleural calcification compared with computed tomography (CT) and differentiate tuberculous pleuritis (TP) and cancerous pleuritis (CP). One hundred six cases of TP and 26 cases of CP were scanned using gray-scale ultrasonography (GSU) and TA to determine the presence of pleural calcification. With CT as the reference standard, 63.3% and 79.6% of patients with pleural calcification were identified with GSU and TA, respectively. The detection rate of TA was higher than that of GSU (p = 0.039). For the whole study population, 37.1% were identified as having pleural calcification with CT, significantly higher than the proportion detected with GSU (25.8%, p = 0.001), but not different from that detected with TA (41.7%, p = 0.327). The sensitivity, specificity, accuracy, positive predictive value and negative predictive value of TA were 79.6%, 80.7%, 80.3%, 70.9% and 87.0%, respectively. The detection rate of TA was significantly higher than that of GSU (p < 0.001). When GSU was combined with TA (GSUTA), the positive rate in the TP group was significantly higher than that in the CP group (χ2 < 0.001). In conclusion, TA is comparable to CT and more sensitive than GSU in the detection of pleural calcification. Evaluation for GSUTA on pleura may help to differentiate TP from CP.

Advances in the diagnosis of tuberculous pleuritis.

Pleural tuberculosis (TB) remains difficult to diagnose. In about two-thirds of the cases the diagnosis is reliant upon clinical suspicion along with consistent fluid biochemistries (i.e., lymphocytic predominant exudates) and exclusion of other potential causes for the effusion. Microbiological methods for a confirmatory diagnosis of pleural TB, which include acid-fast smears (Ziehl-Nelseen), cultures on solid media (Lowenstein-Jensen) and polymerase chain reaction tests from either pleural fluid or sputum samples, remain suboptimal since they are positive in only a minority of patients. Liquid media, however, significantly increase sensitivity while shortening culture positivity as compared with solid cultures. A number of pleural fluid biomarkers such as adenosine deaminase (ADA), interferon-Ƴ, interferon-Ƴ-induced protein of 10 KDa (IP-10) and interleukin-27 (IL-27), have shown promise for the rapid diagnosis of TB, but only ADA combines the accuracy and simplicity required to be considered a mainstay investigative tool for clinical decisions, particularly in areas with medium to high TB prevalence. In countries where ADA is not available, pleural biopsies to evaluate for caseating granulomas are a standard diagnostic approach. They are now frequently performed under ultrasound guidance to optimize yield and patient safety.

Pleural biopsies in undiagnosed pleural effusions; Abrams vs image-guided vs thoracoscopic biopsies.

Pleural biopsies are often necessary if a pleural effusion remains undiagnosed after radiological imaging and pleural fluid analysis. There are many methods of obtaining pleural biopsies, including blind or image-guided procedures, closed-bevel or cutting-edge needles, and percutaneous or thoracoscopic approaches. This article will review recent research relating to these methods, aiming to provide an overview of the strengths and limitations of each technique. Historically pleural biopsies were undertaken using a blind closed 'Abrams' needle method. However, low diagnostic yields and high complication rates are seen with this technique compared with newer methods. Recent research compares image-guided, cutting-needle approaches to traditional Abrams biopsies, and evaluates the role of medical thoracoscopy in comparison to other techniques. Thoracoscopic biopsies are the gold standard for investigating pleural disease. However, this service is not universally available and may be unsuitable for some patients. Image-guided cutting-needle biopsies under computed tomography or ultrasound guidance have high diagnostic rates and are useful in a wide patient population. The main role of Abrams biopsies is in the diagnosis of tuberculous pleuritis in resource-poor settings.

Pleural fluid tests to diagnose tuberculous pleuritis.

This article summarizes current data regarding the accuracy of pleural fluid tests assisting the diagnosis of tuberculous pleuritis (TBP). 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. 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.

Pleural Tuberculosis and its Treatment Outcomes

Purpose: To evaluate the incidence, treatment and clinical outcomes of tuberculosis pleuritis at a hospital in the state of Penang, Malaysia. Methods: A retrospective study was conducted in Hospital of Penang, Malaysia. Patient records were reviewed retrospectively to identify patients with confirmed diagnosis of tuberculous pleuritis from January 2006 to December 2008. Chest x-ray (CXR) and pleural biopsy were carried out on all patients. Directly observed therapy (DOT) was given to all patients. Data were analyzed using SPSS version 16. Results: Of 1548 tuberculosis cases, 80 (5.2 %) patients had tuberculous pleuritis. The mean age of the patients was 35.4 ± 12.87 years, with a male to female ratio of 3.4:1. Ethnically, a plurality (n = 30, 37.7 %) of cases among tuberculosis pleuritis patients were Chinese, followed by Malay (31.2 %). Out of the 80 patients with tuberculous pleuritis, 10 (12.5 %) also had diabetes mellitus, and 8 (10.0 %) HIV/AIDS. Fever, cough, chest pain and shortness of breathing were the most frequently reported symptoms. Treatment success rate was 1.558 times higher among TB group than pleuritis TB group (Odds ratio, 95 % CI, 1.06 – 2.59, p = 0.025). Conclusion: The incidence of TB pleuritis was gender- and race-related, with DM and HIV the most commonly reported risk factors. Treatment success rate was higher among pulmonary TB group than in those with TB pleuritis (extra pulmonary TB).

Rola biomarkerów w diagnostyce gruźliczego wysiękowego zapalenia opłucnej

Although tuberculosis is one of the most common causes of pleural effusion, diagnosis of tuberculous pleuritis still remains a challenge. This is due to paucity of M. tuberculosis organisms in pleural effusion which results in a relatively low sensitivity of the routinely used diagnostic methods. Thus, different biomarkers in pleural effusion have been extensively studied in order to improve the diagnostic accuracy. Pleural fluid deaminase adenosine activity (ADA) and interferon gamma (IFN-γ) concentration have been shown to be the most reliable and cost-effective markers of tuberculous pleurisy. Hence, these markers have been included in different diagnostic algorithms for patients suspected of tuberculous pleurisy. A high variability of the diagnostic performance and/or more advanced technical demands significantly limit the use of other relatively new diagnostic methods, such as nucleic acid amplification tests (NAATs) and IFN-γ releasing assays (IGRAs). The article presents a current data on the potential use of different biomarkers in the diagnosis of tuberculous pleurisy.

Use of pleural fluid levels of adenosine deaminase and interferon gamma in the diagnosis of tuberculous pleuritis

This review aims to define the role of adenosine deaminase (ADA) and interferon gamma (IFN-gamma) in the differential diagnosis of pleural effusion with special attention to their source, mechanism of release and methods of measurement in pleural fluid. The diagnostic performance of ADA and IFN-gamma is analyzed, and the advantages and limitations of their use in differentiating between tuberculous and nontuberculous pleural effusion are discussed. Several potential biomarkers of tuberculous pleurisy have been evaluated, but none have been found to be clearly superior to pleural fluid level of ADA or IFN-gamma. The majority of recent studies confirm the high diagnostic utility of pleural fluid ADA and IFN-gamma measurement; hence, these markers are included in different diagnostic algorithms for patients suspected of tuberculous pleurisy. Other relatively new tests show a high variability [nucleic acid amplification tests (NAATs)] or are technically demanding, costly and give equivocal results in patients with active tuberculosis [IFN-gamma releasing assays (IGRAs)]. Pleural fluid ADA and IFN-gamma are both sensitive and specific biomarkers of tuberculous pleurisy. Their diagnostic accuracy across the different studies shows a smaller variability than that of other tests, for example NAATs. There is also no convincing evidence that IGRAs are superior to pleural fluid ADA or IFN-gamma measurement. Hence, the role of ADA and IFN-gamma in the differential diagnosis of tuberculous pleurisy is pivotal.

Rapid diagnosis of tuberculous pleuritis by a T-cell interferon-γ release assay

To obtain a correct diagnosis of tuberculous pleuritis by analysis of pleural effusions with standard diagnostic tools is difficult. Mycobacterium tuberculosis (MTB)-specific enzyme-linked immunosorbent assay (ELISA) or MTB-specific enzyme-linked immunospot assay (ELISpot) on peripheral blood was not useful because the judgment was indeterminate or negative. However, we recently encountered 2 cases in which tuberculous pleuritis was rapidly diagnosed by performing MTB-specific ELISpot on pleural effusion mononuclear cells (PEMCs), because high levels of MTB-specific cells by ELISpot were demonstrated in pleural effusion of patients with tuberculous pleuritis. to analyze MTB-specific T-cells in pleural effusion mononuclear cells by ELISpot is feasible in routine clinical practice and may be useful for a rapid and accurate diagnosis of tuberculous pleuritis.

P1987 Rapid diagnosis of tuberculous pleuritis by real-time PCR

P1987 Rapid diagnosis of tuberculous pleuritis by real-time PCR

Rapid diagnosis of tuberculous pleuritis by enumeration of MTB-specific cells from pleural effusions

Rapid diagnosis of tuberculous pleuritis by enumeration of MTB-specific cells from pleural effusions

The Prevalence of Pulmonary Parenchymal Tuberculosis in Patients With Tuberculous Pleuritis

To examine the prevalence and characteristics of parenchymal tuberculous pleuritis in adult patients. Prospective cohort study. Three hospitals affiliated with Seoul National University in South Korea. All patients > 15 years old with a diagnosis of tuberculous pleuritis were enrolled prospectively between January 1, 2004, and October 31, 2004. Diagnostic thoracocentesis and CT of the chest were done for each patient. Acid-fast bacilli (AFB) smears and cultures for Mycobacterium tuberculosis were requested if patients produced any sputum. A board-certified radiologist reviewed the chest radiographs for the presence and characteristics of any lesions. One hundred six patients with tuberculous pleuritis were enrolled (median age, 53 years; range 16 to 89 years). Among them, 33 patients (31%) had sputum or bronchial washing findings positive for AFB smears or for M tuberculosis by culture. Lung parenchymal lesions were observed in 91 of the patients (86%) using chest CT; 39 patients (37%) with parenchymal lesions had radiographic characteristics of active pulmonary tuberculosis. In total, 62 patients (59%) had bacteriologically or radiographically active pulmonary tuberculosis. In addition, 78 patients (74%) had features of reactivated pulmonary tuberculosis. Lung parenchymal lesions were more common in this series of patients with tuberculous pleuritis than has been reported in previous studies. The patients mostly had radiographic features of reactivated, rather than primary, tuberculosis.

Pleural fluid and serum procalcitonin as diagnostic tools in tuberculous pleurisy

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.

Nucleic acid amplification tests in the diagnosis of tuberculous pleuritis: a systematic review and meta-analysis.

BackgroundConventional tests for tuberculous pleuritis have several limitations. A variety of new, rapid tests such as nucleic acid amplification tests – including polymerase chain reaction – have been evaluated in recent times. We conducted a systematic review to determine the accuracy of nucleic acid amplification (NAA) tests in the diagnosis of tuberculous pleuritis.MethodsA systematic review and meta-analysis of 38 English and Spanish articles (with 40 studies), identified via searches of six electronic databases, hand searching of selected journals, and contact with authors, experts, and test manufacturers. Sensitivity, specificity, and other measures of accuracy were pooled using random effects models. Summary receiver operating characteristic curves were used to summarize overall test performance. Heterogeneity in study results was formally explored using subgroup analyses.ResultsOf the 40 studies included, 26 used in-house ("home-brew") tests, and 14 used commercial tests. Commercial tests had a low overall sensitivity (0.62; 95% confidence interval [CI] 0.43, 0.77), and high specificity (0.98; 95% CI 0.96, 0.98). The positive and negative likelihood ratios for commercial tests were 25.4 (95% CI 16.2, 40.0) and 0.40 (95% CI 0.24, 0.67), respectively. All commercial tests had consistently high specificity estimates; the sensitivity estimates, however, were heterogeneous across studies. With the in-house tests, both sensitivity and specificity estimates were significantly heterogeneous. Clinically meaningful summary estimates could not be determined for in-house tests.ConclusionsOur results suggest that commercial NAA tests may have a potential role in confirming (ruling in) tuberculous pleuritis. However, these tests have low and variable sensitivity and, therefore, may not be useful in excluding (ruling out) the disease. NAA test results, therefore, cannot replace conventional tests; they need to be interpreted in parallel with clinical findings and results of conventional tests. The accuracy of in-house nucleic acid amplification tests is poorly defined because of heterogeneity in study results. The clinical applicability of in-house NAA tests remains unclear.

Diagnostic value of pleural fluid adenosine deaminase activity in tuberculous pleurisy

Background: Diagnosis of tuberculous pleuritis is difficult because of its nonspecific clinical presentation and insufficient efficiency of traditional diagnostic methods. We investigated the use of adenosine deaminase (ADA) activity in tuberculous pleuritis diagnosis. Methods: We optimized a kinetic assay and retrospectively analysed 210 patients with exudative pleural effusions. Using the ROC curve, we determined the optimal cutoff for TB pleurisy. Results: One hundred forty-seven exudative samples were nontuberculous (non-TB) and 63 were tuberculous (TB). There was statistically significant difference ( p<0.0001) between the means of pleural fluid ADA levels among the TB and non-TB populations. The disease prevalence of TB pleurisy in the studied population was 30%. The cutoff value for diagnosing TB effusions was >55.8 U/L, with a sensitivity of 87.3% (95% CI: 76.5–94.3%) and specificity of 91.8% (95% CI: 86.2–95.7%). The positive predictive value (PPV) was 82.1% and the negative predictive value (NPV) was 94.4%. A pleural fluid ADA value <16.81 IU/L suggests that a tuberculous effusion is highly unlikely (100% sensitive with 100% NPV and 0% negative likelihood ratio for a pleural fluid ADA level≥16.81 U/L). In addition, the area under the ROC curve was 0.933 (S.E.=0.0230, 95% CI: 0.890–0.963). Conclusion: Pleural fluid total ADA assay is a sensitive and specific test suitable for rapid diagnosis of TB pleurisy.

The Usefulness of Pleural IFN-gamma Level in Differential Diagnosis of Tuberculous Pleural Effusion and Malignant Pleural Effusion

Background: It is sometimes difficult to differentiate tuberculous pleural effusion from malignant pleural effusion by clinical symptoms, signs, by routine tests of pleural fluid, and by pathologic studies. And recently, it was discovered that cytokines such as IL-2, IFN-, TNF- are elevated in tuberculous pleural fluid, and there have been several attempts to diagnose tuberculous pleural effusion by using these immunological mediators. There are several studies regarding the diagnostic value of IFN-, and there are two studies in Korea. But the diagnostic values of IFN- in these studies were slightly lower than those in other countries. To compare the diagnostic value of IFN- with those of CEA and ADA, and to determine the sensitivity and specificity of IFN- in Korean, we mesured IFN-, CEA level and ADA activity in pleural effusions. Methods: ADA activity, IFN- level and CEA level as well as cell count, differential count, and biochemical assays such as protein content and lactate dehydrogenase were measured in 40 cases of tuberculous pleuritis and 42 cases of malignant pleural effusion. Results: Tuberculous pleural fluid showed higher levels of IFN- and ADA ( pg/ml and U/L, respectively) than those of malignant pleural effusion ( pg/ml and U/L, respectively) (p, ADA, CEA were 0.97, 0.87, 0.67 and the specificities of IFN-, ADA, CEA were 1.0, 0.97, 1.0, respectively. There was no significant correlation between ADA activity and IFN- level. Conclusion: This study showed that IFN- test would be a very useful clinical test for differential diagnosis of tuberculous pleuritis and malignant pleural effusion because it is very sensitive and specific, although it is an expensive test.

Diagnosis of pleural tuberculosis by detection of specific IgG anti-antigen 60 in serum and pleural fluid.

The objective of this study was the prospective evaluation of the IgG antibody levels to mycobacterial antigen 60 (A60) in serum and pleural fluid and their role in the diagnosis of tuberculous pleuritis. The level of IgG was measured by Elisa in 30 patients with tuberculous pleuritis and 48 control subjects with pleural effusion (24 with carcinoma, 10 with transudative pleural effusion, 11 with empyema or parapneumonic effusion, 1 with pulmonary embolism and 2 due to systemic lupus erythematosus). The median titers of IgG against A60 of both serum and pleural fluid from tuberculous patients [445.6 +/- 133.56 and 263 +/- 72.58 Elisa units (EU) respectively] were significantly higher than those of corresponding median values (97.3 +/- 8.35 and 41.3 +/- 4.93 EU) of the control group (p < 0.01 and p < 0.01, respectively). Considering 240 units as cutoff point for a positive test in serum, the sensitivity was 53.3% and the specificity 100%. In the pleural fluid the cutoff point value was established at 150 units, with a sensitivity of 50% and specificity of 100%. We concluded that Elisa using A60 is a reliable and rapid test with an acceptable sensitivity and magnificent specificity.