Features which discriminate between tuberculosis and haematologic malignancy as the cause of pleural effusions with high adenosine deaminase.

BACKGROUND: Adenosine deaminase (ADA) is a useful biomarker for the diagnosis of tuberculous pleurisy (TBP). However, pleural effusions with high ADA can also be caused by other diseases, particularly hematologic malignant pleural effusion (hMPE). This study aimed to investigate the features that could differentiate TBP and hMPE in patients with pleural effusion ADA ≥ 40 IU/L. METHODS: This was a retrospective observational study of patients with pleural effusion ADA ≥ 40 IU/L, conducted at a Korean tertiary referral hospital with an intermediate tuberculosis burden between January 2010 and December 2017. Multivariable logistic regression analyses were performed to investigate the features associated with TBP and hMPE, respectively. RESULTS: Among 1134 patients with ADA ≥ 40 IU/L, 375 (33.1%) and 85 (7.5%) were diagnosed with TBP and hMPE, respectively. TBP and hMPE accounted for 59% (257/433) and 6% (27/433) in patients with ADA between 70 and 150 IU/L, respectively. However, in patients with ADA ≥ 150 IU/L, they accounted for 7% (9/123) and 19% (23/123), respectively. When ADA between 40 and 70 IU/L was the reference category, ADA between 70 and 150 IU/L was independently associated with TBP (adjusted odds ratio [aOR], 3.11; 95% confidence interval [CI], 1.95-4.95; P < 0.001). ADA ≥ 150 IU/L was negatively associated with TBP (aOR, 0.35; 95% CI, 0.14-0.90; P = 0.029) and positively associated with hMPE (aOR, 13.21; 95% CI, 5.67-30.79; P < 0.001). In addition, TBP was independently associated with lymphocytes ≥ 35% and a lactate dehydrogenase (LD)/ADA ratio < 18 in pleural effusion. hMPE was independently associated with pleural polymorphonuclear neutrophils < 50%, thrombocytopenia, and higher serum LD. A combination of lymphocytes ≥ 35%, LD/ADA < 18, and ADA < 150 IU/L demonstrated a sensitivity of 0.824 and specificity of 0.937 for predicting TBP. CONCLUSION: In patients with very high levels of pleural effusion ADA, hMPE should be considered. Several features in pleural effusion and serum may help to more effectively differentiate TBP from hMPE.

Pleural tuberculosis and endocarditis as complications of multifactorial origin in granulomatosis with polyangiitis: Clinical case report.

We present the case of a 36-year-old woman with a history of granulomatosis with polyangiitis; chronic kidney disease; systemic arterial hypertension. Debut with dyspnea, weakness, and hemoptysis, she was suspected in atypical pneumonia, discarded, persisting with tachypnea, tachycardia, chest pain. The protocol for pulmonary tuberculosis was started with negative sputum samples, positive blood culture for S. haemolyticus, chest tomography with left pneumothorax and ipsilateral pleural effusion, exudate-type pleural fluid was obtained, acid-fast staining, negative PCR for M. tuberculosis; A follow-up echocardiogram was performed due to a new murmur, reporting valvular vegetation, concluding a diagnosis of pleural tuberculosis and endocarditis as complications of multifactorial origin associated with immunosuppression in granulomatosis with polyangiitis.

Interleukin-6 and -27 as potential novel biomarkers for human pleural tuberculosis regardless of the immunological status.

Tuberculosis (TB) is the leading cause of pleural exudative effusions. Inflammatory markers, such as IFNγ and ADA, have been used as proxies for its diagnosis. We evaluated ex vivo levels of several cytokines in 83 pleural effusion specimens from patients with TB (including 10 with HIV co-infection) and 26 patients with other pleuritis using multiplex and ELISA assays. IL-6 and IL-27 levels were higher (p ≤ 0.04) in TB patients, regardless of the HIV status and the approach. IL-2, IL-4, IL-8, IFNγ, TNF and G-CSF showed variable results depending on the assay. This warranty these markers to be further validated.

Diagnostic flowchart for tuberculous pleurisy, pleural infection, and malignant pleural effusion.

BACKGROUND: Several markers for the diagnosis of pleural effusion have been reported; however, a comprehensive evaluation using those markers has not been performed. Therefore, this study aimed to develop a diagnostic flowchart for tuberculous pleurisy, pleural infection, malignant pleural effusion, and other diseases by using these markers. METHODS: We retrospectively collected data from 174 patients with tuberculous pleurisy, 215 patients with pleural infection other than tuberculous pleurisy, 360 patients with malignant pleural effusion, and 209 patients with other diseases at Fukujuji Hospital from January 2012 to October 2022. The diagnostic flowchart for four diseases was developed by using several previously reported markers. RESULTS: The flowchart was developed by including seven markers: pleural ADA ≥40 IU/L, pleural fluid LDH <825 IU/L, pleural fluid ADA/TP < 14, neutrophil predominance or cell degeneration, peripheral blood WBC ≥9200/µL or serum CRP ≥12 mg/dL, pleural amylase ≥75 U/L, and the presence of pneumothorax according to the algorithm of a decision tree. The accuracy ratio of the flowchart was 71.7 % for the diagnosis of the four diseases, with 79.3 % sensitivity and 75.4 % positive predictive value (PPV) for tuberculosis pleurisy, 75.8 % sensitivity and 83.2 % PPV for pleural infection, 88.6 % sensitivity and 68.8 % PPV for malignant pleural effusion, and 33.0 % sensitivity and 60.0 % PPV for other diseases in the flowchart. The misdiagnosis ratios were 4.6 % for tuberculosis pleurisy, 6.8 % for pleural infection, and 8.3 % for malignant pleural effusion. CONCLUSION: This study developed a useful diagnostic flowchart for tuberculous pleurisy, pleural infection, malignant pleural effusion, and other diseases.

Development and validation of a prediction model to assess the probability of tuberculous pleural effusion in patients with unexplained pleural effusion.

Differentiating tuberculous pleural effusion (TPE) from non-tuberculosis pleural effusion remains a challenge in clinical practice. This study aimed to develop and externally validate a novel prediction model using the peripheral blood tuberculous infection of T cells spot test (T-SPOT.TB) to assess the probability of TPE in patients with unexplained pleural effusion. Patients with pleural effusion and confirmed etiology were included in this study. A retrospective derivation population was used to develop and internally validate the predictive model. Clinical, radiological, and laboratory features were collected, and important predictors were selected using the least absolute shrinkage and selection operator. The prediction model, presented as a web calculator, was developed using multivariable logistic regression. The predictive performance of the model was evaluated for discrimination and calibration and verified in an independent validation population. The developed prediction model included age, positive T-SPOT.TB result, logarithm of the ratio of mononuclear cells to multiple nuclear cells in pleural effusion (lnRMMPE), and adenosine deaminase in pleural effusion ≥ 40 U/L. The model demonstrated good discrimination [with area under the curve of 0.837 and 0.903, respectively] and calibration (with a Brier score of 0.159 and 0.119, respectively) in both the derivation population and the validation population. Using a cutoff value of 60%, the sensitivity and specificity for identifying TPE were 70% and 88%, respectively, in the derivation population, and 77% and 92%, respectively, in the validation population. A novel predictive model based on T-SPOT.TB was developed and externally validated, demonstrating good diagnostic performance in identifying TPE.

Left pleural effusion in a young woman with genital tuberculosis.

Disseminated tuberculosis is a rare form of tuberculosis that can cause severe illness if diagnosed and treated late. We present the case of a young Senegalese woman who had a miscarriage due to a pelvic inflammatory disease, followed by the development of a left pleural effusion. Despite laparoscopic findings and a salpinx biopsy that revealed necrotizing granulomas, only microbiological examinations of pleural biopsies revealed the final diagnosis of disseminated, drug-sensitive tuberculosis.

Characteristics of pleural effusion with a high adenosine deaminase level: a case-control study.

BACKGROUND: Increased pleural fluid adenosine deaminase (ADA) is useful for diagnosing tuberculous pleurisy (TB), but high ADA levels are associated with other diseases. In this study, we compare various disease characteristics in patients with high-ADA pleural effusion. METHODS: We retrospectively collected data for 456 patients with pleural fluid ADA levels of ≥ 40 U/L from January 2012 to October 2021. Cases were classified as TB (n = 203), pleural infection (n = 112), malignant pleural effusion (n = 63), nontuberculous mycobacteria (n = 22), malignant lymphoma (ML) (n = 18), autoimmune diseases (n = 11), and other diseases (n = 27), and data were compared among those diseases. Predictive factors were identified by comparing data for a target disease to those for all other diseases. A diagnostic flowchart for TB was developed based on those factors. RESULTS: The most frequent disease was TB, though 60.0% of patients were diagnosed with other diseases. Median ADA levels in patients with TB were 83.1 U/L (interquartile range [IQR] 67.2-104.1), higher than those of patients with pleural infection (median 60.9 [IQR 45.3-108.0], p = 0.004), malignant pleural effusion (median 54.1 [IQR 44.8-66.7], p < 0.001), or autoimmune diseases (median 48.5 [IQR 45.9-58.2], p = 0.008), with no significant difference from NTM (p = 1.000) or ML (p = 1.000). Pleural fluid lactate dehydrogenase (LDH) levels of < 825 IU/L were beneficial for the diagnosis of TB. Neutrophil predominance or cell degeneration, white blood cell count of ≥ 9200/µL or C-reactive protein levels of ≥ 12 mg/dL helped in diagnosing pleural infection. Pleural fluid amylase levels of ≥ 75 U/L and a pleural fluid ADA/total protein (TP) ratio of < 14 helped in diagnosing malignant pleural effusion. High serum LDH and high serum/pleural fluid eosinophils helped in diagnosing ML and autoimmune diseases, respectively. The flowchart was comprised of the following three factors: pleural fluid LDH < 825 IU/L, pleural fluid ADA/TP of < 14, and neutrophil predominance or cell degeneration, which were decided by a decision tree. The diagnostic accuracy rate, sensitivity, and specificity for the diagnosis of TB were 80.9%, 78.8%, and 82.6%, respectively. CONCLUSION: Cases involving high pleural fluid ADA levels should be investigated using several factors to distinguish TB from other diseases.

Age : pleural fluid ADA ratio and other indicators for differentiating between tubercular and malignant pleural effusions.

Most of pleural effusions are caused by tuberculosis and malignant tumor. Difficult sampling and bacterial sparing nature of these diseases challenge doctors' diagnosis in China. This study aimed to develop a new convenient and effective method for the differentiation of tuberculous and malignant pleural effusion. A prospective cohort study of patients hospitalized with malignant (n = 90) and tuberculous (n = 130) pleural effusions from September 2018 to October 2020 was performed. The diagnostic performance of the age to pleural fluid ADA ratio (age/ADA) and other indicators to distinguish tuberculous and malignant pleural effusions was evaluated by receiver operating characteristic (ROC) curve analysis. The areas under the curve (AUC) of age/ADA and pleural fluid ADA were largest. Age/ADA showed sensitivity and specificity of 81.5% (95%CI 73.8%-87.8%) and 97.8% (95%CI 92.2%-99.7%) respectively. The sensitivity and specificity of pleural fluid ADA were 83.1% (95%CI 75.5%-89.1%) and 93.3% (95%CI 86.1%-97.5%) respectively. The positive likelihood [36.69 (95%CI 9.3-144.8)] of age/ADA was significantly higher than that of pleural fluid ADA [12.46 (95%CI 5.7-27.1)]. The AUCs for Cancer Ratio and Cancer Ratio plus were lower and showed a sensitivity of 80.0% (95%CI 72.1%-86.5%), 80.0% (95%CI 70.2%-87.7%) and a specificity of 81.5% (95%CI 73.8%-87.8%), 80.0% (95%CI 70.2%-87.7%) respectively. Age/ADA has a higher diagnostic accuracy than ADA. Age/ADA is a promising diagnostic index for tuberculous and malignant pleural effusion with high sensitivity and specificity, especially the high positive likelihood ratio. The diagnostic accuracy of Cancer Ratio and Cancer Ratio plus are inferior to those of age/ADA and ADA.

A case of paradoxical response during anti-tuberculosis treatment in a patient with ulcerative colitis.

Emerging anti-tumor necrosis factor (TNF)-α antibodies therapy changed treatment strategy to inflammatory bowel diseases because of the efficacy. However, TNF-α inhibitor can be associated with an increased risk of infectious complications, especially tuberculosis. A 71-year-old female with steroid-dependent ulcerative colitis (UC) was admitted due to relapse of UC with endoscopically severe active. Golimumab and adjunctive prednisolone started with 30 mg daily resulted in clinical remission. However, she had general fatigue and fever at the time of seventh injection of golimumab without abdominal symptoms. Based on positive interferon-gamma release assay, polymerase chain reaction positive for tuberculosis (TB) in pleural fluid, and chest computed tomography, she was diagnosed as tuberculous pleuritis. Standard anti-TB treatment (isoniazid, rifampicin, ethambutol, and pyrazinamide) was started without cessation of golimumab, because cessation of TNF-α inhibitors during anti-TB treatment could cause the paradoxical response by skewing from regulatory to inflammatory immune responses. However, four weeks after initiation of anti-TB treatment, she got fever-up and pleural effusion increased. We then started prednisolone 30 mg daily as diagnosis of paradoxical response, resulting in improving the symptoms. This is a suggestive case of paradoxical response during anti-TB treatment despite continuous TNF-α inhibitors.

[A CASE OF PROBABLE LATE-ONSET SYSTEMIC LUPUS ERYTHEMATOSUS WHERE THE INITIAL MANIFESTATION WAS A UNILATERAL PLEURAL EFFUSION].

A 74-year-old man developed with left pleural effusion and was suspected of benign asbestos pleural effusion and tuberculous pleurisy. Because of elevation of ADA level in the pleural effusion, diagnostic treatment for tuberculous pleurisy by anti-tuberculosis drugs was performed. However, right pleural effusion, cutaneous/mucosal lesions, leukocytopenia, and fever elevation occurred. The pathology of skin biopsy was consistent with systemic lupus erythematosus (SLE). Since clinical findings did not improve even after discontinuation of all drugs, he received steroid therapy was started and clinical findings improved. He was suspected of late-onset SLE. In conclusion, lupus pleurisy should also be differentiated when pleural effusion is seen in older. Late-onset SLE and drug-induced lupus should be carefully differentiated based on the clinical course.

Sjögren's Syndrome with Pleural Effusion: Difficult to Distinguish from Tuberculous Pleurisy Because of a High Adenosine Deaminase Level.

An 84-year-old woman visited our hospital for dyspnea due to right pleural effusion, with lymphocytic dominance and a high adenosine deaminase (ADA) level, that had been noted 1 month earlier. She was suspected of having tuberculosis pleurisy; however, anti-tuberculosis treatment yielded no improvements. She was diagnosed with pleural effusion due to primary Sjögren's syndrome (SjS) based on her dry eyes and mouth, positivity for anti-Sjögren's-syndrome-related antigen A/B, and histopathologic findings of a lip biopsy and thoracoscopic pleural biopsy. Her symptoms improved after starting steroid therapy. Cases of pleural effusion due to SjS with a high ADA level may be misdiagnosed as tuberculosis pleurisy.

Visual Diagnosis of Pleural Tuberculosis and its Association with Tissue Biopsy, Culture and Xpert Assay.

INTRODUCTION: The diagnosis of pleural tuberculosis remains a clinical challenge due to the paucibacillary nature of disease. Medical thoracoscopy remains the gold standard in diagnosing tuberculous pleuritis. OBJECTIVE: To establish the diagnostic yield of sago-seed thoracoscopic appearance of pleura in tuberculosis and its correlation with histopathology, tissue AFB culture and tissue Xpert MTB/Rif assay. METHODS: All consecutive patients with lymphocytic exudative pleural effusion, who fulfilled inclusion criteria of the study underwent medical thoracoscopy under local anesthesia and pleural tissue was sent for histopathology, AFB culture and Xpert MTB/Rif assay. Chronic granulomatous inflammation on histopathology and response to anti-tuberculous treatment was taken as reference standard for diagnosis of tuberculous pleurisy. RESULTS: A total of 249 patients were included in the study, out of which 168 had effusion secondary to tuberculosis. Sago-like nodules visualized on thoracoscopy had a sensitivity of 58.9 %, specificity of 92.6 % and diagnostic accuracy of 69.88 % for pleural tuberculosis. There is a strong association between the presence of sago-like nodules and detection of mycobacterium tuberculosis on Xpert MTB/Rif assay and AFB culture of pleura (p-value 0.007). CONCLUSION: Sago seed nodules on pleura have a high positive predictive value for tuberculous pleurisy. In high endemic countries patients with this finding on thoracoscopy can be commenced on anti-tuberculous treatment before histopathology or culture results are available.

Case reports of chronic myeloid leukemia and tuberculosis: Is imatinib the link between the two?

Current standard of care for treatment of CML is based on tyrosine kinase inhibitors (TKI's). Imatinib is most frequently used first line tyrosine kinase inhibitor. Various side effects of TKI's are known, but some may still be unknown. We are reporting three cases of CML who developed tuberculosis while on treatment with imatinib or dasatinib. Two cases developed CNS tuberculosis and other one was tubercular pleural effusion. These cases indicate that imatinib and other TKI's probably interfere with immunological functions and predispose patients for tuberculosis.

Tissue-Resident Memory-Like CD8+ T Cells Exhibit Heterogeneous Characteristics in Tuberculous Pleural Effusion.

Tissue-resident memory T (TRM) cells are well known to play critical roles in peripheral tissues during virus infection and tumor immunology. Our previous studies indicated that CD69+CD4+ and CD69+CD8+ T cells in tuberculous pleural effusion (TPE) were antigen-specific memory T cells. However, the phenotypical and functional characteristics of CD8+ TRM cells in tuberculosis remain unknown. We found that CD103+CD8+ T cells were the predominant subset of CD103+ lymphocytes in TPE; both CD103 and CD69 expressed on memory CD8+ T cells from TPE were significantly increased compared with those from paired peripheral blood. Phenotypically, CD103+CD69+ and CD103+CD69-CD8+ T cells expressed higher levels of CD45RO than CD103-CD69+CD8+ T cells did; CD103+CD69-CD8+ T cells highly expressed CD27, CD127, and CD62L and some chemokine receptors. We further compared the functional differences among the four distinct CD45RO+CD8+ T subsets identified by CD103 and CD69 expression. In consist with our published results, CD69+CD8+ T cells, but not CD103+CD8+, produced high levels of IFN-γ after treatment with BCG in the presence of BFA. Nevertheless, CD103-CD69+ and CD103+CD69+ memory CD8+ T cells expressed higher levels of Granzyme B, while CD103+CD69- memory CD8+ T cells were characterized as a possibly immunosuppressive subset by highly expressing CTLA-4, CD25, and FoxP3. Furthermore, TGF-ß extremely increased CD103 expression but not CD69 in vitro. Together, CD103+CD8+ T cells form the predominant subset of CD103+ lymphocytes in TPE; CD103 and CD69 expression defines distinct CD8+ TRM-like subsets exhibiting phenotypical and functional heterogeneity. Our findings provide an important theoretical basis to optimize and evaluate new tuberculosis vaccines.

Xpert MTB/RIF Ultra enhanced tuberculous pleurisy diagnosis for patients with unexplained exudative pleural effusion who underwent a pleural biopsy via thoracoscopy: A prospective cohort study.

INTRODUCTION: To evaluate the performance of Xpert MTB/RIF Ultra (Xpert-Ultra) in testing pleural tissue and fluid collected by medical thoracoscopy among patients with unexplained exudative pleural effusion. METHODS: Patients with an undiagnosed exudative pleural effusion were prospectively and consecutively recruited. Pleural tissue and fluid were collected by medical thoracoscopy and subjected to culture, Xpert MTB/RIF (Xpert) and Xpert-Ultra assays. Histopathological examination was also performed with the tissue and used as the major reference. RESULTS: Sixty-one patients were enrolled, including: 27 tuberculosis (TB) pleurisy, 15 malignancy and 19 other chronic infection cases. The sensitivity, specificity, positive predictive value, and negative predictive value of Xpert-Ultra for TB diagnosis were 85.19% (23/27), 97.06% (33/34), 95.83% (23/24), and 89.19% (33/37), respectively. Xpert-Ultra testing with the biopsy tissue alone had an equivalent diagnostic capacity to that of pathological examination for the diagnosis of confirmed TB cases. By combining the pathological examination with Xpert-Ultra for biopsy, the percentage of confirmed TB cases greatly increased (i.e. 92.59% (25/27)). The "trace" positive outcome of Xpert-Ultra was highly supportive of TB diagnosis for both biopsy tissue and pleural fluid examinations. CONCLUSION: With the specimens collected by medical thoracoscopy, the Xpert-Ultra assay presented high value in identifying TB among pleurisy patients who had difficulties in etiological diagnosis.

The Utility of Pleural Fluid Lactate Dehydrogenase to Adenosine Deaminase Ratio in Pleural Tuberculosis.

In high-burden settings, the diagnosis of pleural tuberculosis (TB) is frequently inferred in patients who present with lymphocyte predominant exudative effusions and high adenosine deaminase (ADA) levels. Two recent small retrospective studies suggested that the lactate dehydrogenase (LDH)/ADA ratio is significantly lower in TB than in non-TB pleural effusions and that the LDH/ADA ratio may be useful in differentiating pleural TB from other pleural exudates. We compared the pleural LDH/ADA ratios, ADA levels, and lymphocyte predominance of a prospectively collected cohort of patients with proven pleural TB (n = 160) to those with a definitive alternative diagnosis (n = 68). The mean pleural fluid LDH/ADA ratio was lower in patients with pleural TB than alternative diagnoses (6.2 vs. 34.3, p < 0.001). The area under the receiver operating characteristic curve was 0.92 (p < 0.001) for LDH/ADA ratio and 0.88 (p < 0.001) for an ADA ≥40 U/L alone. A ratio of ≤12.5 had the best overall diagnostic efficiency, while a ratio of ≤10 had a specificity of 90% and a positive predictive value of 95%, with a sensitivity of 78%, making it a clinically useful "rule in" value for pleural TB in high incidence settings. When comparing the LDH/ADA ratio to an ADA level ≥40 U/L in the presence of a lymphocyte predominant effusion, the latter performed better. When lymphocyte values are unavailable, our data suggest that the LDH/ADA ratio is valuable in distinguishing TB effusions from other pleural exudates.

Yield of pleural biopsy in different types of tubercular effusions.

INTRODUCTION: The yield of mycobacteria is shown to be very low in pleural effusions as it is a pauci-bacillary disease. The present study looked at the yield of mycobacterium tuberculosis (MTB) in terms of GeneXpert for acid fast bacilli (AFB) and culture using a medical thoracoscopy guided biopsy and analysed whether the yield increases in more complicated effusions. MATERIALS AND METHODS: This is a retrospective analysis of patients who underwent medical thoracoscopy for tubercular pleural effusions at our institute over the last 5-years. Patients who had no or minimal thin septations were considered as simple effusions and were subjected to semi-rigid thoracoscopy (n = 61). While patients who had multiple loculations and thick septations were considered as complicated effusions and were subjected to rigid thoracoscopy (n = 64). We considered granuloma on a biopsy as the standard for diagnosis of Tuberculosis (TB). Xpert MTB/RIF and The BACTEC MGIT was used for culture. RESULTS: Out 125 patients with granulomatous inflammation on biopsy, 56 (44.8%) were positive for either GeneXpert or culture for MTB. Only GeneXpert was positive in 43 and only culture was positive in 13. Amongst 61 patients with simple effusion, 14 had either GeneXpert for AFB or AFB culture being positive and 9 out of these patients had GeneXpert for MTB detected on biopsy sample. Only culture was positive in 5 patients. In complicated pleural effusion group either GeneXpert or culture for mycobacterium was positive in 42 (65.6%) out of 64 patients. Only GeneXpert was positive in 34 and culture alone was positive in 8 patients. CONCLUSION: The yield of MTB increases as the pleural effusion becomes more complicated. GeneXpert in a biopsy sample is a useful marker for MTB yield especially in a complicated effusion.

The comparison of pleural fluid TNF-α levels in tuberculous and nontuberculous pleural effusion.

BACKGROUND: Tuberculous pleural effusion is the manifestation of Mycobacterium tuberculosis infection in pleura. With existing means, it is difficult to establish the diagnosis of tuberculosis (TB) and non-TB pleural effusions; thus, establishing the diagnosis of TB pleural effusion and non-TB pleural effusion is still a clinical problem. Tumour necrosis factor alpha (TNFα) is a potent inflammatory cytokine that plays an important role in immunity to Mycobacterium tuberculosis infections, this level of cytokine increases in pleural effusion due to tuberculosis. OBJECTIVE: To compare the TNF-α level of pleural fluid in TB and non-TB pleural effusion. METHODS: The samples in this study that fulfilled the inclusion criteria were patients with non-TB pleural tuberculosis effusion in the inpatient ward in Pulmonology Unit Dr. Soetomo General Hospital Surabaya, male and female, aged between 15 and 60 years. The data is divided into two: primary data and secondary data of patients who fulfilled inclusion and exclusion criteria. The data with normal distribution was analyzed using independent t2 test and if the data distribution is abnormal, it was analyzed using Fisher's exact test. RESULTS: There were 22 subjects divided into 2 groups that were 11 patients with TB pleural effusion and 11 patients with non-TB pleural effusion. The TNF-α level of pleural fluid in TB pleural effusion was 25.43±13.55pg/mL. The TNF-α level of pleural fluid in non-TB was 5.98±1.89pg/mL. The serum TNF-α level in TB pleural effusion was 83.22±88.15pg/mL. The serum TNF-α level in non-TB was 68.54±57.88pg/mL. There was higher level of TNF-α pleural fluid in TB pleural effusion than in non-TB pleural effusion (25.43±13.55pg/mL vs 5.98±1.89pg/mL, p value <0.05). The serum TNF-α level in patients with TB pleural effusion was higher than TNF-α serum level of non-TB pleural effusion. There was no significant difference between TNF-α level of pleural fluid and serum TNF-α levels in the TB pleural effusion group (p value >0.05). CONCLUSION: The TNF-α level of pleural fluid in TB pleural effusion was higher than non-TB pleural effusions and there was no significant difference between serum TNF-α levels in the TB pleural effusion group and in the non-TB pleural effusion group.

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.