Tuberculous pleural effusion-induced Arg-1+ macrophage polarization contributes to lung cancer progression via autophagy signaling.

BACKGROUND: The association between tuberculous fibrosis and lung cancer development has been reported by some epidemiological and experimental studies; however, its underlying mechanisms remain unclear, and the role of macrophage (MФ) polarization in cancer progression is unknown. The aim of the present study was to investigate the role of M2 Arg-1+ MФ in tuberculous pleurisy-assisted tumorigenicity in vitro and in vivo. METHODS: The interactions between tuberculous pleural effusion (TPE)-induced M2 Arg-1+ MФ and A549 lung cancer cells were evaluated. A murine model injected with cancer cells 2 weeks after Mycobacterium bovis bacillus Calmette-Guérin pleural infection was used to validate the involvement of tuberculous fibrosis to tumor invasion. RESULTS: Increased CXCL9 and CXCL10 levels of TPE induced M2 Arg-1+ MФ polarization of murine bone marrow-derived MФ. TPE-induced M2 Arg-1+ MФ polarization facilitated lung cancer proliferation via autophagy signaling and E-cadherin signaling in vitro. An inhibitor of arginase-1 targeting M2 Arg-1+ MФ both in vitro and in vivo significantly reduced tuberculous fibrosis-induced metastatic potential of lung cancer and decreased autophagy signaling and E-cadherin expression. CONCLUSION: Tuberculous pleural fibrosis induces M2 Arg-1+ polarization, and M2 Arg-1+ MФ contribute to lung cancer metastasis via autophagy and E-cadherin signaling. Therefore, M2 Arg-1+ tumor associated MФ may be a novel therapeutic target for tuberculous fibrosis-induced lung cancer progression.

Accidental Detection of Tuberculous Empyema at Health Check-Up.

BACKGROUND: Patients with tuberculous empyema (TE) can have a serious impact on lung function as their disease progresses, and, if left untreated, can cause damage to other parts of the body such as the thorax and spine, causing pain and inconvenience to the patient. Early diagnosis and the search for appropriate treatment are key to improving the survival rate of the disease. METHODS: We report a case of a young patient with an unexpected finding of right pleural effusion on physical examination, who was eventually diagnosed with TE using next-generation sequencing of pleural tissue. We analyzed the literature to improve clinicians' understanding of TE and how to properly diagnose and treat the disease. RESULTS: Laboratory results of the pleural effusion suggested a possible Mycobacterium tuberculosis infection, but pathogen-related tests were negative, and the diagnosis was eventually successfully confirmed by thoracoscopic pleural biopsy. CONCLUSIONS: The diagnosis of TE should be considered in young patients with pleural thickening of the empyema. Adenosine deaminase may provide diagnostic direction in patients with unexplained thorax abscess. Pleural biopsy, although an invasive procedure, is an essential diagnostic tool in some cases.

Tuberculous Pleural Effusion-Derived Exosomal miR-130b-3p and miR-423-5p Promote the Proliferation of Lung Cancer Cells via Cyclin D1.

Epidemiologic studies have shown an association between tuberculosis and lung cancer. The altered tumor microenvironment after tuberculosis infection appears to contribute to cancer progression. Pleural effusions are enriched in exosomes, which act as mediators of intercellular communication. We hypothesized that tuberculous pleural effusion (TPE)-derived exosomes mediate intercellular communication. Then, we examined the interaction between TPE-derived exosomes and cancer cells. Exosomal miRNA profiling of TPE was performed using a microRNA array. An in vitro lung cancer cell experiment and an in vivo mouse xenograft tumor model were used to evaluate the effects of the selected exosomal microRNAs. TPE-derived exosome treatment enhanced the growth of A549 cells both in vitro and in a nude mouse xenograft model. Neighboring cancer cells were observed to take up TPE-derived exosomes, which promoted cancer cell invasion. Exosome-mediated transfer of the selected microRNAs, including miR-130b-3p and miR-423-5p, to A549 lung cancer cells activated cyclin D1 signaling and increased the expression of phosphorylated p65, a cyclin D1 transcription factor. Inhibitors of miR-130b and miR-423-5p suppressed the promotion of lung cancer by TPE-derived exosomes and reduced the expression of p65 and cyclin D1. These results suggest that TPE-derived exosomal miRNAs can serve as a novel therapeutic target in tuberculous fibrosis-induced lung cancer.

Paraffin-embedded Sample Test Promotes the Diagnosis of Tuberculous Pleurisy.

Context: Tuberculous pleurisy (TP) is the most common manifestation of extrapulmonary tuberculosis and the most frequent cause of pleural effusion (PE). Clinicians make a definitive diagnosis of TP based on the isolation of the mycobacterium tuberculosis (MTB) from PE or a pleural biopsy. Since the currently available tests for TP all have limitations in making a definitive diagnosis, clinicians urgently need new diagnostic tests. Objective: The study intended to compare the value in clinically diagnosing TP of the paraffin-embedded sample test (PEST), using pleural-effusion samples; an adenosine deaminase assay (ADA) using pleural fluid; and the T cell enzyme-linked immunospot test (T-SPOT), using peripheral-blood. Design: The research team performed a retrospective observational study. Setting: The study took place at the Sir Run Run Hospital, Nanjing Medical University in Nanjing, Jiangsu, China. Participants: Participants were 37 patients with suspected TP who had been admitted to the hospital between September 2018 and December 2022. Outcome Measures: The research team assessed the diagnostic performance of PEST, ADA, and T-SPOT in the TP group, calculating the positive rate, sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) of the tests. Results: Among the 37 participants, the testing confirmed that 24 had TP (64.86%), with 13 not having TP (35.14%). The PEST test produced a sensitivity of 83.3% for TP, with 20 out of 24 participants in the TP group testing positive (95% CI: 61.8 to 94.5), which was superior to the ADA, with only 9 out of the 24 participants (37.5%) in the TP group testing positive (95% CI: 19.6 to 59.2), with P < .001. Conclusions: The PEST test possesses a high diagnostic value, and clinicians can use it as a time-saving, noninvasive, and highly sensitive method for TP diagnosis. It can be adjunct method to the currently used tests for diagnosing TP. A combination of several detection methods could promote effective treatment.

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.

The Clinical Experience of Mycobacterial Culture Yield of Pleural Tissue by Pleuroscopic Pleural Biopsy among Tuberculous Pleurisy Patients.

Background and Objectives: Tuberculous pleurisy is a common extrapulmonary TB that poses a health threat. However, diagnosis of TB pleurisy is challenging because of the low positivity rate of pleural effusion mycobacterial culture and difficulty in retrieval of optimal pleural tissue. This study aimed to investigate the efficacy of mycobacterial culture from pleural tissue, obtained by forceps biopsy through medical pleuroscopy, in the diagnosis of TB pleurisy. Materials and Methods: This study retrospectively enrolled 68 TB pleurisy patients. Among them, 46 patients received semi-rigid pleuroscopy from April 2016 to March 2021 in a tertiary hospital. We analyzed the mycobacterial culture from pleural tissue obtained by forceps biopsy. Results: The average age of the study participants was 62.8 years, and 64.7% of them were men. In the pleuroscopic group, the sensitivity of positive Mycobacterium tuberculosis (M. TB) cultures for sputum, pleural effusion, and pleural tissue were 35.7% (15/42), 34.8% (16/46), and 78.3% (18/23), respectively. High sensitivities of M. TB culture from pleural tissue were up to 94.4% and 91.7% when pleural characteristic patterns showed adhesion lesions and both adhesion lesions and presence of micronodules, respectively. Conclusions: M. TB culture from pleural tissue should be considered a routine test when facing unknown pleural effusion during pleuroscopic examination.

The value of single or combined use of pleural fluid interferon gamma release assay in the diagnosis of tuberculous pleurisy.

OBJECTIVE: Tuberculous pleurisy (TP) is a common disease of extrapulmonary tuberculosis, but its diagnosis is challenging. Recently, studies have found that the pleural fluid interferon gamma release assay (PF-IGRA) has important diagnostic value in TP, but the sample size of these studies was small, and the conclusions were inconsistent. Therefore, this study evaluated the diagnostic value of PF-IGRA in TP through a meta-analysis. METHODS: We conducted a literature search in multiple databases to identify studies and calculated the sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), summary receiver operating characteristic (SROC) curve and area under the curve (AUC). RESULTS: All 26 publications, including 30 case-control studies, were eventually included in the meta-analysis. The results showed that the pooled sensitivity, specificity, PLR, NLR, DOR and AUC with their 95% confidence intervals were 0.90 (0.88-0.91), 0.87 (0.85-0.89), 7.64 (4.46-13.07), 0.13 (0.09-0.19), 65.45 (32.13-133.33) and 0.9508, respectively. The subgroup analysis suggested that the sensitivity, specificity and AUC of PF-IGRA for TP in areas with a high tuberculosis burden were significantly higher than those in areas with a low tuberculosis burden. The sensitivity and AUC of the enzyme-linked immunosorbent assay method were higher than those of the enzyme-linked immunosorbent assay method for IGRA, but the specificity was similar. More importantly, PF-IGRA combined with adenosine deaminase (ADA) could increase the diagnostic value of TP. CONCLUSIONS: The current meta-analysis indicated that PF-IGRA has high diagnostic value in diagnosing TP, especially in areas with a high TB burden. We recommended that the combination of PF-IGRA and ADA is the best way to diagnose TP.

Factors associated with negative pleural adenosine deaminase results in the diagnosis of childhood pleural tuberculosis.

BACKGROUND: Until now, the influential factors associated with pleural adenosine deaminase (ADA) activity among children remain unclear. This retrospective study was therefore conducted aiming to investigate the factors associated with negative pleural ADA results in the diagnosis of childhood pleural tuberculosis (TB). METHODS: Between January 2006 and December 2019, children patients with definite or possible pleural TB were recruited for potential analysis. Then, patients were stratified into two categories: negative pleural ADA results group (experimental group, ≤40 U/L) and positive pleural ADA results group (control group, > 40 U/L). Univariate and multivariate logistic regression analyses were performed to estimate risk factors for negative pleural ADA results. RESULTS: A total of 84 patients with pleural TB were recruited and subsequently classified as experimental (n = 17) and control groups (n = 67). Multivariate analysis (Hosmer-Lemeshow goodness-of-fit test: χ2 = 1.881, df = 6, P = 0.930) revealed that variables, such as chest pain (age-adjusted OR = 0.0510, 95% CI: 0.004, 0.583), pleural total protein (≤45.3 g/L, age-adjusted OR = 27.7, 95% CI: 2.5, 307.7), pleural lactate dehydrogenase (LDH, ≤505 U/L, age-adjusted OR = 59.9, 95% CI: 4.2, 857.2) and blood urea nitrogen (≤3.2 mmol/L, age-adjusted OR = 32.0, 95% CI: 2.4, 426.9), were associated with negative pleural ADA results when diagnosing childhood pleural TB. CONCLUSION: Our findings demonstrated that chest pain, pleural total protein, pleural LDH, and blood urea nitrogen were associated with a negative pleural ADA result for the diagnosis of pleural TB among children. When interpreting pleural ADA levels in children with these characteristics, a careful clinical assessment is required for the pleural TB diagnosis.

Evidence that changes in antimicrobial peptides during tuberculosis are related to disease severity, clinical presentation, specific therapy and levels of immune-endocrine mediators.

Given the role of host defense peptides (HDPs) in the defensive response against mycobacteria, we analyzed the circulating levels of LL-37, ß-defensin-2 and -3 in newly diagnosed patients with pulmonary (PTB) or pleural tuberculosis (PLTB) in whom measurements of pleural fluids were also performed. Severe PTB patients displayed higher circulating amounts of ß-defensin-3, statistically different from controls, further decreasing upon antimycobacterial treatment. LL-37 concentrations appeared within the normal range at diagnosis, but tended to increase during treatment, becoming statistically upon its completion in moderate cases. PLTB patients revealed decreased levels of ß-defensin-2 in presence of increased amounts of ß-defensin-3 and LL-37; in their plasma or pleural fluids. Considering the immune-endocrine dysregulation of tuberculosis, we also performed correlation analysis detecting positive associations between levels of cortisol, IL-6 and ß-defensin-3 in plasma from untreated severe patients as did their dehydroepiandrosterone and LL-37 values. Increased presence of ß-defensins, may represent an attempt to improve defensive mechanisms; which also take part in the inflammatory reaction accompanying TB, reinforced by the association with immune-endocrine mediators. The divergent profile of PLTB patients, decreased ß-defensin-2 but increased ß-defensin-3 and LL-37 levels, suggests a differential role of these HDPs in a situation characterized for its better protective response.

Adenosine Deaminase in Pleural Effusion and Its Relationship with Clinical Parameters in Patients with Malignant Pleural Mesothelioma.

Pleural effusion adenosine deaminase (ADA) levels are elevated in various diseases. We investigated whether pleural effusion ADA levels differ among patients with malignant pleural mesothelioma (MPM), lung cancer (LC), and benign diseases, including tuberculous pleurisy. We examined 329 patients from February 2002 to July 2013. There were 131 MPM cases with ADA levels of 32.29 IU/L; 117 LC cases with ADA levels of 21.12 IU/L; 54 benign disease cases with ADA levels of 20.98 IU/L. A significant difference existed in pleural effusion ADA levels between MPM and benign disease patients. Pleural effusion ADA levels were significantly higher in MPM patients.

Differential expression and predictive value of monocyte scavenger receptor CD163 in populations with different tuberculosis infection statuses.

BACKGROUND: Monocytes are the predominant innate immune cells at the early stage of Mycobacterium tuberculosis (M. tb) infection as the host defense against intracellular pathogens. Understanding the profile of different monocyte subpopulations and the dynamics of monocyte-related biomarkers may be useful for the diagnosis and prognosis of tuberculosis. METHODS: We enrolled 129 individuals comprising patients with pulmonary tuberculosis (PTB) (n = 39), tuberculous pleurisy (TBP) (n = 28), malignant pleural effusion (MPE) (n = 21), latent tuberculosis infection (LTBI) (n = 20), and healthy controls (HC) (n = 21). Surface expression of CD14, CD16, and CD163 on monocytes was detected using flow cytometry. In addition, soluble CD163 (sCD163) was determined by enzyme linked immunosorbent assay. RESULTS: Higher frequency of CD14+CD16+ (15.7% vs 7.8%, P < 0.0001) and CD14-CD16+ (5.3% vs 2.5%, P = 0.0011) monocytes and a decreased percentage of CD14+CD16- (51.0% vs 70.4%, P = 0.0110) cells was observed in PTB patients than in HCs. Moreover, PTB patients displayed a higher frequency of CD163+ cells in CD16+ monocytes than those in the HC group (40.4% vs 11.3%, P < 0.0001). The level of sCD163 was elevated in TBP patients and was higher in pleural effusion than in plasma (2116.0 ng/ml vs 1236.0 ng/ml, P < 0.0001). sCD163 levels in pleural effusion and plasma could be used to distinguish TBP from MPE patients (cut-off values: 1950.0 and 934.7 ng/ml, respectively; AUCs: 0.8418 and 0.8136, respectively). Importantly, plasma sCD163 levels in TBP patients decreased significantly after anti-TB treatment. CONCLUSIONS: Higher expression of membrane and soluble CD163 in active tuberculosis patients might provide insights regarding the pathogenesis of tuberculosis, and sCD163 may be a novel biomarker to distinguish TBP from MPE and to predict disease severity.

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

BACKGROUND: In China, tuberculous pleural effusion is the most common cause for pleural effusion. Elevated ADH and positive tuberculin test usually are characteristic of tuberculous pleural effusion. We reported a 71-year-old male patient with elevated ADH and positive tuberculin test firstly misdiagnosed as tuberculous pleural effusion finally proven as pleural mesothelial sarcoma by thoracoscopic pathology. METHODS: Appropriate laboratory tests and thoracentesis were carried out. Thoracoscopy and pathological biopsy were performed to differentiate tuberculous pleural effusion. RESULTS: Chest CT showed right pleural effusion. ADH in pleural effusion was over 45 U/L and PPD test was positive. No abnormal cells were found in pleural effusion pathology. Pathology of thoracoscopic biopsy proved pleural mesothelioma. CONCLUSIONS: Elevated ADH and positive tuberculin test are not a specific index for tuberculosis and thoracoscopic biopsy pathology is crucial for differential diagnosis.

Pleural Cryobiopsy versus Flexible Forceps Biopsy in Subjects with Undiagnosed Exudative Pleural Effusions Undergoing Semirigid Thoracoscopy: A Crossover Randomized Trial (COFFEE Trial).

BACKGROUND: There is no randomized study comparing pleural cryobiopsy (CB) and flexible forceps biopsy (FFB) in subjects undergoing medical thoracoscopy for the diagnosis of pleural effusions. OBJECTIVE: In this crossover study, we compared the diagnostic yield of CB versus FFB in subjects undergoing semirigid thoracoscopy. METHODS: Subjects undergoing semirigid thoracoscopy for undiagnosed pleural effusions were subjected to both CB and FFB, with the order of performing the biopsy randomized in a 1:1 ratio. The primary outcome was the diagnostic yield obtained with CB versus FFB. The secondary outcomes included the biopsy size, depth, histologic interpretability, artefacts, the difficulty of performing biopsy on an operator-rated visual analog scale, the severity of bleeding observed at the time of the biopsy, and the duration of the procedure. RESULTS: Of the 201 subjects screened, 50 (mean age 52.4 years; 18 women) were included. The diagnostic yield of CB (78.0%) was not different from FFB (76.0%, p = 1.00). CB yielded a larger specimen than FFB (median size 7.0 vs. 4.0 mm; p < 0.001), and a greater depth of specimens (up to the pleural fat or deeper, CB vs. FFB 65.2 vs. 40.8%; p = 0.02). The CB procedure was quicker than FFB (median duration 10 vs. 15 min; p < 0.001). There were no significant differences in the difficulty of performing the biopsy, the severity of bleeding, histologic interpretability, or artefacts in the specimens between the CB and FFB groups. CONCLUSION: The diagnostic yield of pleural CB was comparable to FFB during semirigid thoracoscopy.

The diagnostic role of video-assisted thoracoscopic surgery in exudative pleural effusion and follow-up results in patients with nonspecific pleuritis.

OBJECTIVE: To assess the diagnostic value of video-assisted thoracoscopic surgery in exudative pleural effusions, and to evaluated the frequency of malignancy development with long term follow-up of patients defined as nonspecific pleuritis after surgery. . METHODS: The retrospective study was conducted at Yedikule Chest Diseases and Thoracic Surgery Training and Research Hospital, Istanbul, Turkey, and comprised data of patients with undiagnosed exudative pleural effusions seen between January 2008 and December 2013. Data related to clinical, radiological, thoracoscopical, histopathological and follow-up periods were obtained from the hospital records. SPSS 15 was used for data analysis. RESULTS: Of the 229 patients, 145(63.3%) were males and 84(36.7%) were females. The overall mean age was 54.5 }15.1 years. Malignancy was found in 84 (36.6%) patients, and tuberculosis in 26(11.4%). The remaining 119(52%) patients had nonspecific pleuritis and their mean follow-up period was 29.2}27.1 months (range: 1-103 months). Video-assisted thoracoscopic surgery was repeated in 3(2.52%) patients in the 1st, 4th and 16th months of followup period due to the recurrence of pleural effusion. Tuberculosis and mesothelioma were diagnosed in 1(0.8%) and 2(1.7%) cases, respectively. CONCLUSIONS: Video-assisted thoracoscopic surgery was found to be a valuable diagnostic procedure in patients with undiagnosed exudative pleural effusion.

Thoracoscopic pleural biopsy improves yield of Xpert MTB/RIF for diagnosis of pleural tuberculosis.

BACKGROUND AND OBJECTIVE: Extrapulmonary tuberculosis (EPTB) accounts for ~15% of all TB patients, and TB pleural effusion is the second most common site of EPTB. The diagnosis of pleural TB is challenging due to the pauci-bacillary nature of the disease. Histopathology of thoracoscopically obtained pleural biopsy provides the highest diagnostic yield. The Xpert MTB/RIF assay (Xpert) is a PCR test that can identify both Mycobacterium tuberculosis (MTB) and rifampicin resistance. Currently, there is a lack of clarity regarding the value of Xpert on pleural tissue. We report our experience of using Xpert on thoracoscopic pleural biopsy samples. METHODS: We retrospectively reviewed the records of patients who underwent thoracoscopy in our institution over a 1-year period. Relevant clinical details; indications; and results of tests on pleural tissue and fluid, including histopathology, mycobacterial cultures and Xpert, were extracted. RESULTS: Of the 156 patients who underwent thoracoscopy, 73 (47%) had TB, 66 (42%) malignancy and 17 (11%) other conditions. Histopathology was diagnostic in all the 73 TB patients (100%). The yields of the microbiological tests against histopathology on thoracoscopic biopsy sample and pleural fluid were: pleural tissue Xpert 45%, pleural tissue culture 39%, pleural fluid culture 17% and pleural fluid Xpert 14%. Pleural tissue provided higher yields than fluid in both Xpert and culture (P < 0.05). Pleural tissue Xpert provided a higher yield than culture and substantially improved yield compared with closed pleural biopsy as we previously reported. CONCLUSION: Thoracoscopic pleural biopsy results in increased sensitivity on Xpert testing.

Ultrasound-Guided versus Thoracoscopic Pleural Biopsy for Diagnosing Tuberculous Pleurisy Following Inconclusive Thoracentesis: A Randomized, Controlled Trial.

BACKGROUND Traditional diagnostic methods for tuberculosis (TB) cannot be reliably applied to tuberculous pleurisy. Therefore, this prospective, randomized, controlled trial was performed to compare the diagnostic sensitivity and safety of ultrasound-guided cutting-needle pleural biopsy versus thoracoscopic pleural biopsy in patients suspected of tuberculous pleurisy following inconclusive thoracentesis. MATERIAL AND METHODS A total of 196 adult patients with acid-fast bacillus (AFB)-negative exudative pleural effusions clinically suspected of tuberculous pleurisy were recruited. Enrollees were randomized into 2 cohorts: ultrasound-guided cutting-needle pleural biopsy (n=96) or thoracoscopic pleural biopsy (n=96). The overall diagnostic yields, diagnostic sensitivities for tuberculous pleurisy, and post-procedural complications for both cohorts were statistically compared. RESULTS Ultrasound-guided pleural biopsy displayed an overall diagnostic yield of 83%, while thorascopic pleural biopsy displayed a similar overall diagnostic yield of 86% (χ²=1.88, df=1, p=0.17). There were 127 patients conclusively diagnosed with tuberculous pleurisy, resulting in a tuberculous pleurisy prevalence of 65% in this patient population (66% in the ultrasound cohort vs. 63% in the thoracoscopy cohort; p>0.05). Ultrasound-guided pleural biopsy displayed a sensitivity of 82% in detecting tuberculous pleurisy, while thorascopic pleural biopsy displayed a similar sensitivity of 90% (χ²=1.05, df=1, p=0.30). The sensitivities of these 2 modalities did not significantly differ based on the degree of pleural thickening (p>0.05). Post-procedural complications were minor. CONCLUSIONS Ultrasound-guided and thoracoscopic pleural biopsy both display strong (>80%) but statistically similar overall diagnostic yields for diagnosing pleural effusions following inconclusive thoracentesis. Both modalities also display strong (>80%) but statistically similar sensitivities in detecting tuberculous pleurisy.

The value of exfoliative cell cytology in the diagnosis of exudative pleural effusions.

The sensitivity and specificity of exfoliative cell cytology for the diagnosis of exudative pleural effusions varies widely according to the etiologic causes. The aim of this study is to assess the diagnostic value of exfoliative cell cytology for the identification of exudative pleural effusions. This is a retrospective study of the patients with an exudative pleural effusion admitted at our clinic in the last twenty years. We have conducted the clinical, the cytological findings, and the diagnostic results of six hundred patients from hospital records.  Male to female ratio was 2.2:1 with a mean age of 42.8 years (range 18-78 years) among the patients. Samples were processed and evaluated according to the standard methods. Cytology results were reviewed and the patients were stratified according to the final diagnosis of their disease. Of the six hundred exudative effusions, 240 were malignant on exfoliative cytology pleural fluid alone. Adenocarcinoma was the most common type of malignancy. Tuberculosis was the second most frequent etiology for the exudative effusions followed by infection and collagen vascular diseases. Diagnostic accuracy of cytology showed a good correlation with the final diagnosis with an overall 70.1% sensitivity, 62.5% specificity, and a 95.9% positive predictive value for all exudative pleural effusions. Cytologic examination of the pleural fluid is a simple non-invasive procedure as the initial step for the diagnostic work up of patients with a pleural effusion.  Exfoliative cytology provides high a final diagnostic yield for the identification of an exudative pleural effusion etiology. Furthermore, cytologic analysis leads the clinician into the correct diagnostic pathway as the most informative laboratory tool even when it was not diagnostic by itself for equivocal cases.

[Tuberculous Pleurisy Diagnosed by Thoracoscopic Lung Biopsy].

A 44-year-old woman was referred to our hospital with pleural effusion and unknown fever. Mycobacterium tuberculosis was not detected by culture of pleural effusion and sputum and gastric fluid. Pleural fluid was serous and exudative, and cytological examination showed no malignant cells. Computed tomography revealed a little pleural thickening of the right middle lobe and massive pleural effusion. As acute pleurisy was suspected based on the findings of imaging studies, thoracoscopy was performed under general anesthesia. Many yellowish-white, small nodules were seen on the parietal pleura, and white small nodule were seen on the visceral pleura of the right middle lobe. Mycobacterium tuberculosis was not detected by culture and polymerase chain reaction for Mycobacterium tuberculosis( TB-PCR) of parietal pleura and pleural effusion, but was detected by only culture and TB-PCR of visceral pleura, yielding a diagnosis of tuberculous pleurisy. Her symptoms improved and the right pleural effusion decreased with isoniazid (INH), rifampicin (RFP), ethambutol (EB) and pyrazinamide(PZA) treatment.

Tumor Necrosis Factor and Its Receptors Are Crucial to Control Mycobacterium bovis Bacillus Calmette-Guerin Pleural Infection in a Murine Model.

Tumor necrosis factor (TNF) is crucial to control Mycobacterium tuberculosis infection, which remains a leading cause of morbidity and mortality worldwide. TNF blockade compromises host immunity and may cause reactivation of latent infection, resulting in overt pulmonary, pleural, and extrapulmonary tuberculosis. Herein, we investigate the roles of TNF and TNF receptors in the control of Mycobacterium bovis bacillus Calmette-Guerin (BCG) pleural infection in a murine model. As controls, wild-type mice and those with a defective CCR5, a receptor that is crucial for control of viral infection but not for tuberculosis, were used. BCG-induced pleural infection was uncontrolled and progressive in absence of TNF or TNF receptor 1 (TNFR1)/TNFR2 (TNFR1R2) with increased inflammatory cell recruitment and bacterial load in the pleural cavity, and heightened levels of pleural and serum proinflammatory cytokines and chemokines, compared to wild-type control mice. The visceral pleura was thickened with chronic inflammation, which was prominent in TNF(-/-) and TNFR1R2(-/-) mice. The parietal pleural of TNF(-/-) and TNFR1R2(-/-) mice exhibited abundant inflammatory nodules containing mycobacteria, and these mice developed nonresolving inflammation and succumbed from disseminated BCG infection. By contrast, CCR5(-/-) mice survived and controlled pleural BCG infection as wild-type control mice. In conclusion, BCG-induced pleurisy was uncontrolled in the absence of TNF or TNF receptors with exacerbated inflammatory response, impaired bacterial clearance, and defective mesothelium repair, suggesting a critical role of TNF to control mycobacterial pleurisy.

Activation of calpain by renin-angiotensin system in pleural mesothelial cells mediates tuberculous pleural fibrosis.

Pleural fibrosis is defined as an excessive deposition of extracellular matrix (ECM) components that results in destruction of the normal pleural tissue architecture. It can result from diverse inflammatory conditions, especially tuberculous pleurisy. Pleural mesothelial cells (PMCs) play a pivotal role in pleural fibrosis. Calpain is a family of calcium-dependent endopeptidases, which plays an important role in ECM remodeling. However, the role of calpain in pleural fibrosis remains unknown. In the present study, we found that tuberculous pleural effusion (TPE) induced calpain activation in PMCs and that inhibition of calpain prevented TPE-induced collagen-I synthesis and cell proliferation of PMCs. Moreover, our data revealed that the levels of angiotensin (ANG)-converting enzyme (ACE) were significantly higher in pleural fluid of patients with TPE than those with malignant pleural effusion, and ACE-ANG II in TPE resulted in activation of calpain and subsequent triggering of the phosphatidylinositol 3-kinase (PI3K)/Akt/NF-κB signaling pathway in PMCs. Finally, calpain activation in PMCs and collagen depositions were confirmed in pleural biopsy specimens from patients with tuberculous pleurisy. Together, these studies demonstrated that calpain is activated by renin-angiotensin system in pleural fibrosis and mediates TPE-induced collagen-I synthesis and proliferation of PMCs via the PI3K/Akt/NF-κB signaling pathway. Calpain in PMCs might be a novel target for intervention in tuberculous pleural fibrosis.