Search Results (20)

Background and Objectives: Discrimination between various causes of exudative pleural effusion (PE) remains a major clinical challenge, and to date, definitive biochemical markers for this discrimination remain lacking. An increasing number of studies have reported that serum C-reactive protein (CRPs), pleural fluid CRP (CRPpf), and CRPpf/CRPs ratio (CRPr) are useful for the differential diagnosis of exudative PE; however, their efficacy rate is not similar in these studies. The majority of these studies were conducted on small groups of subjects, and the efficacy of the gradient between CRPs and CRPpf (CRPg—calculated as CRPs—CRPpf) in this differentiation has not been previously investigated. This study aims to evaluate the efficacy rate of CRPs, CRPpf, CRPg, and CRPr in the differential diagnoses of various causes of exudative PE in a relatively large cohort of patients. Materials and Methods: The research group included 282 subjects with exudative PE—146 had parapneumonic effusion (PPE), 126 had malignant pleural effusion (MPE), and 10 had tuberculous pleural effusion (TPE). The values are presented as mean ± SD. Results: The mean CRPs level was significantly higher in the PPE group compared to the MPE group (p < 0.0001) and the TPE group (p < 0.001), and also significantly higher in the TPE group than in the MPE group (p = 0.0009). Similarly, the mean CRPpf level was significantly higher in the PPE group than in the MPE group (p < 0.0001) and the TPE group (p = 0.04), and also significantly higher in the TPE group than in the MPE group (p < 0.0001). The mean CRPg level was significantly higher in the PPE group than in both the MPE group (p < 0.0001) and the TPE group (p < 0.002). The mean CRPr level did not differ significantly among these groups of exudate. Conclusions: CRPs, CRPpf, and CRPg are effective in the differential diagnosis of exudative PE, while CRPr was not effective in this regard. The main limitation of this study is that the sample size of the TPE group is very small. Full article

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. Full article

Tuberculous pleurisy (TP) is one of the most common forms of extrapulmonary tuberculosis, but its diagnosis is challenging. Lipoarabinomannan (LAM) antigen is a biomarker for Mycobacterium tuberculosis (Mtb) infection. LAM detection has potential as an auxiliary diagnostic method for TP. We have successfully generated five rabbit anti-LAM monoclonal antibodies (BJRbL01, BJRbL03, BJRbL20, BJRbL52, and BJRbL76). Here, anti-LAM antibodies were tested to detect LAM in the pleural fluid and plasma of patients with TP by sandwich enzyme-linked immunosorbent assays (ELISAs). The results revealed that all of the anti-LAM antibodies were successfully used as capture and detection antibodies in sandwich ELISAs. The BJRbL01/BJRbL01-Bio pair showed better performance than the other antibody pairs for detecting mycobacterial clinical isolates and had a limit of detection of 62.5 pg/mL for purified LAM. LAM levels were significantly higher in the pleural fluid and plasma of patients with TP than in those of patients with malignant pleural effusion or the plasma of non-TB, and LAM levels in the pleural fluid and plasma were positively correlated. Moreover, LAM levels in the pleural fluid sample were significantly higher in confirmed TP patients than in clinically diagnosed TP patients. Our studies provide novel LAM detection choices in the pleural fluid and plasma of TP patients and indicate that LAM detection assay has an auxiliary diagnostic value for TP, which may help to improve the diagnosis of TP. Full article

Toll-like receptor (TLR) is essential for the immune response to Mycobacterium tuberculosis (MTB) infection. However, the mechanism whereby TLR mediates the MTB-induced pleural mesothelial hyperpermeability in tuberculous pleural effusion (TBPE) remains unclear. Pleural effusion size and pleural fluid levels of vascular endothelial growth factor (VEGF) and soluble TLR2 (sTLR2) in patients with TBPE (n = 36) or transudative pleural effusion (TPE, n = 16) were measured. The effects of MTB H37Ra (MTBRa) on pleural mesothelial permeability and the expression of VEGF and zonula occludens (ZO)-1 in human pleural mesothelial cells (PMCs) were assessed. Levels of VEGF and sTLR2 were significantly elevated in TBPE compared to TPE. Moreover, effusion VEGF levels correlated positively, while sTLR2 values correlated negatively, with pleural effusion size in TBPE. In human PMCs, MTBRa substantially activated JNK/AP-1 signaling and upregulated VEGF expression, whereas knockdown of TLR2 remarkably inhibited MTBRa-induced JNK phosphorylation and VEGF overexpression. Additionally, both MTBRa and VEGF markedly reduced ZO-1 expression and induced pleural mesothelial permeability, while TLR2 silencing or pretreatment with anti-VEGF antibody significantly attenuated the MTBRa-triggered effects. Collectively, TLR2 mediates VEGF overproduction and downregulates ZO-1 expression in human PMCs, leading to mesothelial hyperpermeability in TBPE. Targeting TLR2/VEGF pathway may confer a potential treatment strategy for TBPE. Full article

Background: Uganda ranks among the countries with the highest burden of TB the world and tuberculous pericarditis (TBP) affects up to 2% of people diagnosed with pulmonary tuberculosis worldwide. In Africa, it represents the most common cause of pericardial disease. Here, we present the case of a 21-year-old male patient who was diagnosed of cardiac tamponade due to tuberculous pericarditis with a positive urine LF-LAM. Case report: We report a case of a 21-year-old male living in Oyam district, Uganda, who presented to the emergency department with difficulty in breathing, easy fatigability, general body weakness, and abdominal pain. A chest X-ray showed the presence of right pleural effusion and massive cardiomegaly. Thus, percutaneous pericardiocentesis was performed immediately and pericardial fluid resulted negative both for gram staining and real-time PCR test Xpert MTB/RIF. The following day’s urine LF-LAM test resulted positive, and antitubercular therapy started with gradual improvement. During the follow-up visits, the patient remained asymptomatic, reporting good compliance to the antitubercular therapy. Conclusion: Our case highlights the potential usefulness of a LF-LAM-based diagnostic approach, suggesting that, in low-resource settings, this test might be used as part of routine diagnostic workup in patients with pericardial disease or suspected extra-pulmonary tuberculosis. Full article

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. Full article

Tuberculosis (TB) is the leading cause of morbidity, hospitalisations, and mortality in people living with HIV (PLWH). The lower CD4+ T-lymphocyte count in the course of HIV infection, the higher risk of active TB, and the higher odds for atypical clinical and radiologic TB presentation. These HIV-related alterations in TB presentation may cause diagnostic problems in patients not knowing they are infected with HIV. We report on a patient without any background medical conditions, who was referred to a hospital with a 4-month history of chest and feet pains, mild dry cough, fatigue, reduced appetite, and decreasing body weight. Chest X-ray revealed mediastinal lymphadenopathy, bilateral reticulonodular parenchymal opacities, and pleural effusion. A preliminary diagnosis of lymphoma, possibly with a superimposed infection was established. Further differential diagnostic process revealed pulmonary TB in the course of advanced HIV-1 disease, with a CD4+ T-lymphocyte count of 107 cells/mm³. The patient completed anti-tuberculous therapy and successfully continues on antiretroviral treatment. This case underlines the importance of screening for HIV in patients with newly diagnosed TB. Full article

Extracellular matrix production by pleural mesothelial cells in response to Mycobacterium tuberculosis contributes to tuberculous fibrosis. NOX4 is involved in the pathogenesis of tuberculous fibrosis. In this study, we evaluated whether NOX4 gene-targeting microRNAs showed protective effects in tuberculosis fibrosis. TargetScan prediction software was used to identify candidate microRNAs that bind the 3′ UTRs of NOX4, and microRNA-148a (miR-148a) was selected as the best miRNA candidate. A repressed and forced expression assay in Met5A cells was performed to investigate the causal relationship between miR-148a and NOX4. The role of miR-148a in tuberculous pleural fibrosis was studied using a murine model of Mycobacterium bovis bacillus Calmette–Guérin (BCG) pleural infection. Heat-killed M. tuberculosis (HKMT) induces NOX4 and POLDIP2 expression. We demonstrated the inhibitory effect of miR-148a on NOX4 and POLDIP2 expression. The increased expression of miR-148a suppressed HKMT-induced collagen-1A synthesis in PMC cells. In the BCG pleurisy model, miR-148a significantly reduced fibrogenesis and epithelial mesenchymal transition. High levels of miR-148a in tuberculous pleural effusion can be interpreted as a self-limiting homeostatic response. Our data indicate that miR-148a may protect against tuberculous pleural fibrosis by regulating NOX4 and POLDIP2. Full article

Parapneumonic effusions often complicate Mycoplasma pneumoniae (MP) pneumonia, contrary to the notion that they are a rare feature of MP infection. Increased research and evidence on MP parapneumonic effusions (MPPE) can help elucidate its clinical significance as one of the variable manifestations of MP infection. This article aims to summarize the existing literature about the clinical characteristics of MPPE in adults and discuss its diagnostic implications from the perspective of pleural fluid analysis. Approximately 20–25% of adult patients with MP pneumonia develop MPPE, and its frequency in children and adults seems to be similar. Although the pathogenesis of MPPE remains to be elucidated, MP-induced cell-mediated immune mechanisms might be partially associated with the development of MPPE. MPPE usually shows mononuclear leukocyte predominance with elevated adenosine deaminase (ADA) activity, similar to tuberculous pleural effusion (TPE). The degree of increase in pleural fluid ADA levels and serum inflammatory biomarkers may help differentiate between MPPE and TPE. During the acute phase, a single positive IgM and positive polymerase chain reaction results allow for a precise and reliable MP infection diagnosis. The mainstay of treatment is the selection of adequate anti-mycoplasma antibiotics with or without corticosteroid, based on the local epidemiologic data on macrolide resistance. Full article

We aimed to (1) evaluate the incidence of tuberculous pleural effusion (TPE) over 25 years in our centre; (2) measure the yield of different diagnostic techniques; (3) compare TPE features between immigrant and native patients. Retrospective study of patients who underwent diagnostic thoracentesis and pleural biopsy in our hospital between 1995 and 2020. TPE was diagnosed in 71 patients (65% natives, 35% immigrants). Onset was acute in 35%, subacute in 26% and prolonged in 39%. Radiological features were atypical in 42%. Thoracentesis specimens were lymphocyte-predominant in 84.5% of patients, with elevated adenosine deaminase in 75% of patients. Diagnostic yield of pleural biopsy was 78%. Compared with native patients, more immigrants had previous contact with TB (54% vs. 17%, p = 0.001), prior TB (21% vs. 4%, p < 0.02) and atypical radiological features (58% vs. 34%, p < 0.03). TPE incidence was six times higher in the immigrant population (6.7 vs. 1.1 per 100,000 person-years, p < 0.001). TPE has an acute onset and sometimes atypical radiological features. Pleural biopsy has the highest diagnostic yield. Reactivation, prior contact with TB, atypical radiological features, complications, and positive microbiology results are more common in immigrant patients. Full article

(1) Background: Malignant (MPE), parapneumonic (PPE) and tuberculous (TPE) pleural effusions constitute common causes of pleurisy. Discriminating among them is usually challenging. C-reactive protein (CRP) and adenosine deaminase (ADA) pleural levels (p-CRP, p-ADA) have been used as differentiators in many studies showing promising results. This study aims to evaluate the diagnostic value of p-CRP, p-ADA levels and their combination among the three categories. (2) Methods: A prospective study of 100 patients with MPE (n = 59), PPE (n = 34) and TPE (n = 7) from a single centre was performed. p-CRP levels were evaluated between PPE and non-PPE and between complicated (CPPE) and non-complicated PPE. ADA levels were also measured to classify patients among MPE and non- MPE. Eventually, the combination of p-CRP and p-ADA values was used as a discrimination factor among PPE, MPE and TPE. (3) Results: ROC analysis revealed that p-CRP with a cut-off value: 4.4 mg/dL can successfully differentiate PPE (AUC = 0.998). The cut-off level of 10 mg/dL can predict CPPE with sensitivity: 63%, specificity: 71.4%, positive predictive value (PPV): 89%, and negative predictive value (NPV): 33%. Furthermore, patients with ADA levels ≤ 32 U/L were more likely to belong to the malignant group sensitivity: 93%, specificity: 78%, PPV: 85.9%, and NPV: 88.9%. Discriminant analysis showed that the combination of p-CRP and p-ADA levels can discriminate PPE, MPE and TPE in 93% of cases. (4) Conclusion: This study provides evidence that p-CRP and p-ADA levels could be possibly used in clinal practice in order to establish a diagnosis among MPE, PPE and TPE. Full article

While a higher incidence of lung cancer in subjects with previous tuberculous infection has been reported in epidemiologic data, the mechanism by which previous tuberculosis affects lung cancer remains unclear. We investigated the role of NOX4 in tuberculous pleurisy-assisted tumorigenicity both in vitro and in vivo.Heat-killed Mycobacterium tuberculosis-stimulated mesothelial cells augmented the migrationand invasive potential of lung cancer cells in a NOX4-dependent manner. Mice with Mycobacterium bovis bacillus Calmette–Guérin (BCG) pleural infection exhibited increased expression of NOX4 and enhanced malignant potential of lung cancer compared to mice with intrathoracic injection of phosphate-buffered saline. The BCG+ KLN205 (KLN205 cancer cell injection after BCG treatment) NOX4 KO mice group showed reduced tuberculous fibrosis-promoted metastatic potential of lung cancer, increased autophagy, and decreased expression of TGF-β, IL-6, and TNF-α compared to the BCG+KLN205 WT mice group. Finally, NOX4 silencing mitigated the malignant potential of A549 cells that was enhanced by tuberculous pleural effusion and restored autophagy signaling. Our results suggest that the NOX4–autophagy axis regulated by tuberculous fibrosis could result in enhanced tumorigenic potential and that NOX4-P62 might serve as a target for tuberculous fibrosis-induced lung cancer. Full article

Introduction: Pleural fluid culture yield in tuberculous pleural effusion (TPE) is disappointing in immunocompetent hosts. Herein, we attempt to define the role of serial sputum cultures in the diagnosis of TPE. Material and methods: We identified cases diagnosed with TPE over a16-year period in ahigh-prevalence US hospital. Absolute yields of one, two, and three sputa were calculated as well as the incremental yield of adding second and third sputa. These calculations were then performed separately for expectorated and induced sputum and for patients with and without infiltrates on chest X-ray. Results: Sixty sputum collections were performed in 46 patients with TPE. The per-patient sensitivity of sputum culture was 45.6%. On aper-sputum collection basis, the overall yield of the first sputum was 30%, of two sputa 39%, and of three sputa 54%. The corresponding incremental yields were 9% and 15%, respectively. The three-sputum yields of expectorated and induced collections were similar. The three-sputum yield in patients with infiltrates on X-ray was 11% lower than that in those without infiltrates. Conclusions: Serial sputum collection of three specimens can be expected to produce ayield of > 50% in cases of suspected TPE regardless of whether obtained by expectoration or induction, and the yield increases incrementally. Full article

Thrombin is an essential procoagulant and profibrotic mediator. However, its implication in tuberculous pleural effusion (TBPE) remains unknown. The effusion thrombin and plasminogen activator inhibitor-1 (PAI-1) levels were measured among transudative pleural effusion (TPE, n = 22) and TBPE (n = 24) patients. Pleural fibrosis, identified as radiological residual pleural thickening (RPT) and shadowing, was measured at 12-month follow-up. Moreover, in vivo and in vitro effects of thrombin on PAI-1 expression and mesothelial–mesenchymal transition (MMT) were assessed. We demonstrated the effusion thrombin levels were significantly higher in TBPE than TPE, especially greater in TBPE patients with RPT > 10mm than those without, and correlated positively with PAI-1 and pleural fibrosis area. In carbon black/bleomycin-treated mice, knockdown of protease-activated receptor-1 (PAR-1) markedly downregulated α-smooth muscle actin (α-SMA) and fibronectin, and attenuated pleural fibrosis. In pleural mesothelial cells (PMCs), thrombin concentration-dependently increased PAI-1, α-SMA, and collagen I expression. Specifically, Mycobacterium tuberculosis H37Ra (MTBRa) induced thrombin production by PMCs via upregulating tissue factor and prothrombin, and PAR-1 silencing considerably abrogated MTBRa−stimulated PAI-1 expression and MMT. Consistently, prothrombin/PAR-1 expression was evident in the pleural mesothelium of TBPE patients. Conclusively, thrombin upregulates PAI-1 and MMT and may contribute to tuberculous pleural fibrosis. Thrombin/PAR-1 inhibition may confer potential therapy for pleural fibrosis. Full article

Background and Objectives: Plasminogen activator inhibitor-1 (PAI-1) is a fibrinolytic system enzyme whose role in various fibrinolytic processes is currently unknown. In clinical manifestations of pleural liquids of diverse etiology, various levels of fibrinolytic activity can be observed—parapneumonic processes tend to loculate in fibrin septa, while malignant pleural effusion (MPE) does not. The purpose of this study was to determine possible differences in PAI-1 levels in pleural effusions of varied etiology. Material and Methods: PAI-1 level in pleural effusion and serum was determined in 144 patients with pleural effusions of various etiology (cardiac hydrothorax—42 patients (29.2%), MPE—67 patients (46.5%), parapneumonic pleuritis—27 (18.8%), tuberculous pleuritis—6 patients (4.1%), pancreatogenic pleuritis—1 patient (0.7%) and pulmonary artery thromboembolism with pleuritis—1 patient (0.7%)). Results: The median PAI-1 level (ng/mL) was the highest in the parapneumonic pleuritis group both in the effusion and the serum, with values of 291 (213–499) ng/mL and 204 (151–412) ng/mL, respectively, resulting in a statistically significant difference (p < 0.001) from the cardiac hydrothorax and MPE groups. However, there was no statistically significant difference between PAI-1 levels in the pleural effusion and serum in the cardiac hydrothorax and MPE groups. Conclusion: The PAI-1 level in MPE and cardiac hydrothorax was statistically significantly lower than in parapneumonic pleuritis. Full article