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Xin Zhang *, Feng-Shuang Yi *, Huan-Zhong Shi Department of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, Beijing, 100020, People’s Republic of China*These authors contributed equally to this workCorrespondence: Huan-Zhong Shi; Feng-Shuang YiDepartment of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, 8 Gongti Nanlu, Chao-Yang District, Beijing, 100020, People’s Republic of ChinaTel/Fax +86 10 85231890Email shihuanzhong@ccmu.edu.cn; yifengshuang@ccmu.edu.cnBackground: Malignant pleural effusion (MPE) is a frequent complication of advanced malignancies that leads to a poor quality of life and limits treatment options.Objective: The objective of this study was to identify biomarkers of survival in patients with MPE, which will greatly facilitate the clinical management of this complication.Methods: This retrospective study recruited patients who had been pathologically diagnosed with MPE, regardless of the type of primary cancer, at Beijing Chao-Yang Hospital over 158 months. Demographic, clinical, hematological, and pleural fluid data were collected and analyzed as potential predictors of survival, and a new predictive model was developed based on Cox and logistic regression analyses.Results: In our alternative prognostic model (n = 281), four routinely detected variables, namely, carcinoembryonic antigen (CEA) level, monocyte count, N-terminal pro B-type natriuretic peptide (NT-pro-BNP) level, and pleural effusion chloride level on admission, were identified as predictors (the CONCH prognostic score). Patients were divided into three prognosis subgroups based on risk stratification, with median survival periods of 17, 11, and 5 months, respectively. In comparison with the low-risk group, patients in the medium- and high-risk groups showed significantly poorer survival (medium-risk group: hazard ratio [HR], 1.586; 95% confidence interval [CI], 1.047– 2.402; P = 0.029; high-risk group: HR, 4.389; 95% CI, 2.432– 7.921; P < 0.001).Conclusion: Four routinely detected variables were used to develop the CONCH scoring system, which was confirmed to be an accurate prognostic score for patients with MPE. This system can guide the selection of interventions and management for MPE.Keywords: malignant pleural effusion, prognosis, CEA, monocyte, NT-pro-BNP

Pleural effusion (PE) is prevalent in unselected "real-life" populations of multiple myeloma (MM). However, its prognostic value on MM is currently elusive. This study aimed to explore the role of PE on MM prognosis and to develop a novel prognostic nomogram for a cohort of Chinese patients with MM. Patients diagnosed with MM form 2000 through 2017 were retrospectively enrolled. PE was evaluated by chest computed tomography (CT) scans. Independent predictors of overall survival (OS) were identified using a multivariable Cox regression model performed on variables selected by the least absolute shrinkage and selection operator (LASSO) algorithm. A nomogram was constructed based on these variables. The concordance index (C-index) and the calibration curve were used to evaluate the predictive performance of the nomogram. Among 861 patients analyzed, 368 patients developed PE. Multivariate cox regression and restricted mean survival time (RMST) analyses revealed that patients with PE experienced worse OS vs. patients without PE. A nomogram predictive of OS was constructed using PE, plasma cell proportion, international staging system (ISS) stage, Charlson comorbidity index (CCI), 1q21 gain, and autologous hematopoietic stem cell transplantation (HSCT). The nomogram showed satisfactory discrimination in the derivation cohort (C-index=0.729) and the validation cohort (C-index=0.684), outperforming the Durie-Salmon (DS) and ISS staging systems. Moreover, the nomogram accurately classified patients into two distinct high- and low-risk groups. PE is frequently encountered in the disease course for MM patients. We derivated and validated a novel nomogram for MM based on PE, outperforming the DS/ISS staging systems.

Background and Objective:The accurate differential diagnosis of tuberculous pleural effusion (TPE) from other exudative pleural effusions is often challenging. We aimed to validate the accuracy of complement component C1q in pleural fluid (PF) in diagnosing TPE.Methods:The level of C1q protein in the PF from 49 patients with TPE and 61 patients with non-tuberculous pleural effusion (non-TPE) was quantified by enzyme-linked immunosorbent assay, and the diagnostic performance was assessed by receiver operating characteristic (ROC) curves based on the age and gender of the patients.Results:The statistics showed that C1q could accurately diagnose TPE. Regardless of age and gender, with a cutoff of 6,883.9 ng/mL, the area under the curve (AUC), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of C1q for discriminating TPE were 0.898 (95% confidence interval: 0.825–0.947), 91.8 (80.4–97.7), 80.3 (68.2–89.4), 78.9 (69.2–86.2), and 92.5 (82.6–96.9), respectively. In subgroup analysis, the greatest diagnostic accuracy was achieved in the younger group (≤ 50 years of age) with an AUC of 0.981 (95% confidence interval: 0.899–0.999) at the cutoff of 6,098.0 ng/mL. The sensitivity, specificity, PLR, NLR, PPV, and NPV of C1q were 95.0 (83.1–99.4), 92.3 (64.0–99.8), 97.4 (85.2–99.6), and 85.7 (60.6–95.9), respectively.Conclusion:Complement component C1q protein was validated by this study to be a promising biomarker for diagnosing TPE with high diagnostic accuracy, especially among younger patients.

Background Medical thoracoscopy (MT) is recommended in patients with undiagnosed exudative pleural effusion and offers a degree of diagnostic sensitivity for pleural malignancy. However, not all patients who undergo MT receive an exact diagnosis. Our previous investigation from 2014 summarized the long-term outcomes of these patients with nonspecific pleurisy (NSP); now, we offer updated data with the goal of refining our conclusions. Methods Between July 2005 and August 2018, MT with pleural biopsies were performed in a total of 1,254 patients with undiagnosed pleural effusions. One hundred fifty-four patients diagnosed with NSP with available follow-up data were included in the present study, and their medical records were reviewed. Results A total of 154 patients were included in this study with a mean follow-up duration of 61.5 ± 43.7 months (range: 1–180 months). No specific diagnosis was established in 67 (43.5%) of the patients. Nineteen patients (12.3%) were subsequently diagnosed with pleural malignancies. Sixty-eight patients (44.2%) were diagnosed with benign diseases. Findings of pleural nodules or plaques during MT and the recurrence of pleural effusion were associated with malignant disease. Conclusions Although most NSP patients received a diagnosis of a benign disease, malignant disease was still a possibility, especially in those patients with nodules or plaques as noted on the MT and a recurrence of pleural effusion. One year of clinical follow-up for NSP patients is likely sufficient. These updated results further confirm our previous study’s conclusions.

BACKGROUND: There is no standardized system to evaluate pleural effusion size on ultrasound (US). We aimed to explore the role of US in determining the amount of pleural effusion, with an attempt to provide evidence for clinical efficacy evaluation and treatment program selection. METHODS: A total of 98 patients undergoing thoracoscopy at our center were enrolled in this study. The patients take a sitting position, then the maximum depths of the pleural effusion by US at the subscapular line, posterior axillary line, midaxillary line, anterior axillary line, and midclavicular line, as well as the maximum thickness of the pleural effusion at the subscapular line, were measured before pleural effusion drainage. Then, the corresponding values in the lateral position were also measured. The relationships between the actual pleural effusion amounts and the measurements at these lines were analyzed using the multivariate linear regression model (MLRM). RESULTS: The regression equation of the group with a pleural effusion amount of 500–1,000 mL in the sitting position showed statistical significance (P=0.001). The P values of the maximum depths at the subscapular line (X(1)) and midclavicular line (X(5)) and the maximum thickness at the subscapular line (X(6)) were below 0.05. Thus, a final model was established using X(1), X(5), and X(6) as the independent variables. CONCLUSIONS: The combination of US examination and MLRM enables the quantitative determination of pleural effusion.

Yu Kang,1 Zi-Liang Hou,2 Guang-Zhong Yang,3 Xiao-Juan Wang,1 Wen-Ming Chen,3 Huan-Zhong Shi4 1Department of Internal Medicine, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, Beijing Luhe Hospital, Capital Medical University, Beijing, People’s Republic of China; 3Department of Hematology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People’s Republic of China; 4Department of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Huan-Zhong Shi; Wen-Ming Chen Email shihuanzhong@sina.com; 13910107759@163.comPurpose: Pleural effusion (PE) is prevalent in “real-life” populations of multiple myeloma (MM), a common hematologic malignancy. Development of PE likely has prognostic implications. The aim of this study was to investigate the characteristics and identify risk factors for occurrence of PE in MM.Patients and Methods: We reviewed electronic medical records of 907 patients diagnosed with MM.Results: Incidence of PE in MM patients was 42.7%. Small and bilateral PE in most cases. PE developed in all MM subtypes, the median time from diagnosis of multiple myeloma to pleural effusion was 6.8 months (range 0.8– 33.6 months). Patients with PE showed worse survival than those without PE (unadjusted hazard ratio with 95% confidence interval: 2.249 [1.774– 2.852]). No difference in survival was found between patients with small PE and those with moderate to large PE (unadjusted HR, 1.402; 95% CI, 1.037– 1.896). Plasma cell proportion (OR, 1.373; 95% CI, 1.153– 1.634; P = 0.009) and amyloidosis (OR, 1.791; 95% CI, 1.408– 2.279; P = 0.024) were risk factors for the occurrence of PE at the initial diagnosis of MM. Plasma cell proportion (OR, 1.853; 95% CI, 1.451– 2.368; P = 0.038), pneumonia (OR, 1.309; 95% CI, 1.143– 1.498; P = 0.008) and heart failure (OR, 1.815; 95% CI, 1.387– 2.374; P = 0.031) were risk factors for the occurrence of PE at relapse of MM.Conclusion: The incidence of PE in MM patients is notable and PE can occur in all MM subtypes. PE indicates a poor prognosis, even small amounts of effusion. PE is a problem worthy of attention, especially in patients with high plasma cell proportion, amyloidosis or complicated with pneumonia and heart failure.Keywords: pleural effusion, multiple myeloma, incidence, risk factors, overall survival

Background Accurately diagnosing pleural effusion is a frequent and significant problem in clinical practice. Combining pleural biomarkers with patients’ age may be a valuable method for diagnosing TPE. We sought to evaluate the influence of age on diagnostic values of pleural adenosine deaminase (ADA), interferon-gamma (IFN-γ), and interleukin 27 (IL-27) for tuberculous pleural effusion (TPE). Methods Two hundred seventy-four consecutive adult patients with pleural effusion were selected from Beijing and Wuhan between January 1, 2014 and June 30, 2015, and their pleural fluid concentrations of ADA, IFN-γ, and IL-27 were tested. Biomarker performance was analyzed by standard receiver operating characteristic (ROC) curves according to different ages. Results Data from the Beijing cohort showed that ADA, IFN-γ, and IL-27 could all accurately diagnose TPE in young patients (≤ 40 years of age). With a cutoff of 21.4 U/L, the area under the curve (AUC), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of ADA for diagnosing TPE were 1.000 (95% confidence interval: 0.884–1.000), 100.0, 100.0%, 100.0, and 100.0, respectively. In older patients (> 40 years of age), IL-27 and IFN-γ were excellent biomarkers for discriminating TPE versus non-TPE cases. With a cutoff of 591.4 ng/L, the AUC, sensitivity, specificity, PPV, and NPV of IL-27 for diagnosing TPE were 0.976 (95% confidence interval: 0.932–0.995), 96.3, 99.0%, 96.3, and 99.0, respectively. Similar diagnostic accuracy among the three pleural biomarkers was validated in the Wuhan cohort. Conclusions Among young patients, ADA is reliable for diagnosing TPE. Conversely, in older patients, IL-27 and IFN-γ are excellent biomarkers to differentiate TPE versus non-TPE cases.

Background The utility of tumor markers (TMs) for differentiating malignant pleural effusion (MPE) from benign pleural effusion (BPE) has been a subject of controversy. The majority of published studies are single center designed and lack validation. We performed a derivation and validation study in China to evaluate the diagnostic value of carcinoembryonic antigen (CEA) as well as carbohydrate antigen (CA) 15-3, CA 19-9 and CA 125 to differentiate between MPE and BPE. Methods Three hundred and twenty seven pleural effusion (PE) and paired serum samples were collected from consecutive patients with MPE or BPE in Beijing (174 patients, derivation) and Wuhan (153 patients, validation) during the same period. The concentrations of four TMs were tested using chemiluminescent microparticle immunoassay technology. The performance of the TMs was analyzed by standard receiver operating characteristic (ROC) curves. Results The levels of four TMs were significantly higher in MPE than in BPE and the corresponding serum. The concentrations of CEA and CA 15-3 were more stable than the concentrations of CA 125 and CA 19-9. CEA was the best single marker for discriminating MPE from BPE. With a specificity of 100% in the total population, the highest sensitivity (37.8%) using serum was found in CEA. In addition, CEA presented 19.8% sensitivity in PE and 18.0% sensitivity in the Δ(PE-serum). For CA 15-3, the sensitivity was 32.4% in PE, 15.3% in the PE/serum ratio and 25.2% in the Δ(PE-serum). Conclusions CEA and CA 15-3 rather than CA 125 and CA 19-9 are more reliable to differentiate between MPE and BPE. The use of the Δ(PE-serum) value in TMs, such as CEA and CA 15-3, may improve the sensitivity and specificity of the diagnosis etiology of PE.

BackgroundAccurate differentiating diagnosis is essential for choosing treatment for exudative pleural effusions.ObjectiveTo establish the diagnostic accuracy of interleukin 27 for tuberculous pleural effusion (TPE).MethodsFirst, the concentrations of pleural interleukin 27, interferon-gamma and adenosine deaminase were compared between 51 patients with TPE and 103 with non-TPEs (Beijing cohort), and their diagnostic values were evaluated. These were further verified in another independent population (Wuhan cohort, n=120). In the second part of the study, we performed a meta-analysis.ResultsWith a cut-off value of 591.4 ng/L in the Beijing cohort, the area under the curve, sensitivity, specificity, positive predictive value and negative predictive value of interleukin 27 to diagnose TPE were 0.983 (95% CI 0.947 to 0.997), 96.1% (86.5% to 99.5%), 99.0% (94.7% to 100%), 98.0 (89.4 to 99.9) and 98.1 (93.3 to 99.8), respectively. Excellent diagnostic accuracy of interleukin 27 was also found in the Wuhan cohort and was further confirmed in the meta-analysis. The diagnostic performance of interleukin 27 was comparable to that of interferon-gamma and was more accurate than that of adenosine deaminase. Since the post-test probability of a negative result was always ConclusionsInterleukin 27 can be used to diagnose TPE in a high prevalence setting, and a negative result can also be reliably used to rule out TPE in all prevalence settings.

BACKGROUND: Pleural effusions are common complications of various diseases. Patients with malignant pleural effusion (MPE) usually face poor prognosis and short life expectancy. Discriminating between MPE and benign pleural effusion remains to be difficult. The aim of our current study was to evaluate whether CD206(+)CD14(+) macrophages could be a diagnostic biomarker for MPE. METHODS: The percentages of CD14(+), CD86(+)CD14(+) and CD206(+)CD14(+) macrophages in pleural effusions were determined by flow cytometry in 34 patients with MPE and 26 with benign pleural effusion, and their diagnostic performances were evaluated by receiver operating characteristic (ROC) curves. RESULTS: The percentages of CD14(+), CD86(+)CD14(+) and CD206(+)CD14(+) macrophages were remarkably higher in MPE than in benign pleural effusion (all P

Purpose Although some parameters of positron emission tomography with 18F-fluorodeoxyglucose (18F-FDG) and computed tomography (PET-CT) are somehow helpful in differentiating malignant pleural effusion (MPE) from benign effusions, no individual parameter offers sufficient evidence for its implementation in the clinical practice. The aim of this study was to establish the diagnostic accuracy of a scoring system based on PET-CT (the PET-CT score) in diagnosing MPE. Methods One prospective derivation cohort of patients with pleural effusions (84 malignant and 115 benign) was used to develop the PET-CT score for the differential diagnosis of malignant pleural effusion. The PET-CT score was then validated in another independent prospective cohort (n = 74). Results The PET-CT parameters developed for discriminating MPE included unilateral lung nodules and/or masses with increased 18F-FDG uptake (3 points); extrapulmonary malignancies (3 points); pleural thickening with increased 18F-FDG uptake (2 points); multiple nodules or masses (uni- or bilateral lungs) with increased 18F-FDG uptake (1 point); and increased pleural effusion 18F-FDG uptake (1 point). With a cut-off value of 4 points in the derivation cohort, the area under the curve, sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio of the PET-CT score to diagnose MPE were 0.949 (95% CI: 0.908–0.975), 83.3% (73.6%–90.6%), 92.2% (85.7%–96.4%), 10.7 (5.6–20.1), and 0.2 (0.1–0.3), respectively. Conclusions A simple-to-use PET-CT score that uses PET-CT parameters was developed and validated. The PET-CT score can help physicians to differentiate MPE from benign pleural effusions. Electronic supplementary material The online version of this article (10.1007/s00259-019-04287-7) contains supplementary material, which is available to authorized users.

Although it is curable, tuberculosis remains one of the most frequent causes of pleural effusions on a global scale, especially in developing countries. Tuberculous pleural effusion (TPE) is one of the most common forms of extrapulmonary tuberculosis. TPE usually presents as an acute illness with fever, cough and pleuritic chest pain. The pleural fluid is an exudate that usually has predominantly lymphocytes. The gold standard for the diagnosis of TPE 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, Although adenosine deaminase and interferon-γ in pleural fluid have been documented to be useful tests for the diagnosis of TPE. It can be accepted that in areas with high tuberculosis prevalence, the easiest way to establish the diagnosis of TPE in a patient with a lymphocytic pleural effusion is to generally demonstrate a adenosine deaminase level above 40 U/L. The recommended treatment for TPE is a regimen with isoniazid, rifampin, and pyrazinamide for two months followed by four months of two drugs, isoniazid and rifampin.

Background: It is often challenging to distinguish tuberculous pleural effusion (TPE) from malignant pleural effusion (MPE); thoracoscopy is among the techniques with the highest diagnostic ability in this regard. However, such invasive examinations cannot be performed on the elderly, or on those in poor physical condition. The aim of this study was to explore the differential diagnostic value of carbohydrate antigen 125 (CA125), carbohydrate antigen 199 (CA199), carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), and squamous cell carcinoma (SCC) associated antigen in patients with TPE and MPE. Methods: Using electrochemiluminescence, we measured the concentration of tumor markers (TMs) in the pleural effusion and serum of patients with TPE ( n = 35) and MPE ( n = 95). We used receiver operating characteristic (ROC) curve analysis to evaluate the TMs and differentiate between TPE and MPE. Results: The cut-off values for each TM in serum were: CA125, 151.55 U/ml; CA199, 9.88 U/ml; CEA, 3.50 ng/ml; NSE, 13.27 ng/ml; and SCC, 0.85 ng/ml. Those in pleural fluid were: CA125, 644.30 U/ml; CA199, 12.08 U/ml; CEA, 3.35 ng/ml; NSE, 9.71 ng/ml; and SCC, 1.35 ng/ml. The cut-off values for the ratio of pleural fluid concentration to serum concentration (P/S ratio) of each TM were: CA125, 5.93; CA199, 0.80; CEA, 1.47; NSE, 0.76; and SCC, 0.90. The P/S ratio showed the highest specificity in the case of CEA (97.14%). ROC curve analysis revealed that, for all TMs, the area under the curve in pleural fluid (0.95) was significantly different from that in serum (0.85; P Conclusions: TMs in TPE differ significantly from those in MPE, especially when detected in pleural fluid. The combined detection of TMs can improve diagnostic sensitivity.

Background Pleural effusion (PE) drainage can relieve the symptoms of dyspnea; however, details of the resulting hemodynamic changes remain undefined. Methods Subjects older than 12 years with massive PE requiring pleural drainage were included in this study. Hemodynamic parameters were collected using transthoracic echocardiography at pre-drainage, immediately post-drainage, and 24 h after drainage. Results We enrolled 47subjects in this prospective study from June 9, 2015 to September 18, 2016 in Beijing Chaoyang Hospital and 28 subjects were analyzed finally. Draining large-volume PE led to a progressive increase in left ventricular end-diastolic volume index, left atrial volume index, right ventricular area, right atrial area, left ventricular ejection fraction, stroke volume, and tricuspid annular plane systolic excursion, both immediately (P

Background: No data on the incidence of pleural effusion (PE) in Chinese patients with pulmonary embolism are available to date. The aim of the current study was to investigate the frequency of PE in a Chinese population of patients with pulmonary embolism. Methods: This was a retrospective observational single-center study. All data of computed tomography pulmonary angiography (CTPA) performed over 6-year period on adult patients with clinically suspected pulmonary embolism were analyzed. Results: From January 2008 until December 2013, PE was identified in 423 of 3141 patients (13.5%) with clinically suspected pulmonary embolism who underwent CTPA. The incidence of PE in patients with pulmonary embolism (19.9%) was significantly higher than in those without embolism (9.4%) (P < 0.001). Majority of PEs in pulmonary embolism patients were small to moderate and were unilateral. The locations of emboli and the numbers of arteries involved, CT pulmonary obstruction index, and parenchymal abnormalities at CT were not associated with the development of PE. Conclusions: PEs are present in about one fifth of a Chinese population of patients with pulmonary embolism, which are usually small, unilateral, and unsuitable for diagnostic thoracentesis.

Background: The differential diagnosis of pleural effusions can present a considerable challenge, and the etiology of pleural effusions varies depending on the population studied. Objective: This study aimed to assess the efficacy and safety of medical thoracoscopy in the diagnosis of patients with undiagnosed pleural effusions in a Chinese population. Methods: Between July 2005 and June 2014, medical thoracoscopy (MT) using the semirigid instrument was performed in 833 patients with pleural effusions of unknown etiology in our Institute, where diagnostic thoracocentesis or/and blind pleural biopsy had failed to yield an answer. Demographic, radiographic, procedural, and histological data were recorded and analyzed. Results: During this 9-year study, satisfactory pleural biopsy samples were obtained in 833 patients, and MT revealed malignant pleural effusion in 342 (41.1%) patients, benign pleural effusion in 429 (51.5%) patients, and 62 (7.4%) patients could not get definite diagnoses. The overall diagnostic efficiency of MT was 92.6% (771/833). After MT, the only severe complication was empyema, seen in 3 patients (0.4%). The most common minor complication was transient chest pain (44.1%) from the indwelling chest tube. Conclusions: MT is an effective and safe procedure for diagnosing pleural effusions of undetermined causes. In areas with high tuberculosis prevalence, MT should be particularly helpful in the differential diagnosis of tuberculous pleural effusion.

IFN-γ-producing CD4(+) T (Th1) cells and IL-17-producing CD4(+) T (Th17) cells have been found to be involved in multiple malignancies; however, the reciprocal relationship between Th1 and Th17 cells in malignant pleural effusion (MPE) remains to be elucidated.To explore the differentiation and immune regulation of Th1 and Th17 cells in the development of MPE in murine models.The distribution and differentiation of Th1 and Th17 cells in MPE were investigated in IFN-γ(-/-), IL-17(-/-), and wild-type mice. The effects of Th1 and Th17 cells on the development of MPE and the survival of mice bearing MPE were also investigated.We have demonstrated that increased Th1 and Th17 cells could be found in MPE as compared with blood and spleen. Compared with wild-type mice, Th17 cells were markedly augmented in MPE from IFN-γ(-/-) mice, and improved survival could be seen in IFN-γ(-/-) mice. Th1 cell numbers were elevated in MPE from IL-17(-/-) mice, and decreased survival could be seen in IL-17(-/-) mice. The in vitro experiments showed that IFN-γ deficiency promoted Th17-cell differentiation by suppressing the STAT3 pathway and that IL-17 deficiency promoted Th1-cell differentiation by suppressing the STAT1 pathway.In mouse models of MPE, IFN-γ inhibited Th17-cell differentiation, whereas IL-17 inhibited Th1-cell differentiation. IL-17 inhibited the formation of MPE and improved the survival of mice bearing MPE; in contrast, IFN-γ promoted MPE formation and mouse death.

Our previous data have demonstrated that the number of IL-9-producing CD4+ T cells (Th9 cells) in malignant pleural effusion (MPE) was significantly increased when compared with that in blood. The aim of the present study was to investigate the mechanism by which Th9 cells were recruited into MPE and the phenotypic characteristics of pleural Th9 cells. The expression patterns of chemokine receptors (CCRs) on Th9 cells and the chemoattractant activity of chemokine CCL20 for Th9 cells in vitro were observed. The phenotypic features of Th9 cells in MPE were determined by flow cytometry. We found that Th9 cells in both MPE and blood expressed a high level of CCR6 on their surface. An in vitro migration assay confirmed that both MPE and supernatants of cultured pleural mesothelial cells could induce the migration of Th9 cells, and anti-CCL20 mAb significantly inhibited the ability of MPE or supernatants to stimulate Th9 cell chemotaxis. We also noted that pleural Th9 cells expressed high levels of CD45RO and very low levels of CD45RA and CD62L, displaying the phenotype of effector memory cells. Our data revealed that recruitment of Th9 cells into MPE could be induced by pleural CCL20 and that the majority of Th9 cells in MPE displayed the phenotype of effector memory cells.

Background Medical thoracoscopy is an effective and safe procedure for diagnosing pleural effusions of undetermined causes. But there are still a part of patients with pleural effusions were diagnosed as nonspecific pleurisy when no specific biopsy results were found after undergoing thoracoscopic biopsy. The long-term outcome of these patients is unclear, and anxieties about undiagnosed malignancy persist. Methods Between July 2005 and June 2014, medical thoracoscopy using the semi-rigid instrument was performed and pleural biopsy was taken in 833 patients with pleural effusions. Fifty-two patients diagnosed with nonspecific pleurisy with available follow-up data were included in the present study and their medical records were reviewed. Results Fifty-two patients (31 men and 21 women) were included. Mean follow up was 35.5 ± 40.9 months (range, 1–143 months). No specific diagnosis was established in 21 (40.4%) of the patients. Eight of 52 patients with nonspecific pleurisy (15.4%) were subsequently diagnosed with pleural malignancies. 23 of 52 patients (44.2%) were diagnosed as benign diseases. The recurrence of pleural effusion during followed-up and pleural nodules or plaques found in medical thoracoscopy was associated with malignant disease. Conclusion Patients with nonspecific pleurisy after medical thoracoscopy should be closely monitored, especially in those patients with the recurrence of pleural effusion during followed-up, pleural nodules or plaques found in medical thoracoscopy. One year of clinical follow-up for patients found to have nonspecific pleurisy is likely sufficient.

The numbers of IL-27+ CD4+ and IL-27+ CD8+ T cells have been found to be increased in tuberculous pleural effusion (TPE) as compared with malignant pleural effusion (MPE). The objective of the present study was to investigate whether pleural IL-27+ CD4+ and IL-27+ CD8+ T cells can distinguish patients with TPE from those with MPE. Paired specimen of pleural fluid and peripheral blood were collected from 35 patients with TPE and 46 MPE. The numbers of IL-27+ CD4+ and IL-27+ CD8+ T cells were simultaneously determined by flow cytometry. Receiver operating characteristic curve analysis was used to evaluate the capacity of IL-27+ CD4+ and IL-27+ CD8+ T cells to differentiate TPE from MPE. The sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), positive predictive value (PPV) and negative predictive value (NPV) of IL-27+ CD4+ T cells were 94.3%, 93.5%, 14.46, 0.06, 91.7% and 95.6%, respectively. The sensitivity, specificity, PLR, NLR, PPV and NPV of IL-27+ CD8+ T cells were 80.0%, 93.5%, 12.27, 0.21, 90.3% and 86.0%, respectively. The number of IL-27+ CD4+ in pleural fluid is a helpful diagnostic biomarker for the diagnosis of TPE, which performs better than that of IL-27+ CD8+ T cells.

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.

Both T helper interleukin 17 (IL-17)-producing cells (Th17 cells) and regulatory T cells (Tregs) have been found to be increased in human tuberculous pleural effusion (TPE); however, the possible interaction between Th17 cells and Tregs in TPE remains to be elucidated. The objective of the present study was to investigate the distribution of Th17 cells in relation to Tregs, as well as the mechanism of Tregs in regulating generation and differentiation of Th17 cells in TPE. In the present study, the numbers of Th17 cells and Tregs in TPE and blood were determined by flow cytometry. The regulation and mechanism of CD39+Tregs on generation and differentiation of Th17 cells were explored. Our data demonstrated that the numbers of Th17 cells and CD39+Tregs were both increased in TPE compared with blood. Th17 cell numbers were correlated negatively with Tregs in TPE but not in blood. When naïve CD4+T cells were cultured with CD39+Tregs, Th17 cell numbers decreased as CD39+Treg numbers increased, and the addition of the anti-latency-associated peptide monoclonal antibody to the coculture reversed the inhibitory effect exerted by CD39+Tregs. This study shows that Th17/Treg imbalance exists in TPE and that pleural CD39+Tregs inhibit generation and differentiation of Th17 cells via a latency-associated peptide-dependent mechanism.

Pleural effusion caused by sarcoidosis is unusual. Medical thoracoscopy could help clinicians detect associated pleural disease, yet studies on thoracoscopic observations in sarcoidosis pleural involvement are rare. In this article, we report the utility of medical thoracoscopy in diagnosing sarcoid-related pleural disease for three patients. Pleural nodularity was common with solitary and multiple nodules evident; biopsies confirmed the presence of diagnostic noncaseating granulomas.

Background N-terminal pro-brain natriuretic peptide (NT-proBNP) is a biomarker useful in diagnosis of pleural effusion due to heart failure. Thus far, its overall diagnostic accuracy has not been systematically reviewed. The aim of the present meta-analysis was to establish the overall diagnostic accuracy of the measurement of pleural NT-proBNP for identifying pleural effusion due to heart failure. Methods After a systematic review of English-language studies, sensitivity, specificity, and other measures of accuracy of NT-proBNP concentrations in pleural fluid in the diagnosis of pleural effusion resulting from heart failure were pooled using fixed-effects models. Summary receiver operating characteristic curves were used to summarise overall test performance. Results Eight publications met the inclusion criteria. The summary estimates for pleural NT-proBNP in the diagnosis of pleural effusion attributable to heart failure were: sensitivity 0.95 (95% CI 0.92 to 0.97), specificity 0.94 (0.92 to 0.96), positive likelihood ratio 14.12 (10.23 to 19.51), negative likelihood ratio 0.06 (0.04 to 0.09) and diagnostic OR 213.87 (122.50 to 373.40). Conclusions NT-proBNP levels in pleural fluid showed a high diagnostic accuracy and may help accurately differentiate cardiac from non-cardiac conditions in patients presenting with pleural effusion.

BACKGROUND Triggering receptors expressed on myeloid cells (TREM) proteins are a family of cell surface receptors expressed broadly by cells of the myeloid lineage. The aim of this study was to investigate the clinical significance of soluble TREM-1 (sTREM-1) in pleural effusions, and to determine the effects of pneumonia on pleural sTREM-1 concentrations. METHODS Pleural fluid was collected from 109 patients who presented to the respiratory institute (35 with malignant pleural effusion, 31 with tuberculous pleural effusion, 21 with bacterial pleural effusion, and 22 with transudate). The concentrations of sTREM-1, tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) were determined in effusion and serum samples by enzyme linked immunosorbent assay (ELISA). RESULTS The concentrations of sTREM-1 in bacterial pleural effusion were significantly higher than those in malignant, tuberculous, and transudative groups (all P < 0.001). An sTREM-1 cutoff value of 768.1 ng/L had a sensitivity of 86% and a specificity of 93%. Pleural sTREM-1 levels were positively correlated with levels of TNF-alpha and IL-1beta. Patients with complicating bacterial pneumonia did not have elevated concentration of sTREM-1 in pleural effusion when compared with patients without pneumonia. CONCLUSIONS Determination of pleural sTREM-1 may improve the ability of clinicians to differentiate pleural effusion patients of bacterial origin from those with other etiologies. The occurrence of bacterial pneumonia did not affect pleural sTREM-1 concentrations.

Background Conventional tests are not always helpful in making a diagnosis of tuberculous pleurisy. Many studies have investigated the usefulness of interferon (IFN)-γ measurements in pleural fluid for the early diagnosis of tuberculous pleurisy. We conducted a metaanalysis to determine the accuracy of IFN-γ measurements in the diagnosis of tuberculous pleurisy. Methods After a systematic review of English-language studies, sensitivity, specificity, and other measures of accuracy of IFN-γ concentrations in the diagnosis of pleural effusion were pooled using random-effects models. Summary receiver operating characteristic curves were used to summarize overall test performance. Results Twenty-two studies met our inclusion criteria. The summary estimates for IFN-γ in the diagnosis of tuberculous pleurisy in the studies included were as follows: sensitivity, 0.89 (95% confidence interval [CI], 0.87 to 0.91); specificity, 0.97 (95% CI, 0.96 to 0.98); positive likelihood ratio, 23.45 (95% CI, 17.31 to 31.78); negative likelihood ratio, 0.11 (95% CI, 0.07 to 0.16); and diagnostic odds ratio, 272.7 (95% CI, 147.5 to 504.2). Conclusions IFN-γ determination is a sensitive and specific test for the diagnosis of tuberculous pleurisy. The measurement of IFN-γ levels in pleural effusions is thus likely to be a useful tool for diagnosing tuberculous pleurisy. The results of IFN-γ assays should be interpreted in parallel with clinical findings and the results of conventional tests.

Background Differentiating tuberculous pleural effusion from other lymphocytic pleural effusions is often challenging. This retrospective study aimed to assess the efficacy and safety of medical thoracoscopy in patients with suspected tuberculous pleural effusion. Methods Between July 2005 and June 2014, patients with pleural effusions of unknown etiologies underwent medical thoracoscopy in our institute after less invasive means of diagnosis had failed. Demographic, radiographic, procedural, and histological data of patients with tuberculous pleural effusion were analyzed. Results During this 9-year study, 333 of 833 patients with pleural effusion were confirmed to have tuberculous pleurisy. Under thoracoscopy, we observed pleural nodules in 69.4%, pleural adhesion in 66.7%, hyperemia in 60.7%, plaque-like lesions in 6.0%, ulceration in 1.5% of patients with tuberculous pleurisy. Pleural biopsy revealed the presence of Mycobacterium tuberculosis in the pleural tissue or/and demonstration of caseating granulomas in 330 (99.1%) patients. No serious adverse events were recorded, and the most common minor complication was transient chest pain (43.2%) from the indwelling chest tube. Conclusions Our data showed that medical thoracoscopy is a simple procedure with high diagnostic yield and excellent safety for the diagnosis of tuberculous pleural effusion.

Programmed death 1 (PD-1), PD-ligand 1 (PD-L1), and PD-L2 have been demonstrated to be involved in tuberculosis immunity, however, the expression and regulation of PD-1/PD-Ls pathways in pleural mesothelial cells (PMCs) and CD4(+) T cells in tuberculous pleural effusion (TPE) have not been investigated. Expression of PD-1 on CD4(+) T cells and expressions of PD-L1 and PD-L2 on PMCs in TPE were determined. The impacts of PD-1/PD-Ls pathways on proliferation, apoptosis, adhesion, and migration of CD4(+) T cells were explored. Concentrations of soluble PD-l, but not of soluble PD-Ls, were much higher in TPE than in serum. Expressions of PD-1 on CD4(+) T cells in TPE were significantly higher than those in blood. Expressions of PD-Ls were much higher on PMCs from TPE when compared with those from transudative effusion. Interferon-γ not only upregulated the expression of PD-1 on CD4(+) T cells, but also upregulated the expressions of PD-Ls on PMCs. Blockage PD-1/PD-Ls pathways abolished the inhibitory effects on proliferation and adhesion activity of CD4(+) T cells induced by PMCs. PD-1/PD-Ls pathways on PMCs inhibited proliferation and adhesion activity of CD4(+) T cells, suggesting that Mycobacterium tuberculosis might exploit PD-1/PD-Ls pathways to evade host cell immune response in human.

The objective of the present study was to investigate the presence of interleukin (IL)-27 in pleural effusions and to evaluate the diagnostic significance of pleural IL-27. The concentrations of IL-27 were determined in pleural fluids and sera from 68 patients with tuberculous pleural effusion, 63 malignant pleural effusion, 22 infectious pleural effusion, and 21 transudative pleural effusion. Flow cytometry was used to identify which pleural cell types expressed IL-27. It was found that the concentrations of pleural IL-27 in tuberculous group were significantly higher than those in malignant, infectious, and transudative groups, respectively. Pleural CD4(+) T cells, CD8(+) T cells, NK cells, NKT cells, B cells, monocytes, macrophages, and mesothelial cells might be the cell sources for IL-27. IL-27 levels could be used for diagnostic purpose for tuberculous pleural effusion, with the cut off value of 1,007 ng/L, IL-27 had a sensitivity of 92.7% and specificity of 99.1% for differential diagnosing tuberculous pleural effusion from non-tuberculous pleural effusions. Therefore, compared to non-tuberculous pleural effusions, IL-27 appeared to be increased in tuberculous pleural effusion. IL-27 in pleural fluid is a sensitive and specific biomarker for the differential diagnosing tuberculous pleural effusion from pleural effusions with the other causes.

Newly discovered IL-9-producing CD4(+) helper T cells (Th9 cells) have been reported to contribute to tissue inflammation and immune responses, however, differentiation and immune regulation of Th9 cells in tuberculosis remain unknown. In the present study, our data showed that increased Th9 cells with the phenotype of effector memory cells were found to be in tuberculous pleural effusion as compared with blood. TGF-β was essential for Th9 cell differentiation from naïve CD4(+) T cells stimulated with PMA and ionomycin in vitro for 5 h, and addition of IL-1β, IL-4 or IL-6 further augmented Th9 cell differentiation. Tuberculous pleural effusion and supernatants of cultured pleural mesothelial cells were chemotactic for Th9 cells, and this activity was partly blocked by anti-CCL20 antibody. IL-9 promoted the pleural mesothelial cell repairing and inhibited IFN-γ-induced pleural mesothelial cell apoptosis. Moreover, pleural mesothelial cells promoted Th9 cell differentiation by presenting antigen. Collectively, these data provide new information concerning Th9 cells, in particular the collaborative immune regulation between Th9 cells and pleural mesothelial cells in human M. tuberculosis infection. In particular, pleural mesothelial cells were able to function as antigen-presenting cells to stimulate Th9 cell differentiation.

The diagnosis of tuberculous pleurisy by analysis of pleural fluid using standard diagnostic tools is difficult. Recently, T-cell interferon-γ release assays (IGRA) have been introduced for the diagnosis of tuberculous pleurisy. The aim of the present meta-analysis was to establish the overall diagnostic accuracy of IGRA on both pleural fluid and peripheral blood, for diagnosing tuberculous pleurisy.A systematic review was performed of English language publications. Sensitivity, specificity and other measures of the accuracy of IGRA for the diagnosis tuberculous pleurisy using both pleural fluid and blood were pooled using a random-effects model or a fixed-effects model. Receiver operating characteristic curves were used to summarize overall test performance.Seven out of eight studies met the inclusion criteria. The summary estimates of sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, positive predictive value, negative predictive value and diagnostic odds ratio were, for pleural fluid: 0.75, 0.82, 3.49, 0.24, 0.85, 0.70 and 19.04, respectively; and for blood: 0.80, 0.72, 2.86, 0.28, 0.78, 0.74 and 11.06, respectively.As almost 20% of non-tuberculosis patients would be erroneously treated for tuberculosis and 25% of patients with tuberculous pleurisy would be missed, pleural fluid IGRA are not useful for the clinical diagnosis of tuberculous pleurisy.

Background and objective CD4(+)CD25(high) regulatory T cells are increased in tuberculous pleural effusions (TPE). However, the mechanism by which CD4(+)CD25(high) T cells infiltrate into the pleural cavity is unknown. The aim of this study was to investigate whether the chemokines CCL22 and CCL17 are present in TPE, and the chemoattractant activity of these chemokines for infiltration of CD4(+)CD25(high) T cells into the pleural space. Methods The concentrations of CCL22 and CCL17 were measured in pleural effusions from 33 patients with tuberculous pleurisy, 21 patients with pleural bacterial infections and 18 patients with transudative pleural effusions. T lymphocyte subsets in pleural effusions were assessed by flow cytometry. Pleural effusion cells were analysed for the expression of CCL22. The chemoattractant activity of CCL22 for CD4(+)CD25(high) T cells was assessed in vitro. Results The frequency of CD4(+)CD25(high) T cells was significantly higher in TPE than in blood. High concentrations of CCL22 were detected in tuberculous effusions, but not in bacterial effusions or transudates. Macrophages and T cells in TPE expressed CCL22. Tuberculous pleural fluid was chemotactic for CD4(+)CD25(high) T cells in vitro, and anti-CCL22 antibody partly inhibited this chemotactic activity. Conclusions CCL22 appeared to be increased in TPE compared with bacterial pleural effusions or transudates. CCL22 may be responsible for the infiltration of CD4(+)CD25(high) T cells into the pleural space of patients with tuberculous pleurisy.

Purpose: The aim of this study was to explore the presence of the chemokines CCL22 and CCL17 in malignant pleural effusion, and the chemoattractant activity of these chemokines on CD4-positive CD25-positive Foxp3-positive regulatory T cells infiltrating into the pleural space.Experimental Design: The concentrations of CCL22 and CCL17 in both pleural effusions and sera from 33 patients with lung cancer were determined. Flow cytometry was done to determine T lymphocyte subsets in cell pellets of pleural effusion. Pleural cells were analyzed for the expression of CCL22 and CCL17. The chemoattractant activity of CCL22 for regulatory T cells in vitro and in vivo was also observed.Results: The concentration of CCL22 in malignant pleural effusion was significantly higher than that in the corresponding serum. Pleural fluid from lung cancer patients was chemotactic for regulatory T cells, and this activity was partly blocked by an anti-CCL22, but not by an anti-CCL17 antibody. Intrapleural administration of CCL22 of patients produced a marked progressive influx of regulatory T cells into pleural space.Conclusions: Compared with serum, CCL22 seemed to be increased in malignant pleural effusion, and could directly induce regulatory T cell infiltration into the pleural space in patients with malignant effusion.

The aim of this study was to investigate the presence of epithelial neutrophil-activating peptide (ENA)-78 in pleural effusions, as well as the chemoattractant activity of pleural ENA-78 on neutrophils. Pleural effusion and serum samples were collected from 75 patients who presented to the respiratory institute (19 with malignant pleural effusion, 21 with tuberculous pleural effusion, 18 with infectious pleural effusion and 17 with transudative pleural effusion). The concentrations of ENA-78, myeloperoxidase and neutrophil elastase were determined, and the chemoattractant activity of ENA-78 for neutrophils both in vitro and in vivo was also observed. The concentrations of ENA-78, myeloperoxidase and neutrophil elastase in infectious pleural effusion were significantly higher than those in malignant, tuberculous and transudative groups, respectively (all p0.01). Infectious pleural fluid was chemotactic for neutrophils in vitro and anti-ENA-78 antibody could partly inhibit these chemotactic effects. Intrapleural administration of ENA-78 produced a marked progressive influx of neutrophils into pleural space. Compared with noninfectious pleural effusion, ENA-78 appeared to be increased in infectious pleural effusion. Our data suggested that ENA-78 was able to induce neutrophil infiltration into pleural space and might be responsible for pleural neutrophil degranulation.

Background Active suppression by CD4 + CD25 + regulatory T lymphocytes plays an important role in the down-regulation of T cell responses to foreign and self-antigens. This study was conducted to analyze whether the CD4 + CD25 + regulatory T cells exist and function normally in tuberculous pleural effusion. Methods The percentages of CD4 + CD25 + T cells in pleural effusion and peripheral blood from patients with tuberculous pleurisy and peripheral blood from healthy control subjects were determined by flow cytometry. The expression of forkhead transcription factor Foxp3 was also examined. CD4 + CD25 + and CD4 + CD25 - T cells from pleural effusion and blood were isolated, and were cultured to observe the effects of CD4 + CD25 + T cells on proliferation response of CD4 + CD25 - T cells in vitro. Results There were increased numbers of CD4 + CD25 + T cells in tuberculous pleural effusion compared with peripheral blood from both patients with tuberculous pleurisy and normal subjects, and these cells demonstrated a constitutive high-level expression of Foxp3. Moreover, CD4 + CD25 + T cells mediated potent inhibition of proliferation response of CD4 + CD25 - T cells. Conclusion The increased CD4 + CD25 + T cells in tuberculous pleural effusion express a high level of Foxp3 transcription factor, while potently suppressing the proliferation of CD4 + CD25 - T cells.

Background and objective: Conventional tests are not always helpful in making a diagnosis of malignant pleural effusion (MPE). Many studies have investigated the utility of pleural carcinoembryonic antigen (CEA) in the early diagnosis of MPE. The present meta-analysis determined the accuracy of CEA measurement in the diagnosis of MPE. Methods: A systematic review of English language studies was conducted and data on the accuracy of pleural CEA concentrations in the diagnosis of MPE were pooled using random effects models. Receiver operating characteristic curves were used to summarize the overall test performance. Results: Forty-five studies met the inclusion criteria for the meta-analysis. The summary estimates for CEA in the diagnosis of MPE were: sensitivity 0.54 (95% CI: 0.52–0.55), specificity 0.94 (95% CI: 0.93–0.95), positive likelihood ratio 9.52 (95% CI: 6.97–13.01), negative likelihood ratio 0.49 (95% CI: 0.44–0.54) and diagnostic odds ratio 22.5 (95% CI: 15.6–32.5). Analysis of a subset of 11 studies which examined the value of pleural CEA in ruling out a diagnosis of malignant mesothelioma found that the sensitivity and specificity of a CEA level exceeding cut-off values were 0.97 (95% CI: 0.93–0.99) and 0.60 (95% CI: 0.55–0.65), respectively. Conclusions: Measurement of pleural CEA is likely to be a useful diagnostic tool for confirming MPE, and is also helpful in the differential diagnosis between malignant pleural mesothelioma and metastatic lung cancer. The results of CEA assays should be interpreted in parallel with clinical findings and the results of conventional tests.

Conventional tests are not always helpful in making a diagnosis of tuberculous pleurisy. Many studies have investigated the usefulness of interferon (IFN)-gamma measurements in pleural fluid for the early diagnosis of tuberculous pleurisy. We conducted a metaanalysis to determine the accuracy of IFN-gamma measurements in the diagnosis of tuberculous pleurisy.After a systematic review of English-language studies, sensitivity, specificity, and other measures of accuracy of IFN-gamma concentrations in the diagnosis of pleural effusion were pooled using random-effects models. Summary receiver operating characteristic curves were used to summarize overall test performance.Twenty-two studies met our inclusion criteria. The summary estimates for IFN-gamma in the diagnosis of tuberculous pleurisy in the studies included were as follows: sensitivity, 0.89 (95% confidence interval [CI], 0.87 to 0.91); specificity, 0.97 (95% CI, 0.96 to 0.98); positive likelihood ratio, 23.45 (95% CI, 17.31 to 31.78); negative likelihood ratio, 0.11 (95% CI, 0.07 to 0.16); and diagnostic odds ratio, 272.7 (95% CI, 147.5 to 504.2).IFN-gamma determination is a sensitive and specific test for the diagnosis of tuberculous pleurisy. The measurement of IFN-gamma levels in pleural effusions is thus likely to be a useful tool for diagnosing tuberculous pleurisy. The results of IFN-gamma assays should be interpreted in parallel with clinical findings and the results of conventional tests.

Interleukin-16 (IL-16) is a chemoattractant of CD4+ lymphocytes, and it has been implicated in the pathogenesis of various inflammatory diseases. The aim of the present study was to measure IL-16 in pleural effusions caused by tuberculosis and malignancy and its relationship with cell and differential counts as well as lymphocyte subsets.Pleural effusion and venous blood samples were collected from 32 patients with tuberculous pleuritis and 30 lung cancer patients with malignant effusion. Analysis of pleural effusion for total leukocytes and cell differentials of leukocytes was performed. Three-color flow cytometry was performed to determine T lymphocyte subsets in cell pellets of pleural effusion. The concentration of IL-16 in cell-free supernatants of pleural effusion and sera was measured by a sandwich enzyme-linked immunosorbent assay.In all the studied patients, the level of IL-16 was significantly higher in pleural effusion than in serum. The levels of IL-16 were significantly higher in tuberculous than in malignant effusions. In pleural effusion, positive correlations were found between the IL-16 levels and total cell counts, lymphocytes, CD3+ T cells, as well as CD4+ T cells.Compared to malignant pleural effusion, IL-16 appeared to be increased in tuberculous pleural effusion. The pleural effusion IL-16 levels were positively related to the numbers of CD4+ T cells, suggesting that IL-16 might be capable of inducing CD4+ T cell infiltration into pleural space.

Active suppression by CD4(+)CD25(+) regulatory T lymphocytes plays an important role in the downregulation of T-cell responses to foreign and self-antigens.To analyze whether the CD4(+)CD25(+) regulatory T lymphocytes exist and function normally in malignant pleural effusion.The percentages of CD4(+)CD25(+) T lymphocytes in pleural effusion and peripheral blood from patients with lung cancer with malignant effusion, pleural lavage and peripheral blood from patients with lung cancer without effusion, and peripheral blood from healthy control subjects were determined by flow cytometry. The expressions of forkhead transcription factor Foxp3 and cytotoxic lymphocyte-associated antigen-4 were also examined. CD4(+)CD25(+) and CD4(+)CD25(-) T cells from pleural effusion and peripheral blood were isolated, and were cultured to observe the effects of CD4(+)CD25(+) cells on proliferation response of CD4(+)CD25(-) T cells in vitro.There were increased numbers of CD4(+)CD25(+) T cells in malignant pleural effusion from patients with lung cancer compared with pleural lavage from patients with lung cancer without pleural effusion, and that these cells have constitutive high-level expression of Foxp3 and cytotoxic lymphocyte-associated antigen-4. Furthermore, CD4(+)CD25(+) T cells mediate potent inhibition of proliferation response of CD4(+)CD25(-) T cells, and anticytotoxic lymphocyte-associated antigen-4 monoclonal antibody could reduce the inhibitory activity of CD4(+)CD25(+) T cells.The increased CD4(+)CD25(+) T cells found in malignant pleural effusion express high levels of Foxp3 transcription factor and potently suppress the proliferation of CD4(+)CD25(-) T cells, and cytotoxic lymphocyte-associated antigen-4 is involved in the suppressive activity of pleural CD4(+)CD25(+) T cells.

BACKGROUND: Talc pleurodesis has been widely used to control malignant pleural effusion; however, it is still not clear whether talc pleurodesis is more effective than other local therapies. We performed a meta-analysis to evaluate the efficacy and safety of talc pleurodesis in the management of malignant pleural effusion. METHODS: PubMed, Embase, and Web of Science were searched for English-language studies of clinical controlled trials comparing talc pleurodesis with control therapies until August 8, 2013. Success rate and incidence of adverse events were evaluated. Relative risks were estimated using random- or fixed- effects model and statistical heterogeneity was assessed using I² test. RESULTS: Twenty trials involving 1,525 patients with malignant pleural effusion were included. The success rate of talc pleurodesis was significantly higher than that of control therapies (relative risk, 1.21; 95% confidence interval, 1.01-1.45; p = 0.035) with similar adverse events. In addition, thoracoscopic talc poudrage was more effective than bedside talc slurry (relative risk, 1.12; 95% confidence interval, 1.01-1.23; p = 0.026). CONCLUSIONS: The current evidences suggested the benefit for talc pleurodesis in the treatment of malignant pleural effusion. Talc pleurodesis, especially thoracoscopic talc poudrage pleurodesis, should be performed in patients with malignant pleural effusion, especially those with life-expectancy longer than one month.

BACKGROUND: Intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) have been demonstrated to be expressed on pleural mesothelial cells (PMCs), and to mediate leukocyte adhesion and migration; however, little is known about whether adhesion molecule-dependent mechanisms are involved in the regulation of CD4(+) T cells by PMCs in tuberculous pleural effusion (TPE). METHODS: Expressions of ICAM-1 and VCAM-1 on PMCs, as well as expressions of CD11a and CD29, the counter-receptors for ICAM-1 and VCAM-1, respectively, expressed on CD4(+) T cells in TPE were determined using flow cytometry. The immune regulations on adhesion, proliferation, activation, selective expansion of CD4(+) helper T cell subgroups exerted by PMCs via adhesion molecule-dependent mechanisms were explored. RESULTS: Percentages of ICAM-1-positive and VCAM-1‒positive PMCs in TPE were increased compared with PMC line. Interferon-γ enhanced fluorescence intensity of ICAM-1, while IL-4 promoted VCAM-1 expression on PMCs. Percentages of CD11a(high)CD4(+) and CD29(high)CD4(+) T cells in TPE significantly increased as compared with peripheral blood. Prestimulation of PMCs with anti‒ICAM-1 or ‒VCAM-1 mAb significantly inhibited adhesion, activation, as well as effector regulatory T cell expansion induced by PMCs. CONCLUSIONS: Our current data showed that adhesion molecule pathways on PMCs regulated adhesion and activation of CD4(+) T cells, and selectively promoted the expansion of effector regulatory T cells.

Summary Background Conventional tests are not always helpful in making a diagnosis of tuberculous pleurisy. Many studies have investigated the usefulness of adenosine deaminase (ADA) in pleural fluid for the early diagnosis of tuberculous pleurisy. We conducted a meta-analysis to determine the accuracy of ADA measurements in the diagnosis of tuberculous pleurisy. Methods After a systematic review of English language studies, sensitivity, specificity, and other measures of accuracy of ADA concentration in the diagnosis of pleural effusion were pooled using random effects models. Summary receiver operating characteristic curves were used to summarize overall test performance. Results Sixty-three studies met our inclusion criteria. The summary estimates for ADA in the diagnosis of tuberculous pleurisy in the studies included were sensitivity 0.92 (95% confidence interval 0.90–0.93), specificity 0.90 (95% confidence interval 0.89–0.91), positive likelihood ratio 9.03 (95% confidence interval 7.19–11.35), negative likelihood ratio 0.10 (95% confidence interval 0.07–0.14), and diagnostic odds ratio 110.08 (95% confidence interval 69.96–173.20). Conclusions ADA determination is a relative sensitive and specific test for the diagnosis of tuberculous pleurisy. Measurement of ADA in pleural effusion is thus likely to be a useful diagnostic tool for tuberculous pleurisy. The results of ADA assays should be interpreted in parallel with clinical findings and the results of conventional tests.