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Background Malignant pleural effusion (MPE) is common in malignant pleural mesothelioma (MPM). The survival of patients with MPM and MPE is heterogeneous. The LENT and BRIMS scores using routine clinical parameters were developed to predict the survival of patients with unselected MPE and MPM, respectively. This study aimed to stratify the survival of selected MPM patients with MPE. Methods Data were collected from subjects diagnosed with MPM and MPE. The LENT and BRIMS scores were applied using a combination of clinical variables to stratify subjects and compare survival characteristics. Results In total, 101 patients with MPM complicated by MPE were included in the study. The median follow‐up time was 71 months (interquartile range: 24–121 months). Overall median survival was 24 (interquartile range: 12–52 months). Based on the LENT score, the low‐, moderate‐, and high‐risk groups accounted for 65.3% (66 cases), 34.7% (35 cases), and 0%, respectively. The cumulative survival rates of the two groups were statistically significant (p = 0.031). The area under the curve (AUC) of the LENT score was 0.662. Based on the BRIMS score, the first, second, third, and fourth risk groups accounted for 1.0% (1 case), 42.9% (35 cases), 28.7% (29 cases), and 19.4% (36 cases), respectively. Survival was significantly higher in patients in the risk groups 1 and 2 than in patients in the risk groups 3 and 4 (p = 0.037). The AUC of the BRIMS score was 0.605. Conclusions Using routinely available clinical variables, both LENT and BRIMS scores could stratify selected MPM and MPE patients into risk groups with statistically different survival., The individual survival of patients with MPM combined with MPE varied greatly in this study. Both LENT and BRIMS scores could help stratify the survival risk of patients with MPM complicated by MPE with fair‐to‐good performance. More effective predictive models should be established in adequately designed prospective studies.

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.

The complex interactions among different immune cells have important functions in the development of malignant pleural effusion (MPE). Here we perform single-cell RNA sequencing on 62,382 cells from MPE patients induced by non-small cell lung cancer to describe the composition, lineage, and functional states of infiltrating immune cells in MPE. Immune cells in MPE display a number of transcriptional signatures enriched for regulatory T cells, B cells, macrophages, and dendritic cells compared to corresponding counterparts in blood. Helper T, cytotoxic T, regulatory T, and T follicular helper cells express multiple immune checkpoints or costimulatory molecules. Cell-cell interaction analysis identifies regulatory B cells with more interactions with CD4+ T cells compared to CD8+ T cells. Macrophages are transcriptionally heterogeneous and conform to M2 polarization characteristics. In addition, immune cells in MPE show the general up-regulation of glycolytic pathways associated with the hypoxic microenvironment. These findings show a detailed atlas of immune cells in human MPE and enhance the understanding of potential diagnostic and therapeutic targets in advanced non-small cell lung cancer., Detailed immune cell subset identification in human lung (malignant pleural effusion) MPE is important for diagnosis and prognosis. Here the authors use single cell RNA sequencing to identify immune cell types within MPE and show differential gene expression compared to circulating immune cells in blood.

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.

Pneumocystis pneumonia (PCP) is a common opportunistic infectious disease that is prevalent in immunosuppressed hosts. Accumulating evidence shows that B cells play an important role in infectious diseases. In the present study, the immune regulatory role of mature B cells in host defense to Pneumocystis was evaluated. Pneumocystis infection resulted in a decrease in B cells in patients and mice, and the Pneumocystis burden in B cell-deficient mice also progressively increased from weeks 1 to 7 after infection. The clearance of Pneumocystis was delayed in B cell-activating factor receptor (BAFF-R)-deficient mice (BAFF-R−/−mice), which had few B cells and Pneumocystis-specific IgG and IgM antibodies, compared with clearance in wild-type (WT) mice. There were fewer effector CD4+T cells and higher percentages of T helper (Th)1/Th17 cells in BAFF-R−/−mice than in WT mice. Adoptive transfer of naive B cells, mRNA sequencing, and IL-1β neutralization experiments indicated that IL-1β is a likely determinant of the IL-10-producing B cell-mediated suppression of Th1/Th17-cell immune responses in BAFF-R−/−PCP mice. Our data indicated that B cells play a vital role in the regulation of Th cells in response to Pneumocystis infection.

Background The current outbreak of coronavirus disease 2019 (COVID-19) caused by Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Wuhan, Hubei, China, spreads across national and international borders. Methods We prospectively collected medical records of 14 health care workers (HCWs) who were infected with SARS-CoV-2, in neurosurgery department of Wuhan Union Hospital, China. Results Among the 14 HCWs, 12 were conformed cases, the other 2 were suspected cases. Most of them were either exposed to the two index patients or infected coworkers, without knowing they were COVID-19 patients. There were 4 male and 10 female infected HCWs in this cohort, whose mean age was 36 years (SD, 6 years). The main symptoms included myalgia or fatigue (100%), fever (86%) and dry cough (71%). On admission, 79% of infected HCWs showed leucopenia and 43% lymphopenia. Reduced complement C3 could be seen in 57% of the infected HCWs and IL-6 was significantly elevated in 86% of them. The proportion of lymphocytes subsets, concentrations of immunoglobulins, complement C4, IL-2, IL-4, IL-10, TNF-α and IFN-γ were within normal range in these 14 infected HCWs. The most frequent findings on pulmonary computed tomographic images were bilateral multifocal ground-glass opacifications (86%). Conclusions Human-to-human transmission of COVID-19 pneumonia has occurred among HCWs, and most of these infected HCWs with confirmed COVID-19 are mild cases. Our data suggest that in the epidemic area of COVID-19, stringent and urgent surveillance and infection-control measures should be implemented to protect doctors and nurses from COVID-19 infection.

Background: There is still no clinical evidence available to support or to oppose corticosteroid treatment for coronavirus disease 2019 (COVID-19) pneumonia. Objective: To investigate the efficacy and safety of corticosteroid given to the hospitalized patients with COVID-19 pneumonia. Methods: This was a prospective, multicenter, single-blind, randomized control trial. Adult patients with COVID-19 pneumonia who were admitted to the general ward were randomly assigned to either receive methylprednisolone or not for 7 days. The primary end point was the incidence of clinical deterioration 14 days after randomization. Results: We terminated this trial early because the number of patients with COVID-19 pneumonia in all the centers decreased in late March. Finally, a total of 86 COVID-19 patients underwent randomization. There was no difference of the incidence of clinical deterioration between the methylprednisolone group and control group (4.8 vs. 4.8%, p = 1.000). The duration of throat viral RNA detectability in the methylprednisolone group was 11 days (interquartile range, 6–16 days), which was significantly longer than that in the control group (8 days [2–12 days], p = 0.030). There were no significant differences between the 2 groups in other secondary outcomes. Mass cytometry discovered CD3+ T cells, CD8+ T cells, and NK cells in the methylprednisolone group which were significantly lower than those in the control group after randomization (p < 0.05). Conclusions: From this prematurely closed trial, we found that the short-term early use of corticosteroid could suppress the immune cells, which may prolong severe acute respiratory syndrome coronavirus 2 shedding in patients with COVID-19 pneumonia. Trial Registration: ClinicalTrials.gov, NCT04273321.

Rationale: The current outbreak of coronavirus disease (COVID-19) pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Wuhan, China, spreads across national and international borders. The overall death rate of COVID-19 pneumonia in the Chinese population was 4%. Objectives: To describe the process of hospitalization and critical care of patients who died of COVID-19 pneumonia. Methods: This was a multicenter observational study of 109 decedents with COVID-19 pneumonia from three hospitals in Wuhan. Demographic, clinical, laboratory, and treatment data were collected and analyzed, and the final date of follow-up was February 24, 2020. Results: The mean age of 109 decedents with COVID-19 pneumonia was 70.7 years, 35 patients (32.1%) were female, and 85 patients (78.0%) suffered from one or more underlying comorbidities. Multiple organ failure, especially respiratory failure and heart failure, appeared in all patients even at the early stage of disease. Overall, the mean time from onset of symptoms to death was 22.3 days. All 109 hospitalized patients needed admission to an intensive care unit (ICU); however, because of limited availability, only 51 (46.8%) could be admitted. The period from hospitalization to death in the ICU group and non-ICU group was 15.9 days (standard deviation = 8.8 d) and 12.5 days (8.6 d, P = 0.044), respectively. Conclusions: Mortality due to COVID-19 pneumonia was concentrated in patients above the age of 65 years, especially those with major comorbidities. Patients who were admitted to the ICU lived longer than those who were not. Our findings should aid in the recognition and clinical management of such infections, especially with regard to ICU resource allocation.

Emerging evidence indicates that Myo9b is a cancer metastasis-related protein and functions in a variety of immune-related diseases. However, it is not clear whether and how Myo9b functions in malignant pleural effusion (MPE). In this study, our data showed that Myo9b expression levels correlated with lung cancer pleural metastasis, and nucleated cells in MPE from either patients or mice expressed a lower level of Myo9b than those in the corresponding blood. Myo9b deficiency in cancer cells suppressed MPE development via inhibition of migration. Myo9b deficiency in mice suppressed MPE development by decreasing T

Since the outbreak of coronavirus disease 2019 (COVID-19) in China in December 2019, considerable attention has been focused on its elucidation. However, it is also important for clinicians and epidemiologists to differentiate COVID-19 from other respiratory infectious diseases such as influenza viruses.The aim of this study was to explore the different clinical presentations between COVID-19 and influenza A (H1N1) pneumonia in patients with ARDS.This analysis was a retrospective case-control study. Two independent cohorts of patients with ARDS infected with either COVID-19 (n = 73) or H1N1 (n = 75) were compared. Their clinical manifestations, imaging characteristics, treatments, and prognosis were analyzed and compared.The median age of patients with COVID-19 was higher than that of patients with H1N1, and there was a higher proportion of male subjects among the H1N1 cohort (P .05). Patients with COVID-19 exhibited higher proportions of nonproductive coughs, fatigue, and GI symptoms than those of patients with H1N1 (P .05). Patients with H1N1 had higher Sequential Organ Failure Assessment (SOFA) scores than patients with COVID-19 (P .05). The PaoThere were many differences in clinical presentations between patients with ARDS infected with either COVID-19 or H1N1. Compared with H1N1 patients, patients with COVID-19-induced ARDS had lower severity of illness scores at presentation and lower SOFA score-adjusted mortality.

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.

Pleural fibrosis is associated with various inflammatory processes such as tuberculous pleurisy and bacterial empyema. There is currently no ideal therapeutic to attenuate pleural fibrosis. Some pro-fibrogenic mediators induce fibrosis through inflammatory processes, suggesting that blockage of these mediators might prevent pleural fibrosis. The MeT-5A human pleural mesothelial cell line (PMC) was used in this study as an in vitro model of fibrosis; and intra-pleural injection of bleomycin with carbon particles was used as an in vivo mouse model of pleural fibrosis. Calpain knockout mice, calpain inhibitor (calpeptin), and angiotensin (Ang) II type 1 receptor (AT1R) antagonist (losartan) were evaluated in prevention of experimental pleural fibrosis. We found that bleomycin and carbon particles induced calpain activation in cultured PMCs. This in vitro response was associated with increased collagen-I synthesis, and was blocked by calpain inhibitor or AT1R antagonist. Calpain genetic or treatment with calpeptin or losartan prevented pleural fibrosis in a mouse model induced by bleomycin and carbon particles. Our findings indicate that Ang II signaling and calpain activation induce collagen-I synthesis and contribute to fibrotic alterations in pleural fibrosis. Inhibition of Ang II and calpain might therefore be a novel strategy in treatment of pleural fibrosis.

Background Ultrasound is a convenient tool to evaluate cardiac and diaphragm function. The ratio (E/Ea) of mitral Doppler inflow velocity to annular tissue Doppler wave velocity by transthoracic echocardiography (TTE) and diaphragmatic excursion (DE) by diaphragm ultrasound have been confirmed in predicting extubation outcomes independently, however their different roles in the weaning process have not been determined until now. Methods We designed a cohort study to preform diaphragm ultrasound and TTE before and after the spontaneous breathing trial (SBT) in difficult-to-wean patients. Patients considered for enrollment should succeed on a SBT and have been extubated. They were followed up with the events of respiratory failure within 48 h, and divided into the respiratory failure and extubation success subgroups. Relevant risk factors predicting respiratory failure were analysed by a multivariate logistic regression model. Then, each subgroup was assessed with respect to re-intubation within 1 week, and divided into the re-intubation and non-intubation subgroups. Furthermore, relevant risk factors predicting re-intubation were also analysed in each subgroup. The area under the curve (AUC) and optimum cut-off value were identified by the receiver operating characteristic curve. Results Among 60 patients, 29 cases developed respiratory failure within 48 h, and 14 cases were re-intubated or died within 1 week, respectively. Multivariate logistic regression analysis showed that E/Ea (average) after SBT [odds ratio (OR) 1.450, 95% confidence intervals (CI) 1.092-1.926, P = 0.01] and left ventricular ejection fraction were associated with respiratory failure. The AUC of E/Ea (average) after SBT was 0.789, and a cut-off value ≥ 12.5 showed the highest diagnostic accuracy with a sensitivity and specificity of 72.4% and 77.4%, respectively. Furthermore, in the respiratory failure subgroup only DE (average) after SBT was associated with re-intubation (OR 0.690, CI 0.499-0.953, P = 0.024). The AUC of DE (average) after SBT was 0.805, and a cut-off value ≤ 12.6 mm showed the highest diagnostic accuracy with a sensitivity and specificity of 80% and 68.4%, respectively. Conclusions E/Ea (average) after SBT could help predict respiratory failure within 48 h. However, DE (average) after SBT could help predict re-intubation within 1 week in the respiratory failure subgroup. Electronic supplementary material The online version of this article (10.1186/s12890-017-0501-8) contains supplementary material, which is available to authorized users.

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.

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.

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 The novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), infected over 3300 healthcare workers in early 2020 in China. Little information is known about nosocomial infections of healthcare workers in the initial period. We analysed data from healthcare workers with nosocomial infections in Wuhan Union Hospital (Wuhan, China) and their family members. Methods We collected and analysed data on exposure history, illness timelines and epidemiological characteristics from 25 healthcare workers with laboratory-confirmed coronavirus disease 2019 (COVID-19) and two healthcare workers in whom COVID-19 was highly suspected, as well as 10 of their family members with COVID-19, between 5 January and 12 February 2020. The demographics and clinical features of the 35 laboratory-confirmed cases were investigated and viral RNA of 12 cases was sequenced and analysed. Results Nine clusters were found among the patients. All patients showed mild to moderate clinical manifestation and recovered without deterioration. The mean period of incubation was 4.5 days, the mean±sd clinical onset serial interval (COSI) was 5.2±3.2 days, and the median virus shedding time was 18.5 days. Complete genomic sequences of 12 different coronavirus strains demonstrated that the viral structure, with small irrelevant mutations, was stable in the transmission chains and showed remarkable traits of infectious traceability. Conclusions SARS-CoV-2 can be rapidly transmitted from person to person, regardless of whether they have symptoms, in both hospital settings and social activities, based on the short period of incubation and COSI. The public health service should take practical measures to curb the spread, including isolation of cases, tracing close contacts, and containment of severe epidemic areas. Besides this, healthcare workers should be alert during the epidemic and self-quarantine if self-suspected of infection., SARS-CoV-2 can be rapidly transmitted from person to person in nosocomial and social settings, despite patients having no symptoms https://bit.ly/34BHtB5

Background Malignant pleural mesothelioma (MPM) is marked by its difficult diagnosis and poor prognosis. Medical thoracoscopy (MT) is an effective and safe procedure for the diagnosis of exudative pleural effusions and many factors associated with poor prognosis of MPM. We conducted this study to investigate the value of MT for diagnosing of MPM and to identify prognostic factors for MPM patients. Methods From July 2005 through June 2014, a total of 833 patients with undiagnosed pleural effusions underwent MT and pleural biopsies were taken. Clinical data of all patients with MPM were retrospectively analyzed, and those with complete follow-up data were analyzed for prognostic factors. Results Eventually, MPM was the final diagnosis in 40 patients. Diagnostic efficiency of MT for MPM was 87.5%, since diagnosis of MPM failed to be established in 5 patients during the initial MT. Median survival was 17.1 mo (95% confidence interval: 13.6–20.7 mo). MT findings of pleural adhesion and plaques were adverse prognostic factors for MPM. In addition, old age, male gender, smoking history, histological type, poor staging, no treatment, low total protein level in pleural fluid, and computed tomographic findings such as pulmonary consolidation or infiltration, mediastinal lymphopathy, pulmonary mass or nodules, and pleural nodularity were also poor prognostic factors for MPM. Conclusions MT is safe with a high positive rate in the diagnosis of MPM, and pleural adhesion and plaques seen under MT may be the adverse prognostic factors for MPM. Multiple clinical characteristics can affect the survival of MPM patients.

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

Pleural fibrosis is barely reversible and the underlying mechanisms are poorly understood. Pleural mesothelial cells (PMCs) which have apical-basal polarity play a key role in pleural fibrosis. Loss of cell polarity is involved in the development of fibrotic diseases. Partition defective protein (PAR) complex is a key regulator of cell polarity. However, changes of PMC polarity and PAR complex in pleural fibrosis are still unknown. In this study, we observed that PMC polarity was lost in fibrotic pleura. Next we found increased Lethal (2) giant larvae (Lgl) bound with aPKC and PAR-6B competing against PAR-3A in PAR complex, which led to cell polarity loss. Then we demonstrated that Lgl1 siRNA prevented cell polarity loss in PMCs, and Lgl1 conditional knockout (ER-Cre+/-Lgl1flox/flox) attenuated pleural fibrosis in a mouse model. Our data indicated that Lgl1 regulates cell polarity of PMCs, inhibition of Lgl1 and maintenance of cell polarity in PMCs could be a potential therapeutic treatment approach for pleural fibrosis.

Background: Interleukin (IL)-27 has been reported to have anti-proliferate and anti-angiogenic activities on cancer cells. However, the involvement of IL-27 in malignant pleural effusion (MPE) remains unknown. Thus, in this research, we compared the immune functions of IL-27, interferon (IFN)-γ, and IL-17 on lung cancer cells and revealed the regulatory mechanism of IL-27 in MPE. Methods: The distribution of IL-27 in both MPE and blood was evaluated by enzyme-linked immunosorbent assay and flow cytometry. The expressions of cytokine receptors and the levels of the phosphorylated signal transducer and activator of transcription (STAT) signalings were detected by flow cytometry. As well as the effects of proliferation, apoptosis, migration, and adherent activity of IL-27, IFN-γ, and IL-17 on lung cancer cells were also explored. Results: The expression of IL-27 was increased in MPE when compared with blood (147.3 ± 25.1 pg/ml vs. 100.3 ± 13.9 pg/ml, P = 0.04). IL-27 was noted to suppress both proliferation (18.33 ± 0.21 vs. 27.77 ± 0.88, P = 0.0005) and migration (1.82 ± 0.44 vs. 3.13 ± 0.07, P = 0.04) of A549 cells, but obviously promoted apoptosis of A549 cells (9.47 ± 1.14 vs. 4.96 ± 0.17, P = 0.02) by activating STAT1 signaling. Interestingly, IL-27 played totally opposite effects on A549 cells by activating STAT3 pathway. Moreover, IL-27 exerted different intercellular adherent activities of A549 cells to pleural mesothelial cell monolayer by activating different STAT signalings. Conclusions: IL-27 might exert an important immune regulation on lung cancer cells in human pleural malignant environment.

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.

Th22 cells have been reported to be involved in human cancers. However, differentiation and immune regulation of Th22 cells in malignant pleural effusion (MPE) remain unknown. We noted that Th22 cell numbers were increased in MPE, and that IL-22 substantially promoted the proliferation and migratory activity of A549 cells. Moreover, IL-22 could strongly facilitate intercellular adhesion of A549 cells to pleural mesothelial cell monolayers. Our data revealed that the increase in Th22 cells in MPE was due to pleural cytokines and chemokines, and that Th22 exerted an important immune regulation on cancer cells in human pleural malignant environment.

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.

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.

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.

Cytotoxic lymphocyte associated antigen-4 (CTLA-4) is a homologue of CD28, which plays a critical role in the down-regulation of antigen-activated immune response. The aim of the present study was to investigate the concentrations of soluble CTLA-4 in sera of patients with bronchial asthma and the correlation between soluble CTLA-4 concentrations and some clinical measures of asthma. The concentrations of serum soluble CTLA-4 in 31 atopic asthmatics, 20 non-atopic asthmatics, and 28 non-atopic normal control volunteers were determined by ELISA technique, and the relationship between serum soluble CTLA-4 concentrations in asthmatics and airway responsiveness, pulmonary function, blood white cell counts and differentials, respectively, were analyzed. Serum soluble CTLA-4 concentrations in both atopic asthmatics (20.2 +/- 5.4 microg/L) and non-atopic asthmatics (19.2 +/- 6.2 microg/L) were all higher than that in normal controls (1.8 +/- 0.8 microg/L, p = 0.04 and 0.014, respectively). There was no difference in serum soluble CTLA-4 concentrations between atopic and non-atopic asthmatics (p = 0.877). The serum soluble CTLA-4 concentrations in the asthmatics statistically correlated with forced expiratory volume in one second (r = -0.410, p = 0.027), percentage of predicted peak expiratory flow (r = -0.449, p = 0.015), and PaCO2 (r = 0.555, p = 0.002), respectively. Our data also showed that the concentration of soluble CTLA-4 was significantly related to blood lymphocyte numbers. The serum soluble CTLA-4 protein level was significantly elevated in patients with asthma. This level correlated with the severity of asthma. Our data also showed that the concentration of soluble CTLA-4 was significantly related to blood lymphocyte numbers.

The aim of this study was to analyze whether regulatory CD4+CD25+ T lymphocytes exist and function normally in patients with atopic asthma. Our data showed that a significant increase in CD4+CD25+ cell numbers was seen in atopic asthmatics during acute exacerbation, but not in those stable asthmatics, atopic nonasthmatics, and normal subjects. The mean inhibition values of the proliferation response of CD4+CD25− cells by CD4+CD25+ cells from normal controls and asthmatics were almost the same. There was no difference in inhibitory effects on both Th1 and Th2 cytokine production of CD4+CD25− cells by CD4+CD25+ cells in the two groups. These data demonstrated that although CD4+CD25+ cells increase in atopic asthma during exacerbation, these regulatory T cells appear to function normally with regard to suppression of T-cell proliferation as well as Th1–Th2 cytokine production.

Because eosinophils recruited into the airways in allergic diseases are exposed to inhaled allergens, we evaluated whether eosinophils within the endobronchial lumen can function in vivo as antigen-presenting cells for inhaled antigens. We recovered eosinophils from the airways after aerosol antigen challenge in sensitized mice or from the peritoneal cavities of IL-5 transgenic mice and fluorescently labeled these cells ex vivo. These labeled cells, instilled intratracheally into normal mice, migrated into draining paratracheal lymph nodes and localized to T cell-rich paracortical areas. The homing of airway eosinophils to lymph nodes was not governed by eotaxin, because CCR3(-/-) and CCR3(+/+) eosinophils migrated identically. Airway eosinophils, recovered after inhalational antigen challenge in sensitized mice, expressed MHC class II and costimulatory CD80 and CD86 proteins and functioned in vitro as CD80- and CD86-dependent, antigen-specific, antigen-presenting cells. Moreover, when instilled into the airways of antigen-sensitized recipient mice, airway eosinophils recovered after inhalational antigen challenge stimulated antigen-specific CD4(+) T cell proliferation within paratracheal lymph nodes. Thus, eosinophils within the lumina of airways can process inhaled antigens, traffic to regional lymph nodes, and function in vivo as antigen-presenting cells to stimulate responses of CD4(+) T cells.

The aim of the present study was to examine the effects of interleukin-5 (IL-5) inhalation on changes in the activity and number of circulating eosinophils, as well as concentrations of serum total IgE, in allergic asthmatics. A randomized double-blind, placebo-controlled study design was employed in which each subject acted as his or her own control. Eight nonsmoking patients with allergic asthma were administered recombinant human IL-5 by nebulization. Total white blood cell counts and differentials, as well as concentrations of ECP and total IgE in serum, were determined before and at 2, 24, and 48 h after inhalation. Our results demonstrated that eosinophil numbers increased from baseline (3.6 +/- 1.1 x 10(5)/ml) to 6.3 +/- 1.2 x 10(5)/ml (P0.01) at 24 h and to 5.7 +/- 0.9 x 10(5)/ml (P0.01) at 48 h after IL-5 inhalation in asthmatics. Accompanying this significantly increased blood eosinophilia were significantly elevated serum ECP levels. Compared with baseline (6.3 +/- 1.1 ng/ml), ECP levels increased with time following IL-5 inhalation, reaching 17.6 +/- 2.8 ng/ml (P0.01) at 24 h and remaining elevated at 48 h (18.1 +/- 2.9 ng/ml, P0.01). IL-5 inhalation had no significant effect on levels of serum total IgE, however. These findings provide direct evidence that nebulized IL-5 not only induces a significant blood eosinophilia but also results in the activation of circulating eosinophils. Our data further support the importance of IL-5 in the pathogenesis of bronchial asthma in humans.

Background: Both IL-5 and intracellular adhesion molecule-1 (ICAM-1) have been shown to play important roles in the production of allergic inflammation, including atopic asthma. Objective: The aim of this study was to investigate the effects of recombinant human IL-5 on changes of soluble (s) ICAM-1 concentrations in induced sputum from allergic asthmatic subjects. Methods: In a randomized, double-blind, placebo-controlled study design, 8 nonsmoking patients with allergic asthma and 6 nonallergic normal subjects were administered recombinant human IL-5 by nebulization, and the concentrations of sICAM-1 in induced sputum from each subject were determined before and at 2, 24, 48, and 72 hours after inhalation. Results: sICAM-1 levels in sputum within the control group did not appear to change from baseline at any time throughout the study. In allergic asthmatic subjects vehicle challenge was not able to cause any changes in sputum sICAM-1 concentrations. However, there were increases in sputum sICAM-1 concentrations after IL-5 inhalation, which increased with time to significantly greater levels than those at baseline, reaching a maximum at 48 hours and lasting no less than 72 hours. The concentrations of sICAM-1 in sputum after IL-5 challenge exceeded levels that could be accounted for by passive transudation from the circulation on the basis of the magnitude of increases in sputum albumin concentration. Conclusion: Our results indicated that IL-5 inhalation was capable of inducing an elevation of sputum sICAM-1 concentration by stimulating its local release in allergic asthmatic, but not in nonallergic normal, subjects. (J Allergy Clin Immunol 1999;103:463-7.)

In order to investigate the role of interleukin-5 (IL-5) in airway hyperreactivity and eosinophilia, we observed the effect of inhaled recombinant human IL-5 on airway responsiveness to methacholine and cell populations in induced sputum in eight patients with allergic bronchial asthma using a placebo-controlled study design. Our results demonstrated that the inhalation of IL-5 did not alter lung function in allergic asthmatics. In the control experiments receiving either vehicle or 0.4 ng of endotoxin, methacholine PC20 values did not change nor did the numbers of eosinophils or eosinophil cationic protein (ECP) sputum values change from baseline. In contrast, after IL-5 inhalation, methacholine PC20 fell from baseline (0.90 +/- 166 mg/ml) to 0.32 +/- 1.63 mg/ml (p0.01) at 24 h, and to 0.55 +/- 1.49 mg/ml (p0.05) at 48 h. Accompanying this increased airway sensitivity was a significant eosinophilia and elevated concentrations of ECP in induced sputum. Our data provided direct evidence that IL-5 increases airway responsiveness and infiltration of activated eosinophils into the airway in patients with allergic bronchial asthma. It also could be concluded that the observed airway hyperreactivity and eosinophilia were not endotoxin related.

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.

IL-9-producing CD4(+) T cells (Th9 cells) have been reported to be involved in inflammation and immune diseases. However, the involvement of Th9 cells in malignancy has not been investigated.To elucidate the mechanism by which Th9 cells differentiate in malignant pleural effusion (MPE) and to explore the immune regulation of Th9 cells on lung cancer cells.Distribution of Th9 cells in relation to Th17 and Th1 cells in both MPE and blood were determined. The effects and mechanisms of proinflammatory cytokines and regulatory T cells on differentiation of Th9 cells in vitro were explored. The impacts and signal transductions of IL-9, IL-17, and IFN-γ on lung cancer cell lines were also investigated.The numbers of Th9, Th17, and Th1 cells were all increased in MPE when compared with blood. The increase in Th9 cells in MPE was due to the promotion by cytokines and regulatory T cells. By activating STAT3 signaling, both IL-9 and IL-17 substantially promoted the proliferation and migratory activity of lung cancer cells, whereas IFN-γ, which activated STAT1 signaling, was noted to suppress lung cancer cell proliferation and migration. IFN-γ could induce lung cancer cell apoptosis. Moreover, IL-9 and IFN-γ, but not IL-17, could strongly facilitate intercellular adhesion of lung cancer cells to pleural mesothelial cell monolayers.Our data revealed that Th9 cells were increased in MPE and that Th9 cells exerted an important immune regulation on lung cancer cells in human tumor environment.

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.

Interleukin 16 (IL-16) can be detected by ELISA in pleural effusion (PE) and its concentration is higher than in serum. This study investigated the cellular sources of IL-16 in PE.The samples of PE were collected from 34 patients who were newly diagnosed having PE in the pleural cavity. We performed cell culture to purify the pleural mesothelial cells (PMC), Wright staining to count the purity and immunocytochemical stain to identify the cultured cells. The intracellular IL-16 expression was detected by flow cytometry (FCM). The different cells in PE were first separated by magnetic cell sorting (MCAS) then the separated cells were cultured in RPMI1640 with 10% fetal calf serum (FCS). We extracted the supernatant and detected IL-16 concentration by ELISA. The IL-16 protein was detected by immunohistochemistry and double immunofluorescence staining.The percentages of cells which secreted IL-16 were: CD3(+)CD8(-) cells ((74.27 ± 15.56)%, n = 34); CD3(+)CD8(+) cells ((69.86 ± 18.55)%, n = 34); CD19(+) cells ((45.30 ± 18.77)%, n = 15); CD14(+) cells ((16.91 ± 16.69)%, n = 15); and PMC ((2.05 ± 1.85)%, n = 7). The concentrations of IL-16 in the supernatant from cultured cells were: CD4(+) cells ((102.50 ± 42.51) ng/L, n = 5); CD8(+) cells ((92.58 ± 18.34) ng/L, n = 5); CD19(+) cells ((79.85 ± 5.62) ng/L, n = 5); CD14(+) cells ((58.51 ± 25.38) ng/L, n = 5); and PMC ((18.14 ± 8.37) ng/L, n = 5). In lymphocytes, monocytes/macrophages and PMC, we could observe the cells that expressed IL-16 protein. In paraffin-embedded sections, we also could observe by immunohistochemistry the CD4(+)IL-16(+) cells, CD8(+)IL-16(+) cells, CD19(+)IL-16(+) cells, and CD14(+)IL-16(+) cells.IL-16 in PE is mainly secreted by T lymphocytes, including CD3(+)CD8(-) cells and CD3(+)CD8(+) cells. CD19(+) cells and CD14(+) cells can also secrete IL-16, but the percentage of PMC that can secrete IL-16 is very low.

The activation of triggering receptor expressed on myeloid cells-1 (TREM-1) in the presence of microbial components amplifies the inflammatory response. The aim of the present study was to investigate the effect of the modulation of the TREM-1 pathway during empyema in rats.Adult male Wistar rats were subjected to empyema induced by intrapleural injection of Pseudomonas aeruginosa and Staphylococcus aureus. The animals were treated with LP17 (a synthetic TREM-1 inhibitor), a control peptide, or a vehicle (normal saline). Differential cell count, flow cytometry and histological examination were performed to evaluate local inflammatory alterations. Concentrations of tumor necrosis factor-alpha, interleukin-1beta, and interleukin-6 in both pleural effusion and serum were measured by enzyme-linked immunosorbent assay.Although differential counts of each type of leukocytes in pleural effusion were not affected by LP17, a marked reduction in neutrophil numbers was seen in LP17 treated rats due to the reduction of both pleural effusion volume and total cell numbers. LP17 administration impaired concentration elevation in tumor necrosis factor-alpha, interleukin-1beta, and interleukin-6 in both pleural effusion and serum. It was found that survival rate in LP17 treated rats was much higher than that in control rats.The modulation of the TREM-1 pathway by the use of LP17 appears to be beneficial during empyema in rats in attenuating pleural and systemic inflammatory responses.

to investigate the levels of peripheral CD(8)(+)CD(25)(+)Foxp(3)(+) regulatory T cells (CD(8)(+)CD(25)(+)Treg) in stable chronic obstructive pulmonary disease (COPD) patients, and the effect of muscarinic cholinergic receptor antagonist, tiotropium bromide, on the expression of CD(8)(+)CD(25)(+)Treg.from Oct. 2007 to Mar. 2008, 23 patients with stable moderate to severe COPD received tiotropium bromide inhalation (18 microg daily) for 3 months. Before and after the use of tiotropium bromide, lung function was performed and peripheral vein blood samples were collected from the patient. Lymphocytes were isolated by three-color labeled monoclonal antibodies flow cytometry to detect the quantity and percentage of CD(8)(+)T cell, CD(8)(+)CD(25)(+) T cell, CD(8)(+)CD(25)(+)Treg, CD(4)(+)T cell, CD(4)(+)CD(25)(+) T cell and CD(4)(+)CD(25)(+)Treg, respectively. Paired t test was used for comparison between data before and after treatment.in patients with stable COPD, after tiotropium bromide treatment, the percentage of CD(4)(+) T cells was increased from (28 +/- 10)% to (36 +/- 6)%, and the difference was significant (t = 3.20, P0.01). CD(4)(+)CD(25)(+) was decreased from (10 +/- 7)% to (4 +/- 3)% (t = 3.78, P0.01), and CD(8)(+)CD(25)(+)Treg was increased from (8 +/- 8)% to (21 +/- 21)% (t = 2.72, P0.05). At baseline, CD(8)(+) cells, CD(8)(+)CD(25)(+) cells and CD(4)(+)CD(25)(+)Treg were detectable in the peripheral blood, but no significant changes were observed after treatment. After treatment with tiotropium bromide, the lung function was markedly improved; FEV(1), FEV(1)/Pre%, and FEV(1)/FVC were increased from (1.0 +/- 0.3) L, (35 +/- 10)% and (41 +/- 8)% to (1.1 +/- 0.3) L, (40 +/- 11)% and (45 +/- 11)%, respectively (t = 2.65, 2.56 and 2.37, respectively, all P0.05). By linear correlation analysis, the quantity of changes of CD(4)(+) T cells and CD(4)(+)CD(25)(+) T cells were negatively correlated with the rate of change in CD(8)(+)CD(25)(+)Treg (r = -0.61, P0.05 and r = -0.72, P0.01, respectively).in the peripheral blood of patients with stable COPD, there was expression of CD(8)(+)CD(25)(+)Treg and CD(4)(+)CD(25)(+)Treg. The muscarinic receptor antagonist tiotropium bromide, promoted the amplification of CD(4)(+), inhibited the expression of CD(25)(+), and enhanced the expression of CD(8)(+)Treg, suggesting that muscarinic receptor antagonist tiotropium bromide may possess immunomodulation function.

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: The migration and in situ differentiation of CD34+ progenitors contribute to inflammatory eosinophilia in asthma and corticosteroids have been widely used in asthma. However, little is know about whether and how corticosteroids modulate the migration and differentiation of CD34+ progenitors. This study was aimed to investigate the impact of anti-CC chemokine receptor 3 (CCR3) or dexamethasone on inflammatory eosinophilia in asthma and possible mechanism(s) underlying the action of dexamethasone or anti-CCR3 on migration and differentiation of CD34+ progenitors in asthmatic context. Methods: Using an asthmatic mouse model, airway inflammation of anti-CCR3- or dexamethasone-treated mice and that of controls were characterized. And the migration and differentiation of CD34+ progenitor cells were analyzed in vivo, ex vivo or in vitro. Results: Treatment with anti-CCR3 or dexamethasone significantly inhibited allergen-induced eosinophilia and CD34+ progenitor cell infiltration in the lung, which was accompanied by lower levels of airway hyper-responsiveness and mucus production. Moreover, anti-CCR3 inhibited the eotaxin-mediated migration and IL-5/eotaxin-induced differentiation of CD34+ progenitors in vitro. Dexamethasone was also shown to mitigate eotaxin-mediated migration and IL-5 or eotaxin-promoted differentiation of CD34+ progenitor cells ex vivo, which were associated with the down-regulation of CCR3 expression on bone marrow progenitor cells. Conclusions: Treatment with anti-CCR3 or dexamethasone can inhibit the migration and differentiation of CD34+ progenitor cells by regulating the eotaxin/CCR3 axis in asthmatic mice. Our findings provide new insights into understanding the mechanism(s) underlying the action of dexamethasone and CCR3-mediated signaling in allergic inflammation and aid in the design of new immunotherapy for intervention of human asthma.

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.

To investigate the effects of segmental allergen challenge on the concentration of soluble CD86 (sCD86) in BAL fluids in patients with allergic asthma.BAL fluid and peripheral blood were collected at baseline, 24 h after segmental saline solution or allergen challenge by fiberoptic bronchoscopy and venepuncture, respectively, from 10 patients with allergic asthma. Total and differential cell counts in BAL fluid were performed, and sCD86 levels in both BAL fluid and serum were measured by enzyme-linked immunosorbent assay.In allergic asthmatics, there was no significant increase in BAL sCD86 concentrations after saline solution challenge (median, 2.0 IU/L; 25th to 75th percentiles, 0 to 3.4) compared with baseline control subjects (median, 1.2 IU/L; 25th to 75th percentiles, 0 to 3.6 IU/mL; p = 0.735); however, sCD86 concentrations were significantly elevated after allergen challenge (median, 8.1 IU/L; 25th to 75th percentiles, 4.4 to 17.0 IU/mL; p0.001). The concentrations of sCD86 in BAL fluid after allergen challenge exceeded levels that could be accounted for passive transudation from the circulation, based on the magnitude of increases in BAL albumin concentrations.These data indicate that allergen challenge results in a significant local accumulation of sCD86 within the airways, and that the local release of sCD86 may play a role in allergen-induced inflammatory processes in the asthmatic airways.

To explore whether regulatory CD(4)(+)CD(25)(+) cells exist in patients with atopic asthma.The numbers of peripheral blood CD(4)(+)CD(25)(+) cells in peripheral blood of atopic asthmatics and healthy nonatopic subjects were determined using flow cytometry. CD(4)(+)CD(25)(+) and CD(4)(+)CD(25)(-) cells from atopic asthmatics and normal donors were isolated, and were cultured to observe the effects of CD(4)(+)CD(25)(+) cells on proliferation response as well as Th1/Th2 cytokine production of CD(4)(+)CD(25)(-) cells in vitro.A significant increase in CD(4)(+)CD(25)(+) cell numbers was shown in atopic asthmatic patients during acute exacerbation [(14.9 +/- 1.8)%, P0.01], but not in patients with stable asthma [(11.8 +/- 0.7)%] and normal subjects [(11.2 +/- 0.8)%, P0.05]. The mean inhibition values of the proliferation response of CD(4)(+)CD(25)(-) cells by CD(4)(+)CD(25)(+) cells from normal controls [(72 +/- 8)%] and asthmatics [(74 +/- 9)%] were similar (P0.05). There was no difference in inhibitory effects on both Th1 and Th2 cytokine production of CD(4)(+)CD(25)(-) cells by CD(4)(+)CD(25)(+) cells in the two groups.Although CD(4)(+)CD(25)(+) cells increase in atopic asthma during exacerbation, these regulatory T cells appear to function normally with regard to their suppressive activities.

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: The serum soluble cytotoxic T lymphocyte associated antigen-4 (sCTLA-4) concentration is significantly elevated in patients with asthma, and sCTLA-4 concentration correlate with the severity of asthma. The aim of the present study was to investigate effects of allergen inhalation and oral glucocorticoid on concentration of serum sCTLA-4 in patients with allergic asthma. Methods: Allergen inhalation challenge was conducted in allergic asthmatics with isolated early asthma response and those with dual asthma response. In a randomized, double-blind, placebo-controlled, parallel group fashion, prednisolone or placebo was give orally once a day for 2 weeks. Venous blood samples were collected before and after allergen inhalation or prednisolone administration for obtaining sera. The serum sCTLA-4 concentrations were determined using enzyme-linked immunosorbent assay. Results: The serum sCTLA-4 concentrations in the dual responder group increased from 29.0 (14.5–43.7) μg/l [median (25–75 percentiles)] before allergen inhalation to 44.0 (24.3–61.3) μg/l 24 h after allergen inhalation. In the isolated early responders, there were no significant increase in serum sCTLA-4 concentrations after allergen inhalation compared with baseline levels. There was a significant decrease in serum sCTLA-4 concentrations after 2 weeks of glucocorticoid therapy [22.0 (15.5–31.0) μg/l] compared with baseline values [37.0 (19.5–53.0) μg/l], whereas there was no significant difference in the placebo group. Conclusion: This study has demonstrated that serum sCTLA-4 concentrations increased after allergen inhalation in sensitized asthmatic subjects, and that serum sCTLA-4 concentrations were downregulated by prednisolone therapy.

To explore the mode of immune responses of gammadeltaT cells in asthma and the role of gammadeltaT cell subsets in the pathogenesis of asthma.Wistar rats were sensitized and challenged with ovalbumin to establish an asthmatic model (n = 10, for each group). "Attack-panning" method was used to culture selective gammadeltaT cells. The percentage of gammadelta T cells among cultured cells was determined by flow cytometry. The levels of interleukin (IL)-4 and interferon-gamma (IFN-gamma) were measured by ELISA. The expression of IL-4 mRNA and IFN-gamma mRNA was determined by in situ hybridization.In the asthmatic group, IL-4 and IFN-gamma were detectable at the same time in cultured supernatant of gammadeltaT cells in peripheral blood mononuclear cells (PBMC) or broncho-alveolar fluid (BALF), and the level of IL-4 [PBMC: (40.5 +/- 3.7) ng/L, BALF: (49.6 +/- 3.1) ng/L] increased as compared with the control group [PBMC: (26.1 +/- 2.1) ng/L, BALF: (23.6 +/- 1.7) ng/L; all P0.01], while the level of IFN-gamma [PBMC: (17.6 +/- 2.5) ng/L, BALF: (28.5 +/- 3.6) ng/L] decreased as compared with the control group [PBMC: (24.3 +/- 1.7) ng/L, BALF: (38.4 +/- 2.8) ng/L; all P0.01]. In the asthmatic group, the percentage of IL-4 mRNA positive-staining cells [PBMC: (76.2 +/- 7.2)%, BALF: (85.7 +/- 8.4)%] among the gammadeltaT cells significantly increased as compared with the control group [PBMC: (20.6 +/- 5.3)%, BALF: (25.0 +/- 6.8)%; all P0.01], while the percentage of IFN-gammamRNA positive-staining cells [PBMC: (30.9 +/- 6.7)%, BALF: (41.5 +/- 3.6)%] among the gammadeltaT cells significantly decrease as compared with the control group [PBMC: (60.1 +/- 4.2)%, BALF: (53.8 +/- 5.1)%; all P0.01].gammadeltaT cells can secrete both IL-4 and IFN-gamma at the same time, or there are two subsets of gammadeltaT cells which can secrete either IL-4 or IFN-gamma in PBMC or BALF in asthma. Th1/Th2 immune response mode is present in gammadeltaT cells of asthma and Th2-cytokine profile predominates. gammadeltaT cells is involved in the pathogenesis of asthma.

To study the pathological features of airway inflammation and remodeling in rats with chronic bronchitis (CB) and emphysema and to evaluate the protective and therapeutic effects of erythromycin (EM).Forty-three Wistar rats were assigned to eight groups: normal control group (A group, n = 5), normal saline solution group (P group, n = 5), CB group (L group, n = 6), CB and emphysema group (S group, n = 6), low-dose EM-treatment group (E(1) group, n = 5), high-dose EM-treatment group (E(2) group, n = 6), low-dose EM-prevention group (E(10) group, n = 5) and high-dose EM-prevention group (E(20) group, n = 5). The rat model of CB and emphysema was established by intratracheal instillation of lipopolysaccharide (LPS) and daily exposure to cigarette smog. After four weeks, total and differential cell counts in bronchoalveolar lavage fluid (BALF) were observed, and the pathomorphological changes in the lung were analyzed. The thickness of the smooth muscles and collagen in the bronchial wall were measured. Expression and localization of transforming growth factor beta(1) (TGF-beta(1)) were observed in the bronchi and lung tissues by immunohistochemistry. The levels of hyaluronic acid (HA) and procollagen type III (PCIII) in the serum and BALF were determined by the radioimmunoassay (RIA).(1) Compared with A group [(0.9 +/- 0.7) x 10(5)/ml], absolute neutrophil count in BALF from S group [(17.1 +/- 10.8) x 10(5)/ml] were significantly higher (P0.01). (2) Both the pathologic scores obtained from the S group (329 +/- 114) and P group (67 +/- 25), and the thickness of smooth muscles and collagen from S group [(9.6 +/- 2.6)%] and A group [(6.1 +/- 1.8)%] were statistically different (P0.01, P0.05, respectively). Expression of TGF-beta(1) in the lung of S group was significantly higher than that in A group. (3) The levels of HA [(152.5 +/- 36.3) micro g/ml] and PCIII [(40 +/- 8) micro g/ml] in serum and the levels of HA [(94 +/- 35) micro g/ml] and PCIII [(39 +/- 7) micro g/ml] in BALF in S group were higher than those in A group (P0.01). (4) After treatment with 100 mg/kg EM, absolute neutrophil count in BALF, the pathologic scores, the thickness of smooth muscles and collagen in the bronchi, the levels of PCIII and HA in serum and the levels of PCIII and HA in BALF were reduced to (2.1 +/- 1.4) x 10(5)/ml, 187 +/- 61, (6.0 +/- 2.3)%, (9.69 +/- 5.61) micro g/ml, (63.0 +/- 11.6) micro g/ml, (16 +/- 6) micro g/ml, (52 +/- 12) micro g/ml, respectively. Statistical analysis revealed that there were significant differences as compared to those of group S (P0.05).Many inflammatory cells especially neutrophils and alveolar macrophages might play an important role in the airway inflammation of CB and emphysema. Thickening of smooth muscles and collagen in the bronchi and the excessive depositions of extracellular matrix (ECM) constitute the fundamental pathological characteristic of airway remodeling in CB and emphysema. EM may prevent airway inflammation and remodeling to some degree.