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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.

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.

γδT cells are an important source of IL-17A and play an anti- or protumor role depending on the surrounding microenvironment. The precise role of γδT cells in the development of malignant pleural effusions (MPE) remains unknown. Using flow cytometry, we analyzed the distribution and differentiation of γδT cells in wild-type (WT) and IL-10-∕- mice. We carefully elucidated the influence of γδT cells on the formation of MPE by depleting γδT cells from WT, IL-10-∕-, and IL-17a-∕- mice. The distribution of γδT17 cells in human MPE and peripheral blood was also determined. Our data showed that both γδT cells and IL-17A-producing γδT (γδT17) cells accumulated in murine MPE, and IL-10 deficiency enhanced their accumulation. γδT cells were the main source of IL-17A in MPE for both WT and IL-10-∕- mice. IL-10 inhibited the chemotactic response of γδT cells to MPE and the proliferation of these cells. IL-10 suppressed γδT cell secretion of IL-17A via RORγt. The ablation of γδT cells accelerated MPE accumulation in both WT and IL-10-∕- mice, but it did not influence MPE accumulation in IL-17a-∕- mice. Patients with higher frequencies of γδT17 cells had significantly longer survival times than patients with lower frequencies of γδT17 cells. Taken together, our data demonstrate that γδT17 cells play an inhibitory role in the progression of MPE, and the accumulation of γδT17 cells in MPE is suppressed by IL-10.

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.

We appreciate the thoughtful comments of H-J. Yang and co-workers in their correspondence addressing the predictors of mortality for patients with coronavirus disease 2019 (COVID-19) pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Their comments are very helpful to improve the expression and increase the quality of our paper [1]., Author response to the correspondence regarding “Predictors of mortality for patients with COVID-19 pneumonia caused by SARS-CoV-2: a prospective cohort study” https://bit.ly/31X8cal

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.

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.

Inflammatory signaling networks between tumor cells and immune cells contribute to the development of malignant pleural effusion (MPE). B cells have been found in MPE; however, little is known about their roles there. In the present study, by using mouse MPE models, we noted that although the total B cells in MPE were decreased as compared with the corresponding blood and spleen, the percentage of activated naïve B cells expressing higher levels of CD80, CD86, myosin heavy chain-II, CD44, CD69, and programmed cell death-ligand 1 (PD-L1) molecules were increased in wild-type mouse MPE. Compared with wild-type mice, decreased T helper (TH)1 cells and increased TH17 cells were present in B cell-deficient mouse MPE, which paralleled to the reduced MPE volume and longer survival time. Adoptive transfer of activated naïve B cells into B cell-deficient mice was able to increase TH1 cells and decrease TH17 cells in MPE and shorten the survival of mice bearing MPE. Furthermore, we demonstrated that activated naïve B cells inhibited TH17-cell expansion via the PD-1/PD-L1 pathway and promoted naïve CD4+ T-cell differentiation into TH1/TH17 cells through secreting IL-27/IL-6 independent of the PD-1/PD-L1 pathway. Collectively, our data uncovered a mechanism by which naïve B cells promote MPE formation by regulating TH1/TH17 cell responses, making these B cells an attractive target for therapeutic intervention in the fight against cancer.

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.

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.

Toll-like receptor (TLR) 2 has a well-known role in sensing multiple ligands that include microbial products, endotoxin, and some extracellular matrix molecules; however, its role in the development of malignant pleural effusion (MPE) remains unknown. We performed the present study to explore the impact of TLR2 signaling on the development of MPE and to define the underlying mechanisms by which TLR2 works. Development of MPE was compared between TLR2-/- and wild-type (WT) mice. The effect of TLR2 on differentiation of T helper type 17 (Th17), Th9, and Th2 cells in MPE was explored. The mechanisms of TLR2 on survival of mice bearing MPE were also investigated. MPE volume in TLR2-/- mice was lower than that in WT mice, and the survival of TLR2-/- mice bearing MPE was longer than that of WT mice. TLR2 deficiency increased, and TLR2 activation decreased, Th17 cells in MPE, whereas TLR2 signaling showed the contrary effects on Th2 cells. Th9 cells were increased in MPE of TLR2-/- mice but were not influenced by TLR2 signaling. Intraperitoneal injection of anti-IL-17 monoclonal antibody (mAb), anti-IL-9 mAb, or recombinant mouse IL-4 accelerated the death of TLR2-/- mice bearing MPE, and intraperitoneal injection anti-IL-17 mAb in TLR2-/- mice was associated with a significantly shorter survival time than in WT mice. We have demonstrated, for the first time, that TLR2 signaling promotes the development of MPE and accelerates the death of mice bearing MPE by directly suppressing Th17 cell differentiation and directly promoting Th2 cell differentiation, and also by indirectly suppressing Th9 cell differentiation via an IL-17-dependent mechanism.

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

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 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

The aim of this study was to identify factors associated with the death of patients with COVID-19 pneumonia caused by the novel coronavirus SARS-CoV-2.All clinical and laboratory parameters were collected prospectively from a cohort of patients with COVID-19 pneumonia who were hospitalised to Wuhan Pulmonary Hospital (Wuhan City, Hubei Province, China) between 25 December 2019 and 7 February 2020. Univariate and multivariate logistic regression was performed to investigate the relationship between each variable and the risk of death of COVID-19 pneumonia patients.In total, 179 patients with COVID-19 pneumonia (97 male and 82 female) were included in the present prospective study, of whom 21 died. Univariate and multivariate logistic regression analysis revealed that age ≥65 years (OR 3.765, 95% CI 1.146‒17.394; p=0.023), pre-existing concurrent cardiovascular or cerebrovascular diseases (OR 2.464, 95% CI 0.755‒8.044; p=0.007), CD3+CD8+ T-cells ≤75 cells·μL−1 (OR 3.982, 95% CI 1.132‒14.006; p−1 (OR 4.077, 95% CI 1.166‒14.253; p+CD8+ T-cells ≤75 cells·μL−1 and cardiac troponin I ≥0.05 ng·mL−1 remained as predictors for high mortality from COVID-19 pneumonia.We identified four risk factors: age ≥65 years, pre-existing concurrent cardiovascular or cerebrovascular diseases, CD3+CD8+ T-cells ≤75 cells·μL−1 and cardiac troponin I ≥0.05 ng·mL−1. The latter two factors, especially, were predictors for mortality of COVID-19 pneumonia patients.

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

The numbers of IL-27-producing CD4(+) T cells and the concentration of soluble IL-27 have been found to be increased in tuberculous pleural effusion (TPE). The objective of the present study was to explore the mechanism by which IL-27(+)CD4(+) T cells are recruited into the pleural space, and to explore the impact of IL-27 on pleural mesothelial cells (PMCs).The expression profiles of chemokine receptor (CCR) were determined by flow cytometry. The chemoattractant activity of chemokines CCL20 and CCL22 for IL-27(+)CD4(+) T cells in vitro was observed. Effects of IL-27 on wound healing, proliferation and apoptosis of PMCs were also investigated.IL-27(+)CD4(+) T cells in TPE expressed high level of CCR6, medium level of CCR4, and low levels of CCR2, CCR3, CCR5, CCR7, CCR10, and CXCR3. Recruitment of IL-27(+)CD4(+) T cells into TPE could be induced by pleural CCL20 and CCL22. By activating STAT3 signaling, IL-27 significantly improved wound healing and promoted proliferation of PMCs, and completely prevented apoptosis of PMCs induced by IFN-γ.After being recruited into pleural space by CCL20 or/and CCL22, these pleural IL-27-producing CD4(+) T cells may play important roles in tuberculosis immunity by affecting PMC functions.

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.

IL-22-producing helper T cells (Th22 cells) have been reported to be involved in tuberculosis infection. However, differentiation and immune regulation of Th22 cells in tuberculous pleural effusion (TPE) remain unknown.To elucidate the mechanism by which Th22 cells differentiate and recruit into the pleural space.The distribution and phenotypic features of Th22 cells in both TPE and blood were determined. The impacts of proinflammatory cytokines and antigen presentation by pleural mesothelial cells (PMCs) on Th22-cell differentiation were explored. The chemoattractant activity of chemokines produced by PMCs for Th22 cells was observed.Th22 cells were significantly higher in TPE than in blood. IL-1β, IL-6, and/or tumor necrosis factor-α promoted Th22-cell differentiation from CD4(+) T cells. It was found that PMCs expressed CCL20, CCL22, and CCL27, and that TPE and PMC supernatants were chemotactic for Th22 cells. This activity was partly blocked by anti-CCL20, anti-CCL22, and anti-CCL27 antibodies. IL-22 and IL-17 significantly improved PMC wound healing. Moreover, PMCs were able to stimulate CD4(+) T-cell proliferation and Th22-cell differentiation by presenting tuberculosis-specific antigen.The overrepresentation of Th22 cells in TPE may be due to pleural cytokines and to PMC-produced chemokines. Our data suggest a collaborative loop between PMCs and Th22 cells in TPE. In particular, PMCs were able to function as antigen-presenting cells to stimulate CD4(+) T-cell proliferation and Th22-cell differentiation.

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 and objective: 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. Methods: 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. Results: 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. Conclusions: 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.

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.

Summary Background Serum concentrations of soluble mesothelin-related peptides (SMRP) have been reported to be higher in patients with malignant mesothelioma than in healthy subjects and in patients with non-malignant mesothelioma diseases. The aim of the present meta-analysis was to establish the overall diagnostic accuracy of the measurement of SMRPs for diagnosing malignant mesothelioma. Methods After a systematic review of English language studies, sensitivity, specificity, and other measures of accuracy of serum SMRPs in the diagnosis of malignant mesothelioma were pooled using random-effects models. Summary receiver operating characteristic curves were used to summarize overall test performance. Results Eleven publications from 12 studies met our inclusion criteria. The summary estimates for SMRPs in the diagnosis of malignant mesothelioma in the studies included were sensitivity 0.64 (95% confidence interval 0.61–0.68), specificity 0.89 (0.88–0.90), positive likelihood ratio 7.10 (4.44–11.35), negative likelihood ratio 0.39 (0.31–0.48), and diagnostic odds ratio 19.35 (10.95–34.17). Conclusions Serum SMRP determination plays a role in the diagnosis of malignant mesothelioma. The results of SMRP assays should be interpreted in parallel with clinical findings and the results of conventional tests.

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.

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.

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.

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.

Background Both regulatory T cells (Tregs) and T helper IL-17-producing cells (Th17 cells) have been found to be involved in human malignancies, however, the possible implication of Tregs in regulating generation and differentiation of Th17 cells in malignant pleural effusion remains to be elucidated. Methods The numbers of both CD39+Tregs and Th17 cells in malignant pleural effusion and peripheral blood from patients with lung cancer were determined by flow cytometry. The regulation and mechanism of Tregs on generation and differentiation of Th17 cells were explored. Results Both CD39+Tregs and Th17 cells were increased in malignant pleural effusion when compared with blood, and the numbers of CD39+Tregs were correlated negatively with those of Th17 cells. It was also noted that high levels of IL-1β, IL-6, and TGF-β1 could be observed in malignant pleural effusion when compared the corresponding serum, and that pleural CD39+Tregs could express latency-associated peptide on their surface. When naïve CD4+ T cells were cocultured with CD39+Tregs, Th17 cell numbers decreased as CD39+Treg numbers increased, addition of the anti-latency-associated peptide mAb to the coculture reverted the inhibitory effect exerted by CD39+Tregs. Conclusions Therefore, the above results indicate that CD39+Tregs inhibit generation and differentiation of Th17 cells via a latency-associated peptide-dependent mechanism.

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.

Transduction with recombinant, replication-defective adenoviral (rAd) vectors encoding a transgene is an efficient method for gene transfer into dendritic cells (DCs). Livin is a member of the inhibitor of apoptosis protein family. Lung cancer and many other tumors express livin at high levels; whereas, normal fully differentiated cells generally do not. Therefore, livin represents a tumor-specific target for cancer vaccine therapy. Self proteins like livin may not stimulate potent antitumor immune responses due to central immunologic tolerance. Small variations in protein sequence that may exist between homologous proteins of different species can break tolerance to the native antigen. To study immunogenicity of a xenogeneic livin protein, we constructed an recombinant adenoviral vectors containing the human livin alpha genes (rAd-hlivin alpha) and vaccinated C57BL/6 mice with mouse bone marrow dendritic cells (BMDCs) transfected with rAd-hlivin alpha gave rise to potent livin-specific cytotoxic T lymphocyte (CTL) capable of lysing Lewis lung carcinoma (LLC) cells. Moreover, vaccination of mice with rAd-hlivin alpha-transduced DCs (rAd-hlivin alpha DCs) induced a potent protective and therapeutic anti-tumor immunity to LLC in a subcutaneous model along with prolonged survival compared to mice vaccinated with control recombinant adenovirus-transduced DCs(rAd-c DCs) or DCs alone. Therefore, xenogeneic differences between human and murine sequences might be exploited to develop immunogenic tumor vaccines.

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.

Objective It remains controversial whether intensified chemotherapy with hematopoietic progenitors (ICHP) is effective for small-cell lung cancer. This meta-analysis was performed to evaluate the efficacy and safety of ICHP in patients with small-cell lung cancer. Methods MEDLINE and EMBASE databases were searched for English-language studies published through October 12, 2008. Randomized phase II and III clinical trials comparing ICHP with control therapy. Response rates, overall survival, and toxicity were analyzed. Results Five assessable trials were identified including 641 patients. No significant increase in the odds ratio for response was attributable to ICHP (odds ratio, 1.29; 95% confidence interval, 0.87–1.93; p = 0.206). No statistically significant increase in overall survival was found when ICHP were compared to control regimens (hazard ratio, 0.94; 95% confidence interval, 0.80–1.10; p = 0.432). The toxicity of ICHP was significantly higher for hematologic toxicity, including hemoglobin nadir and platelet nadir. Conclusions ICHP was not superior to control chemotherapy in terms of both objective response and overall survival, and was related to more significant hemoglobin nadir and platelet nadir.

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.

Summary Objective Cytologic approaches such as pleural lavage cytology (PLC) are considered as possible aids to assessing prognosis of lung cancer patients. We aimed to comprehensively review the evidence for use of PLC to predict prognosis of lung cancer. Methods Fifteen studies, including 6391 patients, were found to be eligible for the present meta-analysis. A meta-analysis was done on the log hazard ratios and their variances in these studies. Results Four studies dealt with pleural lavage before lung resection, six studies dealt with pleural lavage after lung resection, and five studies had PLC data from both before and after lung resection examination. For before lung resection studies, combined hazard ratios showed that positive PLC results had an unfavorable impact on survival: 3.96 (95% confidence interval 2.48–6.33), 4.55 (2.95–7.04), 5.00 (3.39–7.36), 5.67 (3.81–8.43), and 7.06 (5.04–9.90), for 1-, 2-, 3-, 4- and 5-year, respectively. For after lung resection studies, combined hazard ratios showed that positive PLC results had an unfavorable impact on survival: 6.02 (3.74–9.71), 6.64 (4.53–9.72), 7.06 (4.93–10.12), 7.29 (5.18–10.25), and 8.47 (6.12–11.73), for 1-, 2-, 3-, 4- and 5-year, respectively. Totally, the combined hazard ratio was 5.61 (3.98–7.90), showing a worse survival when PLC was positive. These findings could be overestimated because of publication and reporting bias. Conclusions PLC is a strong prognostic factor for survival in patients with lung cancer.

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.

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.

lnterleukin-4 (IL-4) has been shown to play a crucial role in the pathogenesis of allergic disease including bronchial asthma. In order to investigate the role of IL-4 in airway hyperreactivity, we investigated the effect of inhaled recombinant human IL-4 on airway responsiveness to methacholine and eosinophil numbers in induced sputum in eight patients with allergic asthma using a placebo-controlled study design. Our results demonstrated that in the control experiments receiving vehicle inhalation, methacholine PC20 values did not change nor did the numbers of eosinophils in sputum change from baseline values. In contrast, after IL-4 inhalation, methacholine PC20 fell from baseline (0.43 +/- 1.81 mg/mI) to 0.22 +/- 1.73 mg/mI (p < 0.01) at 24 h, and to 0.21 +/- 1. 74 mg/ml (p < 0.01) at 48 h. Accompanying this increased airway sensitivity was a significant eosinophilia in sputum. Our data indicated that IL-4 increases airway responsiveness by recruiting eosinophils into the airway in patients with allergic bronchial asthma.

Interleukin (IL)-5 is thought to play an important role in asthmatic bronchial mucosal inflammation and is a potential therapeutic target. To investigate the effect of IL-5 on the infiltration of eosinophils in airway in vivo, we compared eosinophil counts and their activation status in airways without and after the topical instillation of recombinant human IL-5. Eight subjects with mild atopic asthma underwent initial bronchoscopy during which control bronchoalveolar lavage (BAL) fluid as well as bronchial mucosa were obtained, and at the same time, normal saline and IL-5 were administered to two sublobar segments separately. The second bronchoscopy were carried out and samples from challenged sites were taken 24 h later. It was found that the total eosinophils (BMK-13+ cells) and the activated eosinophils (EG2+ cells) in bronchial mucosa, the eosinophil numbers in BAL fluid, as well as eosinophil cationic protein (ECP) in BAL fluid from saline-challenged segments were not different from those in unchallenged segments. However, a significant eosinophilia was observed in bronchial mucosa and BAL fluid from IL-5-challenged sites. Eosinophil activation, as assessed by secretion of ECP, was also increased significantly in bronchial mucosa and BAL fluid. The results strongly suggested that IL-5 is capable of inducing eosinophil infiltration into the asthmatic airways, as well as the activation of infiltrating eosinophils.

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.