RESUMEN
Introduction: Pleural tuberculosis (PlTB), the most common site of extrapulmonary TB, is characterized by a paucibacillary nature and a compartmentalized inflammatory response in the pleural cavity, both of which make diagnosis and management extremely challenging. Although transcriptional signatures for pulmonary TB have already been described, data obtained by using this approach for extrapulmonary tuberculosis and, specifically, for pleural tuberculosis are scarce and heterogeneous. In the present study, a set of candidate genes previously described in pulmonary TB was evaluated to identify and validate a transcriptional signature in clinical samples from a Brazilian cohort of PlTB patients and those with other exudative causes of pleural effusion. Methods: As a first step, target genes were selected by a random forest algorithm with recursive feature elimination (RFE) from public microarray datasets. Then, peripheral blood (PB) and pleural fluid (PF) samples from recruited patients presenting exudative pleural effusion were collected during the thoracentesis procedure. Transcriptional analysis of the selected top 10 genes was performed by quantitative RT-PCR (RT-qPCR). Results: Reanalysis of the public datasets identified a set of candidate genes (CARD17, BHLHE40, FCGR1A, BATF2, STAT1, BTN3A1, ANKRD22, C1QB, GBP2, and SEPTIN4) that demonstrated a global accuracy of 89.5% in discriminating pulmonary TB cases from other respiratory diseases. Our validation cohort consisted of PlTB (n = 35) patients and non-TB (n = 34) ones. The gene expressions of CARD17, GBP2, and C1QB in PF at diagnosis were significantly different between the two (PlTB and non-TB) groups (p < 0.0001). It was observed that the gene expressions of CARD17 and GBP2 were higher in PlTB PF than in non-TB patients. C1QB showed the opposite behavior, being higher in the non-TB PF. After anti-TB therapy, however, GBP2 gene expression was significantly reduced in PlTB patients (p < 0.001). Finally, the accuracy of the three above-cited highlighted genes in the PF was analyzed, showing AUCs of 91%, 90%, and 85%, respectively. GBP2 was above 80% (sensitivity = 0.89/specificity = 0.81), and CARD17 showed significant specificity (Se = 0.69/Sp = 0.95) in its capacity to discriminate the groups. Conclusion: CARD17, GBP2, and C1QB showed promise in discriminating PlTB from other causes of exudative pleural effusion by providing accurate diagnoses, thus accelerating the initiation of anti-TB therapy.
Asunto(s)
Derrame Pleural , Tuberculosis Pleural , Tuberculosis Pulmonar , Humanos , Tuberculosis Pleural/diagnóstico , Tuberculosis Pleural/genética , Exudados y Transudados , Derrame Pleural/diagnóstico , Derrame Pleural/genética , Derrame Pleural/metabolismo , Brasil , Butirofilinas , Antígenos CDRESUMEN
Glucose and nutrient uptake is essential in supporting T cell activation and is increased upon CD3/CD28 stimulation. As T cells from pleural effusions secondary to lung cancer show impaired function, we hypothesized that these cells might have altered expression of nutrient transporters. Here, we analysed by flow cytometry the expression of the transferrin receptor CD71, amino acid transporter CD98 and glucose transporter Glut1 and glucose uptake in pleural effusion-derived T cells from lung cancer patients, after stimulation via CD3/CD28 under normoxia or hypoxia (2% O2 ). We compared the response of T cells from pleural effusions secondary to lung cancer with that of T cells from nonmalignant effusions. In memory T cells from both groups, anti-CD3/CD28-stimulation under normoxia upregulated CD98 and CD71 expression (measured as median fluorescence intensity, MFI) in comparison with anti-CD3-stimulation. Costimulation under hypoxia tended to increase CD98 expression compared to CD3-stimulation in memory T cells from both groups. Remarkably, in the cancer group, memory T cells stimulated via CD3/CD28 under hypoxia failed to increase CD71 and Glut1 expression levels compared to the cells receiving anti-CD3 stimulation, a phenomenon that contrasted with the behaviour of memory T cells from nonmalignant effusions. Consequently, glucose uptake by memory T cells from the cancer group was not increased after CD3/CD28 stimulation under hypoxia, implying that their glycolytic metabolism is defective. As this process is required for inducing an antitumoural response, our study suggests that memory T cells are rendered dysfunctional and are unable to eliminate lung tumour cells.
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Antígenos CD28/metabolismo , Complejo CD3/metabolismo , Transportador de Glucosa de Tipo 1/metabolismo , Glucosa/metabolismo , Memoria Inmunológica/inmunología , Neoplasias Pulmonares/metabolismo , Derrame Pleural/metabolismo , Linfocitos T/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Neoplasias Pulmonares/inmunología , Activación de Linfocitos/inmunología , Masculino , Persona de Mediana Edad , Derrame Pleural/inmunología , Linfocitos T/metabolismoRESUMEN
OBJECTIVE: Pleural tuberculosis is the most frequently occurring form of extra pulmonary disease in adults. In up to 40% of cases, the lung parenchyma is concomitantly involved, which can have an epidemiological impact. This study aims to evaluate the pleural and systemic inflammatory response of patients with pleural or pleuropulmonary tuberculosis. METHODS: A prospective study of 39 patients with confirmed pleural tuberculosis. After thoracentesis, a high resolution chest tomography was performed to evaluate the pulmonary involvement. Of the 39 patients, 20 exhibited only pleural effusion, and high resolution chest tomography revealed active associated-pulmonary disease in 19 patients. The total protein, lactic dehydrogenase, adenosine deaminase, vascular endothelial growth factor, interleukin-8, tumor necrosis factor-α, and transforming growth factor-ß(1) levels were quantified in the patient serum and pleural fluid. RESULTS: All of the effusions were exudates with high levels of adenosine deaminase. The levels of vascular endothelial growth factor and transforming growth factor-ß(1) were increased in the blood and pleural fluid of all of the patients with pleural tuberculosis, with no differences between the two forms of tuberculosis. The tumor necrosis factor-α levels were significantly higher in the pleural fluid of the patients with the pleuropulmonary form of tuberculosis. The interleukin-8 levels were high in the pleural fluid of all of the patients, without any differences between the forms of tuberculosis. CONCLUSION: Tumor necrosis factor-α was the single cytokine that significantly increased in the pleural fluid of the patients with pulmonary involvement. However, an overlap in the results does not permit us to suggest that cytokine is a biological marker of concomitant parenchymal involvement. Although high resolution chest tomography can be useful in identifying these patients, the investigation of fast acid bacilli and cultures for M. tuberculosis in the sputum is recommended for all patients who are diagnosed with pleural tuberculosis.
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Biomarcadores/análisis , Derrame Pleural/metabolismo , Tuberculosis Pleural/metabolismo , Adenosina Desaminasa/análisis , Adulto , Citocinas/análisis , Progresión de la Enfermedad , Ensayo de Inmunoadsorción Enzimática , Exudados y Transudados/química , Humanos , Persona de Mediana Edad , Oxidorreductasas/análisis , Derrame Pleural/diagnóstico por imagen , Estudios Prospectivos , Radiografía , Factor de Crecimiento Transformador beta1/análisis , Tuberculosis Pleural/diagnóstico por imagen , Tuberculosis Pulmonar/metabolismo , Factor de Necrosis Tumoral alfa/análisis , Factor A de Crecimiento Endotelial Vascular/análisis , Adulto JovenRESUMEN
OBJECTIVE: Pleural tuberculosis is the most frequently occurring form of extra pulmonary disease in adults. In up to 40% of cases, the lung parenchyma is concomitantly involved, which can have an epidemiological impact. This study aims to evaluate the pleural and systemic inflammatory response of patients with pleural or pleuropulmonary tuberculosis. METHODS: A prospective study of 39 patients with confirmed pleural tuberculosis. After thoracentesis, a high resolution chest tomography was performed to evaluate the pulmonary involvement. Of the 39 patients, 20 exhibited only pleural effusion, and high resolution chest tomography revealed active associated-pulmonary disease in 19 patients. The total protein, lactic dehydrogenase, adenosine deaminase, vascular endothelial growth factor, interleukin-8, tumor necrosis factor-α, and transforming growth factor-β1 levels were quantified in the patient serum and pleural fluid. RESULTS: All of the effusions were exudates with high levels of adenosine deaminase. The levels of vascular endothelial growth factor and transforming growth factor-β1 were increased in the blood and pleural fluid of all of the patients with pleural tuberculosis, with no differences between the two forms of tuberculosis. The tumor necrosis factor-α levels were significantly higher in the pleural fluid of the patients with the pleuropulmonary form of tuberculosis. The interleukin-8 levels were high in the pleural fluid of all of the patients, without any differences between the forms of tuberculosis. CONCLUSION: Tumor necrosis factor-α was the single cytokine that significantly increased in the pleural fluid of the patients with pulmonary involvement. However, an overlap in the results does not permit us to suggest that cytokine is a biological marker of concomitant parenchymal involvement. Although high resolution chest tomography can be useful in identifying these patients, the investigation of fast acid bacilli and cultures for M. tuberculosis in the sputum is recommended for all patients who are diagnosed with pleural tuberculosis.
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Adulto , Humanos , Persona de Mediana Edad , Adulto Joven , Biomarcadores/análisis , Derrame Pleural/metabolismo , Tuberculosis Pleural/metabolismo , Adenosina Desaminasa/análisis , Citocinas/análisis , Progresión de la Enfermedad , Ensayo de Inmunoadsorción Enzimática , Exudados y Transudados/química , Oxidorreductasas/análisis , Estudios Prospectivos , Derrame Pleural , Factor de Crecimiento Transformador beta1/análisis , Tuberculosis Pleural , Tuberculosis Pulmonar/metabolismo , Factor de Necrosis Tumoral alfa/análisis , Factor A de Crecimiento Endotelial Vascular/análisisRESUMEN
In recent years, better diagnostics for tuberculosis (TB) has received increasing attention, especially the diagnosis of tuberculous pleural effusion, which is difficult and at present the main tool in TPE diagnostic is pleural effusion smear and culture, but unfortunately, sensitivities are low, therefore better TPE diagnostic tools are needed. The aim of this study was to find a diagnostic algorithm to assess the progress in TPE diagnostic at the Hospital Vargas de Caracas, that permits identification of the majority of patients, at a satisfactory cost-benefit ratio, evaluating the levels of IFN-gamma and IL-12p40 in pleural effusion and serum, as well as the antibody reactivity in order to compare it with microbiological tests. A total of 60 individuals with pleural effusion were studied; 20 patients with tuberculous pleural effusion (TPE) formed the patient group and 40 patients with non-tuberculous pleural effusion (NTPE) formed the control group. The levels of IFN-gamma and IL-12p40 in effusion and serum and class and subclasses of IgG reactivity to Mycobacterium tuberculosis antigens were measured by ELISA. The utility of these methods for diagnosis of TPE was evaluated using receiver operating characteristic (ROC) curve analysis. The results of the 11 immunological methods evaluated showed that the anti-PPD IgG2 method was able to reach the highest specificity of 95% (CI: 88.3-101.8), positive predictive value (PPV) = 75 (at 30% sensitivity); while that the overall sensitivity of methods was between 95% and 30%, of these, two methods reached higher sensitivities; increased levels of pleural IFN-gamma, with a sensitivity of 95% (CI: 85.5-104.5) with the highest negative predictive value (NPV) = 97, (at 82.5% specificity), followed by decreased levels of serum IL-12p40 with a sensitivity of 95% (CI: 85.5-104.5), NPV = 95.2 (at 50% specificity). In contrast, microbiological methods showed that smear had a sensitivity of only 20%, while smear plus culture had, a sensitivity of 70%. Considering that TPE represents approximately 15 percent of all the TB clinically diagnosed at the Hospital Vargas de Caracas, in those patients with preliminary microbiology negativity in the effusion, the combined analysis of pleural IFN-gamma and anti-PPD IgG2 could represent a fast and effective diagnostic algorithm for improving the diagnosis previous to obtain culture results. In this way treatment against TB could be initiated or the need to cytological and pleural biopsy could be considered.
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Técnicas Inmunológicas , Interferón gamma/análisis , Subunidad p40 de la Interleucina-12/análisis , Derrame Pleural/diagnóstico , Tuberculosis Pleural/diagnóstico , Adolescente , Adulto , Anciano , Algoritmos , Anticuerpos Antibacterianos/sangre , Anticuerpos Antibacterianos/inmunología , Análisis Costo-Beneficio , Estudios Transversales , Femenino , Humanos , Inmunoglobulina G/sangre , Inmunoglobulina G/clasificación , Inmunoglobulina G/inmunología , Técnicas Inmunológicas/economía , Interferón gamma/sangre , Subunidad p40 de la Interleucina-12/sangre , Masculino , Persona de Mediana Edad , Mycobacterium tuberculosis/inmunología , Derrame Pleural/inmunología , Derrame Pleural/metabolismo , Valor Predictivo de las Pruebas , Curva ROC , Sensibilidad y Especificidad , Tuberculosis Pleural/inmunología , Tuberculosis Pleural/metabolismo , Venezuela , Adulto JovenRESUMEN
The role of CD16(-) and CD16(+) Mo subsets in human TB remains unknown. Our aim was to characterize Mo subsets from TB patients and to assess whether the inflammatory milieu from TB pleurisy modulate their phenotype and recruitment. We found an expansion of peripheral CD16(+) Mo that correlated with disease severity and with TNF-α plasma levels. Circulating Mo from TB patients are activated, showing a higher CD14, CD16, and CD11b expression and Mtb binding than HS. Both subsets coexpressed CCR2/CCR5, showing a potential ability to migrate to the inflammatory site. In tuberculous PF, the CD16(+) subset was the main Mo/MΦ population, accumulation that can be favored by the induction of CD16 expression in CD16(-) Mo triggered by soluble factors found in this inflammatory milieu. CD16(+) Mo in PF were characterized by a high density of receptors for Mtb recognition (DC-SIGN, MR, CD11b) and for lipid-antigens presentation (CD1b), allowing them to induce a successful, specific T cell proliferation response. Hence, in tuberculous PF, CD16(+) Mo constitute the main APC population; whereas in PB, their predominance is associated with the severity of pulmonary TB, suggesting a paradoxical role of the CD16(+) Mo subset that depends on the cellular localization.
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Monocitos/inmunología , Receptores CCR2/análisis , Receptores CCR5/análisis , Receptores de IgG/análisis , Tuberculosis Pleural/inmunología , Tuberculosis/inmunología , Adulto , Anciano , Células Presentadoras de Antígenos/inmunología , Células Presentadoras de Antígenos/metabolismo , Separación Celular , Citocinas/análisis , Citocinas/sangre , Ensayo de Inmunoadsorción Enzimática , Femenino , Citometría de Flujo , Proteínas Ligadas a GPI/análisis , Proteínas Ligadas a GPI/inmunología , Proteínas Ligadas a GPI/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Monocitos/metabolismo , Derrame Pleural/inmunología , Derrame Pleural/metabolismo , Receptores CCR2/inmunología , Receptores CCR2/metabolismo , Receptores CCR5/inmunología , Receptores CCR5/metabolismo , Receptores de IgG/inmunología , Receptores de IgG/metabolismo , Tuberculosis/metabolismo , Tuberculosis Pleural/metabolismoRESUMEN
OBJECTIVE: The therapeutic management of parapneumonic pleural effusions (PPE) is controversial in children. Decision-making often relies on parameters such as gross appearance of pleural fluid and on bacteriologic and biochemical analyses. Our goal was to describe the laboratory profile of PPE in children and to assess the influence of previous administration of antibacterial agents on culture and biochemical results. PATIENTS AND METHODS: This was a prospective study including children (age, 1 month to 16 years) with a diagnosis of PPE. Two groups were evaluated: children with or without antibiotic treatment up to 48 hours before analysis of pleural fluid. Results were analyzed using the χ(2) or Mann-Whitney test (α = .05). Odds ratio and 95% confidence intervals (95% CIs) were calculated, with control of previous antibiotic therapy using multivariate logistic regression analysis, to determine the risk of empyema associated with specific biochemical parameters. RESULTS: One hundred ten children were selected. Fifty percent had received antibiotics at least 48 hours before pleural fluid analysis. Differences were observed between the groups in terms of PPE gross appearance (P = .033) and identification of bacteriologic agent by culture or Gram stain (P = .023). Biochemical parameters (pH ≤7.1 and glucose ≤40 mg/dL) were associated with increased odds of receiving a more invasive treatment. For pH, the odds ratio was 9.614 (95% CI, 1.952-47.362; P = .005); and for glucose, 9.201 (95% CI, 1.333-63.496; P = .024). CONCLUSIONS: Previous use of antibacterial agents affected the bacteriologic analysis of pleural fluid in this pediatric sample admitted for PPE. However, it did not interfere significantly with biochemical parameters of pleural fluid.
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Antibacterianos/uso terapéutico , Líquidos Corporales/efectos de los fármacos , Derrame Pleural/metabolismo , Neumonía Bacteriana/tratamiento farmacológico , Adolescente , Técnicas Bacteriológicas , Líquidos Corporales/química , Líquidos Corporales/microbiología , Niño , Preescolar , Femenino , Glucosa/análisis , Humanos , Concentración de Iones de Hidrógeno , Lactante , Recién Nacido , Masculino , Derrame Pleural/microbiología , Neumonía Bacteriana/metabolismo , Neumonía Bacteriana/microbiología , Estudios ProspectivosRESUMEN
In recent years, better diagnostics for tuberculosis (TB) has received increasing attention, especially the diagnosis of tuberculous pleural effusion, which is difficult and at present the main tool in TPE diagnostic is pleural effusion smear and culture, but unfortunately, sensitivities are low, therefore better TPE diagnostic tools are needed. The aim of this study was to find a diagnostic algorithm to assess the progress in TPE diagnostic at the Hospital Vargas de Caracas, that permits identification of the majority of patients, at a satisfactory cost-benefit ratio, evaluating the levels of IFN-g and IL-12p40 in pleural effusion and serum, as well as the antibody reactivity in order to compare it with microbiological tests. A total of 60 individuals with pleural effusion were studied; 20 patients with tuberculous pleural effusion (TPE) formed the patient group and 40 patients with non-tuberculous pleural effusion (NTPE) formed the control group. The levels of IFN-g and IL-12p40 in effusion and serum and class and subclasses of IgG reactivity to Mycobacterium tuberculosis antigens were measured by ELISA. The utility of these methods for diagnosis of TPE was evaluated using receiver operating characteristic (ROC) curve analysis. The results of the 11 immunological methods evaluated showed that the anti-PPD IgG2 method was able to reach the highest specificity of 95% (CI: 88.3-101.8), positive predictive value (PPV)=75 (at 30% sensitivity); while that the overall sensitivity of methods was between 95% and 30%, of these, two methods reached higher sensitivities; increased levels of pleural IFN-g, with a sensitivity of 95% (CI: 85.5-104.5) with the highest negative predictive value (NPV)=97, (at 82.5% specificity), followed by decreased levels of serum IL-12p40 with a sensitivity of 95% (CI: 85.5-104.5), NPV=95.2 (at 50% specificity). In contrast, microbiological methods showed that smear had a sensitivity of only 20%, while smear plus ...
Recientemente existe un gran interés hacia un mejor y más rápido diagnóstico de tuberculosis (TB), especialmente de tuberculosis pleural, el cual es difícil. Al presente las principales herramientas diagnósticas son la baciloscopia y el cultivo de líquido pleural; desafortunadamente, las sensibilidades de estos métodos son bajas, por lo que el desarrollo de nuevas herramientas diagnósticas es necesario. El objetivo del presente estudio consistió en encontrar un algoritmo que permita la rápida identificación de la mayoría de los pacientes con TB pleural que ingresan en el Hospital Vargas de Caracas a un buen costo-beneficio. Para esto se evaluaron los niveles de las citocinas Interferón-gamma (IFN-g) y la Interleucina 12p40 (IL-12p40) en líquido pleural y suero, así como la reactividad de anticuerpos contra antígenos de Mycobacterium tuberculosis. Se estudiaron 60 individuos con derrame pleural; 20 individuos con líquido pleural tuberculoso (LPT) conformaron el grupo de pacientes y 40 individuos con líquido pleural no tuberculoso (LPNT) el grupo de controles. La técnica de inmunoensayo de ELISA fue utilizada para medir los niveles de IFN-g y IL-12p40; así como las reactividades de los diversos isotipos y subclases de inmunoglobulina G (IgG) frente a antígenos del bacilo. La utilidad de los métodos fue evaluada utilizando el análisis de las curvas ROC (receiver operating characteristic). Los resultados de los 11 métodos inmunológicos evaluados mostraron que el método IgG2 anti-PPD alcanzó la mayor especificidad de 95%, (CI: 88,3-101,8) con un valor predictivo positivo (VPP) de 75. La sensibilidad de los métodos estuvo entre 30% y 95%; dos métodos alcanzaron altas sensibilidades: los altos niveles de IFN-g en líquido pleural, con sensibilidad de 95% (CI: 85,5-104,5), con un valor predictivo negativo (VPN) de 97, seguido de los bajos niveles de IL-12p40 en suero, con una sensibilidad de 95% (CI: 85,5-104,5) con un VPN de 95,2. En contraste, ...
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Adolescente , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Técnicas Inmunológicas , Interferón gamma/análisis , /análisis , Derrame Pleural/diagnóstico , Tuberculosis Pleural/diagnóstico , Algoritmos , Anticuerpos Antibacterianos/sangre , Anticuerpos Antibacterianos/inmunología , Análisis Costo-Beneficio , Estudios Transversales , Inmunoglobulina G/sangre , Inmunoglobulina G/clasificación , Inmunoglobulina G/inmunología , Técnicas Inmunológicas/economía , Interferón gamma/sangre , /sangre , Mycobacterium tuberculosis/inmunología , Valor Predictivo de las Pruebas , Derrame Pleural/inmunología , Derrame Pleural/metabolismo , Curva ROC , Sensibilidad y Especificidad , Tuberculosis Pleural/inmunología , Tuberculosis Pleural/metabolismo , VenezuelaRESUMEN
SETTING: A tertiary care research centre in São Paolo, Brazil. OBJECTIVE: To quantify interleukin (IL) 8, tumour necrosis factor alpha (TNF-alpha), vascular endothelial growth factor (VEGF) and transforming growth factor beta(1) (TGF-beta(1)) in pleural fluid from tuberculous patients, correlating its values with the histopathological patterns in pleural biopsies. DESIGN: Cytokines were quantified in patients with transudates secondary to congestive heart failure (n = 8) and exudates secondary to tuberculosis (TB; n = 39). In parietal pleural biopsies from TB patients, the histological patterns of the inflammatory response were quantified by morphometric analysis (stereological point-counting method). RESULTS: IL-8, TNF-alpha, VEGF and TGF-beta(1) levels were higher in TB than in transudates. A positive correlation existed between components of the fibrinoid exudative phase with pleural fluid IL-8 (R = 0.52, P = 0.004) and VEGF (R = 0.42, P = 0.0021) levels. A negative correlation existed between pleural fluid IL-8 (R = -0.37, P = 0.048) and VEGF (R = -0.44, P = 0.0015) levels with tissue components of fibroproliferation. CONCLUSION: The high pleural levels of TNF-alpha, IL-8, VEGF and TGF-beta(1) suggest the involvement of these cytokines in the TB immunological response. The positive correlation between pleural fluid IL-8 and VEGF with the components of the acute exudative phase and the negative correlation between these cytokines with the fibroproliferative components suggest a temporary inflammatory response in the pleural space.
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Citocinas/metabolismo , Exudados y Transudados/metabolismo , Derrame Pleural/metabolismo , Tuberculosis Pleural/inmunología , Adulto , Anciano , Brasil , Exudados y Transudados/inmunología , Femenino , Insuficiencia Cardíaca/inmunología , Insuficiencia Cardíaca/patología , Humanos , Inflamación/etiología , Inflamación/inmunología , Masculino , Persona de Mediana Edad , Derrame Pleural/inmunología , Estudios Prospectivos , Tuberculosis Pleural/patología , Adulto JovenRESUMEN
BACKGROUND: Lung transplantation is the procedure of choice in several end-stage lung diseases. Despite improvements in surgical techniques and immunosuppression, early postoperative complications occur frequently. OBJECTIVE: To evaluate the pleural inflammatory response after surgery. PATIENTS AND METHODS: Twenty patients aged 18 to 63 years underwent unilateral or bilateral lung transplantation between August 2006 and March 2008. Proinflammatory cytokines interleukin (IL)-1beta, IL-6, and IL-8 and vascular endothelial growth factor in pleural fluid and serum were analyzed. For cytokine evaluation, 20-mL samples of pleural fluid and blood (right, left, or both chest cavities) were obtained at 6 hours after surgery and daily until removal of the chest tube or for a maximum of 10 days. Data were analyzed using analysis of variance followed by the Holm-Sidak test. RESULTS: All effusions were exudates according to Light's criteria. Pleural fluid cytokine concentrations were highest at 6 hours after surgery. Serum concentrations were lower than those in pleural fluid, and IL-1beta, IL-6, and IL-8 were undetectable at all time points. CONCLUSIONS: There is a peak concentration of inflammatory cytokines in the first 6 hours after transplantation, probably reflecting the effects of surgical manipulation. The decrease observed from postoperative day 1 and thereafter suggests the action of the immunosuppression agents and a temporal reduction in pleural inflammation.
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Citocinas/análisis , Hepatopatías/cirugía , Trasplante de Pulmón/fisiología , Adulto , Citocinas/sangre , Exudados y Transudados/metabolismo , Femenino , Humanos , Inflamación/sangre , Interleucina-1beta/análisis , Interleucina-1beta/sangre , Interleucina-6/análisis , Interleucina-6/sangre , Interleucina-8/análisis , Interleucina-8/sangre , Hepatopatías/clasificación , Masculino , Persona de Mediana Edad , Derrame Pleural/metabolismo , Complicaciones Posoperatorias/epidemiología , Estudios Retrospectivos , Factor A de Crecimiento Endotelial Vascular/análisis , Factor A de Crecimiento Endotelial Vascular/sangre , Adulto JovenRESUMEN
INTRODUCTION: The local inflammatory reaction aspects of pleural behaviour post-coronary artery by- pass graft surgery (PCABG) are not completely evident, demanding further study and observation. AIM: To evaluate the behaviour of some cytokines and the possible anti-inflammatory activity of IL-6 (a protein involved in cortisone synthesis) on acute PCA- BG pleural fluid, since this cytokine is usually considered as an acute phase reaction protein associated to high concentrations of TNF-alpha and IL-1 beta in immediate inflammatory reactions. MATERIAL AND METHODS: The concentrations of the TNF-alpha, IL-1 beta, IL-2, IL-6, IL-8, VEGF and TGF-beta cytokines in 16 transudates and 43 exudates in acute PCABS pleural fluid of patients were analysed by the ELISA method 2, 24 and 48 hours after surgery at the Instituto do Coração and Serviço de Pneumologia da USP, Brazil. RESULTS: While no increase was seen in either TNF-alpha or IL-2 in any of the three tests, IL-1 beta increased after 24 until 48 hours, coinciding with the TGF-beta curve decline which fell from the beginning to reach the transudates levels. IL-8 reminded higher from the beginning and through the two subsequent tests while VEGF levels were elevated from the first test and continued high for the following 24 and 48 hours. IL-6 had high concentrations from the beginning, suggesting an anti-inflammatory activity at the three times of testing. CONCLUSIONS: We conclude that IL-6 seems to play an important anti-inflammatory part which is superior to the anti-inflammatory activity of TGF-beta in PCABG pleural effusions. This performance of IL-6 breaks with the traditional idea of it being a pro-inflammatory acute phase reaction cytokine, at least in this type of pleural effusion. This seems to be the first study involving the favourable behaviour of IL-6 in the inflammatory reaction of pleura in the acute phase of PCABG surgery.
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Puente de Arteria Coronaria , Interleucinas/metabolismo , Derrame Pleural/metabolismo , Humanos , Interleucina-6/metabolismo , Derrame Pleural/etiología , Factor de Crecimiento Transformador alfa/metabolismo , Factor de Crecimiento Transformador beta/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
OBJECTIVE: The objective of this study was to establish the value of different markers in differentiating reactive mesothelial cells from metastatic adenocarcinomatous cells in serous effusions (SE). METHODS: Forty-five SE were processed for morphological examination (Papanicolaou stain), assessment of ploidy, AgNOR counting and immunocytochemical assay of carcinoembryonic antigen (CEA), epithelial membrane antigens (EMA), Ber-EP4 and Leu-M1. Ploidy was established in an image-analyser in smears stained by the Feulgen stain method. AgNOR dots were counted in the smears stained with the silver nitrate assay for non-histone proteins present in the nucleolar organizer region. CEA, EMA, Ber-EP4 and Leu-M1 were evaluated by immunocytochemistry using the streptavidin-biotin complex method. RESULTS: All the smears with positive cytology were aneuploid. Three false negatives by morphological studies were aneuploid, with AgNOR values in two of them corresponding to the neoplastic group. CEA and Leu-M1 showed a low specificity; EMA and Ber-EP4 showed moderate sensitivity. CONCLUSIONS: The assessment of ploidy and the study of AgNOR were better methods than immunocytochemistry for distinguishing between reactive mesothelial cells and adenocarcinomatous cells in serous fluid.
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Adenocarcinoma/patología , Antígenos Nucleares/metabolismo , Líquido Ascítico/citología , Neoplasias/patología , Proteínas Nucleares/metabolismo , Derrame Pleural/citología , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Líquido Ascítico/metabolismo , Células Epiteliales/metabolismo , Células Epiteliales/patología , Humanos , Inmunohistoquímica/métodos , Neoplasias/genética , Neoplasias/metabolismo , Derrame Pleural/genética , Derrame Pleural/metabolismo , Ploidias , Frotis Vaginal/métodosRESUMEN
The distinction between exudates and transudates is very important in the patient management. Here we evaluate whether the acute-phase protein serum amyloid A (SAA), in comparison with C reactive protein (CRP) and total protein (TP), can be useful in this discrimination. CRP, SAA, and TP were determined in 36 exudate samples (27 pleural and 9 ascitic) and in 12 transudates (9 pleural and 3 ascitic). CRP, SAA, and TP were measured. SAA present in the exudate corresponded to 10% of the amount found in serum, that is, the exudate/serum ratio (E/S) was 0.10 +/- 0.13. For comparison, the exudate/serum ratio for CRP and TP was 0.39 +/- 0.37 and 0.68 +/- 0.15, respectively. There was a strong positive correlation between serum and exudate SAA concentration (r = 0.764; p < 0.0001). The concentration of SAA in transudates was low and did not overlap with that found in exudates (0.02-0.21 versus 0.8-360.5 g/mL). SAA in pleural and ascitic exudates results mainly from leakage of the serum protein via the inflamed membrane. A comparison of the E/S ratio of SAA and CRP points SAA as a very good marker in discriminating between exudates and transudates.
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Proteínas de Fase Aguda/metabolismo , Proteína C-Reactiva/metabolismo , Exudados y Transudados/metabolismo , Proteína Amiloide A Sérica/metabolismo , Ascitis/metabolismo , Biomarcadores/metabolismo , Proteínas Sanguíneas/metabolismo , Humanos , Derrame Pleural/metabolismo , Sensibilidad y Especificidad , Factores de TiempoRESUMEN
STUDY OBJECTIVE: s: To determine whether talc (TL) and silver nitrate (SN), two effective pleurodesis agents, induce a systemic inflammatory response in the acute phase of experimental pleurodesis in rabbits. DESIGN: Samples of blood and pleural fluid were collected after 6, 24, and 48 h from rabbits injected intrapleurally with 3 mL saline solution, TL (400 mg/kg), or 0.5% SN, and were assayed for WBC count, percentage of neutrophils, and levels of lactate dehydrogenase (LDH), interleukin (IL)-8, and vascular endothelial growth factor (VEGF). The pleural liquid production was compared in the three different groups. A sample of blood collected from animals preinjection was used as the control. RESULTS: At 6 h after pleural injection, the mean blood WBC count and percentage of neutrophils were significantly elevated in the TL group, whereas the mean LDH and IL-8 levels were significantly increased in the SN group. VEGF was undetectable in the preinjection serum and saline solution-injected animals, but was increased in the serum after the pleural injection of both TL and SN to a comparable degree. SN elicited a more intense acute pleural inflammation reaction than did TL, with higher WBC count and IL-8 levels found in the pleural fluid, mainly within the first 6 h. LDH and VEGF levels, and pleural liquid production were also higher for SN, and they increased with time. CONCLUSIONS: In the acute phase of pleural injection, TL induced a transient increase in blood WBC count and percentage of neutrophils, while SN induced increases in blood LDH and IL-8 levels. Both TL and SN induced significant increases in blood VEGF levels. SN induced an earlier and more intense acute pleural inflammation than TL. Pleural liquid VEGF levels were higher after SN injection and increased, as did pleural liquid production. These findings suggest that the intrapleural injection of TL and SN produce a systemic inflammatory response that may have a role in the pathogenesis of fever and ARDS, which occur with pleurodesis.
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Mediadores de Inflamación/análisis , Pleurodesia/métodos , Nitrato de Plata/efectos adversos , Talco/efectos adversos , Enfermedad Aguda , Animales , Modelos Animales de Enfermedad , Inflamación/fisiopatología , Inyecciones Intralesiones , Interleucina-8/análisis , Recuento de Leucocitos , Masculino , Derrame Pleural/metabolismo , Derrame Pleural/terapia , Conejos , Distribución Aleatoria , Valores de Referencia , Sensibilidad y Especificidad , Nitrato de Plata/farmacología , Talco/farmacología , Factor A de Crecimiento Endotelial Vascular/análisisRESUMEN
Oxidized low-density lipoprotein (LDL) contains inflammatory agents, including oxidatively fragmented phospholipids that activate the platelet-activating factor (PAF) receptor, but in vivo events caused by these pathologically generated agents are not well defined. Injection of PAF-like lipids derived from oxidized LDL, or C(4)-PAF that is a major PAF-like lipid in these particles, into the pleural cavity of mice resulted in rapid monocyte, neutrophil, and eosinophil accumulation. Increased numbers of intracellular lipid bodies in these cells show they were in an inflammatory environment. Leukocyte recruitment was abolished by a PAF receptor antagonist, as expected. PAF-like lipids induced 5-lipoxygenase expression in leukocytes, mRNA expression for monocyte chemoattractant protein-1 (MCP-1) and other chemokines, synthesis of MCP-1, and leukotriene B(4). The 5-lipoxygenase inhibitor zileuton impaired neutrophil influx, while MCP-1 had a more global role, as determined with MCP-1(-/-) mice. The lack of MCP-1 abrogated leukocyte accumulation and lipid body formation both in vivo and in vitro and chemokine transcription in vivo, and reduced in vivo leukotriene B(4) production. Thus, PAF-like phospholipids in oxidized LDL induce an inflammatory infiltrate through the PAF receptor, chemokine transcription, lipid body formation, and 5-lipoxygenase expression in leukocytes. MCP-1 has a key role in this inflammatory response, and 5-lipoxygenase products are essential for neutrophil recruitment into the inflamed pleural cavity.
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Araquidonato 5-Lipooxigenasa/fisiología , Movimiento Celular/inmunología , Quimiocina CCL2/fisiología , Diterpenos , Leucocitos/enzimología , Leucocitos/inmunología , Lipoproteínas LDL/fisiología , Fosfolípidos/fisiología , Factor de Activación Plaquetaria/fisiología , Animales , Araquidonato 5-Lipooxigenasa/biosíntesis , Movimiento Celular/genética , Quimiocina CCL2/biosíntesis , Quimiocina CCL2/deficiencia , Quimiocina CCL2/genética , Quimiocinas/biosíntesis , Quimiocinas/genética , Modelos Animales de Enfermedad , Eosinófilos/inmunología , Eosinófilos/metabolismo , Eosinófilos/patología , Ginkgólidos , Humanos , Inflamación/enzimología , Inflamación/metabolismo , Inflamación/patología , Lactonas/farmacología , Leucocitos/patología , Lipoproteínas LDL/metabolismo , Ratones , Neutrófilos/inmunología , Neutrófilos/metabolismo , Neutrófilos/patología , Fosfolípidos/aislamiento & purificación , Fosfolípidos/metabolismo , Factor de Activación Plaquetaria/antagonistas & inhibidores , Derrame Pleural/metabolismo , Derrame Pleural/patología , Pleuresia/enzimología , Pleuresia/inmunología , Pleuresia/metabolismo , Pleuresia/patología , ARN Mensajero/biosíntesisRESUMEN
Two infants who developed chylothorax after surgery for congenital heart disease were treated successfully with subcutaneous octreotide. Apart from reducing chyle output, octreotide decreased the triglyceride content of the pleural fluid.
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Quilotórax/tratamiento farmacológico , Hormonas/uso terapéutico , Octreótido/uso terapéutico , Complicaciones Posoperatorias/tratamiento farmacológico , Femenino , Cardiopatías Congénitas/cirugía , Hormonas/administración & dosificación , Humanos , Lactante , Inyecciones Subcutáneas , Masculino , Octreótido/administración & dosificación , Derrame Pleural/metabolismoRESUMEN
INTRODUCTION: Since the criteria of Light and colleagues for differentiating transudates and exudates were described, other tests, including the pleural fluid (PF) cholesterol test, have been proposed for the same purpose. However, the factors influencing PF cholesterol levels have not been clearly delineated. PURPOSE: To analyze the relationships among total cholesterol (CHOL), low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides (TRIG) in serum (S) and PF. METHODS: PF and S from 99 patients (transudates, 13 patients; exudates, 86 patients) were analyzed for CHOL, HDL, LDL, TRIG, apolipoprotein AI, apolipoprotein B, and protein. The relationship between the PF and S level for each of these measurements was analyzed with linear regression and multiple regression using the ratio of PF to S protein for that measurement as a second independent variable. RESULTS: This study demonstrated that CHOL levels in PF are related to S cholesterol levels and to the permeability of the pleura (r = 0.88; p < 0.001). However, the percentage of CHOL associated with LDL and HDL (56%) in the PF was much lower than that associated with LDL and HDL in S (93%), suggesting that lipoproteins are modified once they enter the pleural space. The PF TRIG was not closely related to its S level or to the PF/S protein ratio (r = 0.49). CONCLUSION: PF cholesterol levels can be closely predicted from the S cholesterol levels and the permeability of the pleura, as reflected by the ratio of PF protein to S protein. Therefore, the CHOL ratio should not provide additional information to that provided by the protein ratio when trying to differentiate transudates from exudates. PF lipoproteins (LDL and HDL) undergo metabolic alterations once they enter the pleural space. PF TRIG levels are not closely related to S levels or to the permeability of the pleura.
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Colesterol/sangre , Derrame Pleural/metabolismo , Apolipoproteína A-I/sangre , Apolipoproteínas B/sangre , Proteínas Sanguíneas/metabolismo , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Humanos , Derrame Pleural/diagnóstico , Derrame Pleural/etiología , Valores de Referencia , Triglicéridos/sangreRESUMEN
The effect of fat-rich diets on the acute inflammatory response was examined. Male Wistar rats aged 21 days were fed, for 6 weeks, with a control diet (4% fat content), or a control diet supplemented with coconut or soybean oils (15% fat content). Carrageenan-induced paw oedema and pleurisy were evaluated. Prostaglandin (PG) E2 and leukotriene (LT) C4/D4 concentrations were determined in the pleural exudate (ELISA). Pleural samples were tested for their effect on cutaneous vascular permeability of control rats and the effect of a LTD4 receptor antagonist (L660-711; 10 mg/kg; i.v.) examined. Relative to controls, rats fed both fat-rich diets presented a significant reduction in protein leakage and oedema formation without affecting the number of migrating leukocytes. Production of LTC4/D4 in pleural exudate was significantly increased from 1.8 +/- 0.2 ng/ml in controls to 2.8 +/- 0.2 and 3.0 +/- 0.3 ng/ml in animals fed coconut and soybean oil enriched diets, respectively, without changes in PGE2 production. The activity of these samples on cutaneous vascular permeability was 50% reduced, returning to control values after treatment of testing animals with a LTD4 receptor antagonist. Rats fed fat-rich diets presented a reduced inflammatory response due, at least in part, to the LTC4/D4 mediated vasoconstrictor effect.
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Reacción de Fase Aguda/dietoterapia , Grasas de la Dieta/administración & dosificación , Leucotrieno C4/metabolismo , Leucotrieno D4/metabolismo , Reacción de Fase Aguda/inducido químicamente , Reacción de Fase Aguda/metabolismo , Animales , Permeabilidad Capilar/efectos de los fármacos , Carragenina , Aceite de Coco , Dinoprostona/metabolismo , Edema/inducido químicamente , Edema/metabolismo , Ensayo de Inmunoadsorción Enzimática , Exudados y Transudados/metabolismo , Miembro Posterior/efectos de los fármacos , Antagonistas de Leucotrieno/farmacología , Masculino , Aceites de Plantas/administración & dosificación , Derrame Pleural/metabolismo , Pleuresia/inducido químicamente , Pleuresia/metabolismo , Propionatos/farmacología , Quinolinas/farmacología , Ratas , Ratas Wistar , Piel/irrigación sanguínea , Piel/efectos de los fármacos , Aceite de Soja/administración & dosificaciónRESUMEN
In noninfected rats, challenge with allergen following local IgE sensitization induced a pleurisy marked by intense protein exudation that plateaued from 30 min to 4 h after challenge, reducing thereafter. Infection of rats with Angiostrongylus costaricensis induced a 5-fold increase in blood eosinophil numbers by 25 days postinfection, whereas the numbers of eosinophils in the pleural cavity ranged from normal to a weak increase. In infected rats, identically sensitized, challenge with Ag induced a much shorter duration of pleural edema with complete resolution by 4 h, but no change in the early edema response. In parallel, infection increased the number of eosinophils recovered from the pleural cavity at 4 h, but not at 30 min, following allergen challenge. Pretreatment with IL-5 (100 IU/kg, i.v.) also increased eosinophil numbers in blood and, after allergen challenge, shortened the duration of the pleural edema and increased pleural eosinophil numbers. There were increases in the levels of both PGE2 and lipoxin A4 (LXA4) in pleural exudate. Selective cyclooxygenase (COX)-2 inhibitors, NS-398, meloxicam, and SC-236, did not alter pleural eosinophilia, but reversed the curtailment of the edema in either infected or IL-5-pretreated rats. Pretreatment of noninfected animals with the PGE analogue, misoprostol, or two stable LXA4 analogues did not alter the magnitude of pleural exudation response, but clearly shortened its duration. These results indicate that the early resolution of allergic pleural edema observed during A. costaricensis infection coincided with a selective local eosinophilia and seemed to be mediated by COX-2-derived PGE2 and LXA4.
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Angiostrongylus/inmunología , Dinoprostona/fisiología , Edema/terapia , Eosinofilia/enzimología , Ácidos Hidroxieicosatetraenoicos/fisiología , Hipersensibilidad/terapia , Isoenzimas/metabolismo , Lipoxinas , Prostaglandina-Endoperóxido Sintasas/metabolismo , Infecciones por Strongylida/enzimología , Administración Oral , Animales , Antiinflamatorios no Esteroideos/metabolismo , Antiinflamatorios no Esteroideos/farmacología , Antígenos Helmínticos/administración & dosificación , Corticosterona/sangre , Ciclooxigenasa 2 , Inhibidores de la Ciclooxigenasa 2 , Inhibidores de la Ciclooxigenasa/administración & dosificación , Dinoprostona/metabolismo , Edema/enzimología , Edema/patología , Edema/fisiopatología , Eosinofilia/patología , Eosinofilia/fisiopatología , Exudados y Transudados/efectos de los fármacos , Exudados y Transudados/enzimología , Femenino , Ácidos Hidroxieicosatetraenoicos/metabolismo , Hipersensibilidad/enzimología , Hipersensibilidad/patología , Hipersensibilidad/fisiopatología , Inyecciones Intraperitoneales , Inyecciones Intravenosas , Interleucina-5/administración & dosificación , Isoenzimas/farmacología , Cinética , Leucotrieno C4/metabolismo , Masculino , Misoprostol/administración & dosificación , Derrame Pleural/enzimología , Derrame Pleural/metabolismo , Derrame Pleural/patología , Derrame Pleural/prevención & control , Pleuresia/enzimología , Pleuresia/patología , Pleuresia/fisiopatología , Prostaglandina-Endoperóxido Sintasas/farmacología , Ratas , Ratas Wistar , Infecciones por Strongylida/patología , Infecciones por Strongylida/fisiopatologíaRESUMEN
Justificativa. Derrame pleural é um problema freqüentemente encontrado na prática clínica. Enquanto o derrame pleural transudativo, geralmente, nao apresenta dificuldade no diagnóstico, as efusoes exsudativas necessitam de um diagnóstico diferencial cuidadoso que inclui, necessariamente, tuberculose e neoplasia metastática para a pleura. Métodos. Num estudo transversal, foram estudados 221 pacientes consecutivos, com derrame pleural persistente e/ou nao eslarecido, em um hospital de refência para doenças respiratórias na rede pública estadual, com o objetivo de avaliar a acurácia da determinaçao da atividade da adenosina desaminase (ADA) no líquido pleural para o diagnóstico de tuberculose. Esses pacientes foram enquadrados nos seguintes grupos: a) tuberculose (confirmada, n=150; provável, n=9); b) neoplasia (confirmada, n=21; provável, n=16; linfoma, n=3); e c) miscelânea (n=22). Os pacientes foram submetidos a exame clínico, radiografias de tórax, testes sanguíneos e toracocenteses com biópsias pleurais. No líquido pleural foram realizados os exames de rotina com adicional determinaçao da atividade da ADA pelo método de Giusti. Resultados. Estudando a inter-relaçao entre sensibilidade e especificidade da atividade da ADA em diferentes níveis de corte, foi determinado que o melhor nível seria o de 40U/L. assim, observou-se sensibilidade de 93,3 por cento, especificidade de 93,5 por cento, valor preditivo positivo de 97,2 por cento e valor preditivo negativo de 85,3 por cento, quando analisados apenas os pacientes com tuberculose confirmada e os nao-tuberculosos. Três dos quatro pacientes com elevada atividade da ADA, sem tuberculose, tinham linfoma. Conclusao. A determinaçao da atividade da ADA no líquido pleural é um exame de baixo custo, de técnica simples e rápida, tem alta sensibilidade e especificidade para identificar pacientes com pleurite tuberculosa. Os achados do presente estudo sao comparáveis a outras observaçoes publicadas, demonstrando a utilidade da incorporaçao deste teste na avaliaçao rotineira dos derrames pleurais em áreas com alta prevalência de tuberculose.