联合检测IFN-γ、VEGF-C、CRP及ADA对结核性与恶性胸腔积液鉴别诊断的价值

目的探讨干扰素-γ(IFN-γ)、血管内皮生长因子(VEGF-C)、C-反应蛋白(CRP)及腺苷脱氨酶(ADA)在结核性与恶性胸腔积液鉴别诊断中的应用价值。方法检测122例临床确诊的胸腔积液患者(恶性胸腔积液56例,结核性胸膜炎48例,其他类型18例)胸水和血清中的IFN-γ、VEGF-C、CRP及ADA含量。结果结核组的IFN-γ、CRP浓度及ADA活性明显高于恶性肿瘤组,差异有统计学意义(P0.01),根据受试者工作特征(ROC)曲线结果判断,以100ng/L为临界值,IFN-γ对结核性胸腔积液诊断的灵敏度、特异性分别为83.1%、92.3%;以45U/L为临界值,ADA对结核性胸腔积液诊断的灵敏度、特异性分别为85.6%、96.3%;以110mg/L为临界值,CRP对结核性胸腔积液诊断的灵敏度、特异性分别为79.1%、84.2%;三项指标联合检测,其灵敏度、特异性分别达到87.8%和86.0%。恶性胸腔积液中VEGF-C高于结核性及其他类型胸腔积液(P0.01);VEGF-C/ADA≥8对恶性胸腔积液诊断的灵敏度、特异性分别为86.3%、82.6%;VEGF-C/ADA≤3对结核性胸腔积液诊断的灵敏度、特性度分别为85.1%、87.1%。结论联合检测IFN-γ、VEGF-C、CRP及ADA可以提高结核性胸膜炎诊断的灵敏度及特异性,VEGF-C与ADA浓度比值对胸腔积液的鉴别诊断具有较好的临床价值。     

T-lymphocyte response in a guinea pig model of tuberculous pleuritis.

The ability to induce tuberculous pleuritis in Mycobacterium bovis BCG-vaccinated guinea pigs was investigated as a model of human disease. A pleural effusion of 5 to 10 ml was obtained 6 to 7 days after the bilateral pleural injection of a suspension of heat-killed M. tuberculosis cells. Histological lesions were indicative of granulomatous pleuritis. Comparative studies of T lymphocytes obtained from pleural fluid and peripheral blood revealed increased antigen-driven lymphoproliferation and E rosette formation in pleural effusion lymphocytes. The CD2+ T-lymphocyte population appeared to be expanded or concentrated in pleural fluid, suggesting a compartmentalization of antigen-reactive T lymphocytes. These data demonstrate that experimental tuberculous pleuritis with effusion, closely resembling the human disease, can be produced in BCG-vaccinated guinea pigs.     

Beta 2 microglobulin in pleural effusions

Beta 2 microglobulin (beta 2m) concentrations in serum and pleural fluid from 64 patients with pleural effusion were studied. The level of beta 2m in pleural fluid was generally twice that in serum. The ratio of pleural fluid beta 2m to serum beta 2m in patients groups defined according to the final diagnosis showed an interestingly high value in tuberculous pleuritis and in patients with rheumatoid arthritis with pleural effusion. There was a positive correlation between the beta 2m and lysozyme contents in pleural fluid, suggesting local and simultaneous activation of different cell lines when the pleura is involved. We suggest that pleural fluid and concomitant serum beta 2m measurements should be taken into consideration when pleural effusion of tuberculous origin is suspected. Furthermore, beta 2m determination might help to differentiate between rheumatoid pleural fluid and pleural involvement due to the other systemic diseases.     

Cellular immunity in tuberculous pleural effusions: evidence of spontaneous lymphocyte proliferation and antigen-specific accelerated responses to purified protein derivative (PPD).

The kinetics of in vitro cellular proliferation against a PPD of Mycobacterium tuberculosis or streptococcal antigen (streptokinase-streptodornase) was evaluated in pleural fluid and peripheral blood mononuclear cells (PBMC) from patients with tuberculous and non-tuberculous pleuritis. The peak proliferative response to PPD by mononuclear cells from pleural fluid occurred earlier (day 3) in 65% of patients with tuberculosis, a finding not seen in non-tuberculous effusions. Spontaneous lymphocyte proliferation of both peripheral blood lymphocytes and pleural effusion lymphocytes was frequently observed, irrespective of etiology. However, 20 of 21 tuberculous patients manifesting spontaneous lymphocyte proliferation had accelerated kinetics of proliferation to PPD, which was antigen-specific. These results suggest that spontaneous lymphocyte proliferation occurs as a response to antigen stimulation at the site of disease, and is not a non-specific response to inflammation. Furthermore, enhanced reactivity against mycobacterial antigen, manifested by accelerated kinetics of proliferation, has diagnostic potential in patients with pleural effusions.     

Serum and Pleural Fluid Procalcitonin in Predicting Bacterial Infection in Patients with Parapneumonic Effusion

This study evaluated the value of procalcitonin (PCT) levels in pleural effusion to differentiate the etiology of parapneumonic effusion (PPE). Forty-one consecutive PPE patients were enrolled and were divided into bacterial and non-bacterial PPE. Blood and pleural effusion samples were collected for PCT measurement on admission and analyzed for diagnostic evaluation. PCT of pleural fluid was significantly increased in the bacterial PPE group (0.24 ng/mL) compared to the non-bacterial PPE group (0.09 ng/mL), but there was no significant difference for serum PCT. A PCT concentration of pleural fluid >0.174 ng/mL (best cut-off value) was considered positive for a diagnosis of bacterial PPE (sensitivity, 80%; specificity, 76%; AUC, 0.84). Pleural effusion PCT in the bacterial PPE is significantly different from those of the non-bacterial PPE and control groups, so the diagnostic use of PCT still warrants further investigation.     

Relative abundance and patterns of correlation among six cytokines in pleural fluid measured by cytometric bead array

Several cytokines play significant roles in the development and pathogenesis of pleural effusion. Little is known, however, about possible interactions between individual cytokines in terms of regulation of their relative abundance in the effusion. We studied 93 patients presenting with pleural effusion to the National Sanyo Hospital (68 men and 25 women; mean age, 64 years). Twenty-two patients had tuberculous pleurisy, 40 had malignant pleuritis, and 31 had effusions due to an etiology other than tuberculosis or cancer (miscellaneous). Pleural fluid concentrations of IL-2, IL-4, IL-5, IL-10, TNF-alpha, and INF-gamma were simultaneously measured by cytometric bead array (CBA). The ratios of IL-4/IL-5, IL-4/TNF-alpha, IL-2/TNF-alpha, and IL-10/TNF-alpha were lower in patients with tuberculosis pleurisy compared with other patients. In all three groups of patients significant correlation was seen between abundance of IL-2 vs. IL-4, IL-5, IL-10, or TNF-alpha, between IL-4 vs. IL-10, and between TNF-alpha vs. INF-gamma. In malignant pleural fluid patients, the significant correlation was between IL-2 vs. IL-4, TNF-alpha, or INF-gamma, between IL-4 vs. INF-gamma, and between TNF-alpha vs. INF-gamma. In tuberculosis pleural fluid patients, the significant correlation was between IL-2 vs. TNF-alpha, between IL-4 vs. IL-10, and between TNF-alpha vs. INF-gamma. In miscellaneous pleural fluid patients, the significant correlation was between IL-2 vs. IL-4, IL-10, or TNF-alpha, between IL-4 vs. IL-10, TNF-alpha, and between IL-10 vs. TNF-alpha. No significant correlation was observed between other pairs of cytokines. Strong correlation in abundance between particular cytokines in pleural fluids suggests cross-talk between them, in terms that an altered level of one of them provides a feedback mechanism regulating synthesis and/or secretion of another one. Such interactions may play important roles in pathogenesis and severity of the effusion. The CBA methodology provides a convenient tool to investigate these interactions.     

Complicated parapneumonic effusion and empyema in children.

BACKGROUND AND PURPOSE: Parapneumonic effusion and empyema are recognized complications of bacterial pneumonia. Optimal management in children, especially the duration of parenteral antibiotics and the role of surgery, is controversial. This study analyzed the clinical characteristics, management, outcome, and bacterial etiology of 59 patients with complicated parapneumonic effusion and empyema treated at a single medical center in Kaohsiung from January 1995 to March 2004. METHODS: The diagnosis of complicated parapneumonic effusion was based on the specific characteristics of pleural fluid, computed tomography or ultrasound findings, or direct visualization of loculations during the surgical procedure. RESULTS: Causative agents were culture-confirmed in 42% of the cases. Streptococcus pneumoniae was the leading pathogen in this series (20% of cases). None of the S. pneumoniae isolates were susceptible to penicillin. Mycoplasma pneumoniae accounted for 19% of cases based on immunoglobulin M assay. CONCLUSIONS: An initial combination therapy regimen consisting of cefotaxime or ceftriaxone plus macrolide provided reasonable activity against 80% of the pathogens isolated in this series. This study also revealed that prolonged parenteral antibiotic treatment resulted in longer length of hospital stay.     

Xpert MTB/RIF assay for diagnosis of pleural tuberculosis

We prospectively investigated the diagnostic utility of the Xpert MTB/RIF (Mycobacterium tuberculosis/rifampin [RIF] resistance) assay in 20 cases with confirmed tuberculous pleural effusion. The sensitivity and specificity of the Xpert assay in pleural fluid were 25% and 100%, respectively. All cases positive by the Xpert assay were also positive by pleural fluid culture.     

Gamma Interferon Immunospot Assay of Pleural Effusion Mononuclear Cells for Diagnosis of Tuberculous Pleurisy

Diagnosis of tuberculous pleurisy remains a challenge in the clinic. In this study, we evaluated the usefulness of a previously developed Mycobacterium tuberculosis antigen-specific gamma interferon enzyme-linked immunospot (ELISPOT) assay in the diagnosis of tuberculous pleurisy by testing a cohort of 352 patients with pleural effusion. We found that M. tuberculosis antigen-specific gamma interferon-producing cells were enriched four to five times in pleural fluid compared with their levels in peripheral blood from patients with tuberuclous pleurisy assayed in parallel. The sensitivity, specificity, positive predictive value, and negative predictive value of the pleural fluid mononuclear cell ELISPOT assay for the diagnosis of tuberculous pleurisy were 95.7%, 100%, 100%, and 81.0%, respectively. In comparison, the sensitivity and specificity of the ELISPOT assay using peripheral blood mononuclear cells were 78.3% and 86.3%, respectively. The sensitivity and specificity of the pleural fluid adenosine deaminase activity test were 55.5% and 86.3%, respectively. These results demonstrate that the M. tuberculosis antigen-specific ELISPOT assay performed on pleural fluid mononuclear cells provides an accurate, rapid diagnosis of tuberculous pleurisy.     

胸水多项肿瘤标志物检测的临床价值

目的:通过对胸水中多项肿瘤标志物的联合检测来鉴别癌性、结核性胸水,以提高癌性胸水诊断的阳性率。方法:采用多肿瘤标志物蛋白芯片诊断系统,检测60例癌性胸水和30例结核性胸水中的12种常见肿瘤标志物。结果:癌性胸水组中CEA、NSE、SF、CA125四项肿瘤标志物均值数、阳性率均显著高于结核性胸水组。四种指标联检对癌性胸水的诊断阳性率可达96 7%。结论:胸水CEA、NSE、SF、CA125联检对鉴别良恶性胸水有重要价值,且可显著提高癌性胸水的阳性诊断率。     

Is adenosine deaminase in pleural fluid a useful marker for differentiating tuberculosis from lung cancer or mesothelioma in Japan, a country with intermediate incidence of tuberculosis?

The objective of this study was to evaluate the utility of the determination of adenosine deaminase (ADA) level in pleural fluid for the differential diagnosis between tuberculous pleural effusion (TPE) and malignant pleural effusion (MPE) in Japan, a country with intermediate incidence of tuberculosis (TB). We retrospectively reviewed the clinical records of 435 patients with pleural effusion and investigated their pleural ADA levels as determined by an auto analyzer. ROC analysis was also performed. The study included patients with MPE (n＝188), TPE (n＝124), benign nontuberculous pleural effusion (n＝94), and pleural effusion of unknown etiology (n＝29). The median ADA level in the TPE group was 70.8U/L, which was significantly higher than that in any other groups (p＜0.05). The area under the curve (AUC) in ROC analysis was 0.895. With a cut-off level for ADA of 36U/L, the sensitivity, specificity, positive predictive value, and negative predictive value were 85.5%, 86.5%, 69.7%, and 93.6%, respectively. As many as 9% of patients with lung cancer and 15% of those with mesothelioma were false-positive with this ADA cutoff setting. Although the ADA activity in pleural fluid can help in the diagnosis of TPE, it should be noted that some cases of lung cancer or mesothelioma show high ADA activity in geographical regions with intermediate incidence of TB, in contrast to high prevalence areas.     

Rheumatoid arthritis cells and biochemical changes in turpentine-induced pleuritis in rabbits

When turpentine was instilled into the right pleural cavity in rabbits a pleural effusion developed in half of the animals, with a low pH, low glucose concentration, high lactic dehydrogenase activity and the constant presence of rheumatoid arthritis cells in the affected pleural cavity. The biochemical values in the pleural fluid were significantly different from the values for normal pleural fluid obtained by a special microtechnique. These changes resulting from the experimentally induced, simple, irritative turpentine pleuritis are similar to the findings in the pleural effusion in human rheumatoid pleuritis; this implies that such changes are probably non-specific and without evidence of an immunological background.     

AM、CYFRA21-1、NSE和CEA联合检测对恶性与结核性胸腔积液的鉴别诊断价值

用RIA检测了52例(男32例, 女20例)结核性胸腔积液组和74例(男49例,女25例)恶性胸腔积液组的肾上腺髓质素(AM)、CYFRA21-1、NSE和CEA水平,结果表明: 恶性胸腔积液组四项肿瘤标志物含量均显著高于结核性胸腔积液组, 四项联合检测可进一步提高诊断敏感性和准确性至90.5%和92.9%, 有显著性差异(P＜0.01).结论: 胸腔积液AM、 CYFRA21-1、NSE和CEA联合检测对鉴别恶性与结核性胸腔积液有实用价值, 可显著提高恶性胸腔积液的阳性诊断率.     

Enzyme-linked immunospot assay for interferon-gamma in the diagnosis of tuberculous pleurisy

Patients presenting with pleural effusion of undetermined aetiology were prospectively enrolled, and an enzyme-linked immunospot (ELISPOT) assay on pleural fluid and peripheral blood was performed. Forty patients were studied, including 19 with culture- or biopsy-confirmed ( n  = 15) or clinically compatible ( n  = 4) tuberculous pleurisy, and 21 with pleural effusions due to non-tuberculous causes. The sensitivity, specificity and positive and negative predictive values of the assay were 94.7%, 85.7%, 85.7% and 94.7%, respectively, on pleural fluid, and 77.8%, 90.5%, 87.5% and 82.6%, respectively, on blood. Antigen-specific, interferon-gamma-secreting T-cells were concentrated eight to ten times in pleural fluid as compared with blood. Among the seven patients not suitable for pleural biopsy and three patients whose biopsy results were non-diagnostic, nine had positive ELISPOT result with pleural fluid. The ELISPOT assay for interferon-gamma can accurately diagnose tuberculous pleurisy and is helpful for patients not suitable for pleural biopsy and those whose biopsy results are non-diagnostic.     

血清及胸水中ADA、IL-2、IL-6、IL-10联检对结核性和癌性胸膜炎患者的诊断价值

目的:观察结核性和癌性胸膜炎两组患者血清和胸水ADA、IL-2、IL-6、IL-10的含量变化,能成为鉴别诊断试验。方法:结核性胸水组56例、癌性胸水组53例、正常对照组30例,分别测定血清和胸水中ADA、IL-2、IL-6、IL-10,并进行临床诊断的ROC曲线分析。结果:两组患者血清IL-6水平明显高于对照组,有显著性差异(P<0 05),结核性胸水组的ADA、IL-2、IL-6、IL-10明显高于癌性组,有显著差异(P<0 05),ROC曲线表明两组依次为ADA>IL-10>IL-6>IL-2。结论:胸水的ADA、IL-2、IL-6、IL-10的测定有助于两组的鉴别诊断,总的鉴别诊断价值依次为ADA>IL-10>IL-6 >IL-2,并且ADA与IL-10的联检可明显提高两组胸水的鉴别诊断价值。     

Diagnostic tests for tuberculous pleural effusion

The investigation of pleural effusion has been greatly assisted by advancements in pleural fluid analysis. In the case of tuberculous pleural effusion, diagnosis traditionally requires the demonstration of acid fast bacilli in the pleural space using microbiological or histological techniques. In recent years, there has been progress in pleural fluid analysis in suspected tuberculous effusions, with particular interest in adenosine deaminase and interferon-γ. These individual tests are quite sensitive and specific; however, data are sparse on the benefits that multiple-parameter testing may have when analysed in combination. We reviewed the literature to investigate the evidence for multiple-parameter testing, both biochemical and clinical, in the evaluation of tuberculous effusion.     

Circulating TNF-alpha, TGF-beta, and IL-10 in tuberculosis patients and healthy contacts

Levels of tumour necrosis factor (TNF)-alpha, transforming growth factor (TGF)-beta, and interleukin (IL)-10 in plasma of pulmonary tuberculosis (TB) patients and healthy contacts and plasma and pleural fluid of patients with tuberculous pleuritis were examined by enzyme immunoassay. Plasma TNF-alpha and IL-10 were elevated to significant levels in healthy contacts. High levels of TGF-beta and IL-10 were also detected in plasma from TB patients and healthy contacts. Pleural fluid contained all three cytokines with the level of IL-10 being highest followed by TGF-beta and TNF-alpha. Plasma of tuberculous pleuritis patients also had detectable levels of the three cytokines. Increased levels of TNF-alpha in plasma of contacts and to some extent pleural fluid of pleuritis patients, is perhaps to limit the infection, while elevated IL-10 in plasma of TB patients and contacts and pleural fluid would perhaps modulate excess proinflammation. Elevated TGF-beta in TB patients suggests its role in the immunopathogenesis.     

ADA、ACE、LDH、CEA的联合检测在结核性和恶性胸腔积液中的鉴别诊断价值

目的测定血清和胸水中腺苷脱氨酶（ADA）、血管紧张素转化酶（ACE）、乳酸脱氢酶（LDH）与癌胚抗原（CEA）的水平,探讨其指标联合检测对结核性和恶性胸水的鉴别诊断意义。方法对临床已确诊的72例胸腔积液患者（结核性40例,恶性32例）的胸水和血清分别采用酶免疫法和化学发光法进行ADA、ACE、LDH和CEA含量测定。结果结核性胸水中ADA的含量为（60.2±20.10）U/L,ACE的含量为（35±9.6）U/L,LDH的含量为（338±41）U/L,CEA的含量为（12.8±5.82）μg/L;在恶性胸水中,ADA为（11.02±5.23）U/L,ACE为（16±11.0）U/L,LDH为（379±69.0）U/L,CEA为（39.9±19.7）μg/L。结核性胸水ADA和ACE含量较恶性胸水组明显增高（P〈0.01）,CEA在恶性胸水中含量较结核性胸水组明显增高（P〈0.01）。胸水中ADA和ACE的检测对结性性胸膜积液诊断的敏感性分别为84.3%、87.5%,特异性分别为87.5%、80.0%;而胸水中LDH和CEA的检测对恶性胸膜积液诊断的敏感分别为84.3%、75.0%,特异性分别为80.0%、93.0%。四项指标联合检测敏感性性为78.1%,特异性为97.5%,较单一指标的特异性高。结论胸水中ADA、ACE、LDH和CEA的联合检测对结核性和恶性胸水的鉴别诊断具有一定价值,有助于临床胸水性质的诊断。     

Diagnostic utility of pleural fluid IFN-gamma in tuberculosis pleural effusion.

Pleural fluid interferon-gamma (IFN-gamma) levels are increased in patients with tuberculosis (TB) pleural effusion. Recent studies from the west have found that estimation of pleural fluid IFN-gamma levels is an excellent diagnostic strategy for these patients. The diagnostic utility of pleural effusion IFN-gamma level estimation has not been evaluated in patients from developing countries, however. This work was carried out to study the diagnostic utility of IFN-gamma level estimation in patients with TB pleural effusion and to define the best cutoff of IFN-gamma for diagnosis TB pleural effusion. We studied 101 patients with pleural effusion. Of these, 64 were found to have a TB etiology, established by means of various conventional modalities. Measurement of pleural fluid IFN-gamma levels was done by ELISA technique. The median value of pleural fluid IFN-gamma levels in patients with TB (1480 pg/ml, range 3-14,000 pg/ml) was significantly higher (p < 0.001) compared with the non-TB group (3 pg/ml, range 0-900 pg/ml). The receiver operator characteristic (ROC) curve for IFN-gamma showed an area under the curve (AUC) value of 0.954, and the best cutoff was computed to be 138 pg/ml. Using this cutoff for IFN-gamma levels in pleural fluid for the diagnosis of TB, sensitivity, specificity, negative predictive value, and positive predictive value were found to be 90.2%, 97.3%, 85.7%, and 98.3%, respectively. Estimation of IFN-gamma levels in pleural fluid is a useful diagnostic modality for TB pleural effusion. A cutoff of 138 pg/ml provides the best sensitivity and specificity for diagnosis of TB.     

Aetiologies of pleural effusions in HIV-infected patients in Abidjan, Côte-d'Ivoire

From December 1995 to March 1996 a cross sectional study was carried out in the pulmonary Medicine Unit of Treichville in Abidjan. In order to specify the main aetiologies of pleural effusion, an investigation was conducted among 35 adult patients (19 men and 16 women) suffering from pleuritis. Overall, the mean age was 32.2 years (range: 19-53 years). All the patients underwent a standard chest x-ray a skin test with 10 units of tuberculin, a whole blood cells count with CD4 T cells count and HIV test. The following analysis were performed on the pleural fluid for all patients: cytological, bacteriological and mycobacteriological examination. Some patients underwent as well a pleural biopsy performed by Abram's needle. Pleural fluid was clear in 24 cases (69%). Empyema was found in 8 cases (23%) and hemorrhagic fluid in 3 cases (9%). Tuberculosis was the dominant aetiology of pleuritis noted in 29 patients (83%), followed by far by non-tuberculous bacterial infections in 6 patients (17%). Tuberculosis associated with common bacterial infections was noted in 3 cases.