Factors predictive of the failure of medical treatment in patients with pleural infection

BACKGROUND/AIMS: The clinical outcomes of some patients with pleural infection may be favorable with medical treatment alone, but in others, the disease progresses and requires additional surgical treatment. However, little is known about the factors affecting this difference. The aim of this study was to investigate the factors predictive of failure of medical treatment in patients with pleural infection. METHODS: A cohort of 127 consecutive patients who were admitted to the hospital with pleural infection was studied. Clinical manifestations and laboratory findings in patients in whom medical treatment succeeded or failed were reviewed. RESULTS: In univariate analysis, the significant factors associated with medical treatment outcome were age, smoking history, duration of chief complaint, serum albumin level, and pleural fluid glucose and lactate dehydrogenase levels (p < 0.05). Multivariate logistic regression analysis identified age and duration of chief complaint as independent predictive factors for failure of medical treatment, with odds ratios of 0.871 (p = 0.013) and 0.797 (p = 0.026), respectively. Receiver operating characteristic curve analysis determined cutoff values of 50.5 years for age and 4.5 days for duration of chief complaint. CONCLUSIONS: We demonstrated that a younger age < 50.5 years and shorter duration of chief complaint < 4.5 days were independent predictive factors for the failure of medical treatment in patients with pleural infection. This suggests their role as evaluative criteria in setting indications for the optimal treatment in patients with pleural infection. A larger, prospective study is required to confirm these findings.

Combined pleural fluid cholesterol and total protein in differentiation of exudates and transudates.

Background. The management strategy to be adopted in pleural effusion depends on whether an effusion is a transudate or exudate. Objective. To evaluate the usefulness of pleural fluid cholesterol and/or total protein measurements for differentiating between exudates and transudates, and to compare it with Light’s criteria. Methods. In this prospective study 60 patients with pleural effusion were included. Pleural fluid total protein, lactate dehydrogenase (LDH) and cholesterol as well as serum total protein and LDH levels along with other investigations were studied. Clinical classification of transudate or exudate was done on the basis of aetiology. Results. Based on clinical signs and symptoms, chest radiograph, other investigations and response to treatment, 49 of these effusions were classified as exudates and 11 as transudates. Using pleural fluid cholesterol levels at a cut-off point of greater than 60 mg/dL and/or total protein at a cut-off point of greater than 3 g/dL for distinguishing transudates and exudates, the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV), were 100 percent. Using Light’s criteria for discriminating transudates and exudates, sensitivity, specificity, PPV and NPV were found to be 98%; 100%; 100% and 92%, respectively. The differences resulted from a mis-classification of one expected exudate as transudate by Light’s criteria. Conclusion. Pleural fluid cholesterol and total protein are simple, cost-effective, and useful parameters in distinguishing pleural transudates from exudates, with the advantage of requiring only two laboratory determinations and no simultaneous blood sample, compared to the use of Light’s criteria.

Pleural tuberculosis: is radiological evidence of pulmonary-associated disease related to the exacerbation of the inflammatory response?

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.

Diagnostic accuracy of immunological methods in patients with tuberculous pleural effusion from Venezuela / Precisión diagnóstica de métodos inmunológicos en pacientes con tuberculosis pleural de Venezuela

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, ...

Comparison of telomerase activity between malignant and tuberculous pleural effusions.

OBJECTIVE: To determine if telomerase activity can differentiate malignant from tuberculous pleural effusions. DESIGN: Telomerase activity in malignant and tuberculous pleural effusions was measured in a blinded manner using a PCR-based telomeric repeat amplification protocol (TRAP) assay. MATERIAL AND METHOD: Fifty-two patients with lymphocytic exudative pleural effusions were identified on thoracocentasis over a period of 18 months. RESULTS: Telomerase activity was detected in 34% of malignant pleural fluid samples and 50% of tuberculous pleural effusions. The positive rate of telomerase activity was 30.7% for primary lung cancer and 37.5% for metastatic pleural effusion. The sensitivity and specificity of telomerase activity assay were extremely low (35.7% and 52.9%, respectively), compared with that of cytological examination (52.6% and 65.4%, respectively). Moreover the diagnostic accuracy of telomerase activity in combination with cytology was even lower than cytological examination alone (46.7% vs. 60%, respectively). This finding was in contrast to previous reports and demonstrated that the detection rate of telomerase activity in tuberculous pleural effusions was greater than that observed in malignant pleural exudates. CONCLUSION: Telomerase activity does not appear to be a useful marker for differentiating malignant from tuberculous effusions.

Vascular endothelial growth factor in malignant and tuberculous pleural effusions

The purpose of this study is to assess the usefulness of soluble vascular endothelial growth factor (VEGF) in the effusions of patients with malignant and tuberculous diseases. Using a sandwich enzyme-linked immunoadsorbent assay, VEGF concentration was measured in malignant (n=17) and tuberculous (n=11) pleural effusions. Pleural biopsy, cytology or microbiological methods were used to make final diagnoses. Adenosine deaminase (ADA) levels in tuberculous pleural effusions were significantly higher than those in malignant pleural effusions. The median level of VEGF in patients with malignant effusions (median, 2418 pg/mL; range, 97-62103 pg/mL) was significantly higher than tuberculous effusions (median, 994 pg/mL; range, 44-3552 pg/mL). There were no significant differences in pleural VEGF levels in patients with different histological types of lung cancer. The VEGF level was not correlated with ADA, lactate dehydrogenase and total protein levels of pleural fluid. In conclusion, pleural VEGF levels in patients with malignant effusions were significantly higher than tuberculous effusions, and the measurement of pleural VEGF is helpful in discriminating between malignant and tuberculous effusions. Further studies are needed to determine the clinical value of VEGF as a tumor marker and a prognostic factor.

Vascular endothelial growth factor in malignant and tuberculous pleural effusions

The purpose of this study is to assess the usefulness of soluble vascular endothelial growth factor (VEGF) in the effusions of patients with malignant and tuberculous diseases. Using a sandwich enzyme-linked immunoadsorbent assay, VEGF concentration was measured in malignant (n=17) and tuberculous (n=11) pleural effusions. Pleural biopsy, cytology or microbiological methods were used to make final diagnoses. Adenosine deaminase (ADA) levels in tuberculous pleural effusions were significantly higher than those in malignant pleural effusions. The median level of VEGF in patients with malignant effusions (median, 2418 pg/mL; range, 97-62103 pg/mL) was significantly higher than tuberculous effusions (median, 994 pg/mL; range, 44-3552 pg/mL). There were no significant differences in pleural VEGF levels in patients with different histological types of lung cancer. The VEGF level was not correlated with ADA, lactate dehydrogenase and total protein levels of pleural fluid. In conclusion, pleural VEGF levels in patients with malignant effusions were significantly higher than tuberculous effusions, and the measurement of pleural VEGF is helpful in discriminating between malignant and tuberculous effusions. Further studies are needed to determine the clinical value of VEGF as a tumor marker and a prognostic factor.

Valor da determinaçäo da atividade de adenosina desaminase (ADA) no diagnóstico diferencial dos derrames pleurais / Value of determining the activity of adenosine deaminase (ADA) in the differenrial diagnosis of pleural effusions

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.

Elucidation on acidity and low glucose concentration in parapneumonic effusion.

Studies were conducted on three consecutive patients with parapneumonic effusions by (a) serial analyses of plasma -pleural fluid glucose, pH, PCO2, and antimicrobial levels, and (b) serial analyses to determine the pH and PCO2 levels of pleural fluids that underwent in vitro incubation, before and after antimicrobial administration. The pleural fluid pharmacokinetics of the three antimicrobials followed a large reservoir model by increasing drug levels gradually, reaching the peak values at about two to seven hours following administration, while serial pleural fluid glucose levels showed a delayed rise or no rise in concentration, respectively. The molecular weights of the three antimicrobials are greater than that of the glucose, thus suggesting that over-utilization of glucose within the pleural cavity is more likely the cause of this situation than the transport defect. In the in vitro incubation study, the serial pleural fluid pH and PCO2 levels before antimicrobial administration progressively decreased, while those following the administration of antimicrobials were stable during the first few hours. The results indicate that, in cases of parapneumonic effusion, the inflamed pleurae and the infectious pleural fluid (empyema) over-utilizes pleural fluid glucose leading to increased fluid acidity.

Utilidad diagnostica de los marcadores tumorales en exudados pleurales / Diagnostic value of tumor markers in pleural effusions

Se estudiaron 65 pacientes con derrame pleural cuyo análisis físico-químico demostró la presencia de exudado, con la finalidad de valorar la utilidad de la alfa-fetoproteina (AFP), el antígeno carcinoembrionario (CEA) y la gonadotrofina coriónica humana subundad beta (GNCH Sub-ß) como marcadores tumorales. A todos los pacientes se les realizó estudio citolófico, físico, químico, bacteriológico y dosaje de los marcadores mencionados en el líquido pleural, llegándose al diagnóstico de origen neoplásico del mismo en base a la citologia y/o biopsia pleural. Los pacientes fueron divididos en dos grupos: 1) 33 neoplásicos y 2) 32 no neoplásicos. El CEA fue el único marcador tumoral significativamente más elevado en los derrames pleurales neoplásicos que en los no neoplásicos (p < 0,01). en relación al valor de estos marcadores como métodos de detección del origen neoplásico de un exudado pleural, se halló que el CEA tuvo una sensibilidad del 57% y una especialidad del 97%, la AFP una sensibilidad del 9% y una especificidad del 97% y la GNCH Sub-ß una sensibilidad del 9% y una especificidad del 90%

Isolation & characterization of tumour angiogenesis factor from solid tumours & body fluids from cancer patients.

Tumour angiogenesis factor (TAF) was isolated from malignant solid tumours (10) and from pleural and peritoneal fluids (10) collected from cancer patients. Normal tissues and body fluids from individuals with no clinical history of cancer did not show any detectable levels of TAF. Also, no angiogenic activity was detectable in the benign tumour samples studied (2). The TAFs isolated were all ribonucleoproteins. Molecular weight determination by SDS-PAGE (9%) of the TAFs isolated by DEAE cellulose chromatography of tumour extracts showed them to be 18,000 dalton (D) ribonucleoproteins, while the TAFs isolated by immunoaffinity chromatography (using immobilized anti-TAF IgG) of solid tumour extracts and body fluids had a molecular weight of 38,000 D. The TAFs isolated by both the methods were found to be angiogenic by the chick chorioallantoic membrane and the mouse intradermal assays. Immunoaffinity chromatography could be used for the one-step purification of TAF from solid tumour extracts as well as from body fluids.

Amikacin pharmacokinetics in plasma and pleural fluid.

The pharmacokinetics of amikacin in plasma and pleural fluid were studied in nine adult patients with pleural effusions. After a single intravenous bolus of 7.5 mg of amikacin per kg, concentrations in plasma and pleural fluid were measured by fluorescence polarization immunoassays. Pleural fluid pH and PCO2 were also measured. The plasma pharmacokinetics was similar to other studies. However, in the present study the central compartment was significantly greater than the peripheral compartment. Our study suggested that there might be a significant binding of amikacin to the inflamed and/or damaged pleural as suggested by the significant correlations between the apparent volumes of distributions of central and total compartments with pleural fluid pH and PCO2. In pleural fluid, amikacin kinetics followed a large reservoir model with maximum concentration, 4.34 +/- 0.50 mg/L, occurring at 5.64 +/- 0.67 hours post-dose and its half-life was 13.50 +/- 2.93 hours. This concentration was lower than the minimal inhibitory concentration (MIC) for most of the sensitive strains of Gram-negative bacilli and therefore the antibiotics should be given as early as possible for gram-negative pneumonia.