Profile of Metalloproteinases and Their Association with Inflammatory Markers in Pleural Effusions.

BACKGROUND: Matrix metalloproteinases (MMPs) are responsible for the breakdown of the extracellular matrix and play an important role in the inflammatory processes of pleural exudates. The imbalance between MMPs and their inhibitors (TIMPs) is present in various pathological processes. OBJECTIVE: To evaluate the profile of MMPs and TIMPs in pleural effusions of different etiologies correlated with inflammatory markers. METHODS: The patients with pleural effusion due to tuberculosis (TB), cancer (CA) or transudate were prospectively evaluated. Pleural fluid was submitted to cytological, biochemical, cytokines, MMP, and TIMP analysis. Statistical analysis was performed using ANOVA and Spearman's correlation, and p < 0.05 was considered significant. RESULTS: One hundred and fourteen patients were enrolled, 80 exudates (41 TB and 39 CA) and 34 transudates. The levels of MMP-8 and MMP-9 were higher in exudates compared to transudates. The level of MMP-8 was significantly higher in TB than in CA. TIMP-1 levels were higher in exudates. IL-6, VEGF, and TGF-ß1 showed differences between exudates and transudates. However, IL-6 level was higher in TB than in CA. We found a significant correlation between MMPs and TIMPs with inflammation markers. MMP-1 was correlated with LDH levels. MMP-8 was correlated with LDH, total cell count, neutrophils, and ADA as well as MMP-1 levels. MMP-9 was correlated with IL-6, TGF-ß1, and VEGF. TIMP-1 was correlated with MMP-9 and IL-6. CONCLUSIONS: MMPs and TIMPs are expressed in pleural fluid of different etiologies and correlate with inflammatory mediators. MMPs may be useful in determining the cause of fluid, but more studies are needed to determine the spectrum of diseases associated with the various isoforms of MMPS and TIMPs.

Clinical usefulness of B-type natriuretic peptide in the diagnosis of pleural effusions due to heart failure.

BACKGROUND AND OBJECTIVE: Light's criteria are frequently used to evaluate the exudative or transudative nature of pleural effusions. However, misclassification resulting from the use of Light's criteria has been reported, especially in the setting of diuretic use in patients with heart failure (HF). The objective of this study was to evaluate the utility of B-type natriuretic peptide (BNP) measurements as a diagnostic tool for determining the cardiac aetiology of pleural effusions. METHODS: Patients with pleural effusions attributable to HF (n = 34), hepatic hydrothorax (n = 10), pleural effusions due to cancer (n = 21) and pleural effusions due to tuberculosis (n = 12) were studied. Diagnostic thoracentesis was performed for all 77 patients. Receiver operating characteristic (ROC) curves were constructed to determine the diagnostic accuracy of plasma BNP and pleural fluid BNP for the prediction of HF. RESULTS: The areas under the ROC curves were 0.987 (95% CI 0.93-0.998) for plasma BNP and 0.949 (95% CI 0.874-0.986) for pleural fluid BNP, for distinguishing between patients with pleural effusions caused by HF (n = 34) and those with pleural effusions attributable to other causes (n = 43). The cut-off concentrations with the highest diagnostic accuracy for the diagnosis of HF as the cause of pleural effusion were 132 pg/mL for plasma BNP (sensitivity 97.1%, specificity 97.4%) and 127 pg/mL for pleural fluid BNP (sensitivity 97.1%, specificity 87.8%). CONCLUSIONS: In patients with pleural effusions of suspected cardiac origin, measurements of BNP in plasma and pleural fluid may be useful for the diagnosis of HF as the underlying cause.

Predictive models for diagnosis of pleural effusions secondary to tuberculosis or cancer.

BACKGROUND AND OBJECTIVE: Tuberculosis (TB) and cancer are two of the main causes of pleural effusions which frequently share similar clinical features and pleural fluid profiles. This study aimed to identify diagnostic models based on clinical and laboratory variables to differentiate tuberculous from malignant pleural effusions. METHODS: A retrospective study of 403 patients (200 with TB; 203 with cancer) was undertaken. Univariate analysis was used to select the clinical variables relevant to the models composition. Variables beta coefficients were used to define a numerical score which presented a practical use. The performances of the most efficient models were tested in a sample of pleural exudates (64 new cases). RESULTS: Two models are proposed for the diagnosis of effusions associated with each disease. For TB: (i) adenosine deaminase (ADA), globulins and the absence of malignant cells in the pleural fluid; and (ii) ADA, globulins and fluid appearance. For cancer: (i) patient age, fluid appearance, macrophage percentage and presence of atypical cells in the pleural fluid; and (ii) as for (i) excluding atypical cells. Application of the models to the 64 pleural effusions showed accuracy higher than 85% for all models. CONCLUSIONS: The proposed models were effective in suggesting pleural tuberculosis or cancer.

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-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.

Pulmonary involvement in pleural tuberculosis: how often does it mean disease activity?

OBJECTIVE: To evaluate in chest X-rays and high-resolution computed tomographies of patients with pleural tuberculosis, the incidence of parenchymal and mediastinal lung lesions suggestive of active disease. METHODS: Prospective study (2008-2009) evaluating the radiographic and tomographic abnormalities of 88 HIV-negative patients with pleural tuberculosis (unilateral effusion). The images were reviewed by 3 independent specialists, and the observed changes were classified according to previously established criteria: presence or absence of signs suggestive of disease activity, and nonspecific findings. RESULTS: Abnormal changes were observed in chest X-rays of 22 (25%) patients and in the computed tomography of 55 (63%). Images compatible with active pulmonary tuberculosis were detected by radiography in 9 (10%) patients and by tomography in 38 (43%). Only 4 (4.5%) patients had tomography images suggestive of residual disease. CONCLUSION: The present study demonstrates that pulmonary involvement is quite common in pleural tuberculosis. This finding is mainly observed in high-resolution computed tomography and has important epidemiological implications, since patients with pleural tuberculosis are significant sources of infection and disease dissemination.

Blockage of vascular endothelial growth factor (VEGF) reduces experimental pleurodesis.

BACKGROUND AND OBJECTIVE: Chemical pleurodesis controls recurrent malignant pleural effusion. The mechanism that determines pleural symphysis involves the action of vascular endothelial growth factor (VEGF). We assessed the influence of the anti-VEGF antibody (bevacizumab) on pleurodesis induced by talc or silver nitrate and analyzed the temporal development of pleural angiogenesis. METHODS: Sixty New Zealand rabbits received intrapleural injection (2mL) of talc (400mg/kg) or 0.5% silver nitrate. In each group, half of the animals received an intravenous injection of bevacizumab 30min before the sclerosing agent. Five animals from each group were euthanized 7, 14, or 28 days after the procedure. Adhesions and inflammation (scores: 0-4), thickness (µm), vascular density (vessels/field), and collagen fibers (µm(2)) were evaluated in the visceral pleura. RESULTS: Antibody anti-VEGF interferes in pleurodesis induced by talc or silver nitrate. Pleural inflammation was discreet with no difference between the groups, regardless the anti-VEGF treatment. Concerning the vascular density of the visceral pleura, a smaller number of neoformed vessels was noted in the animals that received bevacizumab. In the animals receiving silver nitrate, the decrement in adhesions and vascular density was associated with reduced thick and thin collagen fibers, resulting in less pleural thickness. CONCLUSION: The anti-VEGF antibody inhibits adhesions between pleural layers. Despite being an experimental study in animals with normal pleura, the results call attention to a likely lack of success in pleurodesis when VEGF blockers are used.

Pleural fluid: Are temperature and storage time critical preanalytical error factors in biochemical analyses?

BACKGROUND: Biochemical analysis of fluid is the primary laboratory approach in pleural effusion diagnosis. Standardization of the steps between collection and laboratorial analyses are fundamental to maintain the quality of the results. We evaluated the influence of temperature and storage time on sample stability. METHODS: Pleural fluid from 30 patients was submitted to analyses of proteins, albumin, lactic dehydrogenase (LDH), cholesterol, triglycerides, and glucose. Aliquots were stored at 21 degrees , 4 degrees , and-20 degrees C, and concentrations were determined after 1, 2, 3, 4, 7, and 14 days. LDH isoenzymes were quantified in 7 random samples. RESULTS: Due to the instability of isoenzymes 4 and 5, a decrease in LDH was observed in the first 24h in samples maintained at -20 degrees C and after 2 days when maintained at 4 degrees C. Aside from glucose, all parameters were stable for up to at least day 4 when stored at room temperature or 4 degrees C. CONCLUSIONS: Temperature and storage time are potential preanalytical errors in pleural fluid analyses, mainly if we consider the instability of glucose and LDH. The ideal procedure is to execute all the tests immediately after collection. However, most of the tests can be done in refrigerated samples, excepting LDH analysis.

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.