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.

Improvements in the 6-min walk test and spirometry following thoracentesis for symptomatic pleural effusions.

BACKGROUND: Impairment in pulmonary capacity due to pleural effusion compromises daily activity. Removal of fluid improves symptoms, but the impact, especially on exercise capacity, has not been determined. METHODS: Twenty-five patients with unilateral pleural effusion documented by chest radiograph were included. The 6-min walk test, Borg modified dyspnea score, FVC, and FEV(1) were analyzed before and 48 h after the removal of large pleural effusions. RESULTS: The mean fluid removed was 1,564 ± 695 mL. After the procedure, values of FVC, FEV(1), and 6-min walk distance increased (P < .001), whereas dyspnea decreased (P < .001). Statistical correlations (P < .001) between 6-min walk distance and FVC (r = 0.725) and between 6-min walk distance and FEV(1) (r = 0.661) were observed. Correlations also were observed between the deltas (prethoracentesis × postthoracentesis) of the 6-min walk test and the percentage of FVC (r = 0.450) and of FEV(1) (r = 0.472) divided by the volume of fluid removed (P < .05). CONCLUSION: In addition to the improvement in lung function after thoracentesis, the benefits of fluid removal are more evident in situations of exertion, allowing better readaptation of patients to routine activities.

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.

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.

Monoclonal anti-vascular endothelial growth factor antibody reduces fluid volume in an experimental model of inflammatory pleural effusion.

BACKGROUND AND OBJECTIVE: Vascular endothelial growth factor (VEGF) is known to increase vascular permeability and promote angiogenesis. It is expressed in most types of pleural effusions. However, the exact role of VEGF in the development of pleural effusions has yet to be determined. The anti-VEGF mAb, bevacizumab, has been used in the treatment of cancer to reduce local angiogenesis and tumour progression. This study describes the acute effects of VEGF blockade on the expression of inflammatory cytokines and pleural fluid accumulation. METHODS: One hundred and twelve New Zealand rabbits received intrapleural injections of either talc or silver nitrate. In each group, half the animals received an intravenous injection of bevacizumab, 30 min before the intrapleural agent was administered. Five animals from each subgroup were sacrificed 1, 2, 3, 4 or 7 days after the procedure. Twelve rabbits were used to evaluate vascular permeability using Evans's blue dye. Pleural fluid volume and cytokines were quantified. RESULTS: Animals pretreated with anti-VEGF antibody showed significant reductions in pleural fluid volumes after talc or silver nitrate injection. IL-8 levels, vascular permeability and macroscopic pleural adhesion scores were also reduced in the groups that received bevacizumab. CONCLUSIONS: This study showed that bevacizumab interferes in the acute phase of pleural inflammation induced by silver nitrate or talc, reinforcing the role of VEGF as a key mediator in the production of pleural effusions. The results also suggest that bevacizumab should probably be avoided in patients requiring pleurodesis.

Talc pleurodesis: evidence of systemic inflammatory response to small size talc particles.

The mechanisms of the systemic response associated with talc-induced pleurodesis are poorly understood. The aim of this study was to assess the acute inflammatory response and migration of talc of small size particles injected in the pleural space. Rabbits were injected intrapleurally with talc solution containing small or mixed particles and blood and pleural fluid samples were collected after 6, 24 or 48 h and assayed for leukocytes, neutrophils, lactate dehydrogenase, IL-8, VEGF, and TGF-beta. The lungs, spleen, liver and kidneys were assessed to study deposit of talc particles. Both types of talc produced an acute serum inflammatory response, more pronounced in the small particles group. Pleural fluid IL-8 and VEGF levels were higher in the small particle talc group. Correlation between pleural VEFG and TGF-beta levels was observed for both groups. Although talc particles were demonstrated in the organs of both groups, they were more pronounced in the small talc group. In conclusion, intrapleural injection of talc of small size particles produced a more pronounced acute systemic response and a greater deposition in organs than talc of mixed particles.

Ultrastructural acute features of active remodeling after chemical pleurodesis induced by silver nitrate or talc.

This study evaluated submicroscopic features of active pleural remodeling associated with chemical pleurodesis. Twenty seven rabbits received intrapleural injection of 0.5% silver nitrate (SN; N = 9) or 400 mg/kg talc slurry (N = 9) in 2 ml of saline solution; control rabbits (N = 9) received 2 ml of saline alone. The rabbits were sacrificed 15 minutes, 24 hours, or 7 days postinjection, and specimens of visceral pleura were obtained, fixed, and photographed for submicroscopic analysis. After 15 minutes of talc or SN exposure, prominent injury to the mesothelial cells and mesothelial cell-mesothelial basement membrane (MC-MBM) union was visible. There was focal remesothelialization of the denuded area through mesothelial cell migration, proliferation, and differentiation. After 24 hours, early wound healing, characterized by a superficial exudate, was evident where myofibroblasts had proliferated through a gap in the MC-MBM. After 7 days, proliferation of highly active myofibroblasts was observed; these cells produced abundant extracellular matrix components in a more organized distribution paralleling the surface. This third stage of remodeling was more evident with SN than talc-induced chemical pleurodesis. Our results suggest that ideal chemical pleurodesis results from injury to the MC-MBM union and abnormal wound healing, involving three essential steps: remesothelialization, fibroblastic proliferation, and extracellular matrix accumulation and remodeling.

Talc and silver nitrate induce systemic inflammatory effects during the acute phase of experimental pleurodesis in rabbits.

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.

Pleurodesis induced by intrapleural injection of silver nitrate or talc in rabbits: can it be used in humans?

OBJECTIVE: To evaluate the pleuropulmonary alterations caused by intrapleural injection of silver nitrate or talc in an experimental model, in order to consider its use in human beings. METHOD: 112 rabbits were randomly selected to receive intrapleural 0.5 percent silver nitrate or 400 mg/kg talc slurry in 2 ml saline. Eight rabbits of each group were sacrificed after 1, 2, 4, 6, 8, 10, or 12 months. Regarding the pleural cavity, the degree of macroscopic pleurodesis (adherences) and microscopic alterations, represented by inflammation and pleural fibrosis, were analyzed. The parenchyma was evaluated regarding the degree of alveolar collapse, intra-alveolar septum edema, and cellularity, on a 0 to 4 scale. RESULTS: Intrapleural injection of silver nitrate produced earlier and more intense pleurodesis than talc slurry injection. The parenchymal damage was more evident with silver nitrate, considered as moderate, and limited to the first evaluation (after one month). From the second month on and throughout the entire one-year follow-up, the parenchymal damage was similar with both substances, only the pleural adherences were more intense with silver nitrate. CONCLUSIONS: Intrapleural silver nitrate produces better and longer-lasting than intrapleural talc injection. The parenchymal alterations, although discreet, are more pronounced when silver nitrate is used, but minimal after two months, and similar to those produced by talc injection during the entire one-year observation period. These effects on the pulmonary parenchyma do not contraindicate the use in humans. Thus, the use of intrapleural silver nitrate to produce fast and effective pleurodesis can be considered in patients in which pleural cavity symphysis is desired.

Lung damage in experimental pleurodesis induced by silver nitrate or talc: 1-year follow-up.

STUDY OBJECTIVE: To compare the lung damage caused by intrapleural silver nitrate (SN) with that caused by talc over a 12-month period. DESIGN: One hundred forty rabbits received an intrapleural injection of 0.5% SN or 400 mg/kg talc slurry in 2 mL saline solution. Groups of 10 rabbits were killed after 1, 2, 4, 6, 8, 10, or 12 months. The macroscopic pleurodesis, microscopic lung changes (ie, collapse, hemorrhage, and edema), and cellular infiltrates (number and proportion of cells) were graded on a scale of 0 to 4. RESULTS: The mean (+/- SEM) adhesion score after SN injection (3.3 +/- 0.1) was higher (p < 0.001) than that after talc injection (2.3 +/- 0.1). The mean alveolar collapse score was greater (p < 0.001) 1 month after SN injection (2.2 +/- 0.3) than after talc injection (0.2 +/- 0.1) and was similar from the second month on. The degree of parenchymal hemorrhage, by alveolar collapse score, (SN injection, 0.2 +/- 0.1; talc injection, 0.2 +/- 0.0) and edema (SN injection, 0.4 +/- 0.1; talc injection, 0.3 +/- 0.1) was minimal in both groups (p > 0.05). One month after the injection, the total number of inflammatory cells was greater (p < 0.001) in rabbits that had received SN injections (2.7 +/- 0.3) than in those that had received talc injections (1.2 +/- 0.1). From the second month on, cellularity decreased and became similar in both groups. The cellular profile was different, with a predominantly neutrophilic reaction after talc injection and a predominantly eosinophilic reaction after SN injection. CONCLUSIONS: Rabbits injected with intrapleural 0.5% SN had significantly higher scores for adhesions than did those that had received talc injections, with mild and reversible alveolar collapse and an eosinophilic responses, conditions showing a clear tendency to normalize with time.