Eduardo H. Genofre

Evidence that mesothelial cells regulate the acute inflammatory response in talc pleurodesis

Intrapleural instillation of talc is used to produce pleurodesis in cases of recurrent malignant pleural effusions. The mechanisms by which pleurodesis is produced remain unknown but may involve either injury or activation of the mesothelium. The aim of the current study was to assess the inflammatory response of pleural mesothelial cells to talc in an experimental model in rabbits. A group of 10 rabbits were injected intrapleurally with talc (200 mg·kg-1) and undiluted pleural fluid was collected after 6, 24 or 48 h for measurement of interleukin (IL)-8, vascular endothelial growth factor (VEGF) and transforming growth factor (TGF)-β1. Samples of pleura were studied to assess the inflammatory infiltrate and mesothelial cell viability. The pleural fluid IL-8 concentration peaked at 6 h, whereas VEGF and TGF-β1 concentrations increased steadily over 48 h. Immunohistochemistry for cytokeratin showed a preserved layer of mesothelial cells despite the intense inflammatory pleural reaction. In conclusion, it is proposed that the mesothelial cell, although injured by the talc, may actively mediate the primary inflammatory pleural response in talc-induced pleurodesis.

Inflammation and clinical repercussions of pleurodesis induced by intrapleural talc administration

Although reports on pleurodesis date back to the beginning of the 20th century, the search for the ideal sclerosing agent is ongoing. Several agents have been studied and used, but talc continues to be the most popular. However, potentially harmful systemic side effects have been associated with talc pleurodesis. In this article we discuss the likely mechanisms of pleural inflammation and pleurodesis with emphasis on the systemic response due to the instillation of talc into the pleural space.

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.

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.

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.

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.

Acute inflammatory response secondary to intrapleural administration of two types of talc

Intrapleural instillation of talc has been used in the treatment of recurrent pleural effusions but can, in rare instances, result in respiratory failure. Side-effects seem to be related to composition, size and inflammatory power of talc particles. The aim of this study was to evaluate the inflammatory response to intrapleural injection of talc containing small particles (ST) or talc containing particles of mixed size (MT). 100 rabbits received intrapleural talc, 50 with ST (median 6.41 μm) and 50 with MT (median 21.15 μm); the control group was composed of 35 rabbits. Cells, lactate dehydrogenase, C-reactive protein (CRP), interleukin (IL)-8 and vascular endothelial growth factor were evaluated in serum and bronchoalveolar lavage at 6, 24, 48, 72 and 96 h. Lung histology and the presence of talc were also analysed. Statistics were performed using ANOVA and an unpaired t-test. Most of the parameters showed greater levels in the animals injected with talc than in the controls, suggesting a systemic and pulmonary response. Higher serum levels of CRP and IL-8 were observed in the animals injected with ST. Talc particles were observed in both lungs with no differences between groups. Lung cell infiltrate was more evident in the ST group. In conclusion, talc with larger particles should be the preferred choice in clinical practice in order to induce safer pleurodesis.

Reexpansion pulmonary edema

O edema pulmonar de reexpansao e uma entidade rara, mas de notavel mortalidade. Sua fisiopatologia ainda nao e bem esclarecida, porem envolve fatores conhecidos, como a diminuicao do surfactante pulmonar, e outros ainda incertos, como o papel dos mediadores inflamatorios na genese e manutencao do processo. E imperativo o diagnostico precoce, uma vez que o desfecho depende da agilidade no reconhecimento e tratamento dessa entidade. Tendo em vista a alta mortalidade, as medidas de prevencao ainda sao a melhor estrategia no manuseio dos pacientes com doencas que podem levar ao edema pulmonar de reexpansao. Esta revisao discute os principais aspectos relacionados a fisiopatologia, diagnostico, tratamento e prevencao do edema pulmonar de reexpansao, com recomendacoes praticas para o reconhecimento e adequada abordagem dessa entidade.

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

Background and objective:  Lights criteria are frequently used to evaluate the exudative or transudative nature of pleural effusions. However, misclassification resulting from the use of Lights 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.

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.