Abrasion Plus Local Fibrin Sealant Instillation Produces Pleurodesis Similar to Pleurectomy in Rabbits.

BACKGROUND: Pleurodesis performed either by pleurectomy or pleural abrasion is recommended in the approach to primary spontaneous pneumothorax to avoid recurrence. However, the efficacy of parietal pleural abrasion in producing pleurodesis is questioned. This study aims to determine the efficacy of apical abrasion alone, abrasion plus fibrin sealant application, and pleurectomy in producing pleurodesis in rabbits. METHODS: Rabbits were subjected to video-assisted thoracic surgery alone (control) or to video-assisted thoracic surgery with apical gauze abrasion, abrasion plus fibrin sealant instillation, or apical pleurectomy. Blood samples were collected preoperatively and 48 h and 28 days postoperatively to measure total leukocytes (white blood cell count), neutrophil counts, and serum interleukin (IL)-8 levels. After 28 days the animals were sacrificed for macroscopic evaluation of the degree of apical pleurodesis and microscopic evaluation of local pleural fibrosis and collagen deposition. RESULTS: White blood cell and neutrophil counts were similar in all groups, whereas the serum IL-8 level peaked at 48 h in all groups and decreased after 28 days, except in the pleurectomy group. After 28 days the abrasion plus fibrin sealant and pleurectomy groups had significantly more pleural adhesions, pleural fibrosis, and collagen deposition than the abrasion alone group, mainly due to thick mature fibers. CONCLUSIONS: Abrasion with local fibrin sealant instillation is as effective as pleurectomy in producing pleurodesis in rabbits. Apical pleurectomy elicits a more persistent elevation of serum IL-8 levels than apical abrasion alone or abrasion plus fibrin adhesive instillation.

Selectins and platelet-derived growth factor (PDGF) in schistosomiasis-associated pulmonary hypertension.

PURPOSE: The aim of this study was to evaluate the expression profiles of the relevant selectins and PDGF in schistosomiasis-associated pulmonary hypertension. METHODOLOGY: Patients with three distinct clinical profiles were enrolled in the study: IPAH(n = 11), schistosomiasis-associated PH (Sch-PH))(n = 13), and schistosomiasis without PH (Sch) (n = 13). Healthy volunteers, were recruited as a control group(n = 13). Echocardiography was performed in all groups, and the PH patients underwent right heart catheterization. Plasma soluble adhesion molecules E- and P-Selectin, PDGF-AB, PDGF-BB were determined by ELISA. RESULTS: E-selectin was significantly increased in the IPAH group compared with the other groups [the control, Sch + PH and Sch groups) (p < 0.001) (Fig. 2)]. P-selectin was lower in Sch (20.2 + 8.9 × 103 pg/mL) as compared to the control, (43 16.8 × 103 pg/mL), IPAH (35.8 7.8 × 103 pg/mL), and Sch + PH (36.8 ± 15.7 × 103 pg/mL) (p = 0.005) groups. Serum PDGF-BB levels were higher in the control group (8.9 ± 4.8 × 103 pg/mL) compared with the IPAH (3.7 ± 2.17 × 103 pg/mL), Sch + PH (5.2 ± 3.7 × 103 pg/mL) and Sch (2.4 ± 1.7 × 103 pg/mL) groups (p < 0.05). PDGF-AB levels were also higher in the control group (25.6 ± 8.6 × 103 pg/mL), compared with the other three groups, being the Sch group the one with lower serum levels of this marker (11.4 ± 8.6 × 103 pg/mL) (p = 0.006). CONCLUSIONS: In conclusion, vascular inflammation in schistosomiasis, with or without PH, is different from IPAH suggesting distinct pathophysiological mechanisms associated with the development of pulmonary hypertension.

Effectiveness and safety of iodopovidone in an experimental pleurodesis model.

OBJECTIVES: Chemical pleurodesis is an important therapeutic tool to control recurrent malignant pleural effusion. Among the various sclerosing agents, iodopovidone is considered effective and safe. However, in a recent study, ocular changes were described after iodopovidone was used in recurrent pneumothorax. The aim of the study was to evaluate the efficacy and morbidity of iodopovidone pleurodesis in an experimental model. METHODS: New Zealand rabbits were submitted to intrapleural injection of iodopovidone at concentrations of 2%, 4% and 10%. Biochemical (lactic dehydrogenase, proteins, triiodothyronine, free thyroxine, urea and creatinine) and immunological (Interleukin-8 [IL-8], VEGF and TGFß) parameters were measured in the pleural fluid and blood. After 1, 3, 7, 14 and 28 days, groups of animals were euthanized, and macro- (pleura) and microscopic (pleura and retina) analyses were performed. RESULTS: An early pleural inflammatory response with low systemic repercussion was observed without corresponding changes in thyroid or renal function. The higher concentrations (4% and 10%) correlated with greater initial exudation, and maximum pleural thickening was observed after 28 days. No changes were observed in the retinal pigment epithelium of the rabbits. CONCLUSION: Iodopovidone is considered to be an effective and safe sclerosing agent in this animal model. However, its efficacy, tolerance and safety in humans should be further evaluated.

Effectiveness and safety of iodopovidone in an experimental pleurodesis model

OBJECTIVES: Chemical pleurodesis is an important therapeutic tool to control recurrent malignant pleural effusion. Among the various sclerosing agents, iodopovidone is considered effective and safe. However, in a recent study, ocular changes were described after iodopovidone was used in recurrent pneumothorax. The aim of the study was to evaluate the efficacy and morbidity of iodopovidone pleurodesis in an experimental model. METHODS: New Zealand rabbits were submitted to intrapleural injection of iodopovidone at concentrations of 2%, 4% and 10%. Biochemical (lactic dehydrogenase, proteins, triiodothyronine, free thyroxine, urea and creatinine) and immunological (Interleukin-8 [IL-8], VEGF and TGFβ) parameters were measured in the pleural fluid and blood. After 1, 3, 7, 14 and 28 days, groups of animals were euthanized, and macro- (pleura) and microscopic (pleura and retina) analyses were performed. RESULTS: An early pleural inflammatory response with low systemic repercussion was observed without corresponding changes in thyroid or renal function. The higher concentrations (4% and 10%) correlated with greater initial exudation, and maximum pleural thickening was observed after 28 days. No changes were observed in the retinal pigment epithelium of the rabbits. CONCLUSION: Iodopovidone is considered to be an effective and safe sclerosing agent in this animal model. However, its efficacy, tolerance and safety in humans should be further evaluated. .

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.

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.

Monoclonal antibodies anti-TGFß1 and anti-VEGF inhibit the experimental pleurodesis induced by silver nitrate.

BACKGROUND: The mechanisms underlying pleural inflammation and pleurodesis are poorly understood. We hypothesized that the cytokines transforming growth factor ß (TGFß1) and vascular endothelial growth factor (VEGF) play a major role in pleurodesis after intrapleural silver nitrate (SN) injection. METHOD: Forty rabbits received intrapleurally 0.5% SN alone or 0.5% SN + anti-TGFß1, anti-IL-8, or anti-VEGF. After 28 days, the animals were euthanized and macroscopic pleural adhesions, microscopic pleural fibrosis, and collagen deposition were analyzed for characterization of the degree of pleurodesis (scores 0-4). RESULTS: Scores of pleural adhesions, pleural fibrosis, total collagen, and thin collagen fibers deposition after 28 days were significantly lower for 0.5% SN + anti-TGFß1 and 0.5% SN + anti-VEGF. Significant correlations were found between macroscopic adhesion and microscopic pleural fibrosis with total collagen and thin collagen fibers. CONCLUSIONS: We conclude that both TGFß1 and VEGF, but not IL-8, mediate the pleural inflammatory response and pleurodesis induced by SN.

Sleep in patients with large pleural effusion: impact of thoracentesis.

PURPOSE: This study aimed to evaluate the sleep quality and impact of thoracentesis on sleep in patients with a large pleural effusion. METHODS: Patients with large unilateral pleural effusion were evaluated by the Pittsburgh Sleep Quality Index (PSQI) questionnaire and dyspnea Borg scale. Full polysomnography (PSG) was performed on the night before and 36 h after thoracentesis. RESULTS: We studied 19 patients, 11 males and 8 females, age 55 ± 18 years and body mass index of 26 ± 5 kg/m(2). The baseline sleep quality was poor (PSQI = 9.1 ± 3.5). Thoracentesis removed 1.624 ± 796 mL of pleural fluid and resulted in a significant decrease in dyspnea Borg scale (2.3 ± 2.1 vs. 0.8 ± 0.9, p < 0.001). The PSG before and after thoracentesis showed no significant change in apnea-hypopnea index and sleep time with oxygen saturation <90%. There was a significant improvement in sleep efficiency (76% vs. 81%, p = 0.006), decrease percent sleep stage 1 (16% vs. 14%, p = 0.002), and a trend improvement in total sleep time (344 ± 92 vs. 380 ± 69 min, p = 0.056) and percentage of rapid eye movement sleep (15% vs. 20%, p = 0.053). No significant changes occurred in six patients that performed two consecutive PSG before thoracentesis. The improvement in sleep quality was not associated with the volume of pleural fluid withdrawn or changes in dyspnea. CONCLUSIONS: Patients with large pleural effusion have poor subjective and objective sleep quality that improves after thoracentesis.

Proinflammatory and antiinflammatory cytokine levels in complicated and noncomplicated parapneumonic pleural effusions.

OBJECTIVES: This study aimed to evaluate a panel of proinflammatory and antiinflammatory cytokines in noncomplicated and complicated parapneumonic pleural effusions and to correlate their levels with pleural fluid biochemical parameters. METHODS: Serum and pleural effusion were collected from 60 patients with noncomplicated (n = 26) or complicated (n = 34) parapneumonic effusions and assayed for cytologic, biochemical, and proinflammatory and antiinflammatory cytokines. Student t test was used to compare serum and pleural fluid values, Spearman correlation to analyze the relationship between pleural fluid cytokines and biochemical parameters, and accuracy of pleural fluid cytokine levels to determine the optimal cutoff value for identification of complicated effusions. Corrections for multiple comparisons were applied and a P value < .05 was accepted as significant. RESULTS: Serum and pleural fluid cytokine levels of IL-8, vascular endothelial growth factor (VEGF), IL-10, and tumor necrosis factor (TNF) soluble receptor (sR) II were similar between groups. In contrast, complicated effusions had higher levels of pleural fluid IL-1ß, IL-1 receptor antagonist (ra), and TNF sRI. Negative correlations were found between pleural fluid glucose with IL-1ß and TNF sRI and positive correlations between lactic dehydrogenate (LDH) with IL-1ß, IL-8, and VEGF. Pleural fluid levels of IL-1ß, IL-1ra, and TNF sRI were more accurate than IL-8, VEGF, IL-10, and TNF sRII in discriminating complicated effusions. CONCLUSIONS: Both proinflammatory and antiinflammatory cytokine levels in pleural fluid are elevated in complicated in comparison with noncomplicated parapneumonic pleural effusions, and they correlate with both pleural fluid glucose and LDH levels. IL-1ß, IL-1ra, and TNF sRI had higher sensitivity and specificity than IL-8, VEGF, IL-10, and TNF sRII in discriminating complicated effusions.

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.

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.

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.

Low doses of silver nitrate induce pleurodesis with a limited systemic response.

BACKGROUND AND OBJECTIVE: Both talc and 0.5% silver nitrate have been shown to induce effective pleurodesis. However, acute adverse systemic inflammatory effects have been described with both agents. The aim of this study was to assess in rabbits the systemic effects associated with a new technique of pleurodesis using repeated low doses of 0.1% silver nitrate. METHODS: Rabbits were injected intrapleurally through a chest tube with 0.1% silver nitrate at 0, 24 and 48 h. Other groups received a single injection of 0.5% silver nitrate or 400 mg/kg of talc. Blood samples were collected at 24, 48 and 72 h, and at 7 days, and cytological and biochemical measurements were performed. After 28 days, the presence of macroscopic pleural adhesions and microscopic pleural fibrosis in the pleural cavity were evaluated. RESULTS: Both talc and 0.5% silver nitrate caused significant increases in blood neutrophils, serum LDH, IL-8, transforming growth factor-beta and CRP in comparison with control at almost all time points, whereas sequential doses of 0.1% silver nitrate only increased LDH and CRP in the first 24 h and transforming growth factor-beta at all time points. All groups showed efficient pleurodesis, with no differences in pleural adhesions or fibrosis. CONCLUSIONS: Sequential doses of 0.1% silver nitrate produced efficient pleurodesis in rabbits, with a low systemic inflammatory response in comparison with 400 mg/kg of talc or 0.5% silver nitrate.

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.

Influence of parecoxib (cox-2 inhibitor) in experimental pleurodesis.

BACKGROUND: The intrapleural instillation of a sclerosing agent produces an inflammatory process frequently followed by pain. The treatment can include the use of analgesics or anti-inflammatory drugs. Previously, it was demonstrated (experimental studies) that corticoids and nonsteroidal anti-inflammatory drugs (diclofenac) reduce the inflammation and fibrosis produced by talc but not by transforming growth factor-beta or silver nitrate. The objective of this study was to determine whether parecoxib (COX-2 inhibitor) affects pleurodesis induced by talc or silver nitrate. METHODS: 140 rabbits received intrapleural injection (2mL) of 400mg/kg of talc or 0.5% silver nitrate. A subgroup of 70 animals received additional daily intramuscular parecoxib (1mg/kg). They were sacrificed at 4, 24, 48, 72h or 7, 14, or 28 days after the procedure. The pleural fluid was quantified; biochemical examinations (glucose, lactic dehydrogenase, and proteins) and immunologic dosages (interleukin-8, vascular endothelial growth factor, and transforming growth factor-beta(1)) were analyzed in pleural fluid and blood. Finally, macro- and microscopic pleura and lung studies were performed. RESULTS: Evaluation after 28 days demonstrated that parecoxib reduced pleural and pulmonary inflammation but not pleural adhesions. The changes were observed precociously (congruent with 72h) and were more evident after silver nitrate injection. CONCLUSION: Systemic parecoxib injection does not interfere with talc or silver nitrate pleurodesis. These results suggest that use of COX-2 inhibitors can be considered and depending of the results of other studies, recommended in human pleurodesis.