A cost comparison of benralizumab, mepolizumab, and dupilumab in patients with severe asthma: A US third-party payer perspective.

BACKGROUND: Clinical trials and real-world evidence (RWE) studies of biologics have demonstrated reduced exacerbations, decreased use of oral corticosteroids (OCS), and improvements in daily symptoms and health-related quality of life in patients with severe eosinophilic asthma (SEA). OBJECTIVE: To compare direct health care costs associated with biologic use for the treatment of SEA from a US third-party payer perspective. METHODS: We developed a cost-minimization model to compare costs and cost offsets associated with 3 biologics-benralizumab, mepolizumab, and dupilumab-for 2- and 4-year periods. The model relied on longitudinal data from clinical trials to inform the primary (base case) analysis cost comparison and RWE study data, in a separate scenario, to compare costs in nonclinical trial settings. Primary model outcomes included exacerbations (including hospitalizations), OCS-dependent years (including associated complications), and total direct health care biologic costs. Results were calculated at the per patient and population level (per 1,000 patients). Sensitivity analyses with key model parameters were performed. RESULTS: Benralizumab had the lowest total biologic costs per patient for both the 2- and 4-year periods. Over 4 years, the marginal cost difference in total biologic costs per patient was $23,061 lower for benralizumab vs mepolizumab and $17,242 lower for benralizumab vs dupilumab. The 4-year population level analysis of benralizumab vs mepolizumab revealed $4.8 million in marginal cost offsets due to 582 fewer exacerbations and 153 fewer OCS-dependent years and a marginal total cost savings of $27.9 million per 1,000 patients for benralizumab. The 4-year population level analysis of benralizumab vs dupilumab revealed $2.3 million in marginal cost offsets due to 291 fewer exacerbations and 64 fewer OCS-dependent years and marginal total cost savings of $19.5 million per 1,000 patients for benralizumab. RWE data were available for a 2-year cost comparison scenario of benralizumab vs mepolizumab, which showed similar results to the base case analysis. Sensitivity analyses varying assumptions on key model parameter estimates confirmed results, with benralizumab having lower total direct health care costs in all scenarios tested, and showed that model results were most sensitive to changes in biologic costs and exacerbation reduction rates. CONCLUSIONS: Patients receiving benralizumab had higher nonbiologic cost offsets because of reductions in exacerbations and OCS-dependent years, leading to greater cost savings for third-party payers compared with patients receiving mepolizumab or dupilumab. Taken together with biologic costs, benralizumab presents greater savings in health care costs for payers than patients with SEA who use mepolizumab or dupilumab. DISCLOSURES: This study was funded by AstraZeneca (Cambridge, UK). Drs Xu, Chung, Genofre, and Katial are or were AstraZeneca employees at the time this research was conducted and may be shareholders of AstraZeneca. Ms Schaefer and Dr Szende are employees of Labcorp Drug Development, which received funding from AstraZeneca to perform this research.

Impact of benralizumab on asthma exacerbation-related medical healthcare resource utilization and medical costs: results from the ZEPHYR 2 study.

BACKGROUND AND AIM: Benralizumab is a biologic add-on treatment for severe eosinophilic asthma that can reduce the rate of asthma exacerbations, but data on the associated medical utilization are scarce. This retrospective study evaluated the economic value of benralizumab by analyzing healthcare resource utilization (HRU) and medical costs in a large patient population in the US. METHODS: Insurance claims data (11/2016-6/2020) were analyzed. A pre-post design was used to compare asthma exacerbation rates, medical HRU and medical costs in the 12 months pre vs. post index (day after benralizumab initiation). Patients were aged ≥12 years, with ≥2 records of benralizumab and ≥2 asthma exacerbations pre index, and constituted non-mutually exclusive cohorts: biologic-naïve, biologic-experienced (switched from omalizumab or mepolizumab to benralizumab), or with extended follow-up (18 or 24 months). RESULTS: In all cohorts (mean age 51-53 years; 67-70% female; biologic-naïve, N = 1,292; biologic-experienced, N = 349; 18-month follow-up, N = 419; 24-month follow-up, N = 156), benralizumab treatment reduced the rate of asthma exacerbation by 53-68% (p < .001). In the biologic-naïve cohort, inpatient admissions decreased by 58%, emergency department visits by 54%, and outpatient visits by 58% post index (all p < .001), with similar reductions in exacerbation-related medical HRU in other cohorts. Exacerbation-related mean total medical costs decreased by 51% in the biologic-naïve cohort ($4691 pre-index, $2289 post-index), with cost differences ranging from 16% to 64% across other cohorts (prior omalizumab: $2686 to $1600; prior mepolizumab: $5990 to $5008; 18-month: $3636 to $1667; 24-month: $4014 to $1449; all p < .001). Medical HRU and cost reductions were durable, decreasing by 64% in year 1 and 66% in year 2 in the 24 month follow-up cohort. CONCLUSION: Patients treated with benralizumab with prior exacerbations experienced reductions in asthma exacerbations and exacerbation-related medical HRU and medical costs regardless of prior biologic use, with the benefits observed for up to 24 months after treatment initiation.

Benralizumab is a biologic approved as an add-on treatment for severe eosinophilic asthma. Previous real-world studies and clinical trials have shown that benralizumab can reduce the rate of asthma exacerbations and systemic corticosteroid use. However, there is little information on the economic value of benralizumab in real-world patient populations. This study showed that patients with severe asthma in the United States had lower rates of asthma exacerbations after starting treatment with benralizumab. The patients also had fewer asthma exacerbation-related hospitalizations, emergency department visits, and outpatient visits as well as lower medical costs related to asthma exacerbations compared with before the treatment. These benefits were observed in patients who had never taken and those who had been previously treated with biologic therapies, and for up to 24 months after starting benralizumab treatment. These results show that the clinical value of benralizumab translates into reduced medical utilization for patients with severe asthma.

Real-world effectiveness of benralizumab in US subspecialist-treated adults with severe asthma: Findings from CHRONICLE.

BACKGROUND: Patients with eosinophilic severe asthma (SA) have an increased risk of asthma exacerbations. Benralizumab is approved for eosinophilic SA, and there is great value in understanding real-world effectiveness. OBJECTIVE: The aim of this analysis was to examine the effectiveness of benralizumab in a real-world cohort of subspecialist-treated US patients with eosinophilic SA. METHODS: CHRONICLE is an ongoing, noninterventional study of subspecialist-treated US adults with SA receiving biologics, maintenance systemic corticosteroids, or those persistently uncontrolled by high-dose inhaled corticosteroids with additional controllers. For this analysis, eligible patients enrolled from February 2018 to February 2021, had received ≥ 1 dose of benralizumab, and had study data for ≥ 3 months before and after benralizumab initiation. The primary analysis included patients with prior exacerbations reported and 12 months of outcomes data before and after initiation. Patient outcomes occurring 6-12 months before and after initiation were also evaluated. RESULTS: A total of 317 patients had ≥ 3 months of follow-up before and after first benralizumab dose. For patients with 12 months (n = 107) and 6-12 months (n = 166) of data, significant reductions were observed in annualized rates of exacerbations (62%; P < 0.001 and 65%; P < 0.001, respectively), with similar reductions in the rates of hospitalizations and emergency department visits. Benralizumab recipients with blood eosinophil counts (BEC) of ≥ 300/ µL and < 300/ µL at baseline and 12 months of data also had significant reductions in exacerbations (68%; P < 0.001, 61%; P < 0.001). CONCLUSION: This real-world, noninterventional analysis reinforces the clinical value of benralizumab in the management of patients with eosinophilic SA.

The effects of benralizumab on airway geometry and dynamics in severe eosinophilic asthma: a single-arm study design exploring a functional respiratory imaging approach.

BACKGROUND: Severe eosinophilic asthma (SEA) is characterised by elevated blood/sputum eosinophil counts and airway inflammation, which can lead to mucus plug-mediated airway obstruction, increased exacerbation frequency, declines in lung function, and death. Benralizumab targets the alpha-subunit of the interleukin-5 receptor found on eosinophils, leading to rapid and near complete eosinophil depletion. This is expected to result in reduced eosinophilic inflammation, reduced mucus plugging and improved airway patency and airflow distribution. METHODS: BURAN is an interventional, single-arm, open-label, uncontrolled, prospective, multicentre study during which participants will receive three 30 mg subcutaneous doses of benralizumab at 4-week intervals. This study will use functional respiratory imaging (FRI), a novel, quantitative method of assessing patients' lung structure and function based on detailed, three-dimensional models of the airways, with direct comparison of images taken at Weeks 0 and 13. Patients aged ≥ 18 years with established SEA who may be receiving oral corticosteroids and/or other asthma controller medications, who are inadequately controlled on inhaled corticosteroid-long-acting ß2-agonist therapies and who have had ≥ 2 asthma exacerbations in the previous 12 months will be included. The objectives of BURAN are to describe changes in airway geometry and dynamics, measured by specific image-based airway volume and other FRI endpoints, following benralizumab therapy. Outcomes will be evaluated using descriptive statistics. Changes in FRI parameters, mucus plugging scores and central/peripheral ratio will be quantified as mean percent change from baseline (Week 0) to Week 13 (± 5 days) and statistical significance will be evaluated using paired t-tests. Relationships between FRI parameters/mucus plugging scores and conventional lung function measurements at baseline will be assessed with linear regression analyses for associations between outcomes, scatterplots to visualise the relationship, and correlation coefficients (Spearman's rank and Pearson's) to quantify the strength of these associations. CONCLUSIONS: The BURAN study will represent one of the first applications of FRI-a novel, non-invasive, highly sensitive method of assessing lung structure, function and health-in the field of biologic respiratory therapies. Findings from this study will increase understanding of cellular-level eosinophil depletion mechanisms and improvements in lung function and asthma control following benralizumab treatment. Trial registration EudraCT: 2022-000152-11 and NCT05552508.

Real-World Effectiveness Study of Benralizumab for Severe Eosinophilic Asthma: ZEPHYR 2.

BACKGROUND: Benralizumab is an mAb therapy for severe eosinophilic asthma. Real-world data on its clinical impact in various patient populations such as patients with varying eosinophil levels, previous biologic use, and extended follow-up in the United States are limited. OBJECTIVE: To determine the effectiveness of benralizumab in different asthmatic patient cohorts and its long-term clinical impact. METHODS: Patients with asthma treated with benralizumab from November 2017 to June 2019 with 2 or more exacerbations in the 12 months before benralizumab initiation (index) were included in this pre-post cohort study that used medical, laboratory, and pharmacy US insurance claims. Asthma exacerbation rates in the 12 months pre and post index were compared. Nonmutually exclusive patient cohorts were defined by blood eosinophil counts (<150, ≥150, 150-<300, <300, and ≥300 cells/µL), a switch from another biologic, or follow-up for 18 or 24 months post index. RESULTS: There were 429 patients in the eosinophil cohort, 349 in the biologic-experienced cohort, and 419 in the extended follow-up cohort. In all eosinophil cohort subgroups, the asthma exacerbation rate decreased from 3.10-3.55 per patient-year (PPY) pre index to 1.11-1.72 PPY post index (52%-64% decrease; P < .001). Similar decreases were observed in patients switching from omalizumab (3.25 to 1.25 PPY [62%]) or mepolizumab (3.81 to 1.78 PPY [53%]) to benralizumab and those followed up for 18 months (3.38 to 1.18 PPY [65%]) or 24 months (3.38 to 1.08 PPY [68%]) (all P < .001). In the extended follow-up cohort, 39% and 49% had no exacerbations in the 0 to 12 months and the 12 to 24 months post index, respectively. CONCLUSIONS: Benralizumab achieved significantly improved asthma control in real-world patients with different blood eosinophil counts, including eosinophil counts ranging from less than 150 to greater than or equal to 300 cells/µL, switching from other biologics, or treated for up to 24 months.

Biologic use and outcomes among adults with severe asthma treated by US subspecialists.

BACKGROUND: Multiple biologics are now available for severe asthma (SA) treatment and can improve outcomes for patients. However, few available data describe the real-world use and effectiveness of multiple approved biologics, including biologic switching, among subspecialists in the United States. OBJECTIVE: To evaluate biologic use and associated exacerbation outcomes in a large cohort of subspecialist-treated US adults with SA. METHODS: CHRONICLE is an ongoing, noninterventional study of subspecialist-treated US adults with SA receiving biologics, maintenance systemic corticosteroids, or those persistently uncontrolled by high-dose inhaled corticosteroids with additional controllers. For enrolled patients, sites report asthma exacerbations and medication use starting 12 months before enrollment. For patients enrolled between February 2018 and February 2021, biologic use and exacerbation outcomes before and after biologic initiation are described. RESULTS: Among 2793 enrolled patients, 66% (n = 1832) were receiving biologics. The most used biologic (> 1 biologic use per patient allowed) was omalizumab (47%), followed by benralizumab (27%), mepolizumab (26%), dupilumab (18%), and reslizumab (3%). Overall, 16% of patients had biologic switches, 13% had stops, and 89% had ongoing biologic use. Patients starting and switching biologics experienced a 58% (1.80 vs 0.76 per patient-year) and 49% (1.47 vs 0.75 per patient-year) reduction in exacerbations, respectively (both P < .001), with a numerically greater reduction observed among those starting non-anti-immunoglobulin E biologics compared with anti-immunoglobulin E. CONCLUSION: Real-world starting and switching of biologic therapies for SA were associated with meaningful reductions in exacerbations. With increasing biologic options available, individualized approaches to therapy may improve patient outcomes. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03373045.

Diagnosis and management of asthma, COPD and asthma-COPD overlap among primary care physicians and respiratory/allergy specialists: A global survey.

INTRODUCTION: Asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO) is a heterogenous condition with clinical features shared by both asthma and COPD. OBJECTIVES: This online global survey of respiratory/allergy specialists and primary care practitioners (PCPs) was performed to understand current clinical approaches to the differential diagnosis and management of asthma, COPD and ACO. METHODS: Respondents were recruited through: (a) a global online physician respondent community (49,980 PCPs and 7205 specialists); (b) market research agents; (c) experts; (d) professional societies; (e) colleague invitation. Respondents were presented with a survey including hypothetical clinical scenarios of diagnostic uncertainty to identify management approaches. RESULTS: 891 responses (447 PCPs and 444 specialists) were collected across 13 countries. Reported features used for diagnosis of asthma and COPD were consistent with practice guidelines, but there was variability in those selected for ACO diagnosis. Features typically selected by specialists focused on spirometry/history, while PCPs focused on previous treatment/symptoms. Most respondents could correctly diagnose patients with features of ACO; however, features selected for theoretical diagnosis were often different to those selected in the case scenarios. Additionally, treatment selection was often inconsistent with guidelines, with over half of respondents not recommending inhaled corticosteroids in a patient with ACO and dominant features of asthma. CONCLUSION: While most PCPs and respiratory/allergy specialists can reach a working diagnosis of ACO, there remains uncertainty around which diagnostic features are most important and what constitutes optimal management. It is imperative that clinical studies including patients with ACO are initiated, allowing the generation of evidence-based management strategies.

Differentiating between tuberculosis-related and lymphoma-related lymphocytic pleural effusions by measuring clinical and laboratory variables: is it possible?

OBJECTIVE: To describe clinical and laboratory characteristics in patients with tuberculosis-related or lymphoma-related lymphocytic pleural effusions, in order to identify the variables that might contribute to differentiating between these diseases. METHODS: This was a retrospective study involving 159 adult HIV-negative patients with tuberculosis-related or lymphoma-related lymphocytic effusions (130 and 29 patients, respectively), treated between October of 2008 and March of 2010 at the Pleural Diseases Outpatient Clinic of the University of São Paulo School of Medicine Hospital das Clínicas Heart Institute, in the city of São Paulo, Brazil. RESULTS: Mean age and the mean duration of symptoms were lower in the tuberculosis group than in the lymphoma group. The levels of proteins, albumin, cholesterol, amylase, and adenosine deaminase (ADA) in pleural fluid, as well as the serum levels of proteins, albumin, and amylase, were higher in the tuberculosis group, whereas serum cholesterol and triglycerides were higher in the lymphoma group. Pleural fluid leukocyte and lymphocyte counts were higher in the tuberculosis group. Of the tuberculosis group patients, none showed malignant cells; however, 4 showed atypical lymphocytes. Among the lymphoma group patients, cytology for neoplastic cells was positive, suspicious, and negative in 51.8%, 24.1%, and 24.1%, respectively. Immunophenotyping of pleural fluid was conclusive in most of the lymphoma patients. CONCLUSIONS: Our results demonstrate clinical and laboratory similarities among the patients with tuberculosis or lymphoma. Although protein and ADA levels in pleural fluid tended to be higher in the tuberculosis group than in the lymphoma group, even these variables showed an overlap. However, none of the tuberculosis group patients had pleural fluid ADA levels below the 40-U/L cut-off point.

É possível diferenciar derrames pleurais linfocíticos secundários a tuberculose ou linfoma através de variáveis clínicas e laboratoriais? / Differentiating between tuberculosis-related and lymphoma-related lymphocytic pleural effusions by measuring clinical and laboratory variables: Is it possible?

OBJETIVO: Descrever características clínicas e laboratoriais em pacientes com derrames pleurais linfocíticos secundários a tuberculose ou linfoma, a fim de identificar as variáveis que possam contribuir no diagnóstico diferencial dessas doenças. MÉTODOS: Estudo retrospectivo com 159 pacientes adultos HIV negativos com derrame pleural linfocítico secundário a tuberculose ou linfoma (130 e 29 pacientes, respectivamente) tratados no Ambulatório da Pleura, Instituto do Coração, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo (SP), entre outubro de 2008 e março de 2010. RESULTADOS: A média de idade e de duração dos sintomas foi menor no grupo tuberculose que no grupo linfoma. Os níveis pleurais de proteínas, albumina, colesterol, amilase e adenosina desaminase (ADA), assim como os níveis séricos de proteínas, albumina e amilase, foram maiores no grupo tuberculose, enquanto os níveis séricos de colesterol e triglicérides foram maiores no grupo linfoma. As contagens de leucócitos e linfócitos no líquido pleural foram maiores no grupo tuberculose. Células malignas estavam ausentes no grupo tuberculose, entretanto, linfócitos atípicos foram observados em 4 desses pacientes. No grupo linfoma, a citologia para células neoplásicas foi positiva, suspeita e negativa em 51,8%, 24,1% e 24,1% dos pacientes, respectivamente. A imunofenotipagem do líquido pleural foi conclusiva na maioria dos pacientes com linfoma. CONCLUSÕES: Nossos resultados demonstram semelhanças clínicas e laboratoriais entre os pacientes com tuberculose ou linfoma. Embora os níveis de proteínas e ADA no líquido pleural tendam a ser mais elevados no grupo tuberculose que no grupo linfoma, mesmo essas variáveis mostraram uma sobreposição. Entretanto, nenhum paciente com tuberculose apresentou níveis de ADA no líquido pleural inferiores ao ponto de corte (40 U/L).

OBJECTIVE: To describe clinical and laboratory characteristics in patients with tuberculosis-related or lymphoma-related lymphocytic pleural effusions, in order to identify the variables that might contribute to differentiating between these diseases. METHODS: This was a retrospective study involving 159 adult HIV-negative patients with tuberculosis-related or lymphoma-related lymphocytic effusions (130 and 29 patients, respectively), treated between October of 2008 and March of 2010 at the Pleural Diseases Outpatient Clinic of the University of São Paulo School of Medicine Hospital das Clínicas Heart Institute, in the city of São Paulo, Brazil. RESULTS: Mean age and the mean duration of symptoms were lower in the tuberculosis group than in the lymphoma group. The levels of proteins, albumin, cholesterol, amylase, and adenosine deaminase (ADA) in pleural fluid, as well as the serum levels of proteins, albumin, and amylase, were higher in the tuberculosis group, whereas serum cholesterol and triglycerides were higher in the lymphoma group. Pleural fluid leukocyte and lymphocyte counts were higher in the tuberculosis group. Of the tuberculosis group patients, none showed malignant cells; however, 4 showed atypical lymphocytes. Among the lymphoma group patients, cytology for neoplastic cells was positive, suspicious, and negative in 51.8%, 24.1%, and 24.1%, respectively. Immunophenotyping of pleural fluid was conclusive in most of the lymphoma patients. CONCLUSIONS: Our results demonstrate clinical and laboratory similarities among the patients with tuberculosis or lymphoma. Although protein and ADA levels in pleural fluid tended to be higher in the tuberculosis group than in the lymphoma group, even these variables showed an overlap. However, none of the tuberculosis group patients had pleural fluid ADA levels below the 40-U/L cut-off point.

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.

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.

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.

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.

Apesar dos relatos sobre pleurodese remontarem ao início do século XX, ainda hoje se busca o agente esclerosante ideal. Diversos agentes foram estudados e utilizados, mas o talco é considerado o mais popular. No entanto, efeitos sistêmicos potencialmente tóxicos tem sido associados à pleurodese pelo talco. Neste artigo discutimos os prováveis mecanismos de inflamação pleural e pleurodese, com ênfase na resposta sistêmica produzida pela instilação intrapleural de talco.

Derrame pleural de origem indeterminada / Undiagnosed pleural effusion

Apesar do progresso nos métodos diagnósticos, cerca de 20 por cento dos derrames pleurais podem permanecer sem diagnóstico etiológico definido após os exames convencionais. Para tentar determinar a origem destes derrames, métodos não convencionais e procedimentos mais invasivos devem ser utilizados com o objetivo de tentar esclarecer a etiologia do derrame pleural e instituir a terapêutica mais adequada.

In spite of the progress in the diagnostic methods, about 20 percent of the pleural effusions may remain without a proper diagnosis after the use of conventional exams. In order to determine the origin of these effusions, alternative methods and invasive procedures shall be used aiming to determine the etiology of the undiagnosed pleural effusions and institute the most appropriate therapeutics.