Regular treatment with formoterol and an inhaled corticosteroid versus regular treatment with salmeterol and an inhaled corticosteroid for chronic asthma: serious adverse events

BACKGROUND: An increase in serious adverse events with both regular formoterol and regular salmeterol in chronic asthma has been demonstrated in comparison with placebo in previous Cochrane reviews. This increase was significant in trials that did not randomise participants to an inhaled corticosteroid, but less certain in the smaller numbers of participants in trials that included an inhaled corticosteroid in the randomised treatment regimen.OBJECTIVES: We set out to compare the risks of mortality and non-fatal serious adverse events in trials which have randomised patients with chronic asthma to regular formoterol versus regular salmeterol, when each are used with an inhaled corticosteroid as part of the randomised treatmentSEARCH STRATEGY: Trials were identified using the Cochrane Airways Group Specialised Register of trials. Manufacturers' web sites of clinical trial registers were checked for unpublished trial data and Food and Drug Administration (FDA) submissions in relation to formoterol and salmeterol were also checked. The date of the most recent search was July 2009.SELECTION CRITERIA: Controlled clinical trials with a parallel design, recruiting patients of any age and severity of asthma were included if they randomised patients to treatment with regular formoterol versus regular salmeterol (each with a randomised inhaled corticosteroid), and were of at least 12 weeks duration.DATA COLLECTION AND ANALYSIS: Two authors independently selected trials for inclusion in the review and extracted outcome data. Unpublished data on mortality and serious adverse events were sought from the sponsors and authors.MAIN RESULTS: Eight studies met the eligibility criteria of the review recruiting 6,163 adults and adolescents. There were seven studies (involving 5,935 adults and adolescents) comparing formoterol and budesonide to salmeterol and fluticasone. All but one study administered the products as a combined inhaler, and most used formoterol 50 mcg and budesonide 400 mcg twice daily versus salmeterol 50 mcg and fluticasone 250 mcg twice daily. There were two deaths overall (one on each combination) and neither were thought to be related to asthma. There was no significant difference between treatment groups for non-fatal serious adverse events, either all-cause (Peto OR 1.14; 95% CI 0.82 to 1.59, I2 = 26%) or asthma-related (Peto OR 0.69; 95% CI 0.37 to 1.26, I2 = 33%). Over 23 weeks the rates for all-cause serious adverse events were 2.6% on formoterol and budesonide and 2.3% on salmeterol and fluticasone, and for asthma-related serious adverse events, 0.6% and 0.8% respectively. There was one study (228 adults) comparing formoterol and beclomethasone to salmeterol and fluticasone, but there were no deaths or hospital admissions. No studies were found in children.AUTHORS' CONCLUSIONS: The seven identified studies in adults did not show any significant difference in safety between formoterol and budesonide in comparison with salmeterol and fluticasone. Asthma-related serious adverse events were rare, and there were no reported asthma-related deaths. There was a single small study comparing formoterol and beclomethasone to salmeterol and fluticasone in adults, but no serious adverse events occurred in this study. No studies were found in children. Overall there is insufficient evidence to decide whether regular formoterol and budesonide or beclomethasone have equivalent or different safety profiles from salmeterol and fluticasone.Univ Fed Sao Paulo, Dept Med, Disciplina Pneumol, BR-04023062 Sao Paulo, BrazilUniv Fed Sao Paulo, Dept Med, Disciplina Pneumol, BR-04023062 Sao Paulo, BrazilWeb of Scienc

Nível de controle da asma e seu impacto nas atividades de vida diária em asmáticos no Brasil

OBJECTIVE:To evaluate the impact of asthma on activities of daily living and on health status in patients with controlled, partially controlled, or uncontrolled asthma in Brazil.METHODS:We used data related to 400 patients in four Brazilian cities (São Paulo, Rio de Janeiro, Salvador, and Curitiba), obtained in a survey conducted throughout Latin America in 2011. All study subjects were > 12 years of age and completed a standardized questionnaire in face-to-face interviews. The questions addressed asthma control, hospitalizations, emergency room visits, and school/work absenteeism, as well as the impact of asthma on the quality of life, sleep, and leisure. The level of asthma control was determined in accordance with the Global Initiative for Asthma criteria.RESULTS:Among the 400 respondents, asthma was controlled in 37 (9.3%), partially controlled in 226 (56.5%), and uncontrolled in 137 (34.2%). The numbers of patients with uncontrolled or partially controlled asthma who visited the emergency room, who were hospitalized, and who missed school/work were higher than were those of patients with controlled asthma (p = 0.001, p = 0.05, and p = 0.01, respectively). Among those with uncontrolled asthma, the impact of the disease on activities of daily living, sleep, social activities, and normal physical exertion was greater than it was among those with controlled or partially controlled asthma (p 12 anos e responderam a um questionário padronizado por meio de entrevista presencial. As questões abordavam o controle da asma, número de hospitalizações, de consultas de urgência, absenteísmo na escola/trabalho e impacto da asma na qualidade de vida, sono e lazer. O nível de controle da asma foi verificado segundo os critérios da Global Initiative for Asthma.RESULTADOS:Entre 400 entrevistados, a asma estava controlada em 37 (9,3%); parcialmente controlada, em 226 (56,5%); e não controlada, em 137 (34,2%). O número de pacientes com asma não controlada ou parcialmente controlada que apresentaram hospitalizações, visitas ao pronto-socorro e faltas na escola/trabalho foi maior do que o daqueles com asma controlada (p = 0,001, p = 0,05 e p = 0,01, respectivamente). Os participantes com asma não controlada apresentaram um maior impacto da doença em atividades da vida diária, sono, atividades sociais e esforço físico normal do que aqueles com asma parcialmente controlada ou controlada (p < 0,001).CONCLUSÕES:Medidas terapêuticas devem ser mais intensamente adotadas em nosso país para melhorar o controle da asma e estimular a aderência ao tratamento. Isso, seguramente, proporcionará uma melhor qualidade de vida aos pacientes e uma redução do impacto negativo da doença.Federal University of São Paulo Paulista School of MedicineSao Camilo University CenterMerck, Sharp &amp; Dohme Corp.University of Puerto Rico School of Public HealthUNIFESP, EPMSciEL

Linguistic validation of cystic fibrosis quality of life questionnaires

OBJECTIVE: The purpose of this study was to validate the Portuguese translations of four cystic fibrosis quality of life questionnaires (CFQ). The first three were developed for patients with cystic fibrosis aged from 6 to 11 years, from 12 to 13 years and 14 years or more, while the fourth was developed for the parents of patients aged 6 to 13 years. MATERIAL AND METHODS: The four CFQ translations contained from 35 to 50 questions covering nine domains and were validated as follows: translation from English to Portuguese, pilot application, back translation and then approval by the author of the English versions. The four translations were applied to 90 stable patients (30 from each age group) and the parents of patients aged 6-13 years (n = 60), on two occasions with a 13 to 17 day interval. Intraclass Correlation Coefficients (ICC) were used to measure reproducibility. This study was approved by the Commission for Ethics in Research at the institution. RESULTS:Reproducibility was good (ICC = 0.62 to 0.99) for the four translations in all domains, with the exceptions of the Digestion domain for the 6 to 11 and 12 to 13 years age groups with ICC = 0.59 and 0.47, respectively and the Social Role domain for the 14 and over age group (ICC = -0.19 ) CONCLUSION: The translation and cultural adaptation for Brazil resulted in four CFQ versions that are easy to understand and offer good reproducibility.OBJETIVO: O propósito deste estudo foi validar em português as quatro versões de questionários de qualidade de vida em fibrose cística, desenvolvidos para pacientes com fibrose cística de 6 a 11 anos, de 12 a 13 e mais de 14 anos, e para os pais de pacientes de 6 a 13 anos. MATERIAL E MÉTODOS: A validação das quatro versões de questionários de qualidade de vida em fibrose cística (de 35 e 50 questões, abrangendo nove domínios) constou de: versão inglês-português, aplicação-piloto, tradução retrógrada e aprovação da autora da versão inglesa. As quatro versões foram aplicadas a 90 pacientes estáveis (30 de cada grupo etário) e aos pais de doentes de 6-13 anos (n = 60), em duas entrevistas, com intervalo de 13-17 dias. Foi avaliada a reprodutibilidade pelo coeficiente de correlação intraclasse (CCI). O estudo foi aprovado pela comissão de ética em pesquisa da instituição. RESULTADOS: A reprodutibilidade foi boa (CCI = 0,62 a 0,99) para as quatro versões, em todos os domínios, exceto o digestivo (CCI = 0,59 e CCI = 0,47) para os grupos etários de 6 a 11 e 12 a 13 anos, respectivamente, e domínio papel social (CCI = -0,19 ) para o grupo acima de 14 anos. CONCLUSÃO: A tradução e a adaptação à língua e à cultura brasileiras das quatro versões de questionários de qualidade de vida em fibrose cística mostraram-se de fácil entendimento e boa reprodutibilidade.Universidade de São Paulo Faculdade de Medicina Departamento de PediatriaUniversidade Federal de São Paulo (UNIFESP) Escola Paulista de MedicinaFaculdade de Medicina do ABCUNIFESP-EPM Centro de Reabilitação PulmonarUniversidade de São Paulo Faculdade de Medicina Hospital das ClínicasUniversity of Miami Department of PsychologyUNIFESP, EPM, Centro de Reabilitação PulmonarSciEL

Nível de controle da asma e sua relação com o uso de medicação em asmáticos no Brasil

OBJECTIVE:To assess asthma patients in Brazil in terms of the level of asthma control, compliance with maintenance treatment, and the use of rescue medication.METHODS:We used data from a Latin American survey of a total of 400 asthma patients in four Brazilian state capitals, all of whom completed a questionnaire regarding asthma control and treatment.RESULTS:In that sample, the prevalence of asthma was 8.8%. Among the 400 patients studied, asthma was classified, in accordance with the Global Initiative for Asthma criteria, as controlled, partially controlled, and uncontrolled in 37 (9.3%), 226 (56.5%), and 137 (34.3%), respectively. In those three groups, the proportion of patients on maintenance therapy in the past four weeks was 5.4%, 19.9%, and 41.6%, respectively. The use of rescue medication was significantly more common in the uncontrolled asthma group (86.9%; p < 0.001).CONCLUSIONS:Our findings suggest that, in accordance with the established international criteria, asthma is uncontrolled in the vast majority of asthma patients in Brazil. Maintenance medications are still underutilized in Brazil, and patients with partially controlled or uncontrolled asthma are more likely to use rescue medications and oral corticosteroids.OBJETIVO:Avaliar pacientes asmáticos no Brasil em relação ao grau de controle da asma, a aderência ao tratamento de manutenção e o uso de medicação de alivio em pacientes asmáticos.MÉTODOS:Foram utilizados os dados de um inquérito latino-americano, obtidos em quatro capitais brasileiras, de 400 pacientes com asma através de um questionário sobre o controle e o tratamento da doença.RESULTADOS:A prevalência de asma nesta amostra foi de 8,8%. Dos 400 pacientes estudados, 37 (9,3%), 226 (56,5%) e 137 (34,3%), respectivamente, foram classificados, segundo critérios da Global Initiative for Asthma, como tendo asma controlada, parcialmente controlada e não controlada. A proporção de pacientes em terapia de manutenção nas últimas quatro semanas naqueles três grupos, respectivamente, foi de 5,4%, 19,9% e 41,6%. O uso de medicação de alivio foi significativamente mais comum nos pacientes com asma não controlada (86,9%; p < 0,001).CONCLUSÕES:Nossos achados sugerem que a grande maioria dos pacientes com asma no Brasil não apresenta sua doença controlada segundo critérios internacionais. As medicações de manutenção ainda são subutilizadas no Brasil, e o uso de medicações de alívio e corticoide oral é mais frequente em pacientes com asma parcialmente controlada ou não controlada.Federal University of São Paulo Paulista School of MedicineMerck, Sharp &amp; Dohme Corp.UNIFESP, EPMSciEL

Diferenças entre os sexos na percepção de asma e sintomas respiratórios em uma amostra populacional em quatro cidades brasileiras

OBJECTIVE: To evaluate the impact of asthma, by gender, in a population sample of asthma patients in Brazil. METHODS: We conducted face-to-face interviews with 400 subjects (> 12 years of age) included in a national probability telephone sample of asthma patients in the Brazilian state capitals of São Paulo, Rio de Janeiro, Curitiba, and Salvador. Each of those 400 subjects completed a 53-item questionnaire that addressed five asthma domains: symptoms; impact of asthma on quality of life; perception of asthma control; exacerbations; and treatment/medication. RESULTS: Of the 400 patients interviewed, 272 (68%) were female. In relation to respiratory symptoms, the proportion of women reporting extremely bothersome symptoms (cough with sputum, tightness in the chest, cough/shortness of breath/tightness in the chest during exercise, nocturnal shortness of breath, and nocturnal cough) was greater than was that of men. Daytime symptoms, such as cough, shortness of breath, wheezing, and tightness in the chest, were more common among women than among men. Women also more often reported that their asthma interfered with normal physical exertion, social activities, sleep, and life in general. Regarding the impact of asthma on quality of life, the proportion of subjects who reported that asthma caused them to feel that they had no control over their lives and affected the way that they felt about themselves was also greater among women than among men. CONCLUSIONS: Among women, asthma tends to be more symptomatic, as well as having a more pronounced effect on activities of daily living and on quality of life.OBJETIVO: Avaliar o impacto da asma em relação ao sexo em uma amostra populacional de pacientes asmáticos no Brasil. MÉTODOS: Foram entrevistados pessoalmente 400 pacientes asmáticos com idade > 12 anos de uma amostra probabilística nacional por contato telefônico nas cidades de São Paulo, Rio de Janeiro, Curitiba e Salvador. Os indivíduos responderam um questionário de 53 questões relacionadas com cinco domínios da asma: sintomas; impacto da asma na vida; percepção do controle da asma; exacerbações; tratamento e medicação. RESULTADOS: Dos 400 pacientes entrevistados, 272 (68%) eram do sexo feminino. Em relação aos sintomas respiratórios, uma maior proporção de mulheres relatou se sentir extremamente incomodada com seus sintomas (tosse com secreção, sensação de aperto no peito, tosse/falta de ar/sensação de aperto no peito durante exercícios, falta de ar noturna e tosse noturna) do que os homens. Sintomas diurnos, como tosse, falta de ar, chiado e sensação de aperto no peito, foram mais comuns nas mulheres que nos homens. Além disso, a asma interferiu mais frequentemente nos esforços físicos normais, atividades sociais, durante o sono e na vida em geral nas mulheres. Sobre o impacto da asma na qualidade de vida, as mulheres relataram mais frequentemente que os homens que a asma causava uma sensação de falta de controle sobre a própria vida e que eram afetadas na forma como se sentiam em relação a si mesmas. CONCLUSÕES: As mulheres asmáticas apresentam mais sintomas e são mais afetadas em suas atividades diárias e qualidade de vida.Federal University of São Paulo Paulista School of MedicineUniversity of Puerto Rico School of Public HealthMerck Sharp &amp; Dohme Corp.UNIFESP, EPMSciEL

Questionário Functional Assessment of Cancer Therapy-Brain: tradução e adaptação linguística para o português do Brasil

CONTEXT AND OBJECTIVE: Quality of life assessment among patients with brain tumors is important, given that new treatments have increased patient survival. The aim of this study was to translate the Functional Assessment of Cancer Therapy-Brain (FACT-Br) questionnaire (version 4) into Portuguese, carry out cross-cultural adaptation and assess its reproducibility. DESIGN AND SETTING: Cohort at the Universidade Federal de São Paulo (UNIFESP). METHODS: Forty patients with a brain tumor seen at the neuro-oncology outpatient clinic participated in the study. The process of translation and back-translation was carried out, along with adaptation to the Portuguese language and Brazilian culture. The intraclass correlation coefficient (ICC) was used to test the reproducibility of the FACT-Br (version 4). RESULTS: The reproducibility of the questionnaire was excellent (ICC = 0.95; 95% confidence interval, CI: 0.89-0.97). The ICC with a mean interval of 15 days between applications of the questionnaire was very good in all domains (ICC = 0.87 to 0.95). The mean time taken to answer the questionnaire was 6.27 ± 2.26 minutes, ranging from 3 to 11 minutes. CONCLUSION: The translated version of the FACT-Br questionnaire (version 4) adapted to the Portuguese language and Brazilian culture proved to be easily understood and achieved very good reproducibility among patients with diagnoses of brain tumors.CONTEXTO E OBJETIVOS: A avaliação da qualidade de vida dos pacientes com tumor cerebral é importante, considerando que novos tratamentos têm aumentado sua sobrevida. O objetivo deste trabalho foi traduzir o questionário Functional Assessment of Cancer Therapy-Brain (FACT-Br) (versão 4) para a língua portuguesa, realizar a adaptação cultural e avaliar sua reprodutibilidade. DESIGN E LOCAL: Estudo de coorte realizado na Universidade Federal de São Paulo (UNIFESP). MÉTODO: Quarenta pacientes com tumor cerebral provenientes do Ambulatório de Neuro-oncologia participaram do estudo. O processo de tradução inicial e retrógrada foi realizado, além da adaptação cultural para a língua e cultura brasileira. O coeficiente de correlação intraclasse (CCI) foi utilizado para testar a reprodutibilidade do FACT-Br (versão 4). RESULTADOS: A reprodutibilidade do questionário foi excelente (CCI = 0,95; intervalo de confiança, IC 95% 0,89-0,97). O CCI com intervalo médio de 15 dias entre aplicações do questionário, em todos os domínios, foi muito bom (CCI = 0,87 a 0,95). O tempo médio de resposta ao questionário foi de 6,27 minutos ± 2,26 minutos, variando de 3 minutos a 11 minutos. CONCLUSÃO: A tradução e a adaptação à língua e à cultura brasileira do questionário FACT-Br (versão 4) mostrou-se de fácil entendimento e com muito boa reprodutibilidade em pacientes com diagnóstico de tumor cerebral.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Universidade Federal de São Paulo (UNIFESP) Respiratory Division Neurosurgery Physiotherapy Research GroupUniversidade Federal de São Paulo (UNIFESP) Neurology DivisionUniversidade Federal de São Paulo (UNIFESP) Physiotherapy DepartmentUniversidade Federal de São Paulo (UNIFESP) Respiratory DivisionUNIFESP Pulmonary Rehabilitation CenterLar Escola São FranciscoUNIFESP, Respiratory Division Neurosurgery Physiotherapy Research GroupUNIFESP, Neurology DivisionUNIFESP, Physiotherapy DepartmentUNIFESP, Respiratory DivisionUNIFESP, Pulmonary Rehabilitation CenterSciEL

Efficacy of the FEV1/FEV6 ratio compared to the FEV1/FVC ratio for the diagnosis of airway obstruction in subjects aged 40 years or over

The present cross-sectional, population-based study was designed to evaluate the performance of the FEV1/FEV6 ratio for the detection of airway-obstructed subjects compared to the FEV1/FVC <0.70 fixed ratio test, as well as the lower limit of normality (LLN) for 1000 subjects ³40 years of age in the metropolitan area of São Paulo, SP, Brazil. After the exclusion of 37 (3.7%) spirometries, a total of 963 pre-bronchodilator (BD) and 918 post-BD curves were constructed. The majority of the post-BD curves (93.1%) were of very good quality and achieved grade A (762 curves) or B (93 curves). The FEV1/FEV6 and FEV1/FVC ratios were highly correlated (r² = 0.92, P < 0.000). Two receiver operator characteristic curves were constructed in order to express the imbalance between the sensitivity and specificity of the FEV1/FEV6 ratio compared to two FEV1/FVC cut-off points for airway obstruction: equal to 70 (area under the curve = 0.98, P < 0.0001) and the LLN (area under the curve = 0.97, P < 0.0001), in the post-BD curves. According to an FEV1/FVC <0.70, the cut-off point for the FEV1/FEV6 ratio with the highest sum for sensitivity and specificity was 0.75. The FEV1/FEV6 ratio can be considered to be a good alternative to the FEV1/FVC ratio for the diagnosis of airway obstruction, both using a fixed cut-off point or below the LLN as reference. The FEV1/FEV6 ratio has the additional advantage of being an easier maneuver for the subjects and for the lung function technicians, providing a higher reproducibility than traditional spirometry maneuvers.Universidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Disciplina de Pneumologia e Centro de Reabilitação PulmonarUniversidade Católica do SalvadorFaculdade de Tecnologia e CiênciasNational Institute of Respiratory DiseasesUniversidade Federal da Bahia Disciplina de PneumologiaUniversidade Federal de Pelotas Programa de Pós-graduação em EpidemiologiaPLATINO GroupUNIFESP, EPM, Disciplina de Pneumologia e Centro de Reabilitação PulmonarSciEL

Chronic obstructive pulmonary disease is underdiagnosed and undertreated in São Paulo (Brazil): results of the PLATINO study

Chronic obstructive pulmonary disease (COPD) is a common disease in adults over 40 years of age and has a great social and economic impact. It remains little recognized and undertreated even in developed countries. However, there are no data about its diagnosis and treatment in Brazil. The objectives of the present study were to evaluate the proportion of COPD patients who had never been diagnosed and to determine if the COPD patients who had been identified were receiving appropriate treatment. The Latin American Project for the Investigation of Obstructive Lung Disease (PLATINO) was a randomized epidemiological study of adults over 40 years living in five metropolitan areas, including São Paulo. The studied sample was randomly selected from the population after a division of the metropolitan area of São Paulo in clusters according to social characteristics. All subjects answered a standardized questionnaire on respiratory symptoms, history of smoking, previous diagnosis of lung disease, and treatments. All subjects performed spirometry. The criterion for the diagnosis of COPD was defined by a post-bronchodilator FEV1/FVC ratio lower than 0.7. A total of 918 subjects were evaluated and 144 (15.8%) met the diagnostic criterion for COPD. However, 126 individuals (87.5%) had never been diagnosed. This undiagnosed group of COPD patients had a lower proportion of subjects with respiratory symptoms than the previously diagnosed patients (88.9 vs 54.8%) and showed better lung function with greater FEV1 (86.8 ± 20.8 vs 68.5 ± 23.6% predicted) and FVC (106.6 ± 22.4 vs 92.0 ± 24.1% predicted). Among the COPD patients, only 57.3% were advised to stop smoking and 30.6% received the influenza vaccine. In addition, 82.3% did not receive any pharmacological treatment. In conclusion, COPD is underdiagnosed and a large number of COPD patients are not treated appropriately.Universidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Centro de Reabilitação PulmonarUniversidade Federal da BahiaUniversidade Católica de Salvador Faculdade de Tecnologia e CiênciasUniversidade Federal de Pelotas Programa de Pós-graduação em EpidemiologiaNational Institute of Respiratory DiseasesPLATINO GroupUNIFESP, EPM, Centro de Reabilitação PulmonarSciEL