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Publications 32

Objective: To validate the Pediatric Obstructive Sleep Apnea Screening tool for use in Brazil. Materials and methods: The Brazilian version of this questionnaire, originally validated and tested in the United States, was developed as follows: (a) translation; (b) back‐translation; (c) completion of the final version; (d) pre‐testing. The questionnaire was applied prior to polysomnography to children aged 3–9 years from October 2015 to October 2016, and its psychometric properties (i.e., validity and reliability) were evaluated. The accuracy was assessed from comparisons between polysomnographic results and corresponding questionnaire scores. Results: Sixty patients were enrolled, and based on polysomnographic findings, 48% patients had normal apnea‐hypopnea index, while the remaining 52% met the criteria for obstructive sleep apnea. Minimum O2 saturation level was obstructive sleep apnea children (p = 0.021). Satisfactory concordance was found between individual apnea-hypopnea index and questionnaire scores. Bland–Altman plot‐derived bias was 0.1 for the difference between measures, with 5.34 (95% CI: 4.14–6.55) and −5.19 (95%CI: −6.39 to −3.98) for the upper and lower agreement range. Internal consistency derived from Cronbach's alpha was 0.84 (95%CI: 0.78–0.90). Conclusion: The questionnaire was translated to and validated into Brazilian‐Portuguese version, and showed good reliability and concordance with apnea‐hypopnea index. This questionnaire offers a reliable screening option for sleep‐disordered breathing in children. Resumo: Objetivo: Validar o questionário Pediatric Obstructive Sleep Apnea Screening Tool para o seu uso no Brasil. Materiais e métodos: A versão brasileira desse questionário, originalmente validado e testado nos Estados Unidos, foi desenvolvida a partir das seguintes etapas: a) tradução; b) retrotradução; c) conclusão da versão final; d) pré‐teste. O questionário foi aplicado previamente ao início da polissonografia em crianças de 3 a 9 anos incluídas no estudo de outubro de 2015 a outubro de 2016. As propriedades psicométricas avaliadas foram validade e confiabilidade. A acurácia foi avaliada pela comparação entre os resultados da polissonografia com o escore do questionário. Resultados: Foram incluídos no estudo 60 pacientes. Conforme a polissonografia, 48% dos pacientes apresentaram índices de apneia e hipopneia normais e 51% apresentaram resultados alterados. A SpO2 mínima foi significativamente menor (p = 0,021) nas crianças com diagnóstico de síndrome de apneia obstrutiva do sono. O índice de apneia e hipopneia apresentou concordância satisfatória com os resultados do questionário. O viés médio de Bland‐Altman foi de 0,1 para a diferença entre as medidas, com um limite superior de 5,34 (IC95%4,14 a 6,55) e um limite inferior de ‐5,19 (IC95%‐6,39 a ‐3,98). A consistência interna do questionário avaliada pelo α de Cronbach foi de 0,84 (IC95%0,78 a 0,90). Conclusão: O questionário foi traduzido e validado adequadamente para a versão em português brasileiro, apresentando boa confiabilidade e concordância com o índice de apneia e hipopneia. Esse questionário oferece uma opção confiável de triagem de distúrbios respiratórios do sono em crianças. Keywords: Questionnaire, Sleep‐disordered breathing, Pediatrics, Validation, Palavras‐chave: Questionário, Distúrbios respiratórios do sono, Pediatria, Validação

Abstract Objective: The aim of this review was to address advances in management and treatment of acute viral bronchiolitis in infants. Sources: A systematic review search was made including all articles published in English between 2010 and 2017, and available in the electronic databases PubMed and Cochrane Central Register of Controlled Trials (CENTRAL) and specialized register of the Acute Respiratory Infections Group (Cochrane review group). The following MESH terms in English were included, using different Boolean operators for the search strategy: “bronchiolitis, viral,” “diagnosis,” “epidemiology,” “etiology,” “therapy,” “virology,” “prevention and control,” “respiratory syncytial virus, human.” Additional filters were used. Summary of findings: Few effective interventions are recommended for the management of RSV bronchiolitis in young infants. The main goal is to ensure an adequate oxygen supplementation and fluid balance whenever deemed necessary. Hypertonic saline nebulization is helpful only for hospitalized infants. Numerous antiviral drugs and specific vaccines for RSV are under evaluation and foretell advances in disease management in the near future. Conclusion: A number of promising new technologies are advancing in the field. Until new interventions became feasible, early detection and modification of preventable risk factors is essential to improve outcomes.

Objective: The aim of this review was to address advances in management and treatment of acute viral bronchiolitis in infants. Sources: A systematic review search was made including all articles published in English between 2010 and 2017, and available in the electronic databases PubMed and Cochrane Central Register of Controlled Trials (CENTRAL) and specialized register of the Acute Respiratory Infections Group (Cochrane review group). The following MESH terms in English were included, using different Boolean operators for the search strategy: “bronchiolitis, viral,” “diagnosis,” “epidemiology,” “etiology,” “therapy,” “virology,” “prevention and control,” “respiratory syncytial virus, human.” Additional filters were used. Summary of findings: Few effective interventions are recommended for the management of RSV bronchiolitis in young infants. The main goal is to ensure an adequate oxygen supplementation and fluid balance whenever deemed necessary. Hypertonic saline nebulization is helpful only for hospitalized infants. Numerous antiviral drugs and specific vaccines for RSV are under evaluation and foretell advances in disease management in the near future. Conclusion: A number of promising new technologies are advancing in the field. Until new interventions became feasible, early detection and modification of preventable risk factors is essential to improve outcomes.

Objective: To validate the Pediatric Obstructive Sleep Apnea Screening tool for use in Brazil. Materials and methods: The Brazilian version of this questionnaire, originally validated and tested in the United States, was developed as follows: (a) translation; (b) back-translation; (c) completion of the final version; (d) pre-testing. The questionnaire was applied prior to polysomnography to children aged 3–9 years from October 2015 to October 2016, and its psychometric properties (i.e., validity and reliability) were evaluated. The accuracy was assessed from comparisons between polysomnographic results and corresponding questionnaire scores. Results: Sixty patients were enrolled, and based on polysomnographic findings, 48% patients had normal apnea-hypopnea index, while the remaining 52% met the criteria for obstructive sleep apnea. Minimum O2 saturation level was significantly lower among obstructive sleep apnea children (p = 0.021). Satisfactory concordance was found between individual apnea-hypopnea index and questionnaire scores. Bland–Altman plot-derived bias was 0.1 for the difference between measures, with 5.34 (95% CI: 4.14–6.55) and −5.19 (95%CI: −6.39 to −3.98) for the upper and lower agreement range. Internal consistency derived from Cronbach's alpha was 0.84 (95%CI: 0.78–0.90). Conclusion: The questionnaire was translated to and validated into Brazilian-Portuguese version, and showed good reliability and concordance with apnea-hypopnea index. This questionnaire offers a reliable screening option for sleep-disordered breathing in children. Resumo: Objetivo: Validar o questionário Pediatric Obstructive Sleep Apnea Screening Tool para o seu uso no Brasil. Materiais e métodos: A versão brasileira desse questionário, originalmente validado e testado nos Estados Unidos, foi desenvolvida a partir das seguintes etapas: a) tradução; b) retro-tradução; c) conclusão da versão final; d) pré-teste. O questionário foi aplicado previamente ao início da polissonografia em crianças de 3 a 9 anos incluídas no estudo no período de outubro de 2015 a outubro de 2016. As propriedades psicométricas avaliadas foram validade e confiabilidade. A acurácia foi avaliada pela comparação entre os resultados da polissonografia com o escore do questionário. Resultados: Foram incluídos no estudo 60 pacientes. Conforme a polissonografia, 48% dos pacientes apresentaram índices de apneia e hipopneia normais e 51% apresentaram resultados alterados. A SpO2 mínima foi significativamente menor (p = 0,021) nas crianças com diagnóstico de síndrome de apneia obstrutiva do sono. O índice de apneia e hipopneia apresentou concordância satisfatória com os resultados do questionário. O viés médio de Bland-Altman foi de 0,1 para a diferença entre as medidas, com um limite superior de 5,34 (IC95%4,14 a 6,55) e um limite inferior de -5,19 (IC95%-6,39 a -3,98). A consistência interna do questionário avaliada pelo α de Cronbach foi de 0,84 (IC95%0,78 a 0,90). Conclusão: O questionário foi traduzido e validado adequadamente para a versão em português brasileiro, apresentando boa confiabilidade e concordância com o índice de apneia e hipopneia. Esse questionário oferece uma opção confiável de triagem de distúrbios respiratórios do sono em crianças. Keywords: Questionnaire, Sleep-disordered breathing, Pediatrics, Validation, Palavras-chave: Questionário, Distúrbios respiratórios do sono, Pediatria, Validação

Objective: To review the mechanisms of action of macrolides in pediatric respiratory diseases and their clinical indications. Sources: Review in the PubMed database, comprising the following terms in English: “macrolide and asthma”; “macrolide and cystic fibrosis”; “macrolide bronchiolitis and viral acute”; “macrolide and bronchiolitis obliterans” and “macrolide and non-CF bronchiectasis”. Summary of the findings: The spectrum of action of macrolides includes production of inflammatory mediators, control of mucus hypersecretion, and modulation of host-defense mechanisms. The potential benefit of macrolide antibiotics has been studied in a variety of lung diseases, such as cystic fibrosis (CF), bronchiectasis, asthma, acute bronchiolitis, and non-CF bronchiectasis. Several studies have evaluated the benefits of macrolides in asthma refractory to therapy, but the results are controversial and indications should be limited to specific phenotypes.In viral bronchiolitis, there is no consistent benefit in acute conditions, although recent data have shown an effect in recurrent wheezing prevention. In patients with CF results are also contradictory, but the consensus states there is a small clinical benefit, especially for patients infected with P. aeruginosa. There was also no positive action of macrolides in patients with post-infectious bronchiolitis obliterans. Children with non-CF bronchiectasis seem to have clear benefits regarding the use of macrolides, which showed clinical advantages in parenchyma protection and lung function. Conclusions: The long-term use of macrolides should be limited to highly selected situations, especially in patients with bronchiectasis. Careful evaluation of the benefits and potential damage are tools for their indication in specific groups. Resumo: Objetivo: revisar os mecanismos de ação de macrolídeos em doenças respiratórias pediátricas e as suas indicações clínicas. Fonte de dados: revisão na base de dados Pubmed, compreendendo os termos em inglês referente ao tema básico. Síntese dos dados: O seu espectro de ação estende-se desde a produção de mediadores inflamatórios, o controle da hipersecreção de muco e modulação de mecanismos de defesa do hospedeiro. O potencial benefício dos antibióticos macrolídeos foi estudado em doenças pulmonares como a fibrose cística, as bronquiectasias, a asma, a bronquiolite aguda e as bronquiectasias não ligadas à fibrose cística. Diversos estudos avaliaram os benefícios dos macrolídeos na asma resistente a terapia, porém, os resultados são controversos e as indicações devem ser limitadas a fenótipos específicos. Na bronquiolite viral não há benefícios consistentes nos quadros agudos, embora dados recentes mostrem um efeito na prevenção de sibilância recorrente. Em pacientes com fibrose cística os resultados também são contraditórios, mas o consenso é de que há um pequeno benefício clínico, especialmente para os pacientes infectados por P. aeruginosa. Também não foi observada ação positiva dos macrolídeos em pacientes com bronquiolite obliterante pós-infecciosa. Crianças com bronquiectasias não relacionadas à fibrose cística parecem ter claros benefícios em relação ao uso de macrolídeos, os quais mostraram vantagens clínicas, de proteção ao parênquima e na função pulmonar. Conclusões: O uso em longo prazo de macrolídeos deve ser limitado a situações altamente selecionadas, especialmente em pacientes com bronquiectasias. Avaliação cuidadosa dos benefícios e potenciais danos são ferramentas para indicação em grupos específicos. Keywords: Pulmonary diseases, Macrolides, Inflammation, Children, Adolescents, Palavras-chave: Doenças pulmonares, Macrolídeos, Inflamação, Crianças, Adolescentes

Objective: The aim of this review was to address advances in management and treatment of acute viral bronchiolitis in infants. Sources: A systematic review search was made including all articles published in English between 2010 and 2017, and available in the electronic databases PubMed and Cochrane Central Register of Controlled Trials (CENTRAL) and specialized register of the Acute Respiratory Infections Group (Cochrane review group). The following MESH terms in English were included, using different Boolean operators for the search strategy: “bronchiolitis, viral,” “diagnosis,” “epidemiology,” “etiology,” “therapy,” “virology,” “prevention and control,” “respiratory syncytial virus, human.” Additional filters were used. Summary of findings: Few effective interventions are recommended for the management of RSV bronchiolitis in young infants. The main goal is to ensure an adequate oxygen supplementation and fluid balance whenever deemed necessary. Hypertonic saline nebulization is helpful only for hospitalized infants. Numerous antiviral drugs and specific vaccines for RSV are under evaluation and foretell advances in disease management in the near future. Conclusion: A number of promising new technologies are advancing in the field. Until new interventions became feasible, early detection and modification of preventable risk factors is essential to improve outcomes. Resumo: Objetivo: O objetivo desta análise é abordar avanços no manejo e no tratamento de bronquiolite viral aguda em neonatos. Fontes: Uma pesquisa de análise sistemática foi realizada e incluiu todos os artigos publicados em inglês entre 2010 e 2017 e disponíveis nas bases de dados eletrônicas PubMed, no Registro Central de Ensaios Controlados (CENTRAL) da Cochrane e no registro especializado do Grupo de Infecções Respiratórias Agudas (grupo de revisão Cochrane). Os seguintes termos MESH em inglês foram incluídos na abordagem utilizando diferentes operadores booleanos para a estratégia de pesquisa: “bronquiolite, viral”, “diagnóstico”, “epidemiologia”, “etiologia”, “terapia”, “virologia”, “prevenção e controle”, “vírus sincicial respiratório, humano”. Foram utilizados filtros adicionais. Resumo dos achados: Poucas intervenções efetivas são recomendadas para o manejo da bronquiolite por VSR em neonatos jovens. O principal objetivo é garantir uma suplementação de oxigênio adequada e equilíbrio de fluidos sempre que considerado necessário. A nebulização de solução salina hipertônica ajuda apenas em casos de neonatos hospitalizados. Vários medicamentos antivirais e vacinas específicas contra VSR estão em fase de avaliação e predizem avanços no manejo da doença no futuro próximo. Conclusão: Várias novas tecnologias promissoras estão avançando no campo. Até que as novas intervenções se tornem viáveis, a detecção precoce e a modificação de fatores de risco de prevenção são fundamentais para melhorar os resultados. Keywords: Viral bronchiolitis, Infants, Respiratory syncytial virus, Palavras-chave: Bronquiolite viral, Neonatos, Vírus sincicial respiratório

SUMMARY Episodes of lower respiratory illnesses (LRIs) in the first years of life have been associated with recurrent wheeze in studies of high-risk and community-based cohorts. Respiratory syncytial virus (RSV) is an agent especially associated with severe cases of bronchiolitis affecting young infants in winter months and has a typical seasonal pattern. Data from the Children's Respiratory Study from Arizona and a hospital-based Swedish study have been interpreted as evidence that severe RSV bronchiolitis is associated with a 30-40% likelihood of subsequent asthma. Other respiratory viruses, especially Rhinovirus, have been identified to be importantly associated with recurrent wheeze in children at risk for asthma. A case-control study of palivizumab given in the first year of life to preterm infants has shown a 50% reduction in the occurrence of recurrent wheeze even after controlling for potential confounding variables. Prospective trials with anti-viral strategies, including potential new vaccines, should give us better understanding of the role of viral infections in early life in the causation of childhood asthma.

Summary Pneumonia is highly prevalent in both developed and developing countries. In this review we list the main organisms affecting children with pnuemonia and we propose a summary of the best possible diagnostic and therapeutic measures.

OBJETIVO: A bronquite plástica é uma doença infreqüente na criança, sendo caracterizada por moldes ou cilindros mucofibrinosos na árvore traqueobrônquica. Faz parte do diagnóstico diferencial de crianças com insuficiência respiratória de início agudo, e o tratamento precoce é importante para a resolução do quadro. O objetivo deste relato é descrever um caso de bronquite plástica tratado com sucesso por endoscopia, em paciente portador de talassemia alfa. DESCRIÇÃO: Criança do sexo masculino, 3 anos de idade, sem antecedentes mórbidos significativos, apresentou quadro de insuficiência respiratória aguda, com achados radiológicos de atelectasia pulmonar sugestivos de aspiração de corpo estranho. Não havia sintomas respiratórios ou antecedentes de alergia ou infecções respiratórias de repetição. A realização de broncoscopia flexível, complementada por endoscopia rígida e exame anatomopatológico, evidenciou a presença de bronquite plástica. Após a realização da endoscopia, a criança evoluiu satisfatoriamente, com curva térmica afebril e extubação em 72 horas. Foram utilizadas medicações sintomáticas, sem necessidade de antimicrobianos. Dez dias após a alta, a radiografia de tórax encontrava-se normal. A talassemia alfa foi diagnosticada através da eletroforese de hemoglobina. COMENTÁRIOS: A importância clínica da bronquite plástica reside no fato de apresentar um quadro semelhante ao de outras doenças mais prevalentes, como a aspiração de corpo estranho e a asma brônquica. A suspeita do quadro recomenda a realização de endoscopia para diagnóstico e tratamento. É reconhecida a ocorrência de bronquite plástica em crianças com fibrose cística, pós-operatório de cirurgia cardíaca e anemia falciforme. No presente artigo, foi observada uma associação com talassemia alfa.
OBJECTIVE: Plastic bronchitis is an unusual condition in children, associated with formation of mucofibrinous casts and mucous plugging of the tracheobronchial tree. Given that this illness is part of the differential diagnosis of acute respiratory failure, early treatment is important for improved prognosis. The aim of this report is to describe a case of plastic bronchitis in a child with alpha-thalassemia that was treated successfully with endoscopy. DESCRIPTION: A three year old, black, male child, previously healthy, presented with acute respiratory failure and a chest x-ray showing pulmonary atelectasis. There was no evidence of respiratory symptoms or previous allergy state. The diagnosis of plastic bronchitis was made using flexible and rigid bronchoscopy, and confirmed by histopathologic findings. The child progressed well, treatment was based on supportive care and antibiotics were not used. Ten days after discharge, radiographic appearance was normal. Alpha thalassemia was diagnosed through hemoglobin electrophoresis. COMMENTS: Plastic bronchitis is clinically important because has similar presentation to other prevalent diseases, such as foreign body aspiration and asthma. When plastic bronchitis is suspected, endoscopy is indicated in order to confirm diagnosis and define treatment. Plastic bronchitis has been previously described in patients with cystic fibrosis, cardiac surgery and sickle cell disease. In this case, an association with alpha-thalassemia was observed.

OBJETIVO: Avaliar o impacto de amamentação exclusiva e a introdução de leite de vaca no primeiro ano de vida no diagnóstico de asma, sibilância e atopia em crianças entre 3 e 4 anos de vida. MÉTODOS: Estudo de coorte aninhado a ensaio de campo randomizado que investigou a efetividade de orientações nutricionais no primeiro ano de vida de crianças, na cidade de São Leopoldo, RS. As crianças acompanhadas em relação a sua dieta no primeiro ano de vida, nesse estudo primário, foram revisitadas três anos mais tarde. Seus pais responderam, então, a um questionário relacionado a problemas respiratórios em seus domicílios, aplicado por entrevistadores treinados. As crianças também realizaram testes cutâneos para avaliar a resposta a alérgenos ambientais comuns. RESULTADOS: Do total de 397 crianças acompanhadas no primeiro ano de vida, 354 foram reavaliadas entre 3 e 4 anos de idade. A prevalência de sibilos, avaliada no período referente aos 12 meses prévios ao questionário, foi 21,3%, a de asma, 5,5% e a de atopia, 28,7%. Crianças que consumiram leite de vaca antes de 4 meses de vida tinham chance significativamente maior de apresentar asma entre 3 e 4 anos (OR 3,22; IC95%: 1,05-9,80). Aleitamento exclusivo por período menor de 6 meses foi marginalmente associado à atopia. CONCLUSÕES: A introdução precoce do leite de vaca mostrou-se importante fator de risco para o desencadeamento de sintomas da asma aos 4 anos de idade. Aleitamento materno por período superior a 6 meses está também potencialmente associado à proteção no desenvolvimento de atopia. Os resultados deste estudo sugerem haver um potencial de intervenção para diminuir o impacto da asma através de intervenções na dieta no primeiro ano de vida.
OBJECTIVE: To evaluate the impact of exclusive breastfeeding and introduction of cow's milk in the first year of life on the diagnosis of asthma, wheezing, and atopy in children aged 3 to 4 years. METHODS: This is a cohort study nested in a randomized field trial investigating the effectiveness of dietary guidelines during the first year of life of children in the city of São Leopoldo, southern Brazil. Children who had their diet monitored during the first year of life, in a primary study, were revisited three years later, when their parents answered a questionnaire related to respiratory problems, applied during home visits by trained interviewers. Children were also skin-prick tested to assess responses to common environmental allergens. RESULTS: Of the 397 children followed during the first year of life, 354 were reassessed between 3 and 4 years of age. Prevalence of wheezing, evaluated for the 12 months prior to questionnaires, was 21.3%, while prevalence of asthma and atopy was 5.5 and 28.7%, respectively. Children fed cow's milk previous to being four months of life were significantly more likely to have asthma between three and four years of age (OR 3.22; 95%CI 1.05-9.80). In the same line, exclusive breastfeeding for a period shorter than six months was marginally associated with atopy. CONCLUSIONS: The early introduction of cow's milk was an important risk factor for triggering asthma/wheeze symptoms at the age of 4 years. Exclusive breastfeeding for longer than six months was also potentially associated with protection against the development of atopy. The results of this study suggest that dietary interventions during the first year of life have the potential to reduce the impact of asthma, and possibly, atopy.

OBJETIVO: Apresentar os resultados dos estudos mais importantes e recentes sobre a genética da asma. Estes dados devem auxiliar os clínicos gerais a compreender o impacto da genética sobre este distúrbio complexo e como os genes e polimorfismos influenciam a asma e a atopia. FONTES DOS DADOS: Os dados foram coletados do banco de dados MEDLINE. Os estudos de associação genética foram selecionados do Genetic Association Database, um repositório de estudos de associação genética de doenças e distúrbios complexos organizado pelo National Institutes of Health. SÍNTESE DOS DADOS: Considerando os dados de diversos importantes estudos de gêmeos sobre a genética da asma, a heritabilidade, que mensura a contribuição dos fatores genéticos para a variância da asma, pode ser estimada entre 0,48 e 0,79. Uma grande quantidade de estudos de associação genética tentou identificar genes de susceptibilidade à asma. Os resultados mais replicados nos estudos de associação genética envolvem as cinco regiões do genoma humano a seguir: 5q31-32, 6p21, 11q12-13, 16p11-12, e 20p13. Recentemente, outro gene de susceptibilidade à asma (ORMDL3), considerado determinante crítico para a asma infantil, foi identificado por um estudo genômico de associação. CONCLUSÕES: É possível estimar que a contribuição genética à asma varia entre 48 e 79%. Diversos loci parecem influenciar a susceptibilidade à asma. Os genes localizados no cromossomo 5q (ADRB2, IL13 e IL4) e o gene ORMDL3, no cromossomo 17, identificado recentemente, parecem ser determinantes para a asma infantil. O diagnóstico e a farmacogenética podem ser as primeiras implicações clínicas de estudos extensivos sobre a genética da asma.
OBJECTIVE: To present the most important and recent results of studies on asthma genetics. These data may help general physicians understand the impact of genetics on this complex disorder and how genes and polymorphisms influence asthma and atopy. SOURCES: Data were collected from MEDLINE. Genetic association studies were selected from the Genetic Association Database, which is an archive of human genetic association studies of complex diseases and disorders organized by the National Institutes of Health. SUMMARY OF THE FINDINGS: Considering the data from several important twin studies on asthma genetics, heritability, which measures the contribution of genetic factors to the variance of asthma, may be estimated in 0.48-0.79. A huge number of genetic association studies have been trying to identify asthma susceptibility genes. The most replicated results in the genetic association studies involve the following five regions of the human genome: 5q31-32, 6p21, 11q12-13, 16p11-12, and 20p13. Only recently a new asthma susceptibility gene (ORMDL3) has been identified by a whole genome association study, considered to be a major determinant for childhood asthma. CONCLUSIONS: Genetic contribution to asthma may be estimated ranging from 48 to 79%. Several different loci seem to influence asthma susceptibility. Genes located on chromosome 5q (ADRB2, IL13 and IL4) and the recently identified ORMDL3, on chromosome 17, seem to be determinants of childhood asthma. Diagnostics and pharmacogenetics may be the first clinical implication of extensive studies on asthma genetics.

Abstract Respiratory syncytial virus (RSV) is a common cause of childhood lower respiratory tract infections. The recent failure of a vaccine candidate based on recombinant F protein underlines the urgent need to better understand the protective human memory immune response against RSV. Signal transducer and activator of transcription 3 (STAT3) protein is a transcription factor that promotes the maturation of the memory CD8 T cell response in cooperation with IL-10 and IL-21. However, the role of STAT3 in the memory CD8 T cell response during RSV infection remains to be elucidated. We found that in infants with bronchiolitis infected with RSV, the expression of STAT3 detected in nasal washes is reduced when compared to that in infants infected by other viruses. In vitro, RSV impairs STAT3 phosphorylation induced by IL-21 in purified human memory CD8 T cells. In addition, RSV decreases granzyme B production by memory CD8 T cells, reducing its cytotoxic activity against RSV-infected epithelial pulmonary cell lines. Together, these data indicate that RSV modulates the IL-21/STAT3 pathway in human memory CD8 T cells, and this could be a mechanism to be further explored to improve the memory response against the infection.

OBJETIVO: Verificar a prevalência de sintomas de distúrbios respiratórios do sono em crianças de baixo nível socioeconômico no Sul do Brasil. MÉTODOS: Foi realizado um estudo transversal em Uruguaiana (RS), utilizando questionário específico sobre sintomas de distúrbios respiratórios do sono, respondido pelos pais, em uma amostra de escolares de 9 a 14 anos participantes do International Study of Asthma and Allergies in Childhood (ISAAC). RESULTADOS: Foram respondidos 998 questionários de um total de 1.011 escolares elegíveis. Relato de ronco habitual ocorreu em 27,6% das crianças, apnéia em 0,8%, respiração oral diurna em 15,5% e sonolência diurna excessiva em 7,8%. Crianças com sonolência diurna excessiva apresentaram maior risco de ronco habitual (OR = 2,7; IC95% 1,4-5,4), apnéia (OR = 9,9; IC95% 1,2-51), respiração oral (OR = 13,1; IC95% 6,2-27,4) e problemas de aprendizado (OR = 9,9; IC95% 1,9-51,0). Rinite, fumo materno e testes cutâneos alérgicos estiveram significativamente associados a ronco habitual e respiração oral diurna. CONCLUSÕES: A prevalência de sintomas de distúrbios respiratórios do sono é elevada em crianças de 9 a 14 anos na cidade de Uruguaiana. A prevalência de ronco habitual foi quase duas vezes maior que a descrita nessa faixa etária em outras populações. Crianças com sonolência diurna excessiva parecem ter quase 10 vezes mais risco de problemas de aprendizado.
OBJECTIVE: To identify the prevalence of symptoms of sleep-disordered breathing among children of low socioeconomic status in the South of Brazil. METHODS: This was a cross-sectional study, carried out in the city of Uruguaiana, RS, in which specific questionnaire about the symptoms of sleep-disordered breathing was completed by the parents of a sample of schoolchildren aged 9 to 14 years, enrolled on the International Study of Asthma and Allergies in Childhood (ISAAC). RESULTS: From the total of 1,011 eligible schoolchildren, 998 questionnaires were completed. The parents of 27.6% of the children reported habitual snoring, while 0.8% reported apnea, 15.5% described daytime mouth breathing and 7.8% complained of excessive daytime sleepiness. Children with excessive daytime sleepiness were at greater risk of habitual snoring (OR = 2.7; 95%CI 1.4-5.4), apnea (OR = 9.9; 95%CI 1.2-51), mouth breathing (OR = 13.1; 95%CI 6.2-27.4) and learning difficulties (OR = 9.9; 95%CI 1.9-51.0). Rhinitis, maternal smoking and positive allergy skin test results were significantly associated with habitual snoring and daytime mouth breathing. CONCLUSIONS: There is an elevated prevalence of symptoms of sleep-disordered breathing among children from 9 to 14 in the city of Uruguaiana. The prevalence of habitual snoring was almost twice that described in this age group in other populations. Children with excessive daytime sleepiness appear to have almost 10 times the risk of learning difficulties.

OBJETIVO: O objetivo deste estudo foi determinar se a administração de ciproheptadina é capaz de induzir ganho de peso em pacientes com fibrose cística. MÉTODOS: Foi realizado um estudo duplo-cego, controlado com placebo em dois centros no Brasil. Vinte e cinco pacientes com fibrose cística entre 5 e 18 anos completaram o estudo. Os pacientes foram randomizados em dois grupos, para receber ciproheptadina 4 mg três vezes por dia durante 12 semanas ou placebo. Todos os dados foram coletados no início e no final do período de estudo e incluíram peso, altura e espirometria. RESULTADOS: O ganho de peso médio foi de 0,67 kg e 1,61 kg nos grupos placebo e ciproheptadina, respectivamente (p = 0,036). O índice de massa corporal (IMC) diminuiu 0,07 kg/m² no grupo placebo e aumentou 0,46 kg/m² no grupo intervenção (p = 0,027). A mudança no IMC para a idade (escore z) foi de -0,19 no grupo placebo e 0,20 no grupo ciproheptadina (p = 0,003). O IMC escore z diminuiu 0,19 no grupo placebo e aumentou 0,2 no grupo ciproheptadina (p = 0,003). Alterações na função pulmonar não foram estatisticamente diferentes. CONCLUSÃO: O uso de ciproheptadina em pacientes com fibrose cística foi bem tolerado, apresentando um ganho de peso significativo e um aumento no IMC após 12 semanas. Foi encontrado um tamanho de efeito clinicamente relevante para o peso/idade (escore z) e IMC para idade (escore z). Tais achados sugerem que a prescrição de ciproheptadina pode ser uma abordagem alternativa para pacientes que precisam de suporte nutricional por um curto período de tempo.

OBJETIVO: Determinar a prevalência de infecção por rinovírus em lactentes menores de 6 meses hospitalizados por bronquiolite aguda. MÉTODOS: Foram selecionados de forma prospectiva lactentes hospitalizados com diagnóstico de bronquiolite aguda, no Hospital São Lucas da Pontifícia Universidade Católica do Rio Grande do Sul, no período entre maio e setembro de 2002. Foi pesquisada a presença de vírus respiratórios no aspirado nasofaríngeo (ANF), através de imunofluorescência direta para vírus sincicial respiratório, parainfluenza, influenza e adenovírus. Para detecção do rinovírus, foi utilizada a reação de transcrição reversa, seguida de reação em cadeia da polimerase, específicas para picornavírus, seguidas de hibridização com sonda específica para rinovírus. RESULTADOS: Foram selecionados 45 lactentes hospitalizados com diagnóstico de bronquiolite aguda. A mediana da idade dos pacientes selecionados foi de 2 meses. Foram encontradas amostras positivas para vírus respiratórios em 35/45 (77,8%) casos. Foi detectado mais de um vírus em 7/35 (20%) amostras. Das amostras positivas, o vírus sincicial respiratório foi detectado em 33/35 (94%) casos. O rinovírus foi detectado em 6/35 casos (17%). CONCLUSÕES: O rinovírus foi o segundo agente mais freqüentemente detectado em secreção nasal de lactentes jovens hospitalizados por bronquiolite aguda.
OBJECTIVE: To determine the prevalence of rhinovirus infection in hospitalized young infants with acute bronchiolitis. METHODS: Hospitalized children with acute bronchiolitis admitted to the Hospital São Lucas/PUCRS between May and September 2002 were selected prospectively. Nasopharyngeal samples were assayed for respiratory syncytial virus, parainfluenza, influenza and adenovirus by immunofluorescence. For rhinovirus test a reverse transcription-polymerase chain reaction for picornavirus was used, followed by hybridization with rhinovirus specific probes. RESULTS: Forty-five patients were selected for the study. The median age of the subjects studied was 2 months. Positive samples for respiratory viruses were found in 35/45 (77.8%) subjects and 7/35 (20%) patients had dual infection. Respiratory syncytial virus was detected in 33/35 (94%) cases. Rhinovirus was detected in 6/35 patients (17%). CONCLUSIONS: Rhinovirus was the second most common agent detected in nasal secretions from young infants hospitalized with acute bronchiolitis.

Descreve-se uma apresentação rara de bronquiolite obliterante associada a hemossiderose pulmonar, em paciente de nove anos com sintomas respiratórios persistentes iniciados após episódio de bronquiolite aguda grave aos sete meses. Após o episódio agudo, apresentou sintomas respiratórios persistentes, piorando significativamente aos sete anos, quando começou a apresentar dificuldade respiratória em pequenos esforços. A tomografia computadorizada de tórax demonstrou achados compatíveis com bronquiolite obliterante. A biópsia pulmonar a céu aberto demonstrou numerosos macrófagos corados com hemossiderina, além dos achados compatíveis com bronquiolite obliterante. O diagnóstico de hemossiderose pulmonar pode estar ocasionalmente associado a bronquiolite obliterante em crianças com seqüela pós-viral grave.
In the present report, we describe an unusual presentation of post-infectious bronchiolitis obliterans accompanied by pulmonary hemosiderosis in a nine-year-old boy with persistent respiratory symptoms subsequent to an episode of acute bronchiolitis occurring at the age of seven months. After the episode, the persistent respiratory symptoms worsened significantly, and, by the age of seven, the patient began to have difficulty breathing after minimal exertion. Computed tomography of the chest presented findings consistent with bronchiolitis obliterans. Open lung biopsy revealed numerous hemosiderin-laden macrophages, as well as other findings consistent with bronchiolitis obliterans. Pulmonary hemosiderosis can occasionally be accompanied by bronchiolitis obliterans in children with severe sequelae after an episode of viral infection.

Dietary fibers and SCFAs can exert a protective effect against respiratory syncytial virus (RSV). Here, the authors report that microbiota-derived acetate protects mice against RSV infection via GPR43- mediated type 1 interferon response induction in the lungs.

Objective We aimed to assess the profile of respiratory viruses in young children hospitalized for acute lower respiratory tract infection (ALRI) and its association with disease severity, defined as need for pediatric intensive care unit (PICU) admission. Design Prospective observational cohort study. Setting A tertiary-care university hospital in Brazil. Patients Children younger than three years attending the pediatric emergency room with ALRI who were admitted to the hospital. Interventions None. Measurements and main results Nasopharyngeal aspirates were collected from patients from June 1st, 2008 to May 31st, 2009within the first 48 hours of hospitalization. Nasopharyngeal aspirates were tested for 17humanrespiratory viruses by molecular and immunofluorescence based assays. Simple and multiple log-binomial regression models were constructed to assess associations of virus type with a need for PICU admission. Age, prematurity, the presence of an underlying disease and congenital heart disease were covariates. Nasopharyngeal aspirates were positive for at least one virus in 236 patients. Rhinoviruses were detected in 85.6% of samples, with a preponderance of rhinovirus C (RV-C) (61.9%). Respiratory syncytial virus was detected in 59.8% and human coronavirus (HCoV) in 11% of the samples. Co-detections of two to five viruses were found in 78% of the patients. The detection of HCoV alone (adjusted relative risk (RR) 2.18; 95% CI 1.15–4.15) or in co-infection with RV-C (adjusted RR 2.37; 95% CI 1.23–4.58) was independently associated with PICU admission. Conclusions The detection of HCoV alone or in co-infection with RV-C was independently associated with PICU admission in young children hospitalized for ALRI.

Compelling evidence suggests a causal relation between exposure to parental cigarette smoking and respiratory symptoms during childhood. Still, the roles of prenatal versus postnatal parental smoking need clarification. In this study, the authors assessed the effects of passive smoking on respiratory symptoms in a cohort of over 1, 000 children born during 1980–1984. The children were enrolled in the Tucson Children’s Respiratory Study in Tucson, Arizona, and were followed from birth to age 11 years. The population was generally middle class and consisted of two main ethnic groups, non-Hispanic Whites (75%) and Hispanics (20%), reflecting Tucson‘s population. Information on parental smoking and on wheeze and cough in their children was elicited from parents by using questionnaires at five different surveys. Data were analyzed both cross-sectionally and by using the generalized estimation equation approach, a longitudinal mixed-effects model. The best-fitting model indicated that maternal prenatal but not postnatal smoking was associated with current wheeze (odds ratio = 2.3, 95% confidence interval 1.4–3.8) independently of a family history of asthma, socioeconomic factors, and birth weight. This effect was time dependent and significant only below age 3 years; although independent of gender, the association was stronger for girls (odds ratio = 3.6, 95% confidence interval 1.6–8.0). Cough was not associated with parental smoking during the first decade of life. This transitory effect of maternal prenatal smoking on wheezing could be due to changes that affect the early stages of lung development. Am J Epidemiol 1999; 149: 1030–7.