Avaliação dos níveis de alfabetismo em saúde, conhecimento em asma e qualidade de vida de pais associados ao controle da doença em crianças e adolescentes com diagnóstico de asma de centros especializados / Evaluation of levels of literacy in health, knowledge in asthma and quality of life of parents associated with disease control in children and adolescents diagnosed with asthma from specialized centers

Objetivo: avaliar o nível de conhecimento em asma, alfabetismo em saúde e qualidade de vida de cuidadores de crianças e adolescentes com diagnóstico da doença, bem como, a associação com o controle da asma, adesão ao tratamento e qualidade de vida. Métodos: estudo transversal, realizado com cuidadores e pacientes de dois centros especializados de referência no Sul do Brasil, entre março de 2018 e novembro de 2018. Participaram pais e cuidadores de crianças e adolescentes com diagnóstico de asma, com idade a partir de 18 anos. Foram aplicados os questionários: sociodemográfico, Short Assessment of Health Literacy for Portuguese-Speaking Adults, Questionário de Conhecimento em Asma Pediátrica e Paediatric Asthma Caregiver's Quality of Life Questionnaire. Para fins estatísticos, foram utilizados o teste t, qui-quadrado e Regressão Logística Binária. Resultados: foram incluídos 125 cuidadores, sendo 89 (71,2%) mães, com idade média de 35,7±9,2 anos, 65 (52%) com ensino médio completo e 100 (80%) pertencentes à classe econômica C. Do total, 74 (59,2%) apresentaram níveis inadequados de alfabetismo em saúde e 117 (94,4%) inadequados níveis de conhecimento em asma. A asma não estava controlada em 91 (72,8%) dos pacientes, estando associado a menor qualidade de vida deles e de seus cuidadores (p<0,001). A Regressão Logística verificou se o alfabetismo em saúde, o conhecimento em asma e a qualidade de vida dos cuidadores estavam associados ao controle da asma dos pacientes, sendo esse modelo significativo [X2(4) = 22,083; p<0,001, R2Nagelkerke = 0,484]. As variáveis categóricas utilizadas como referência foram as que apresentaram maior frequência (asma não controlada e conhecimentos inadequados). O alfabetismo em saúde (OR = 3,650; IC95% = 1,335 - 9,984) e qualidade de vida (OR = 3,095; IC95% = 1,850 ­ 5,178) também foram significativos. Conclusão: a população analisada apresentou níveis de alfabetismo em saúde e conhecimento em asma insatisfatórios. Ainda, os níveis de controle da doença foram baixos podendo estar associados aos níveis de qualidade de vida.

Aims: to evaluate the level of knowledge in asthma, health literacy and quality of life of caregivers of children and adolescents diagnosed with the disease, as well as the association with asthma control, treatment adherence and quality of life. Methods: this cross-sectional study was conducted with caregivers and patients from two specialized referral centers in southern Brazil, between March 2018 and November 2018. Parents and caregivers of children and adolescents diagnosed with asthma, aged 18 years and older, participated in the study. The following questionnaires were applied: sociodemographic, Short Assessment of Health Literacy for Portuguese-Speaking Adults and Paediatric Asthma Caregiver's Quality of Life Questionnaire. For statistical purposes, the t-test, chi-square and Binary Logistic Regression were used. Results: a total of 125 caregivers were included, 89 (71.2%) mothers, with a mean age of 35.7±9.2 years, 65 (52%) with completed high school and 100 (80%) belonging to economy class C. Of the total, 74 (59.2%) inadequate levels of literacy in health and 117 (94.4%) inadequate levels of knowledge in asthma. Asthma was not controlled in 91 (72.8%) of the patients, being associated with a lower quality of life of them and their caregivers (p<0.001). Logistic Regression verified whether health literacy, asthma knowledge and caregivers' quality of life were associated with asthma control of patients, and this model was significant [X2(4) = 22.083; p<0.001, R2Nagelkerke = 0.484]. The categorical variables used as reference were the ones with the highest frequency (uncontrolled asthma and inadequate knowledge). Health literacy (OR = 3,650; CI95% = 1.335 - 9.984) and quality of life (OR = 3.095; CI95% = 1.850 - 5.178) were also significant. Conclusion: the analyzed population presented levels of literacy in health and knowledge in asthma unsatisfactory. Furthermore, the levels of disease control were low and may be associated with quality of life levels.

Desenvolvimento e Validação do Questionário de Conhecimento em Asma Pediátrica (Q-CAP) para população brasileira / Development and validation of Knowledge in Pediatric Asthma questionnaire (Q-CAP) for brazilian population

OBJETIVO: Desenvolver e validar o Questionário de Conhecimento em Asma Pediátrica (Q-CAP), na língua portuguesa brasileira. MÉTODOS: o questionário foi desenvolvido com base em instrumentos internacionais reconhecidos. Especialistas analisaram o instrumento, juntamente com pais de crianças com asma. Foram realizados os testes de validade de construto e conteúdo, alfa de Cronbach, coeficiente de correlação intraclasse, correlação de Pearson, análise de Kappa e curva ROC. RESULTADOS: participaram do estudo 132 pais de crianças com asma, sendo 117 (88,6%) do sexo feminino, idade média de 35,9±9,1 anos, 78 (59,1%) com ensino médio completo, 73 (59,8%) pertencente a classe econômica C. A versão final do instrumento possuí 20 questões, com ponto de corte de ≥14 pontos. Os escores totais obtiveram conceito "A" nos testes de validade/constructo e valor de 0,69 no alfa de Cronbach. Na avaliação da correlação do coeficiente intraclasse o questionário possui níveis dentro dos aceitáveis (ICC=0,69; IC95%=0,61~0,77; p<0,001). A sensibilidade e especificidade apresentaram área de 0,93 (IC95%: 0,84~1,0; p=0,002) e valores de 80% e 97,1%, respectivamente. Após a aplicação da versão final do Q-CAP, apenas 5 (3,8%) dos pais demonstraram níveis satisfatórios de conhecimento em asma. CONCLUSÃO: o Q-CAP demonstrou ser confiável, claro e com adequados índices de reprodutibilidade e consistência interna. Sua aplicação é fácil e abrange os aspectos culturais brasileiros essenciais, além de grande precisão em mensurar o nível de conhecimento sobre asma.

AIMS: To develop and validate the Knowledge Questionnaire in Pediatric Asthma, in the brazilian Portuguese language. METHODS: The questionnaire was developed based on recognized international instruments. Experts have examined the instrument, along with parents of children with asthma. The tests of construct validity and contents, Cronbach's alpha, intraclass correlation coefficient, Pearson Correlation, analysis of Kappa and ROC curve. RESULTS: Participated in this study 132 parents of children with asthma, and 117 (88.6%) female, average age of 35.9 ± 9.1 years, 78 (59.1%) with full high school, 73 (59.8%) in the economy class C. The final version of the instrument possessing 20 questions, with cut-off of ≥ 14 points. The total scores obtained "A" concept validity tests/construct and value of 0.69 on Cronbach's alpha. In the evaluation of correlation intraclass coefficient the questionnaire has within the acceptable levels (ICC = 0.69; 95% CI = 0.61 ~ 0.77; p < 0.001). The sensitivity and specificity have lodged area of 0.93 (95% CI: 0.84 ~ 1.0; p = 0.002) and values of 80% and 97.1%, respectively. After applying the final version of the questionnaire of knowledge in Pediatric Asthma, only 5 (3.8%) the parents showed satisfactory levels of knowledge in asthma. CONCLUSION: The Knowledge questionnaire in Pediatric Asthma has proven to be reliable, clear and with suitable levels of reproducibility and internal consistency. Your application is easy and covers the cultural aspects, as well as Brazilian great accuracy in measuring the level of knowledge about asthma.

Mesenchymal stem cells improves survival in LPS-induced acute lung injury acting through inhibition of NETs formation.

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are syndromes of acute hypoxemic respiratory failure resulting from a variety of direct and indirect injuries to the gas exchange parenchyma of the lungs. During the ALI, we have an increase release of proinflammatory cytokines and high reactive oxygen species (ROS) formation. These factors are responsible for the release and activation of neutrophil-derived proteases and the formation of neutrophil extracellular traps (NETs). The excessive increase in the release of NETs cause damage to lung tissue. Recent studies have studies involving the administration of mesenchymal stem cells (MSCs) for the treatment of experimental ALI has shown promising results. In this way, the objective of our study is to evaluate the ability of MSCs, in a lipopolysaccharide (LPS)-induced ALI model, to reduce inflammation, oxidative damage, and consequently decrease the release of NETs. Mice were submitted lung injury induced by intratracheal instillation of LPS and subsequently treated or not with MSCs. Treatment with MSCs was able to modulate pulmonary inflammation, decrease oxidative damage, and reduce the release of NETs. These benefits from treatment are evident when we observe a significant increase in the survival curve in the treated animals. Our results demonstrate that MSCs treatment is effective for the treatment of ALI. For the first time, it is described that MSCs can reduce the formation of NETs and an experimental model of ALI. This finding is directly related to these cells modulate the inflammatory response and oxidative damage in the course of the pathology.

Modulatory potential of resveratrol during lung inflammatory disease.

Neutrophils are the first cells to achieve the sites of infection or inflammation in the lungs. The massive accumulation of these cells is associated with acute and chronic lung injury. Therefore, they have been implicated in the pathogenesis of many lung diseases through the release of reactive oxygen intermediates, proteolytic enzymes and Neutrophil Extracellular Traps (NETs). The excessive and continuous release of NETs, fibers composed by decondensed chromatin coated with neutrophil proteins, are associated to the impairment of lung function in different pathological settings. Flavonoids inhibit the respiratory burst of neutrophils in mammals. However, one of these flavonoids, resveratrol has a particular chemical property. It reduce Cu(II) to Cu(I) form with concomitant formation of reactive oxygen species, which can produce DNA breakage as reported in several in vitro models. We hypothesize that direct resveratrol administration in lungs can cleave DNA in NETs, improving lung function during acute airway infections or chronic inflammatory lung diseases. If the hypothesis is correct, the control of NET formation can be used to reduce the inflammatory environment in lung after neutrophil stimuli. Additionally, the production of proinflammatory cytokines by neutrophils could be also diminished by resveratrol administration. In this sense, this flavonoid provides a multifaceted opportunity for treatment of lung diseases with strong or chronic neutrophil activation.

Lack of association between viral load and severity of acute bronchiolitis in infants.

OBJECTIVE:: To investigate the correlation between respiratory syncytial viral load and length of hospitalization in infants with acute wheezing episodes. METHODS:: This was a two-year, cross-sectional study of infants ≤ 12 months of age with bronchiolitis at the time of admission to a tertiary hospital. For the identification of respiratory viruses, nasopharyngeal secretions were collected. Samples were analyzed (throughout the study period) by direct immunofluorescence and (in the second year of the study) by quantitative real-time PCR. We screened for three human viruses: rhinovirus, respiratory syncytial virus, and metapneumovirus. RESULTS:: Of 110 samples evaluated by direct immunofluorescence, 56 (50.9%) were positive for a single virus, and 16 (14.5%) were positive for two or more viruses. Among those 72 samples, the most prevalent virus was respiratory syncytial virus, followed by influenza. Of 56 samples evaluated by quantitative real-time PCR, 24 (42.8%) were positive for a single virus, and 1 (1.7%) was positive for two viruses. Among those 25 samples, the most prevalent virus was again respiratory syncytial virus, followed by human rhinovirus. Coinfection did not influence the length of the hospital stay or other outcome s. In addition, there was no association between respiratory syncytial virus load and the length of hospitalization. CONCLUSIONS:: Neither coinfection nor respiratory syncytial viral load appears to influence the outcomes of acute bronchiolitis in infants. OBJETIVO:: Investigar a correlação entre a carga viral do vírus sincicial respiratório e o tempo de internação hospitalar em lactentes com episódios de sibilância aguda. MÉTODOS:: Este foi um estudo transversal de dois anos envolvendo lactentes de até 12 meses de idade com bronquiolite no momento da internação em um hospital terciário. Para a identificação dos vírus respiratórios foram coletadas secreções nasofaríngeas. As amostras foram analisadas (por todo o período do estudo) por imunofluorescência direta e (no segundo ano do estudo) por PCR quantitativa em tempo real para três vírus humanos (rinovírus, vírus sincicial respiratório e metapneumovírus). RESULTADOS:: Das 110 amostras avaliadas por imunofluorescência direta, 56 (50,9%) foram positivas para um único vírus, e 16 (14,5%) foram positivas para dois ou mais vírus. Nessas 72 amostras, o vírus mais prevalente foi o vírus sincicial respiratório, seguido por influenza. Das 56 amostras avaliadas por PCR quantitativa em tempo real, 24 (42,8%) foram positivas para um único vírus, e 1 (1,7%) foi positiva para dois vírus. Nessas 25 amostras, o vírus mais prevalente foi o vírus sincicial respiratório, seguido por rinovírus humano. A coinfecção não influenciou o tempo de internação ou outros desfechos. Além disso, não houve associação entre a carga viral de vírus sincicial respiratório e o tempo de internação. CONCLUSÕES:: A coinfecção e a carga viral do vírus sincicial respiratório não parecem influenciar os desfechos em lactentes com bronquiolite aguda.

Lack of association between viral load and severity of acute bronchiolitis in infants / Falta de associação entre carga viral e gravidade da bronquiolite aguda em lactentes

ABSTRACT Objective: To investigate the correlation between respiratory syncytial viral load and length of hospitalization in infants with acute wheezing episodes. Methods: This was a two-year, cross-sectional study of infants ≤ 12 months of age with bronchiolitis at the time of admission to a tertiary hospital. For the identification of respiratory viruses, nasopharyngeal secretions were collected. Samples were analyzed (throughout the study period) by direct immunofluorescence and (in the second year of the study) by quantitative real-time PCR. We screened for three human viruses: rhinovirus, respiratory syncytial virus, and metapneumovirus. Results: Of 110 samples evaluated by direct immunofluorescence, 56 (50.9%) were positive for a single virus, and 16 (14.5%) were positive for two or more viruses. Among those 72 samples, the most prevalent virus was respiratory syncytial virus, followed by influenza. Of 56 samples evaluated by quantitative real-time PCR, 24 (42.8%) were positive for a single virus, and 1 (1.7%) was positive for two viruses. Among those 25 samples, the most prevalent virus was again respiratory syncytial virus, followed by human rhinovirus. Coinfection did not influence the length of the hospital stay or other outcome s. In addition, there was no association between respiratory syncytial virus load and the length of hospitalization. Conclusions: Neither coinfection nor respiratory syncytial viral load appears to influence the outcomes of acute bronchiolitis in infants.

RESUMO Objetivo: Investigar a correlação entre a carga viral do vírus sincicial respiratório e o tempo de internação hospitalar em lactentes com episódios de sibilância aguda. Métodos: Este foi um estudo transversal de dois anos envolvendo lactentes de até 12 meses de idade com bronquiolite no momento da internação em um hospital terciário. Para a identificação dos vírus respiratórios foram coletadas secreções nasofaríngeas. As amostras foram analisadas (por todo o período do estudo) por imunofluorescência direta e (no segundo ano do estudo) por PCR quantitativa em tempo real para três vírus humanos (rinovírus, vírus sincicial respiratório e metapneumovírus). Resultados: Das 110 amostras avaliadas por imunofluorescência direta, 56 (50,9%) foram positivas para um único vírus, e 16 (14,5%) foram positivas para dois ou mais vírus. Nessas 72 amostras, o vírus mais prevalente foi o vírus sincicial respiratório, seguido por influenza. Das 56 amostras avaliadas por PCR quantitativa em tempo real, 24 (42,8%) foram positivas para um único vírus, e 1 (1,7%) foi positiva para dois vírus. Nessas 25 amostras, o vírus mais prevalente foi o vírus sincicial respiratório, seguido por rinovírus humano. A coinfecção não influenciou o tempo de internação ou outros desfechos. Além disso, não houve associação entre a carga viral de vírus sincicial respiratório e o tempo de internação. Conclusões: A coinfecção e a carga viral do vírus sincicial respiratório não parecem influenciar os desfechos em lactentes com bronquiolite aguda.

Valor do emprego do questionário WHOQOL-BREF na avaliação da qualidade de vida de pais de crianças com asma / Usefulness of the WHOQOL-BREF questionnaire in assessing the quality of life of parents of children with asthma

Objetivo:Avaliar a qualidade de vida (QV) de pais de crianças asmáticas e analisar a consistência interna do instrumento genérico de qualidade de vida World Health Organization Quality of Life, versão abreviada (WHOQOL-BREF).Métodos:Foi avaliada a QV de pais de crianças asmáticas e hígidas entre oito-16 anos, por meio do questionário genérico WHOQOL-BREF. Foi avaliada também a consistência interna, por meio do alfa de Cronbach (αC), para determinar se o instrumento tem boa validade para o público alvo.Resultados:Participaram do estudo 162 indivíduos, com idade média de 43,8±13,6 anos, dos quais 104 eram do sexo feminino (64,2%) e 128 casados (79,0%). Na avaliação do nível de qualidade de vida, o grupo de pais de crianças saudáveis apresentou escores acima do grupo de pais de asmáticos nos quatro domínios do instrumento (físico, psicológico, social e meio ambiente) que indicam melhor qualidade de vida. Na análise de consistência interna, o WHOQOL-BREF obteve valores de αC=0,86 pontos para o grupo de pais de asmáticos e 0,88 para o grupo de pais de hígidos.Conclusões:Pais de crianças asmáticas apresentam comprometimento da qualidade de vida em função da doença de seus filhos. Além disso, o WHOQOL-BREF, mesmo sendo um instrumento genérico, se mostrou prático e eficiente para avaliar a qualidade de vida de pais de crianças asmáticas.

Objective::To evaluate the quality of life (QOL) of parents of children with asthma and to analyze the internal consistency of the generic QOL tool World Health Organization Quality of Life, abbreviated version (WHOQOL-BREF).Methods::We evaluated the QOL of parents of asthmatic and healthy children aged between 8 and 16, using the generic WHOQOL-BREF questionnaire. We also evaluated the internal consistency using Cronbach's alpha (αC), in order to determine whether the tool had good validity for the target audience.Results::The study included 162 individuals with a mean age of 43.8±13.6 years, of which 104 were female (64.2%) and 128 were married (79.0%). When assessing the QOL, the group of parents of healthy children had higher scores than the group of parents of asthmatic children in the four areas evaluated by the questionnaire (Physical, Psychological Health, Social Relationships and Environment), indicating a better quality of life. Regarding the internal consistency of the WHOQOL-BREF, values of ˛C were 0.86 points for the group of parents of asthmatic children, and 0.88 for the group of parents of healthy children.Conclusions::Parents of children with asthma have impaired quality of life due to their children's disease. Furthermore, the WHOQOL-BREF, even as a generic tool, showed to be practical and efficient to evaluate the quality of life of parents of asthmatic children.

[Usefulness of the WHOQOL-BREF questionnaire in assessing the quality of life of parents of children with asthma]. / Valor do emprego do questionário WHOQOL-BREF na avaliação da qualidade de vida de pais de crianças com asma.

OBJECTIVE: To evaluate the quality of life (QOL) of parents of children with asthma and to analyze the internal consistency of the generic QOL tool World Health Organization Quality of Life, abbreviated version (WHOQOL-BREF). METHODS: We evaluated the QOL of parents of asthmatic and healthy children aged between 8-16, using the generic WHOQOL-BREF questionnaire. We also evaluated the internal consistency using Cronbach's alpha (αC), in order to determine whether the tool had good validity for the target audience. RESULTS: The study included 162 individuals with a mean age of 43.8±13.6 years, of which 104 were female (64.2%) and 128 were married (79.0%). When assessing the QOL, the group of parents of healthy children had higher scores than the group of parents of asthmatic children in the four areas evaluated by the questionnaire (Physical, Psychological Health, Social Relationships and Environment), indicating a better quality of life. Regarding the internal consistency of the WHOQOL-BREF, values of αC were 0.86 points for the group of parents of asthmatic children, and 0.88 for the group of parents of healthy children. CONCLUSIONS: Parents of children with asthma have impaired quality of life due to their children's disease. Furthermore, the WHOQOL-BREF, even as a generic tool, showed to be practical and efficient to evaluate the quality of life of parents of asthmatic children.

Proposed short-term model of acute allergic response, without adjuvant use, in the lungs of mice.

OBJECTIVE: To determine whether a short-term protocol using subcutaneous sensitization with ovalbumin, without the use of adjuvants, would induce an eosinophilic response in the lungs of mice similar to that observed in previous, well-established protocols. METHODS: Adult female BALB/c mice were randomized and divided into groups according to the number of sensitizations with ovalbumin and the number/dosage of intranasal ovalbumin challenges. The short-term protocol (10 days) consisted of one sensitization with ovalbumin and three ovalbumin challenges (100 µg). Total and differential cell counts in BAL fluid, levels of eosinophil peroxidase in lung tissue, and histopathological examination of the lungs were performed 24 h after the last ovalbumin challenge. RESULTS: No significant differences were found among the groups regarding the variables studied. The short-term protocol, as well as the other protocols studied, induced an eosinophilic response similar to that obtained in the positive control. CONCLUSIONS: Subcutaneous sensitization with ovalbumin and without the use of adjuvants resulted in a significant allergic response in the lungs of mice, even in the short-term protocol group. Our findings suggest that this short-term protocol can be used as a first-line pre-clinical test for the study of new medications, reducing the costs and observation periods.

Proposta de um modelo murino de curta duração de resposta pulmonar alérgica aguda sem utilização de adjuvante / Proposed short-term model of acute allergic response, without adjuvant use, in the lungs of mice

OBJETIVO: Determinar se um protocolo curto de sensibilização com ovalbumina subcutânea, sem adjuvante, induziria uma resposta pulmonar eosinofílica em pulmões de camundongos similar àquela encontrada em protocolos previamente estabelecidos. MÉTODOS: Fêmeas adultas de camundongos BALB/c foram randomizadas e divididas em grupos de acordo com o número de sensibilizações com ovalbumina e o número/dosagem de provocação intranasal. O protocolo curto (10 dias) consistiu de uma sensibilização e três provocações com ovalbumina (100 µg). A contagem total e diferencial de células no lavado broncoalveolar, o nível de peroxidase eosinofílica no tecido pulmonar e o exame histopatológico dos pulmões foram realizados 24 h após a última provocação. RESULTADOS: Não houve diferenças significativas entre os grupos em relação às variáveis estudadas. O protocolo curto, assim como os outros protocolos estudados, induziu uma resposta eosinofílica pulmonar semelhante àquela do grupo controle positivo. CONCLUSÕES: A sensibilização por ovalbumina subcutânea sem o uso de adjuvante resultou em uma significativa resposta pulmonar alérgica em ratos, mesmo no grupo de protocolo curto. Nossos achados sugerem que esse protocolo curto pode ser utilizado como teste pré-clínico de primeira linha para a pesquisa de novos fármacos, reduzindo custos e o tempo de observação.

OBJECTIVE: To determine whether a short-term protocol using subcutaneous sensitization with ovalbumin, without the use of adjuvants, would induce an eosinophilic response in the lungs of mice similar to that observed in previous, well-established protocols. METHODS: Adult female BALB/c mice were randomized and divided into groups according to the number of sensitizations with ovalbumin and the number/dosage of intranasal ovalbumin challenges. The short-term protocol (10 days) consisted of one sensitization with ovalbumin and three ovalbumin challenges (100 µg). Total and differential cell counts in BAL fluid, levels of eosinophil peroxidase in lung tissue, and histopathological examination of the lungs were performed 24 h after the last ovalbumin challenge. RESULTS: No significant differences were found among the groups regarding the variables studied. The short-term protocol, as well as the other protocols studied, induced an eosinophilic response similar to that obtained in the positive control. CONCLUSIONS: Subcutaneous sensitization with ovalbumin and without the use of adjuvants resulted in a significant allergic response in the lungs of mice, even in the short-term protocol group. Our findings suggest that this short-term protocol can be used as a first-line pre-clinical test for the study of new medications, reducing the costs and observation periods.

Modelos murinos para pesquisas em asma: uma análise crítica atualizada / Murine models for asthma research: An updated critical analysis

Objetivos: discutir as vantagens e limitações de pesquisas com modelos murinos em asma e suas aplicações mais imediatas.Fonte de Dados: foi realizada revisão da literatura no PubMed. Os descritores utilizados foram: mice, asthma, animal model e murine model. Síntese dos Dados: modelos experimentais murinos têm sido muito utilizados para elucidar a fisiopatogenia da asma brônquica e para avaliar novos alvos terapêuticos. Diversas críticas surgiram nos últimos anos em relação aos modelos utilizados. Os modelos animais diferem bastante da asma em humanos, particularmente em relação à utilização de adjuvante, via de administração e dose dos alergenos, além do tipo de resposta inflamatória pulmonar.Conclusões: novos modelos experimentais devem reproduzir da forma mais próxima possível as características da asma em humanos. Embora o modelo murino apresente inúmeras vantagens em relação a outros modelos animais, as limitações inerentes a esse tipo de estudo devem ser levadas em consideração no momento da extrapolação dos resultados para a doença em humanos.

Aims: To discuss the advantages and limitations of studies using murine models in asthma and the most immediate applications. Source of Data: A review of the literature using PubMed database was performed. The keywords used were: mice, asthma, animal model and murine model. Summary of Findings: Experimental models have been used to elucidate the pathophysiology of asthma and to evaluate new therapeutic targets. Several limitations related to the models currently used have emerged in recent years. Animal models are very different from the human asthma, particularly regarding to the use of adjuvant, administration route, dose of allergen and the type of pulmonary inflammatory response. Conclusions: New experimental models must reproduce the characteristics of human asthma as close as possible. Although murine models show several advantages in relation to other animals, the inherent limitations of this type of study must be considered before the extrapolation of results to human pathology.

Airway resistance in children measured using the interrupter technique: reference values.

OBJECTIVE: The interrupter technique is used for determining interrupter resistance (Rint) during quiet breathing. This noninvasive method requires minimal cooperation and can therefore be useful in evaluating airway obstruction in uncooperative children. To date, no reference values have been determined for Rint in a Brazilian population. The objective of this study was to define a prediction equation for airway resistance using the interrupter technique for healthy children aged 3-13 years. METHODS: This was a prospective, cross-sectional study involving preschool and school children in Porto Alegre, Brazil, in whom Rint was measured during peak expiratory flow. RESULTS: One-hundred and ninety-three children were evaluated. Univariate analysis using linear regression showed that height, weight and age correlated significantly and independently with Rint. Multiple regression with height, weight, age and gender as variables resulted in a model in which only height and weight were significant, independent predictors of Rint. Collinearity was identified among height, weight and age. CONCLUSIONS: Reference values and an equation for calculating Rint in healthy children were obtained and are adjusted for height.

Resistência de vias aéreas em crianças medida pela técnica do interruptor: valores de referência / Airway resistance in children measured using the interrupter technique: reference values

OBJETIVO: A técnica do interruptor é usada para determinar interrupter resistance (Rint, medida de resistência das vias aéreas através da técnica do interruptor) durante respiração tranqüila. Este método não-invasivo requer mínima cooperação e, por isso, pode ser útil para avaliar obstrução de vias aéreas em crianças não-colaborativas. Não existem dados publicados de valores de referência para Rint na população brasileira até o momento. O objetivo deste estudo foi definir uma equação para prever a resistência das vias aéreas pela técnica do interruptor em crianças saudáveis de 3 a 13 anos de idade. MÉTODOS: Este estudo transversal prospectivo com crianças pré-escolares e escolares em Porto Alegre, Brasil, mensurou Rint durante pico de fluxo expiratório no volume corrente. RESULTADOS: Cento e noventa e três crianças completaram as medidas. Estatura, peso corporal e idade mostraram correlação significante e independente com Rint na análise univariada usando regressão linear. A regressão múltipla com estatura, peso corporal, idade e gênero como variáveis resultou em um modelo no qual somente estatura e peso corporal foram significativos e independentes para predizer Rint. Colinearidade foi identificada entre estatura, peso corporal e idade. CONCLUSÕES: Valores e equação de referência para Rint em crianças saudáveis foram obtidos e são relacionados a estatura.

OBJECTIVE: The interrupter technique is used for determining interrupter resistance (Rint) during quiet breathing. This noninvasive method requires minimal cooperation and can therefore be useful in evaluating airway obstruction in uncooperative children. To date, no reference values have been determined for Rint in a Brazilian population. The objective of this study was to define a prediction equation for airway resistance using the interrupter technique for healthy children aged 3-13 years. METHODS: This was a prospective, cross-sectional study involving preschool and school children in Porto Alegre, Brazil, in whom Rint was measured during peak expiratory flow. RESULTS: One-hundred and ninety-three children were evaluated. Univariate analysis using linear regression showed that height, weight and age correlated significantly and independently with Rint. Multiple regression with height, weight, age and gender as variables resulted in a model in which only height and weight were significant, independent predictors of Rint. Collinearity was identified among height, weight and age. CONCLUSIONS: Reference values and an equation for calculating Rint in healthy children were obtained and are adjusted for height.

Prevalência de vírus respiratórios em lactentes com bronquiolite aguda e sibilância recorrente em uma emergência pediátrica no sul do Brasil / Prevalence of respiratory virus in infants with acute bronchiolitis abd recurrent wheezing in an emergency room in south Brasil

Objetivo: descrever a prevalência de vírus em lactentes hospitalizados, comparando o primeiro episódio de sibilância (bronquiolite aguda) com sibilância recorrente. Métodos: Foram coletadas amostras de secreção nasofaríngea para pesquisa de vírus respiratórios no período de maio a setembro, 2000 e em 2001, de pacientes que internaram na Emergência Pediátrica com quadro de infecção respiratória aguda de vias aéreas inferiores. Resultados: foram selecionados para o estudo 124 pacientes. O número de coletas positivas para vírus foi de 84 (67,7%), sendo a grande maioria (67,8) pelo vírus sincicial respiratório (VSR). Foi diagnosticada bronquiolite aguda em 77 pacientes (62%) e sibilância.

Effect of clarithromycin on the cell profile of bronchoalveolar lavage fluid in mice with neutrophil-predominant lung disease.

OBJECTIVE: Macrolide antibiotics have anti-inflammatory properties in lung diseases. The aim of this study was to investigate the effect of clarithromycin in pulmonary cellular inflammatory response in mice. METHOD: Eight adult Swiss mice were studied. All animals received an intranasal challenge (80 micro L) with dead Pseudomonas aeruginosa (1.0 x 10(12) CFU/mL). Bronchoalveolar lavage was performed 2 days later, with total cell count and differential cell analysis. The study group (n = 4) received clarithromycin treatment (50 mg/kg/day, intraperitoneal) for 5 days. Treatment was initiated 2 days before intranasal challenge. RESULTS: There was no significant difference in total cell count between the groups (mean: 2.0 x 10(6) and 1.3 x 10(6), respectively). In both groups, there was a predominance of neutrophils. However, the study group had a higher percentage of lymphocytes in the bronchoalveolar lavage than the control group (median of 19% vs 2.5%, P =.029). CONCLUSION: Clarithromycin alters the cytological pattern of bronchoalveolar lavage of Swiss mice with neutrophil pulmonary inflammation, significantly increasing the percentage of lymphocytes.

Discrepancy between cytokine production from peripheral blood mononuclear cells and nasal secretions among infants with acute bronchiolitis.

BACKGROUND: Many studies have measured cytokine production derived from peripheral blood mononuclear cells (PBMCs) to evaluate the immune response in acute bronchiolitis (AB), but no previous reports have examined the association between PBMC release of cytokines and concomitant airway immune response. OBJECTIVE: To determine whether interferon-gamma (IFN-gamma), interleukin 4 (IL-4), and IL-10 levels from PBMCs are associated with concurrent cytokine release in the airways of infants with AB. METHODS: Infants with acute viral-associated first episode of wheezing who required hospitalization between May and September 2002 were recruited. Nasopharyngeal aspirates (NPAs) and PBMC samples were collected simultaneously. The concentrations of IFN-gamma, IL-4, and IL-10 in NPA and PBMC supernatants were determined by enzyme-linked immunosorbent assay. RESULTS: Twenty infants with AB were enrolled in the study of whom 17 (85%) had positive NPA immunofluorescence results for viral detection and respiratory syncytial virus. Median total cell count and viability from NPA samples were 2.2 x 10(6) cells/mL (SD, 1.7 cells/mL) and 92% (SD, 6.0%), respectively. There was a significant correlation between IL-4 levels from NPA and PBMC samples (r = 0.5, P = .02); however, we did not find an association between IFN-gamma and IL-10 levels. CONCLUSIONS: Cytokines produced by in vitro PBMCs may not necessarily reflect the concurrent cytokine pattern production at the mucosal surface in the respiratory tract of infants with AB. Further studies are required to determine whether peripheral blood is a reliable sample for airway inflammation evaluation and to explain the discrepancies of cytokine productions found in this study.

Effect of clarithromycin on the cell profile of bronchoalveolar lavage fluid in mice with neutrophil-predominant lung disease

OBJETIVO: Os antibióticos macrolídeos podem apresentar um efeito antiinflamatório em doenças pulmonares. O objetivo deste estudo é investigar o efeito da claritromicina na resposta inflamatória celular pulmonar em camundongos Swiss. MÉTODO: Foram utilizados 8 camundongos Swiss adultos (6-8 semanas). Todos os animais receberam um desafio intranasal (80 µL) com Pseudomonas aeruginosa mortas (1 x 1012 UFC/mL). Dois dias após o desafio, foi realizado lavado broncoalveolar (LBA) com contagem total de células (CTC) e exame citológico diferencial. O grupo em estudo (n=4) recebeu tratamento com claritromicina (50mg/kg/dia, intraperitoneal) por 5 dias, sendo iniciado o tratamento 2 dias antes do desafio intranasal. O grupo controle (n=4) não recebeu tratamento com claritromicina. RESULTADOS: Não houve diferença significativa na CTC entre os grupos (média de 2x106 e 1,3x106, respectivamente). Em ambos os grupos, houve predomínio absoluto de neutrófilos. Contudo, o grupo tratado com claritromicina, apresentou um número percentual significativamente maior de linfócitos no LBA (mediana de 2,5% vs 19%, p=0,029). CONCLUSÃO: O uso de claritromicina altera o exame citológico diferencial do lavado bronco-alveolar de camundongos Swiss com inflamação pulmonar neutrofílica, aumentando significativamente o número percentual de linfócitos.