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ABSTRACT Objective: To evaluate the seasonality of acute bronchiolitis in Brazil during the 2020-2022 season and compare it with the previous seasons. Methods: Data from the incidence of hospitalizations due to acute bronchiolitis in infants <1 year of age were obtained from the Department of Informatics of the Brazilian Public Health database for the period between 2016 and 2022. These data were also analyzed by macro-regions of Brazil (North, Northeast, Southeast, South, and Midwest). To describe seasonal and trend characteristics over time, we used the Seasonal Autoregressive Integrated Moving Averages Model. Results: Compared to the pre-COVID-19 period, the incidence of hospitalizations related to acute bronchiolitis decreased by 97% during non-pharmacological interventions (March 2020 - August 2021) but increased by 95% after non-pharmacological interventions relaxation (September 2021 - December 2022), resulting in a 16% overall increase. During the pre-COVID-19 period, hospitalizations for acute bronchiolitis followed a seasonal pattern, which was disrupted in 2020-2021 but recovered in 2022, with a peak occurring in May, approximately 4% higher than the pre-COVID-19 peak. Conclusions: This study underscores the significant influence of COVID-19 interventions on acute bronchiolitis hospitalizations in Brazil. The restoration of a seasonal pattern in 2022 highlights the interplay between public health measures and respiratory illness dynamics in young children.
RESUMO Objetivo: Avaliar a sazonalidade da bronquiolite aguda no Brasil durante a temporada 2020-2022 e compará-la com a das temporadas anteriores. Métodos: Os dados de incidência de internações por bronquiolite aguda em lactentes <1 ano de idade foram obtidos do Departamento de Informática da base de dados da Saúde Pública Brasileira para o período entre 2016 e 2022. Esses dados também foram analisados por macrorregiões do Brasil (Norte, Nordeste, Sudeste, Sul e Centro-Oeste). Para descrever características sazonais e de tendência ao longo do tempo, utilizamos o Modelo de Médias Móveis Integradas Autorregressivas Sazonais. Resultados: Em comparação com o período pré-COVID-19, a incidência de hospitalizações relacionadas com bronquiolite aguda diminuiu 97% durante as intervenções não farmacológicas (março de 2020 - agosto de 2021), mas aumentou 95% após a flexibilização das intervenções não farmacológicas (setembro de 2021 - dezembro de 2022), resultando no aumento geral de 16%. Durante o período pré-COVID-19, as hospitalizações por bronquiolite aguda seguiram um padrão sazonal, que foi interrompido em 2020-2021, mas recuperaram-se em 2022, com um pico ocorrido em maio, aproximadamente 4% superior ao pico pré-COVID-19. Conclusões: Este estudo ressalta a influência significativa das intervenções contra a COVID-19 nas hospitalizações por bronquiolite aguda no Brasil. A restauração de um padrão sazonal em 2022 sublinha a interação entre as medidas de saúde pública e a dinâmica das doenças respiratórias em crianças pequenas.
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OBJECTIVE: To evaluate the seasonality of acute bronchiolitis in Brazil during the 2020-2022 season and compare it with the previous seasons. METHODS: Data from the incidence of hospitalizations due to acute bronchiolitis in infants <1 year of age were obtained from the Department of Informatics of the Brazilian Public Health database for the period between 2016 and 2022. These data were also analyzed by macro-regions of Brazil (North, Northeast, Southeast, South, and Midwest). To describe seasonal and trend characteristics over time, we used the Seasonal Autoregressive Integrated Moving Averages Model. RESULTS: Compared to the pre-COVID-19 period, the incidence of hospitalizations related to acute bronchiolitis decreased by 97% during non-pharmacological interventions (March 2020 - August 2021) but increased by 95% after non-pharmacological interventions relaxation (September 2021 - December 2022), resulting in a 16% overall increase. During the pre-COVID-19 period, hospitalizations for acute bronchiolitis followed a seasonal pattern, which was disrupted in 2020-2021 but recovered in 2022, with a peak occurring in May, approximately 4% higher than the pre-COVID-19 peak. CONCLUSIONS: This study underscores the significant influence of COVID-19 interventions on acute bronchiolitis hospitalizations in Brazil. The restoration of a seasonal pattern in 2022 highlights the interplay between public health measures and respiratory illness dynamics in young children.
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Bronquiolitis , COVID-19 , Hospitalización , Análisis de Series de Tiempo Interrumpido , Estaciones del Año , Humanos , Brasil/epidemiología , Lactante , Bronquiolitis/epidemiología , Bronquiolitis/terapia , Incidencia , Hospitalización/estadística & datos numéricos , Hospitalización/tendencias , COVID-19/epidemiología , Recién Nacido , Enfermedad AgudaRESUMEN
Abstract Objectives: Despite the global impact of the Respiratory Syncytial Virus (RSV) infection in children, only one monoclonal antibody (Palivizumab) has been approved for clinical use. However, advances in the knowledge of RSV immunology may enable the development of safe and effective new vaccines and monoclonal antibodies in a few years. The purpose of this review is to summarize available data on approved and developing passive and active immunizations against RSV in childhood and pregnancy. Data source: A non-systematic review of RSV immunoprophylaxis in childhood and pregnancy was carried out in PubMed, path.org and clinical trial registries, without language restrictions, up to September 2022. Data synthesis: Three monoclonal antibodies and 17 active immunization candidates are under development in phase 1 to 3 clinical studies. Regarding the first group, Nirsevimab is a monoclonal antibody with a prolonged half-life whose approval for clinical use is expected in the next months. Among the vaccines under development, six techniques are being used: protein subunit, viral particles, live attenuated virus, recombinant viral vector, chimeric, and mRNA. The first two approaches are being tested primarily in pregnancy, while the others are being developed for the pediatric population. Conclusion: The approval of extended half-life monoclonal antibodies is the next expected advance in RSV prevention, although the costs may be a barrier to the implementation. Regarding active immunizations, maternal and infant vaccination are complementary strategies and there are many promising candidates in clinical studies using different platforms.
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OBJECTIVES: Despite the global impact of the Respiratory Syncytial Virus (RSV) infection in children, only one monoclonal antibody (Palivizumab) has been approved for clinical use. However, advances in the knowledge of RSV immunology may enable the development of safe and effective new vaccines and monoclonal antibodies in a few years. The purpose of this review is to summarize available data on approved and developing passive and active immunizations against RSV in childhood and pregnancy. DATA SOURCE: A non-systematic review of RSV immunoprophylaxis in childhood and pregnancy was carried out in PubMed, path.org and clinical trial registries, without language restrictions, up to September 2022. DATA SYNTHESIS: Three monoclonal antibodies and 17 active immunization candidates are under development in phase 1 to 3 clinical studies. Regarding the first group, Nirsevimab is a monoclonal antibody with a prolonged half-life whose approval for clinical use is expected in the next months. Among the vaccines under development, six techniques are being used: protein subunit, viral particles, live attenuated virus, recombinant viral vector, chimeric, and mRNA. The first two approaches are being tested primarily in pregnancy, while the others are being developed for the pediatric population. CONCLUSIONS: The approval of extended half-life monoclonal antibodies is the next expected advance in RSV prevention, although the costs may be a barrier to the implementation. Regarding active immunizations, maternal and infant vaccination are complementary strategies and there are many promising candidates in clinical studies using different platforms.
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Infecciones por Virus Sincitial Respiratorio , Vacunas contra Virus Sincitial Respiratorio , Virus Sincitial Respiratorio Humano , Lactante , Embarazo , Femenino , Niño , Humanos , Vacunas contra Virus Sincitial Respiratorio/uso terapéutico , Palivizumab/uso terapéutico , Virus Sincitial Respiratorio Humano/genética , Infecciones por Virus Sincitial Respiratorio/prevención & control , Inmunización Pasiva , Anticuerpos Monoclonales/uso terapéuticoRESUMEN
Aim: To present nurses' experience in the decision-making process for implementing a therapeutic support limitation plan in the PICU. Method: Qualitative exploratory research was conducted through semi-structured interviews with 25 intensive care nurses from January to June 2019. The textual corpus was then submitted for content analysis. Results: Two categories emerged: the nurse and decision-making process of the TSLP and ambivalence of the participating nurse's feelings in implementing the TSLP. These categories are interrelated in that the decision-making process mobilizes the ambivalence of the participating nurses' feelings. Final considerations and implications for practice: The starting point of communication between the health teams consists of acquiring information about the concerned child's end-of-life care plan with no prospect of cure and with some form of therapeutic limit admitted to the PICU. Therefore, this study helps to map possible research gaps on the topic and mobilize researchers to build educational materials, protocols, and tools for comprehensive care that can be used by nurses when faced with ethical dilemma, such as decision-making through TSLP.
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Enfermeras y Enfermeros , Cuidado Terminal , Niño , Comunicación , Toma de Decisiones , Humanos , Investigación CualitativaRESUMEN
Point-of-care serological tests for SARS-CoV-2 have been used for COVID-19 diagnosis. However, their accuracy over time regarding the onset of symptoms is not fully understood. We aimed to assess the accuracy of a point-of-care lateral flow immunoassay (LFI). Subjects, aged over 18 years, presenting clinical symptoms suggestive of acute SARS-CoV-2 infection were tested once by both nasopharyngeal and oropharyngeal RT-PCR and LFI. The accuracy of LFI was assessed in periodic intervals of three days in relation to the onset of symptoms. The optimal cut-off point was defined as the number of days required to achieve the best sensitivity and specificity. This cut-off point was also used to compare LFI accuracy according to participants' status: outpatient or hospitalized. In total, 959 patients were included, 379 (39.52%) tested positive for SARS-CoV-2 with RT-PCR, and 272 (28.36%) tested positive with LFI. LFI best performance was achieved after 10 days of the onset of symptoms, with sensitivity and specificity of 84.9% (95%CI: 79.8-89.1) and 94.4% (95%CI: 91.0-96.8), respectively. Although the specificity was similar (94.6% vs. 88.9%, p = 0.051), the sensitivity was higher in hospitalized patients than in outpatients (91.7% vs. 82.1%, p = 0.032) after 10 days of the onset of symptoms. Best sensitivity of point-of-care LFI was found 10 days after the onset of symptoms which may limit its use in acute care. Specificity remained high regardless of the number of days since the onset of symptoms.
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COVID-19 , SARS-CoV-2 , Adulto , Brasil , Prueba de COVID-19 , Humanos , Persona de Mediana Edad , Sensibilidad y EspecificidadRESUMEN
Point-of-care serological tests for SARS-CoV-2 have been used for COVID-19 diagnosis. However, their accuracy over time regarding the onset of symptoms is not fully understood. We aimed to assess the accuracy of a point-of-care lateral flow immunoassay (LFI). Subjects, aged over 18 years, presenting clinical symptoms suggestive of acute SARS-CoV-2 infection were tested once by both nasopharyngeal and oropharyngeal RT-PCR and LFI. The accuracy of LFI was assessed in periodic intervals of three days in relation to the onset of symptoms. The optimal cut-off point was defined as the number of days required to achieve the best sensitivity and specificity. This cut-off point was also used to compare LFI accuracy according to participants' status: outpatient or hospitalized. In total, 959 patients were included, 379 (39.52%) tested positive for SARS-CoV-2 with RT-PCR, and 272 (28.36%) tested positive with LFI. LFI best performance was achieved after 10 days of the onset of symptoms, with sensitivity and specificity of 84.9% (95%CI: 79.8-89.1) and 94.4% (95%CI: 91.0-96.8), respectively. Although the specificity was similar (94.6% vs. 88.9%, p = 0.051), the sensitivity was higher in hospitalized patients than in outpatients (91.7% vs. 82.1%, p = 0.032) after 10 days of the onset of symptoms. Best sensitivity of point-of-care LFI was found 10 days after the onset of symptoms which may limit its use in acute care. Specificity remained high regardless of the number of days since the onset of symptoms.
Os testes sorológicos no local de atendimento (point-of-care) para a infecção pelo SARS-CoV-2 têm sidos utilizados para o diagnóstico da COVID-19. Entretanto, não está plenamente elucidada a acurácia dos testes ao longo do tempo em relação ao início dos sintomas. Nosso objetivo foi de avaliar a acurácia, no local de atendimento, do imunoensaio de fluxo lateral (LFI). Pacientes com ≥ 18 anos de idade que apresentavam sintomas clínicos sugestivos de infecção aguda pelo SARS-CoV-2 foram testados uma vez com RT-PCR da nasofaringe e orofaringe, além do LFI. A acurácia do LFI foi avaliada com intervalos periódicos de 3 dias a partir do início dos sintomas. O ponto de corte ótimo foi definido como o número necessário de dias para atingir a melhor sensibilidade e especificidade. Esse ponto foi utilizado também para comparar a acurácia do LFI de acordo com a situação do paciente (ambulatorial ou hospitalizado). Foram incluídos 959 pacientes, dos quais 379 (39,52%) testaram positivos para SARS-CoV-2 pelo RT-PCR e 272 (28,36%) pelo LFI. Foi atingido o melhor desempenho para o LFI com 10 dias a partir do início dos sintomas, com sensibilidade e especificidade de 84,9% (IC95%: 79,8-89,1) e 94,4% (IC95%: 91,0-96,8), respectivamente. Embora a especificidade não tenha sido diferente entre os grupos de pacientes (94,6% vs. 88,9%, p = 0,051), a sensibilidade foi mais alta nos pacientes hospitalizados que nos ambulatoriais (91,7% vs. 82,1%, p = 0,032) no dia 10 depois do início dos sintomas. A melhor sensibilidade do LFI no local de atendimento ocorre 10 dias depois do início dos sintomas, o que pode limitar seu uso no atendimento agudo. A especificidade permanece alta, independentemente do número de dias desde o início dos sintomas.
Los puestos de atención para pruebas serológicas del SARS-CoV-2 han sido usado para la diagnosis de la COVID-19. No obstante, su precisión a lo largo del tiempo, en lo que respecta a la aparición de los síntomas, no se ha comprendido completamente. Nuestro objetivo fue evaluar la precisión de un puesto de atención de inmunoanálisis de flujo lateral (LFI). Se hizo pruebas a individuos ≥ 18 años, presentando síntomas clínicos compatibles con una infección aguda de SARS-CoV-2, tanto vía nasofaríngea y orofaríngea RT-PCR, como LFI. La precisión de LFI fue evaluada en intervalos periódicos de 3 días con respecto a la aparición de los síntomas. El punto óptimo de corte se definió como el número de días requerido para alcanzar la mejor sensibilidad y especificidad. Este punto también se usó para comparar la precisión del LFI, según el estatus de los participantes: ambulatorios u hospitalizados. Se incluyeron a 959 pacientes, 379 (39,52%) dieron positivo en las pruebas de SARS-CoV-2 RT-PCR, y 272 (28,36%) fueron positivos en los LFI. Se alcanzó el mejor rendimiento de los LFI tras 10 días de la aparición de los síntomas, con una sensibilidad y especificidad de un 84,9% (IC95%: 79,8-89,1) y 94,4% (IC95%: 91,0-96,8), respectivamente. A pesar de que la especificidad no fue diferente (94,6% vs. 88,9%, p = 0,051), la sensibilidad fue mayor en pacientes hospitalizados que en los ambulatorios (91,7% vs. 82,1%, p = 0,032) tras 10 días desde la aparición de los síntomas. La mejor sensibilidad LFI del puesto de cuidado se produce tras 10 días de la aparición de los síntomas, lo que quizás limite su uso en el cuidado de urgencias. La especificidad permanece alta independientemente del número de días desde la aparición de los síntomas.
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Humanos , Adulto , SARS-CoV-2 , COVID-19 , Brasil , Sensibilidad y Especificidad , Prueba de COVID-19 , Persona de Mediana EdadRESUMEN
Abstract Objective: The aim of this study was to evaluate the association between possible functional interleukin-10 (IL-10) polymorphisms, IL-10 expression and regulatory T cells (Tregs) frequency, and/or asthma severity in a sample of children and adolescents. Methods: This is a nested case-control genetic association study. The study sample consisted of children and adolescents aged 8-14 from public schools. Four polymorphisms of the IL-10 gene (rs1518111, rs3024490, rs3024496, rs3024491) were genotyped in asthmatic subjects and controls using real-time PCR. Tregs cells and IL-10 were analyzed in peripheral blood mononuclear cells by flow cytometry. The severity of asthma was defined according to the Global Initiative for Asthma (GINA) guideline. Results: One hundred twenty-three asthmatic subjects and fifty-eight controls participated in the study. The single nucleotide polymorphism (SNP) rs3024491 (T allele) showed association with asthma severity, presenting a higher frequency in patients in the moderate asthma group. The T allele of variant rs3024491 also showed an association with reduced IL-10 levels (p = 0.01) and with increased Tregs frequency (p = 0.01). The other variants did not present consistent associations. Conclusions: Our results suggest that moderate asthma is associated with a higher frequency of the T allele in the SNP rs3024491. In addition, the variant rs3024491 (TT) was associated with a reduction in IL-10 production and an increased percentage of Tregs cells, suggesting possible mechanisms that influence asthma severity.
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Humanos , Niño , Adolescente , Asma/genética , Interleucina-10/genética , Leucocitos Mononucleares , Polimorfismo de Nucleótido Simple/genética , Factores de Transcripción Forkhead , Subunidad alfa del Receptor de Interleucina-2RESUMEN
OBJECTIVE: The aim of this study was to evaluate the association between possible functional interleukin-10 (IL-10) polymorphisms, IL-10 expression and regulatory T cells (Tregs) frequency, and/or asthma severity in a sample of children and adolescents. METHODS: This is a nested case-control genetic association study. The study sample consisted of children and adolescents aged 8-14 from public schools. Four polymorphisms of the IL-10 gene (rs1518111, rs3024490, rs3024496, rs3024491) were genotyped in asthmatic subjects and controls using real-time PCR. Tregs cells and IL-10 were analyzed in peripheral blood mononuclear cells by flow cytometry. The severity of asthma was defined according to the Global Initiative for Asthma (GINA) guideline. RESULTS: One hundred twenty-three asthmatic subjects and fifty-eight controls participated in the study. The single nucleotide polymorphism (SNP) rs3024491 (T allele) showed association with asthma severity, presenting a higher frequency in patients in the moderate asthma group. The T allele of variant rs3024491 also showed an association with reduced IL-10 levels (p=0.01) and with increased Tregs frequency (p=0.01). The other variants did not present consistent associations. CONCLUSIONS: Our results suggest that moderate asthma is associated with a higher frequency of the T allele in the SNP rs3024491. In addition, the variant rs3024491 (TT) was associated with a reduction in IL-10 production and an increased percentage of Tregs cells, suggesting possible mechanisms that influence asthma severity.
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Asma , Interleucina-10 , Adolescente , Asma/genética , Niño , Factores de Transcripción Forkhead , Humanos , Interleucina-10/genética , Subunidad alfa del Receptor de Interleucina-2 , Leucocitos Mononucleares , Polimorfismo de Nucleótido Simple/genéticaRESUMEN
During chronic inflammatory disease, such asthma, leukocytes can invade the central nervous system (CNS) and together with CNS-resident cells, generate excessive reactive oxygen species (ROS) production as well as disbalance in the antioxidant system, causing oxidative stress, which contributes a large part to neuroinflammation. In this sense, the aim of this study is to investigate the effects of treatment with neostigmine, known for the ability to control lung inflammation, on oxidative stress in the cerebral cortex of asthmatic mice. Female BALB/cJ mice were submitted to asthma model induced by ovalbumin (OVA). Control group received only Dulbecco's phosphate-buffered saline (DPBS). To evaluate neostigmine effects, mice received 80 µg/kg of neostigmine intraperitoneally 30 min after each OVA challenge. Our results revealed for the first time that treatment with neostigmine (an acetylcholinesterase inhibitor that no crosses the BBB) was able to revert ROS production and change anti-oxidant enzyme catalase in the cerebral cortex in asthmatic mice. These results support the communication between the peripheral immune system and the CNS and suggest that acetylcholinesterase inhibitors, such as neostigmine, should be further studied as possible therapeutic strategies for neuroprotection in asthma.
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Asma/tratamiento farmacológico , Corteza Cerebral/efectos de los fármacos , Corteza Cerebral/metabolismo , Inhibidores de la Colinesterasa/farmacología , Neostigmina/farmacología , Fármacos Neuroprotectores/farmacología , Estrés Oxidativo/efectos de los fármacos , Animales , Antioxidantes/metabolismo , Antioxidantes/farmacología , Asma/inducido químicamente , Asma/patología , Líquido del Lavado Bronquioalveolar , Catalasa/metabolismo , Inhibidores de la Colinesterasa/uso terapéutico , Femenino , Inyecciones Intraperitoneales , Ratones , Ratones Endogámicos BALB C , Neostigmina/uso terapéutico , Neuroprotección , Fármacos Neuroprotectores/uso terapéutico , Ovalbúmina , Especies Reactivas de Oxígeno/metabolismo , ATPasa Intercambiadora de Sodio-Potasio/metabolismo , Superóxido Dismutasa-1/metabolismoRESUMEN
OBJECTIVE: A significant proportion of the infants developed recurrent wheezing after an acute bronchiolitis (AB) event. Recent studies have demonstrated protection for recurrent wheeze and lower respiratory morbidity in infants treated with azithromycin during an acute respiratory wheezing. The aim of the present study was to test the hypothesis that administration of azithromycin during an AB event reduces subsequent wheezing and hospital re-admissions. METHODS: This is a secondary analysis of a randomized, double-blinded, placebo-controlled trial, including unpublished data of wheezing and hospitalizations during the initial 6 months following admission for acute viral bronchiolitis. The study was performed in a tertiary University hospital. Infants (<12 months of age) hospitalized with AB were randomized to receive either azithromycin or placebo, administered orally, for 7 days. Families were contacted by telephone at 3 and 6 months after the initial acute event and answered to a standardized questionnaire in order to identify recurrent wheezing and hospital readmissions. RESULTS: One hundred and four patients were included (Azithromycin group, n= 50; placebo group, n=54). Considering the total of patients contacted 3 months after hospitalization (n=70), the recurrence rate of wheezing in the azithromycin group was significantly lower than in the placebo group (RR = 0.48; CI = 0.24-0.98; p = 0.038). CONCLUSION: Azithromycin significantly reduces the risk of subsequent wheezing between 0 and 3 months after hospital admission due to acute bronchiolitis irrespective of the presence of respiratory syncytial virus.
OBJETIVO: Uma proporção significativa de lactentes desenvolve sibilância recorrente após um evento de bronquiolite aguda (BA). Estudos recentes demonstraram proteção para sibilância recorrente e menor morbidade respiratória em lactentes tratados com azitromicina durante uma crise de sibilância. O objetivo do presente estudo foi testar a hipótese de que a administração de azitromicina durante um evento BA reduz sibilos e reinternações hospitalares subsequentes. MÉTODOS: Trata-se de uma análise secundária de um estudo randomizado, duplo-cego, controlado por placebo, incluindo dados não publicados de sibilância e hospitalizações durante os seis meses iniciais após a internação por bronquiolite aguda. O estudo foi realizado em um hospital universitário terciário. Os bebês (<12 meses de idade) hospitalizados com BA foram randomizados para receber azitromicina ou placebo, administrados por via oral, por sete dias. As famílias foram contatadas por telefone aos três e seis meses após o evento agudo inicial, e responderam a um questionário padronizado para identificar sibilos recorrentes e reinternações hospitalares. RESULTADOS: Cento e quatro pacientes foram incluídos (grupo Azitromicina, n=50; grupo Placebo, n=54). Considerando o total de pacientes contatados com sucesso três meses após a hospitalização (n=70), a taxa de recorrência de sibilância no grupo da azitromicina foi significativamente menor do que no grupo placebo (RR=0,48; CI=0,24-0.98; p=0,038). CONCLUSÕES: A azitromicina reduziu significativamente o risco de sibilância subsequente entre zero e três meses após a admissão hospitalar por bronquiolite aguda.
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Azitromicina/uso terapéutico , Bronquiolitis/tratamiento farmacológico , Azitromicina/administración & dosificación , Bronquiolitis/diagnóstico , Hospitalización , Humanos , Lactante , Recurrencia , Ruidos Respiratorios , Resultado del TratamientoRESUMEN
OBJECTIVE: To investigate the effect of levels of physical activity on asthma control in children. METHODS: A cross-sectional study, including public school students aged 8 to 12 years, of both sexes, with asthma, from a capital and a medium-sized cities in Southern Brazil. At home, the students answered the questionnaire on levels of physical activity and disease control. RESULTS: A total of 482 schoolchildren with asthma participated in the study, with mean age of 10.9±2.2 years, and 253 (52%) were girls. Regarding disease control, 50% had controlled asthma, and 67% were considered sedentary. Schoolchildren with controlled asthma were more active than those with uncontrolled asthma (p=0.032). Active schoolchildren were more likely to have asthma controlled (OR=1.5; 95%CI: 1.04-2.25). CONCLUSION: The results demonstrated an association between physical activity levels and asthma control. More active schoolchildren were more likely to have asthma controlled.
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Asma/prevención & control , Ejercicio Físico/fisiología , Estudiantes/estadística & datos numéricos , Adolescente , Brasil , Niño , Estudios Transversales , Femenino , Humanos , Masculino , Conducta Sedentaria , Factores Socioeconómicos , Encuestas y CuestionariosRESUMEN
Asthma is characterized by the influx of inflammatory cells, especially of eosinophils as well as reactive oxygen species (ROS) production, driven by the release of the T helper 2 (Th2)-cell-associated cytokines. The cholinergic anti-inflammatory pathway (CAP) inhibit cytokines production and controls inflammation. Thus, we investigated the effects of pharmacological activation of CAP by neostigmine on oxidative stress and airway inflammation in an allergic asthma model. After the OVA challenge, mice were treated with neostigmine. We showed that CAP activation by neostigmine reduced the levels of pro-inflammatory cytokines (IL-4, IL-5, IL-13, IL-1ß, and TNF-α), which resulted in a decrease of eosinophils influx. Furthermore, neostigmine also conferred airway protection against oxidative stress, attenuating ROS production through the increase of antioxidant defense, evidenced by the catalase (CAT) activity. We propose, for the first time, that pharmacological activation of the CAP can lead to new possibilities in the therapeutic management of allergic asthma.
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Asma/inmunología , Inflamación/inmunología , Neuroinmunomodulación/fisiología , Estrés Oxidativo/inmunología , Animales , Asma/metabolismo , Asma/patología , Inhibidores de la Colinesterasa/farmacología , Modelos Animales de Enfermedad , Femenino , Inflamación/metabolismo , Inflamación/patología , Ratones , Ratones Endogámicos BALB C , Neostigmina/farmacología , Neuroinmunomodulación/efectos de los fármacosRESUMEN
Studies have shown autophagy participation in the immunopathology of inflammatory diseases. However, autophagy role in asthma and in eosinophil extracellular traps (EETs) release is poorly understood. Here, we attempted to investigate the autophagy involvement in EETs release and in lung inflammation in an experimental asthma model. Mice were sensitized with ovalbumin (OVA), followed by OVA challenge. Before the challenge with OVA, mice were treated with an autophagy inhibitor, 3-methyladenine (3-MA). We showed that 3-MA treatment decreases the number of eosinophils, eosinophil peroxidase (EPO) activity, goblet cells hyperplasia, proinflammatory cytokines, and nuclear factor kappa B (NFκB) p65 immunocontent in the lung. Moreover, 3-MA was able to improve oxidative stress, mitochondrial energy metabolism, and Na+ , K+ -ATPase activity. We demonstrated that treatment with autophagy inhibitor 3-MA reduced EETs formation in the airway. On the basis of our results, 3-MA treatment can be an interesting alternative for reducing lung inflammation, oxidative stress, mitochondrial damage, and EETs formation in asthma.
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Adenina/análogos & derivados , Antiasmáticos/farmacología , Asma/tratamiento farmacológico , Autofagia/inmunología , Trampas Extracelulares/inmunología , Adenina/farmacología , Animales , Asma/inducido químicamente , Asma/patología , Líquido del Lavado Bronquioalveolar/citología , Citocinas/metabolismo , Modelos Animales de Enfermedad , Metabolismo Energético/efectos de los fármacos , Peroxidasa del Eosinófilo/metabolismo , Eosinófilos/inmunología , Femenino , Células Caliciformes/patología , Pulmón/patología , Ratones , Ratones Endogámicos BALB C , Mitocondrias/metabolismo , Ovalbúmina , Estrés Oxidativo/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Factor de Transcripción ReIA/metabolismoRESUMEN
RESUMO Objetivo Uma proporção significativa de lactentes desenvolve sibilância recorrente após um evento de bronquiolite aguda (BA). Estudos recentes demonstraram proteção para sibilância recorrente e menor morbidade respiratória em lactentes tratados com azitromicina durante uma crise de sibilância. O objetivo do presente estudo foi testar a hipótese de que a administração de azitromicina durante um evento BA reduz sibilos e reinternações hospitalares subsequentes. Métodos Trata-se de uma análise secundária de um estudo randomizado, duplo-cego, controlado por placebo, incluindo dados não publicados de sibilância e hospitalizações durante os seis meses iniciais após a internação por bronquiolite aguda. O estudo foi realizado em um hospital universitário terciário. Os bebês (<12 meses de idade) hospitalizados com BA foram randomizados para receber azitromicina ou placebo, administrados por via oral, por sete dias. As famílias foram contatadas por telefone aos três e seis meses após o evento agudo inicial, e responderam a um questionário padronizado para identificar sibilos recorrentes e reinternações hospitalares. Resultados Cento e quatro pacientes foram incluídos (grupo Azitromicina, n=50; grupo Placebo, n=54). Considerando o total de pacientes contatados com sucesso três meses após a hospitalização (n=70), a taxa de recorrência de sibilância no grupo da azitromicina foi significativamente menor do que no grupo placebo (RR=0,48; CI=0,24-0.98; p=0,038). Conclusões A azitromicina reduziu significativamente o risco de sibilância subsequente entre zero e três meses após a admissão hospitalar por bronquiolite aguda.
ABSTRACT Objective A significant proportion of the infants developed recurrent wheezing after an acute bronchiolitis (AB) event. Recent studies have demonstrated protection for recurrent wheeze and lower respiratory morbidity in infants treated with azithromycin during an acute respiratory wheezing. The aim of the present study was to test the hypothesis that administration of azithromycin during an AB event reduces subsequent wheezing and hospital re-admissions. Methods This is a secondary analysis of a randomized, double-blinded, placebo-controlled trial, including unpublished data of wheezing and hospitalizations during the initial 6 months following admission for acute viral bronchiolitis. The study was performed in a tertiary University hospital. Infants (<12 months of age) hospitalized with AB were randomized to receive either azithromycin or placebo, administered orally, for 7 days. Families were contacted by telephone at 3 and 6 months after the initial acute event and answered to a standardized questionnaire in order to identify recurrent wheezing and hospital readmissions. Results One hundred and four patients were included (Azithromycin group, n= 50; placebo group, n=54). Considering the total of patients contacted 3 months after hospitalization (n=70), the recurrence rate of wheezing in the azithromycin group was significantly lower than in the placebo group (RR = 0.48; CI = 0.24-0.98; p = 0.038). Conclusion Azithromycin significantly reduces the risk of subsequent wheezing between 0 and 3 months after hospital admission due to acute bronchiolitis irrespective of the presence of respiratory syncytial virus.
Asunto(s)
Humanos , Lactante , Bronquiolitis/tratamiento farmacológico , Azitromicina/uso terapéutico , Recurrencia , Bronquiolitis/diagnóstico , Ruidos Respiratorios , Resultado del Tratamiento , Azitromicina/administración & dosificación , HospitalizaciónRESUMEN
ABSTRACT Objective To investigate the effect of levels of physical activity on asthma control in children. Methods A cross-sectional study, including public school students aged 8 to 12 years, of both sexes, with asthma, from a capital and a medium-sized cities in Southern Brazil. At home, the students answered the questionnaire on levels of physical activity and disease control. Results A total of 482 schoolchildren with asthma participated in the study, with mean age of 10.9±2.2 years, and 253 (52%) were girls. Regarding disease control, 50% had controlled asthma, and 67% were considered sedentary. Schoolchildren with controlled asthma were more active than those with uncontrolled asthma (p=0.032). Active schoolchildren were more likely to have asthma controlled (OR=1.5; 95%CI: 1.04-2.25). Conclusion The results demonstrated an association between physical activity levels and asthma control. More active schoolchildren were more likely to have asthma controlled.
RESUMO Objetivo Investigar o efeito dos níveis de atividade física no controle da asma em crianças. Métodos Estudo transversal, incluindo escolares da rede pública, de 8 a 12 anos, de ambos os sexos, com asma, de uma capital e de uma cidade de porte médio da Região Sul do Brasil. Os escolares responderam, em seus domicílios, um questionário de níveis de atividade física e de controle da doença. Resultados Participaram da pesquisa 482 escolares com asma, com média de idade de 10,9±2,2 anos, e 253 (52%) eram meninas. Quanto ao controle da doença, 50% apresentavam asma controlada e 67% foram considerados sedentários. Os escolares com asma controlada foram mais ativos do que os com asma não controlada (p=0,032). Os escolares ativos tiveram mais chance de ter a asma controlada (RC=1,5; IC95%: 1,04-2,25). Conclusão Os resultados demonstraram associação entre os níveis de atividade física e controle da asma. Os escolares mais ativos apresentaram mais chance de ter a asma controlada.
Asunto(s)
Humanos , Masculino , Femenino , Niño , Adolescente , Asma/prevención & control , Estudiantes/estadística & datos numéricos , Ejercicio Físico/psicología , Factores Socioeconómicos , Brasil , Estudios Transversales , Encuestas y Cuestionarios , Conducta SedentariaRESUMEN
BACKGROUND: Respiratory viral infections are the leading cause of asthma exacerbations. Eosinophil activation results in the formation of eosinophil extracellular traps (EETs), which release web-like structures of DNA and proteins that bind, disarm and extracellularly kill pathogens. OBJECTIVE: We investigated whether the respiratory syncytial virus (RSV) in vitro could induce EETs in bronchoalveolar lavage fluid eosinophils in a murine model of asthma. METHODS: BALB/cJ mice (6-8 weeks old) were sensitized with 2 subcutaneous injections of ovalbumin (20 µg) on days 0 and 7, followed by three intranasal challenges with ovalbumin (100 µg) on days 14, 15, and 16 of the protocol. The control group received Dulbecco's phosphate-buffered saline. Bronchoalveolar lavage fluid eosinophils of ovalbumin group or control group were stimulated with RSV (103 PFU/mL) in vitro for 3 hours. After that, culture supernatant was collected to perform the analyses proposed in this study. RESULTS: We verified an increase in extracellular DNA concentration in bronchoalveolar lavage fluid eosinophils from ovalbumin group stimulated with RSV (103 PFU/mL) in vitro, which was confirmed by confocal microscopy. We demonstrated that most cells are negative for annexin V and propidium iodide in all groups evaluated. Also, RSV in vitro decreased interferon-É£ in culture supernatant when compared to the ovalbumin group. CONCLUSION: In this study, we demonstrated for the first time that RSV in vitro induces EETs formation in eosinophils from asthmatic mice.
RESUMEN
OBJETIVO: Analisar as características da asma entre escolares de região metropolitana e região agrícola. MÉTODOS: Os escolares de ambos locais, responderam questionário de diagnóstico epidemiológico da asma e características clínicas da asma, rinite e atopia conforme ISAAC. Também foram avaliados pelo Teste de Controle da Asma e medida de atividade física. RESULTADOS: Entre os 290 e 123 asmáticos avaliados na região metropolitana e região agrícola, respectivamente, a prevalência de asma foi 20,4% e 19,2%. Os asmáticos da região agrícola apresentaram maior frequência de rinite (87% vs. 48,8%, p< 0,001) e atopia (81,4% vs. 63,5%, p=0,005) Não foi observada diferença em medidas de controle da doença (51,9% vs. 47,2%, p=0,378). A combinação asma com rinite ou atopia apresentou risco significativo para o controle da doença nos escolares da região agrícola (OR: 2,300; IC95%:1,867-2,833). CONCLUSÃO: Não houve diferença na frequência de asma e controle da doença entre os escolares estudados. Contudo, os escolares da região agrícola apresentam maiores taxas de rinite e atopia o que interferiu negativamente no controle da asma. Estes achados sugerem que asma em populações com meio ambientes distintos têm características clínicas distintas, que devem ser levadas em conta na definição de estratégias de prevenção e manejo clínico.
AIM: To analyze the characteristics of asthma among students from metropolitan and agricultural regions. METHODS: Students from both locations answered a questionnaire for epidemiological diagnosis of asthma and clinical characteristics of asthma, rhinitis and atopy according to ISAAC. They were also evaluated by the Asthma Control Test and measure of physical activity. RESULTS: Among the 290 and 123 asthmatics evaluated in the metropolitan region and agricultural region, respectively, the prevalence of asthma was 20.4% and 19.2%. Asthmatics in the agricultural region had a higher frequency of rhinitis (87% vs. 48.8%, p<0.001) and atopy (81.4% vs. 63.5%, p=0.005) No difference was observed in disease control measures (51.9% vs. 47.2%, p=0.378). The combination asthma with Rhinitis or atopy presented significant risk for disease control in schoolchildren in the agricultural region (OR: 2,300; 95% CI: 1,867-2,833). CONCLUSION: There was no difference in asthma frequency and disease control among the students studied. However, the students of agricultural region have higher rates of rhinitis and atopy which negatively interfered with asthma control. These findings suggest that Asthma in populations with different environments have different clinical characteristics, which should be taken into account when defining prevention strategies and clinical management.
Asunto(s)
Rinitis , Asma , Neumología , MedicinaRESUMEN
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.
Asunto(s)
Antioxidantes/uso terapéutico , Pulmón/efectos de los fármacos , Estilbenos/uso terapéutico , Lesión Pulmonar Aguda/patología , Cromatina/metabolismo , Daño del ADN , Flavonoides/uso terapéutico , Humanos , Inflamación , Pulmón/patología , Modelos Teóricos , Neutrófilos/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Pruebas de Función Respiratoria , ResveratrolRESUMEN
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.