Seasonality of the incidence of bronchiolitis in infants — Brazil, 2016-2022: An interrupted time-series analysis / Sazonalidade da incidência de bronquiolite em lactentes — Brasil, 2016-2022: Uma análise de série temporal interrompida

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.

Deficiency of Peptidylglycine-alpha-amidating Monooxygenase, a Cause of Sarcopenic Diabetes Mellitus.

CONTEXT: Peptidylglycine-α-amidating monooxygenase (PAM) is a critical enzyme in the endocrine system responsible for activation, by amidation, of bioactive peptides. OBJECTIVE: To define the clinical phenotype of carriers of genetic mutations associated with impaired PAM-amidating activity (PAM-AMA). DESIGN: We used genetic and phenotypic data from cohort studies: the Malmö Diet and Cancer (MDC; 1991-1996; reexamination in 2002-2012), the Malmö Preventive Project (MPP; 2002-2006), and the UK Biobank (UKB; 2012). SETTING: Exome-wide association analysis was used to identify loss-of-function (LoF) variants associated with reduced PAM-AMA and subsequently used for association with the outcomes. PATIENTS OR OTHER PARTICIPANTS: This study included n∼4500 participants from a subcohort of the MDC (MDC-Cardiovascular cohort), n∼4500 from MPP, and n∼300,000 from UKB. MAIN OUTCOME MEASURES: Endocrine-metabolic traits suggested by prior literature, muscle mass, muscle function, and sarcopenia. RESULTS: Two LoF variants in the PAM gene, Ser539Trp (minor allele frequency: 0.7%) and Asp563Gly (5%), independently contributed to a decrease of 2.33 [95% confidence interval (CI): 2.52/2.15; P = 2.5E-140] and 0.98 (1.04/0.92; P = 1.12E-225) SD units of PAM-AMA, respectively. The cumulative effect of the LoF was associated with diabetes, reduced insulin secretion, and higher levels of GH and IGF-1. Moreover, carriers had reduced muscle mass and function, followed by a higher risk of sarcopenia. Indeed, the Ser539Trp mutation increased the risk of sarcopenia by 30% (odds ratio 1.31; 95% CI: 1.16/1.47; P = 9.8E-06), independently of age and diabetes. CONCLUSION: PAM-AMA genetic deficiency results in a prediabetic sarcopenic phenotype. Early identification of PAM LoF carriers would allow targeted exercise interventions and calls for novel therapies that restore enzymatic activity.

Seasonality of the incidence of bronchiolitis in infants - Brazil, 2016-2022: An interrupted time-series analysis.

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.

Mechanosensitive membrane domains regulate calcium entry in arterial endothelial cells to protect against inflammation.

Endothelial cells (ECs) in the descending aorta are exposed to high laminar shear stress, and this supports an antiinflammatory phenotype. High laminar shear stress also induces flow-aligned cell elongation and front-rear polarity, but whether these are required for the antiinflammatory phenotype is unclear. Here, we showed that caveolin-1-rich microdomains polarize to the downstream end of ECs that are exposed to continuous high laminar flow. These microdomains were characterized by high membrane rigidity, filamentous actin (F-actin), and raft-associated lipids. Transient receptor potential vanilloid (TRPV4) ion channels were ubiquitously expressed on the plasma membrane but mediated localized Ca2+ entry only at these microdomains where they physically interacted with clustered caveolin-1. These focal Ca2+ bursts activated endothelial nitric oxide synthase within the confines of these domains. Importantly, we found that signaling at these domains required both cell body elongation and sustained flow. Finally, TRPV4 signaling at these domains was necessary and sufficient to suppress inflammatory gene expression and exogenous activation of TRPV4 channels ameliorated the inflammatory response to stimuli both in vitro and in vivo. Our work revealed a polarized mechanosensitive signaling hub in arterial ECs that dampened inflammatory gene expression and promoted cell resilience.

Excess of body weight is associated with accelerated T-cell senescence in hospitalized COVID-19 patients.

BACKGROUND: Several risk factors have been involved in the poor clinical progression of coronavirus disease-19 (COVID-19), including ageing, and obesity. SARS-CoV-2 may compromise lung function through cell damage and paracrine inflammation; and obesity has been associated with premature immunosenescence, microbial translocation, and dysfunctional innate immune responses leading to poor immune response against a range of viruses and bacterial infections. Here, we have comprehensively characterized the immunosenescence, microbial translocation, and immune dysregulation established in hospitalized COVID-19 patients with different degrees of body weight. RESULTS: Hospitalised COVID-19 patients with overweight and obesity had similarly higher plasma LPS and sCD14 levels than controls (all p < 0.01). Patients with obesity had higher leptin levels than controls. Obesity and overweight patients had similarly higher expansions of classical monocytes and immature natural killer (NK) cells (CD56+CD16-) than controls. In contrast, reduced proportions of intermediate monocytes, mature NK cells (CD56+CD16+), and NKT were found in both groups of patients than controls. As expected, COVID-19 patients had a robust expansion of plasmablasts, contrasting to lower proportions of major T-cell subsets (CD4 + and CD8+) than controls. Concerning T-cell activation, overweight and obese patients had lower proportions of CD4+CD38+ cells than controls. Contrasting changes were reported in CD25+CD127low/neg regulatory T cells, with increased and decreased proportions found in CD4+ and CD8+ T cells, respectively. There were similar proportions of T cells expressing checkpoint inhibitors across all groups. We also investigated distinct stages of T-cell differentiation (early, intermediate, and late-differentiated - TEMRA). The intermediate-differentiated CD4 + T cells and TEMRA cells (CD4+ and CD8+) were expanded in patients compared to controls. Senescent T cells can also express NK receptors (NKG2A/D), and patients had a robust expansion of CD8+CD57+NKG2A+ cells than controls. Unbiased immune profiling further confirmed the expansions of senescent T cells in COVID-19. CONCLUSIONS: These findings suggest that dysregulated immune cells, microbial translocation, and T-cell senescence may partially explain the increased vulnerability to COVID-19 in subjects with excess of body weight.

Global disease burden of and risk factors for acute lower respiratory infections caused by respiratory syncytial virus in preterm infants and young children in 2019: a systematic review and meta-analysis of aggregated and individual participant data.

BACKGROUND: Infants and young children born prematurely are at high risk of severe acute lower respiratory infection (ALRI) caused by respiratory syncytial virus (RSV). In this study, we aimed to assess the global disease burden of and risk factors for RSV-associated ALRI in infants and young children born before 37 weeks of gestation. METHODS: We conducted a systematic review and meta-analysis of aggregated data from studies published between Jan 1, 1995, and Dec 31, 2021, identified from MEDLINE, Embase, and Global Health, and individual participant data shared by the Respiratory Virus Global Epidemiology Network on respiratory infectious diseases. We estimated RSV-associated ALRI incidence in community, hospital admission, in-hospital mortality, and overall mortality among children younger than 2 years born prematurely. We conducted two-stage random-effects meta-regression analyses accounting for chronological age groups, gestational age bands (early preterm, <32 weeks gestational age [wGA], and late preterm, 32 to <37 wGA), and changes over 5-year intervals from 2000 to 2019. Using individual participant data, we assessed perinatal, sociodemographic, and household factors, and underlying medical conditions for RSV-associated ALRI incidence, hospital admission, and three severity outcome groups (longer hospital stay [>4 days], use of supplemental oxygen and mechanical ventilation, or intensive care unit admission) by estimating pooled odds ratios (ORs) through a two-stage meta-analysis (multivariate logistic regression and random-effects meta-analysis). This study is registered with PROSPERO, CRD42021269742. FINDINGS: We included 47 studies from the literature and 17 studies with individual participant-level data contributed by the participating investigators. We estimated that, in 2019, 1 650 000 (95% uncertainty range [UR] 1 350 000-1 990 000) RSV-associated ALRI episodes, 533 000 (385 000-730 000) RSV-associated hospital admissions, 3050 (1080-8620) RSV-associated in-hospital deaths, and 26 760 (11 190-46 240) RSV-attributable deaths occurred in preterm infants worldwide. Among early preterm infants, the RSV-associated ALRI incidence rate and hospitalisation rate were significantly higher (rate ratio [RR] ranging from 1·69 to 3·87 across different age groups and outcomes) than for all infants born at any gestational age. In the second year of life, early preterm infants and young children had a similar incidence rate but still a significantly higher hospitalisation rate (RR 2·26 [95% UR 1·27-3·98]) compared with all infants and young children. Although late preterm infants had RSV-associated ALRI incidence rates similar to that of all infants younger than 1 year, they had higher RSV-associated ALRI hospitalisation rate in the first 6 months (RR 1·93 [1·11-3·26]). Overall, preterm infants accounted for 25% (95% UR 16-37) of RSV-associated ALRI hospitalisations in all infants of any gestational age. RSV-associated ALRI in-hospital case fatality ratio in preterm infants was similar to all infants. The factors identified to be associated with RSV-associated ALRI incidence were mainly perinatal and sociodemographic characteristics, and factors associated with severe outcomes from infection were mainly underlying medical conditions including congenital heart disease, tracheostomy, bronchopulmonary dysplasia, chronic lung disease, or Down syndrome (with ORs ranging from 1·40 to 4·23). INTERPRETATION: Preterm infants face a disproportionately high burden of RSV-associated disease, accounting for 25% of RSV hospitalisation burden. Early preterm infants have a substantial RSV hospitalisation burden persisting into the second year of life. Preventive products for RSV can have a substantial public health impact by preventing RSV-associated ALRI and severe outcomes from infection in preterm infants. FUNDING: EU Innovative Medicines Initiative Respiratory Syncytial Virus Consortium in Europe.

Changes in lung function in adolescents with substance use disorders: an exploratory study / Alterações da função pulmonar em adolescentes com transtornos relacionados ao uso de substâncias: estudo exploratório

ABSTRACT Objective: To compare lung function between adolescents with and without substance use disorder (SUD). Methods: This was an observational, cross-sectional exploratory study. The sample consisted of 16 adolescents with SUD and 24 age-matched healthy controls. The adolescents in the clinical group were recruited from a psychiatric inpatient unit for detoxification and rehabilitation; their primary diagnosis was SUD related to marijuana, cocaine, or polysubstance use. Questionnaires and pulmonary function tests were applied for clinical evaluation. Results: We found that FVC, FEV1, and their percentages of the predicted values were significantly lower in the adolescents with SUD than in those without. Those differences remained significant after adjustment for BMI and the effects of high levels of physical activity. The largest effect size (Cohen's d = 1.82) was found for FVC as a percentage of the predicted value (FVC%), which was, on average, 17.95% lower in the SUD group. In addition, the years of regular use of smoked substances (tobacco, marijuana, and crack cocaine) correlated negatively with the FVC%. Conclusions: This exploratory study is innovative in that it demonstrates the early consequences of smoked substance use for the lung health of adolescents with SUD.

RESUMO Objetivo: Comparar a função pulmonar de adolescentes com e sem transtornos relacionados ao uso de substâncias (TUS). Métodos: Trata-se de um estudo exploratório transversal observacional. A amostra foi composta por 16 adolescentes com TUS e 24 controles saudáveis emparelhados pela idade. Os adolescentes do grupo clínico foram recrutados em uma unidade de internação psiquiátrica para desintoxicação e reabilitação; seu diagnóstico primário era o de TUS (maconha, cocaína ou polissubstâncias). Foram aplicados questionários e testes de função pulmonar para a avaliação clínica. Resultados: A CVF, o VEF1 e seus valores em porcentagem do previsto foram significativamente mais baixos nos adolescentes com TUS do que naqueles sem TUS. Essas diferenças permaneceram significativas após os ajustes para levar em conta o IMC e os efeitos de altos níveis de atividade física. O maior tamanho de efeito (d de Cohen = 1,82) foi o observado em relação à CVF em porcentagem do previsto (CVF%), que foi, em média, 17,95% menor no grupo TUS. Além disso, os anos de uso regular de substâncias fumadas (tabaco, maconha e crack) correlacionaram-se negativamente com a CVF%. Conclusões: Este estudo exploratório é inovador na medida em que demonstra as consequências precoces do uso de substâncias fumadas para a saúde pulmonar de adolescentes com TUS.

Intra-breath oscillometry for the evaluation of lung function in children and adolescents with a history of preterm birth / Oscilometria intra-breath para avaliação da função pulmonar em crianças e adolescentes com história de prematuridade

ABSTRACT Objective: To assess respiratory system impedance (Zrs) and spirometric parameters in children and adolescents with and without a history of preterm birth. Methods: We evaluated a sample of 51 subjects between 11 and 14 years of age: 35 who had a history of preterm birth (preterm group) and 16 who had been born at term (full-term group). Lung function was measured by spirometry, spectral oscillometry, and intra-breath oscillometry. Results: Neither spirometry nor spectral oscillometry revealed any statistically significant differences between the preterm and full-term groups. However, intra-breath oscillometry demonstrated significant differences between the two groups in terms of the change in resistance, reactance at end-inspiration, and the change in reactance (p < 0.05 for all). Conclusions: Our findings suggest that abnormalities in Zrs persist in children and adolescents with a history of preterm birth and that intra-breath oscillometry is more sensitive than is spectral oscillometry. Larger studies are needed in order to validate these findings and to explore the impact that birth weight and gestational age at birth have on Zrs later in life.

RESUMO Objetivo: Avaliar a impedância do sistema respiratório (Zsr) e parâmetros espirométricos em crianças e adolescentes com e sem história de prematuridade. Métodos: Foi analisada uma amostra de 51 indivíduos entre 11 e 14 anos de idade: 35 com história de prematuridade (grupo pré-termo) e 16 nascidos a termo (grupo a termo). A função pulmonar foi medida por meio de espirometria, oscilometria espectral e oscilometria intra-breath. Resultados: A espirometria e a oscilometria espectral não revelaram diferenças estatisticamente significativas entre os grupos pré-termo e a termo. No entanto, a oscilometria intra-breath demonstrou diferenças significativas entre os dois grupos quanto à alteração da resistência, à reatância ao final da inspiração e à alteração da reatância (p < 0,05 para todas). Conclusões: Nossos achados sugerem que as anormalidades na Zsr persistem em crianças e adolescentes com história de prematuridade e que a oscilometria intra-breath é mais sensível do que a oscilometria espectral. São necessários estudos maiores para validar esses achados e para explorar o impacto do peso e idade gestacional ao nascer na Zsr mais tarde na vida.

Association between interleukin-10 polymorphisms and CD4+CD25+FOXP3+ T cells in asthmatic children

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.

Técnica de oscilações forçadas na avaliação e manejo de crianças asmáticas: uma revisão narrativa / Forced oscillation technique in the assessment and management of asthmatic children: a narrative review

Asthma is considered the most prevalent chronic disease in children. The pulmonary function measurements are important in the evaluation of the disease, being able to confirm the diagnosis by demonstrating the reversibility of the obstruction as well as detecting risks of poor prognosis in the control of asthma. However, the most common methods for analyzing pulmonary function in this age group have restrictions on its applicability, especially due to the need for cooperation on the part of patients. The forced oscillation technique (FOT) is considered a modern tool capable of estimating measures of respiratory mechanics related to the lungs. This method is easily applicable due to the low need for patient cooperation, an important element in the assessment of children. The aim of this study is to review the clinical utility of the Forced Oscillation Technique in the pulmonary assessment of asthmatic children. The bibliographic search covered the years between 1950 and 2019, in the databases: Medical Literature Analysis and Retrieval System Online (MEDLINE) and Latin American and Caribbean Literature in Health Sciences (LILACS). It was used as a search strategy the combination of the following Medical Subject Headings (MeSH) terms: "asthma", "oscillometry" and "child" crossed through the AND and OR Boolean connectors. In asthmatic children, FOT showed greater accuracy in the evaluation of smaller caliber peripheral airways, which can be applied as a complementary method to spirometry to strengthen the diagnosis, enabling a better understanding of the disease and its progression.

A asma é considerada a doença crônica de maior incidência em crianças. As medidas de função pulmonar são importantes na avaliação da doença, podendo confirmar o diagnóstico pela demonstração de reversibilidade da obstrução assim como detectar riscos de mau prognóstico no controle da asma. Entretanto, os métodos mais usuais para análise da função pulmonar nesta faixa etária apresentam restrições em sua aplicabilidade, especialmente pela necessidade de cooperação por parte dos pacientes. A técnica de oscilações forçadas (FOT) é considerada uma ferramenta moderna capaz de estimar medidas da mecânica respiratória relativas aos pulmões. Este método apresenta fácil aplicabilidade pela baixa necessidade de cooperação do paciente, elemento importante na avaliação de crianças. O objetivo deste estudo é revisar a utilidade clínica da Técnica de Oscilações Forçadas na avaliação pulmonar de crianças asmáticas. A busca bibliográfica contemplou os anos entre 1950 e 2019, nas bases de dados: Medical Literature Analysis and Retrieval System Online (MEDLINE) e Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS). Foi utilizada como estratégia de busca a combinação dos seguintes Medical Subject Headings(MeSH) terms: "asthma", "oscillometry" e "child" cruzados por meio dos conectores booleanos AND e OR. Em crianças asmáticas, a FOT mostrou maior acurácia na avaliação de vias aéreas periféricas de menor calibre, podendo ser aplicada como método complementar a espirometria para encorpar o diagnóstico, possibilitando compreender melhor a doença e sua progressão.

Prevalence and impact of asthma in schoolchildren in the city of Caxias do Sul-RS / Prevalência e impacto da asma em escolares do município de Caxias do Sul-RS

Abstract Objective: To analyze the prevalence and impact of asthma in schoolchildren from the city of Caxias do Sul, RS, Brazil. Methods: Cross-sectional observational and case-control study with children and adolescents between 7 and 15 years old, from public schools in Caxias do Sul, RS. The study is composed of two phases: Phase I analyzed the prevalence of asthma in the delimited population, investigating 1915 schoolchildren; Phase II quality of life questionnaires, asthma control and classification (for the asthmatic group), physical activity, school performance, pulmonary function tests and anthropometric measures were applied to 266 asthmatics and 288 controls. Results: The estimated prevalence of asthma was 16.1%. In the comparison between asthmatics and nonasthmatics premature birth (p < 0.001) and diagnosis of another chronic disease at birth (p < 0.001) were found. Regarding pulmonary function, significant differences were found in the values between groups in FEV1, FEV1/FVC and forced expiratory flow in the 25 and 75% (FEF25-75%), being that asthmatics presented lower values. Among asthmatics, 133 (50.8%) did not have the disease controlled. In the anthropometric variables, significant differences were observed, with higher values in controls, in the the waist-to-height ratio (p = 0.009) and in the perception of health (p < 0.001). Quality of life is lower in asthmatics in the physical well-being domain (p = 0.001) and in the total score (p = 0.016). The total school performance score did not present a statistically significant difference between the groups. Conclusion: The prevalence of asthma is similar to that of other industrialized urban centers and may negatively affect some areas of the development of schoolchildren.

Resumo Objetivo: Analisar a prevalência e o impacto da asma em escolares do município de Caxias do Sul-RS. Métodos: Estudo analítico observacional transversal e caso-controle, com crianças e adolescentes entre sete e 15 anos, de escolas da rede pública de Caxias do Sul-RS. O estudo é composto por duas fases: Fase I analisou a prevalência da asma na população delimitada e investigou 1.915 escolares; Fase II foram aplicados a 266 asmáticos e 288 controles, questionários de qualidade de vida, classificação e controle da asma (para o grupo asmático), atividade física, desempenho escolar, espirometria e antropometria. Resultados: A prevalência de asma estimada foi de 16,1%. Na comparação entre asmáticos e não asmáticos foram encontradas diferenças na prematuridade (p< 0,001) e ter diagnóstico de outra doença crônica ao nascer (p< 0,001). Na espirometria foram encontradas diferenças significativas entre os grupos nos valores de VEF1, VEF1/CVF e fluxo expiratório forçado nos momentos 25 e 75% (FEF25-75%); os asmáticos apresentaram valores inferiores. Entre os asmáticos, 133 (50,8%) não tem a doença controlada. Nas variáveis antropométricas foram observadas diferenças significativas, com valores superiores entre os controles, na classificação razão cintura/estatura (p = 0,009) e na percepção da própria saúde (p< 0,001). A qualidade de vida é menor nos asmáticos no domínio bem estar físico (p = 0,001) e no escore total (p = 0,016). O escore total do desempenho escolar não apresentou diferença estatisticamente significativa entre os grupos de estudo. Conclusão: A prevalência de asma se assemelha à de outros centros urbanos industrializados e pode impactar negativamente alguns domínios do desenvolvimento dos escolares.

Reference values for spirometry in Brazilian children / Valores de referência de espirometria para crianças brasileiras

ABSTRACT Objective: To generate reference values for spirometry in Brazilian children 3-12 years of age and to compare those values with the values employed in the equations currently in use in Brazil. Methods: This study involved healthy children, 3-12 years of age, recruited from 14 centers (primary data) and spirometry results from children with the same characteristics in six databases (secondary data). Reference equations by quantile regressions were generated after log transformation of the spirometric and anthropometric data. Skin color was classified as self-reported by the participants. To determine the suitability of the results obtained, they were compared with those predicted by the equations currently in use in Brazil. Results: We included 1,990 individuals from a total of 21 primary and secondary data sources. Of those, 1,059 (53%) were female. Equations for FEV1, FVC, the FEV1/FVC ratio, FEF between 25% and 75% of the FVC (FEF25-75%) and the FEF25-75%/FVC ratio were generated for white-, black-, and brown-skinned children. The logarithms for height and age, together with skin color, were the best predictors of FEV1 and FVC. The reference values obtained were significantly higher than those employed in the equations currently in use in Brazil, for predicted values, as well as for the lower limit of normality, particularly in children with self-reported black or brown skin. Conclusions: New spirometric equations were generated for Brazilian children 3-12 years of age, in the three skin-color categories defined. The equations currently in use in Brazil seem to underestimate the lung function of Brazilian children 3-12 years of age and should be replaced by the equations proposed in this study.

RESUMO Objetivo: Gerar valores de referência para espirometria em crianças brasileiras de 3-12 anos de idade e comparar os resultados obtidos com as equações em uso no Brasil. Métodos: Foram incluídas crianças sadias de 3-12 anos recrutadas em 14 centros (dados primários) e resultados de espirometria de crianças com as mesmas características de seis bancos de dados (dados secundários). As equações quantílicas foram geradas após transformações logarítmicas dos dados espirométricos e antropométricos. A classificação por cor da pele foi autodeclarada. Os resultados obtidos foram comparados com os previstos nas equações em uso no Brasil para testar sua adequação. Resultados: Foram incluídos 1.990 indivíduos de 21 fontes de dados primários e secundários, sendo 1.059 (53%) do sexo feminino. Equações para VEF1, CVF, VEF1/CVF, FEF25-75% e FEF25-75%/CVF foram geradas para crianças brancas e para crianças negras e pardas. Os logaritmos da estatura e da idade e a cor da pele foram os melhores preditores para VEF1 e CVF. Os resultados obtidos foram significativamente maiores do que as estimativas geradas pelas equações em uso no Brasil, tanto para valores previstos quanto para o limite inferior da normalidade, particularmente em crianças negras e pardas. Conclusões: Novas equações espirométricas foram geradas para crianças brasileiras de 3-12 anos de cor branca, negra e parda. As equações atualmente em uso no Brasil parecem subestimar a função pulmonar de crianças brasileiras menores de 12 anos de idade e deveriam ser substituídas pelas equações propostas neste estudo.

A azitromicina administrada para bronquiolite aguda pode ter um efeito de proteção na sibilância recorrente / Azithromycin administered for acute bronchiolitis may have a protective effect on subsequent wheezing

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.

The impact of asthma in Brazil: a longitudinal analysis of data from a Brazilian national database system / Impacto da asma no Brasil: análise longitudinal de dados extraídos de um banco de dados governamental brasileiro

ABSTRACT Objective: To present official longitudinal data on the impact of asthma in Brazil between 2008 and 2013. Methods: This was a descriptive study of data collected between 2008 and 2013 from an official Brazilian national database, including data on asthma-related number of hospitalizations, mortality, and hospitalization costs. A geographical subanalysis was also performed. Results: In 2013, 2,047 people died from asthma in Brazil (5 deaths/day), with more than 120,000 asthma-related hospitalizations. During the whole study period, the absolute number of asthma-related deaths and of hospitalizations decreased by 10% and 36%, respectively. However, the in-hospital mortality rate increased by approximately 25% in that period. The geographic subanalysis showed that the northern/northeastern and southeastern regions had the highest asthma-related hospitalization and in-hospital mortality rates, respectively. An analysis of the states representative of the regions of Brazil revealed discrepancies between the numbers of asthma-related hospitalizations and asthma-related in-hospital mortality rates. During the study period, the cost of asthma-related hospitalizations to the public health care system was US$ 170 million. Conclusions: Although the numbers of asthma-related deaths and hospital admissions in Brazil have been decreasing since 2009, the absolute numbers are still high, resulting in elevated direct and indirect costs for the society. This shows the relevance of the burden of asthma in middle-income countries.

RESUMO Objetivo: Apresentar dados longitudinais oficiais sobre o impacto da asma no Brasil entre 2008 e 2013. Métodos: Estudo descritivo de dados extraídos de um banco de dados do governo brasileiro entre 2008 e 2013, no qual foram analisados as hospitalizações e óbitos por asma, bem como o custo das hospitalizações. Foi também realizada uma subanálise geográfica. Resultados: Em 2013, 2.047 pessoas morreram de asma no Brasil (5 óbitos/dia), com mais de 120.000 hospitalizações por asma. Durante o período de estudo, o número absoluto de óbitos e hospitalizações por asma diminuiu 10% e 36%, respectivamente. No entanto, a taxa de mortalidade hospitalar aumentou aproximadamente 25%. A subanálise geográfica mostrou que as regiões Norte/Nordeste e Sudeste apresentaram as maiores taxas de hospitalização e mortalidade hospitalar por asma, respectivamente. A análise dos estados representativos de cada região mostrou discrepâncias entre as hospitalizações por asma e as taxas de mortalidade hospitalar por asma. Durante o período de estudo, as hospitalizações por asma custaram US$ 170 milhões ao sistema público de saúde. Conclusões: Embora os óbitos e hospitalizações por asma no Brasil estejam diminuindo desde 2009, os números absolutos ainda são altos, com elevados custos diretos e indiretos para a sociedade, o que mostra a relevância do impacto da asma em países de renda média.

Bronchodilator response cut-off points and FEV 0. 75 reference values for spirometry in preschoolers / Pontos de corte da resposta ao broncodilatador e valores de referência para VEF 0. 75 em espirometria de pré-escolares

ABSTRACT Objective: To determine the cut-off points for FEV1, FEV0.75, FEV0.5, and FEF25-75% bronchodilator responses in healthy preschool children and to generate reference values for FEV0.75. Methods: This was a cross-sectional community-based study involving children 3-5 years of age. Healthy preschool children were selected by a standardized questionnaire. Spirometry was performed before and after bronchodilator use. The cut-off point of the response was defined as the 95th percentile of the change in each parameter. Results: We recruited 266 children, 160 (60%) of whom were able to perform acceptable, reproducible expiratory maneuvers before and after bronchodilator use. The mean age and height were 57.78 ± 7.86 months and 106.56 ± 6.43 cm, respectively. The success rate for FEV0.5 was 35%, 68%, and 70% in the 3-, 4-, and 5-year-olds, respectively. The 95th percentile of the change in the percentage of the predicted value in response to bronchodilator use was 11.6%, 16.0%, 8.5%, and 35.5% for FEV1, FEV0.75, FEV0.5, and FEF25-75%, respectively. Conclusions: Our results provide cut-off points for bronchodilator responsiveness for FEV1, FEV0.75, FEV0.5, and FEF25-75% in healthy preschool children. In addition, we proposed gender-specific reference equations for FEV0.75. Our findings could improve the physiological assessment of respiratory function in preschool children.

RESUMO Objetivo: Determinar os pontos de corte de resposta ao broncodilatador do VEF1, VEF0,75, VEF0,5 e FEF25-75% em crianças pré-escolares saudáveis e gerar valores de referência para o VEF0,75. Métodos: Foi realizado um estudo transversal de base comunitária em crianças de 3-5 anos de idade. Pré-escolares saudáveis foram selecionados por um questionário padronizado. Foi realizada espirometria antes e depois do uso de broncodilatador. Foram definidos os pontos de corte dessa resposta como o percentil 95 de variação em cada parâmetro. Resultados: Foram recrutadas 266 crianças, e 160 (60,0%) foram capazes de gerar manobras expiratórias aceitáveis e reprodutíveis antes e depois do uso de broncodilatador. As médias de idade e estatura dos participantes foram 57,78 ± 7,86 meses e 106,56 ± 6,43 cm, respectivamente. A taxa de sucesso para o VEF0,5 foi de 35%, 68% e 70%, respectivamente, nos participantes com 3, 4 e 5 anos de idade. O percentil 95 de variação percentual do valor previsto na resposta ao broncodilatador foram, respectivamente, de 11,6%, 16,0%, 8,5% e 35,5%, para VEF1, VEF0,75, VEF0,5 e FEF25-75%. Conclusões: Nossos resultados definiram pontos de corte de resposta ao broncodilatador para o VEF1, VEF0,75, VEF0,5 e FEF25-75 em crianças pré-escolares saudáveis. Adicionalmente, foram propostas equações de referência para o VEF0,75, separadas por sexo. Os achados deste estudo podem melhorar a avaliação fisiológica da função respiratória em pré-escolares.

Growth, lung function, and physical activity in schoolchildren who were very-low-birth-weight preterm infants / Crescimento, função pulmonar e atividade física em escolares nascidos prematuros e com muito baixo peso

ABSTRACT Objective: To compare somatic growth, lung function, and level of physical activity in schoolchildren who had been very-low-birth-weight preterm infants (VLBWPIs) or normal-birth-weight full-term infants. Methods: We recruited two groups of schoolchildren between 8 and 11 years of age residing in the study catchment area: those who had been VLBWPIs (birth weight < 1,500 g); and those who had been normal-birth-weight full-term infants (controls, birth weight ≥ 2,500 g). Anthropometric and spirometric data were collected from the schoolchildren, who also completed a questionnaire regarding their physical activity. In addition, data regarding the perinatal and neonatal period were collected from the medical records of the VLBWPIs. Results: Of the 93 schoolchildren screened, 48 and 45 were in the VLBWPI and control groups, respectively. No significant differences were found between the groups regarding anthropometric characteristics, nutritional status, or pulmonary function. No associations were found between perinatal/neonatal variables and lung function parameters in the VLBWPI group. Although the difference was not significant, the level of physical activity was slightly higher in the VLBWPI group than in the control group. Conclusions: Among the schoolchildren evaluated here, neither growth nor lung function appear to have been affected by prematurity birth weight, or level of physical activity.

RESUMO Objetivo: Comparar o crescimento somático, a função pulmonar e o nível de atividade física entre escolares nascidos prematuros com muito baixo peso e escolares nascidos a termo e com peso adequado. Métodos: Foram recrutados escolares com idade de 8 a 11 anos residentes na mesma área de abrangência do estudo: prematuros e com peso < 1.500 g e controles (nascidos a termo e com peso ≥ 2.500 g). Foram obtidas medidas antropométricas e espirométricas e aplicado um questionário sobre a atividade física. Além disso, foram coletadas informações do período perinatal/neonatal dos recém-nascidos com muito baixo peso (RNMBP) de seus prontuários médicos. Resultados: Dos 93 escolares avaliados, 48 crianças no grupo RNMBP e 45 no grupo controle. Não houve diferenças significativas entre os grupos em relação às características antropométricas e nutricionais ou aos parâmetros de função pulmonar. Não foram encontradas associações entre as variáveis perinatais/neonatais e parâmetros da função pulmonar dos escolares no grupo RNMBP. Embora sem diferença significativa em relação aos níveis de atividade física, o grupo RNMBP apresentou uma tendência de ser mais ativo que o grupo controle. Conclusões: Nos escolares aqui estudados o crescimento e a função pulmonar parecem não ser afetados por prematuridade, peso ao nascimento ou nível de atividade física.

Prediction equations for spirometry in four- to six-year-old children / Equações de predição da espirometria em crianças de quatro a seis anos

Abstract Objective To generate prediction equations for spirometry in 4- to 6-year-old children. Methods Forced vital capacity, forced expiratory volume in 0.5 s, forced expiratory volume in one second, peak expiratory flow, and forced expiratory flow at 25–75% of the forced vital capacity were assessed in 195 healthy children residing in the town of Sete Lagoas, state of Minas Gerais, Southeastern Brazil. The least mean squares method was used to derive the prediction equations. The level of significance was established as p < 0.05. Results Overall, 85% of the children succeeded in performing the spirometric maneuvers. In the prediction equation, height was the single predictor of the spirometric variables as follows: forced vital capacity = exponential [(−2.255) + (0.022 × height)], forced expiratory volume in 0.5 s = exponential [(−2.288) + (0.019 × height)], forced expiratory volume in one second = exponential [(−2.767) + (0.026 × height)], peak expiratory flow = exponential [(−2.908) + (0.019 × height)], and forced expiratory flow at 25–75% of the forced vital capacity = exponential [(−1.404) + (0.016 × height)]. Neither age nor weight influenced the regression equations. No significant differences in the predicted values for boys and girls were observed. Conclusion The predicted values obtained in the present study are comparable to those reported for preschoolers from both Brazil and other countries.

Resumo Objetivo Gerar equações de predição da espirometria em crianças de quatro a seis anos. Métodos Capacidade vital forçada, volume expiratório forçado em 0,5 segundo, volume expiratório forçado em um segundo, pico de fluxo expiratório e fluxo expiratório forçado com 25-75% da capacidade vital forçada foram avaliados em 195 crianças saudáveis que residem em Sete Lagoas, Estado de Minas Gerais, Sudeste do Brasil. O método dos mínimos quadrados foi usado para derivar as equações de predição. O nível de significância foi estabelecido como p < 0,05. Resultados No geral, 85% das crianças foram bem-sucedidas ao fazer as manobras espirométricas. Na equação de predição, a estatura foi a única variável preditora das variáveis espirométricas, da seguinte forma: capacidade vital forçada = exponencial [(-2,255) + (0,022 x estatura)], volume expiratório forçado em 0,5 segundo = exponencial [(-2,288) + (0,019 x estatura)], volume expiratório forçado em um segundo = exponencial [(-2,767) + (0,026 x estatura)], pico do fluxo expiratório = exponencial [(-2,908) + (0,019 x estatura)] e fluxo expiratório forçado com 25-75% da capacidade vital forçada = exponencial [(-1,404) + (0,016 x estatura)]. Nem a idade nem o peso influenciaram as equações de regressão. Não foi observada diferença significativa nos valores previstos em meninos e meninas. Conclusão Os valores previstos obtidos neste estudo são comparáveis àqueles relatados em crianças em idade pré-escolar tanto do Brasil quanto de outros países.

Evaluating bronchodilator response in pediatric patients with post-infectious bronchiolitis obliterans: use of different criteria for identifying airway reversibility / Avaliação da resposta ao broncodilatador em pacientes pediátricos com bronquiolite obliterante pós-infecciosa: uso de diferentes critérios de identificação de reversibilidade das vias aéreas

ABSTRACT Objective: Post-infectious bronchiolitis obliterans (PIBO) is a clinical entity that has been classified as constrictive, fixed obstruction of the lumen by fibrotic tissue. However, recent studies using impulse oscillometry have reported bronchodilator responses in PIBO patients. The objective of this study was to evaluate bronchodilator responses in pediatric PIBO patients, comparing different criteria to define the response. Methods: We evaluated pediatric patients diagnosed with PIBO and treated at one of two pediatric pulmonology outpatient clinics in the city of Porto Alegre, Brazil. Spirometric parameters were measured in accordance with international recommendations. Results: We included a total of 72 pediatric PIBO patients. The mean pre- and post-bronchodilator values were clearly lower than the reference values for all parameters, especially FEF25-75%. There were post-bronchodilator improvements. When measured as mean percent increases, FEV1 and FEF25-75%, improved by 11% and 20%, respectively. However, when the absolute values were calculated, the mean FEV1 and FEF25-75% both increased by only 0.1 L. We found that age at viral aggression, a family history of asthma, and allergy had no significant effects on bronchodilator responses. Conclusions: Pediatric patients with PIBO have peripheral airway obstruction that is responsive to treatment but is not completely reversible with a bronchodilator. The concept of PIBO as fixed, irreversible obstruction does not seem to apply to this population. Our data suggest that airway obstruction is variable in PIBO patients, a finding that could have major clinical implications.

RESUMO Objetivo: A bronquiolite obliterante pós-infecciosa (BOPI) é uma entidade clínica que tem sido classificada como obstrução fixa e constritiva do lúmen por tecido fibrótico. Entretanto, estudos recentes utilizando oscilometria de impulso relataram resposta ao broncodilatador em pacientes com BOPI. O objetivo deste estudo foi avaliar a resposta broncodilatadora em pacientes pediátricos com BOPI, comparando critérios diferentes para a definição da resposta. Métodos: Foram avaliados pacientes pediátricos com diagnóstico de BOPI tratados em um de dois ambulatórios de pneumologia pediátrica na cidade de Porto Alegre (RS). Parâmetros espirométricos foram medidos de acordo com recomendações internacionais. Resultados: Foram incluídos 72 pacientes pediátricos com BOPI no estudo. As médias dos valores pré- e pós-broncodilatador foram claramente inferiores aos valores de referência para todos os parâmetros, especialmente FEF25-75%. Houve uma melhora pós-broncodilatador. Quando medidos como aumentos percentuais médios, VEF1 e FEF25-75% melhoraram em 11% e 20%, respectivamente. Entretanto, quando os valores absolutos foram calculados, as médias de VEF1 e FEF25-75% aumentaram somente em 0,1 l. Verificamos que a idade da agressão viral, história familiar de asma e alergia não tiveram efeitos significativos na resposta ao broncodilatador. Conclusões: Pacientes pediátricos com BOPI têm uma obstrução das vias aéreas periféricas que responde ao tratamento, mas não uma reversão completa com o broncodilatador. O conceito de BOPI como obstrução fixa e irreversível parece não se aplicar a essa população. Nossos dados sugerem que a obstrução de vias aéreas em pacientes com BOPI é variável, e esse achado pode ter importantes implicações clínicas.