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Introduction: Streptococcus pneumoniae colonization patterns are influenced by host and environmental factors, which may be related to Invasive Pneumococcal Disease (IPD). Interestingly, COVID-19 pandemic witnessed a decline in the incidence of IPDs. Investigations with diligent data collection on the prevalence of nasopharyngeal colonization and associated serotypes during this unique period can yield novel insights. The aim of the current study was to assess the prevalence of S. pneumoniae carriage among children and adults who have sought care at emergency departments with suspected COVID-19. Methods: In this cross-sectional study, adults and children presenting with signs and symptoms likely associated with COVID-19 in two outpatient clinics in Southern Brazil were invited to participate. RT-PCR with a comprehensive molecular panel for pneumococcal identification of the 21 most prevalent serotypes in Latin America was performed on all enrolled subjects. Prevalence of pneumococcal carriage was assessed in the age groups (< 2, ≥ 2–5, ≥ 5–11, ≥ 11–18, ≥ 18–60, ≥ 60). Results: A total of 1644 subjects were included in the study. Pneumococcal carriage was detected by PCR testing in 14.9% (245/1,644), and serotype identification occurred in 42.0% (103/245) of the participants, with a total frequency of 111. The most frequent serotype identified was 19A (25.2%, n = 28/111), followed by 6C/6D (17.1%, n = 19/111), and 23A (11.7%, n = 13/111), also highlighting the high frequency of non-vaccine serotypes found across all age groups. Discussion: 19A serotype, as well other most frequent serotypes identified are not covered by the PCV-10 in a community setting where PCV-10 is widely available. This finding reinforces the need for continuous surveillance to determine the impact of pneumococcal vaccination and guide public health decision-making. High 19A serotype prevalence is critical in the decision-making process for electing the best options for pneumococcal conjugate vaccines.

Abstract Respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory tract infection in young children and the second leading cause of infant death worldwide. While global circulation has been extensively studied for respiratory viruses such as seasonal influenza, and more recently also in great detail for SARS-CoV-2, a lack of global multi-annual sampling of complete RSV genomes limits our understanding of RSV molecular epidemiology. Here, we capitalise on the genomic surveillance by the INFORM-RSV study and apply phylodynamic approaches to uncover how selection and neutral epidemiological processes shape RSV diversity. Using complete viral genome sequences, we show similar patterns of site-specific diversifying selection among RSVA and RSVB and recover the imprint of non-neutral epidemic processes on their genealogies. Using a phylogeographic approach, we provide evidence for air travel governing the global patterns of RSVA and RSVB spread, which results in a considerable degree of phylogenetic mixing across countries. Our findings highlight the potential of systematic global RSV genomic surveillance for transforming our understanding of global RSV spread.

BackgroundPersistent symptoms and exercise intolerance have been reported after COVID-19, even months after the acute disease. Although, the long-term impact on exercise capacity and health-related quality of life (HRQoL) is still unclear.Research questionTo assess the long-term functional capacity and HRQoL in patients hospitalized due to COVID-19.Study design and methodsThis is a prospective cohort study, conducted at two centers in Brazil, that included post-discharge COVID-19 patients and paired controls. The cohort was paired by age, sex, body mass index and comorbidities, using propensity score matching in a 1:3 ratio. Patients were eligible if signs or symptoms suggestive of COVID-19 and pulmonary involvement on chest computed tomography. All patients underwent cardiopulmonary exercise testing (CPET) and a HRQoL questionnaire (SF-36) 6 months after the COVID-19. The main outcome was the percentage of predicted peak oxygen consumption (ppVO2). Secondary outcomes included other CPET measures and HRQoL.ResultsThe study sample comprised 47 post-discharge COVID-19 patients and 141 healthy controls. The mean age of COVID-19 patients was 54 ± 14 years, with 19 (40%) females, and a mean body mass index of 31 kg/m2 (SD, 6). The median follow-up was 7 months (IQR, 6.5–8.0) after hospital discharge. PpVO2 in COVID-19 patients was lower than in controls (83% vs. 95%, p = 0.002) with an effect size of 0.38 ([95%CI], 0.04–0.70). Mean peak VO2 (22 vs. 25 mL/kg/min, p = 0.04) and OUES (2,122 vs. 2,380, p = 0.027) were also reduced in the COVID-19 patients in comparison to controls. Dysfunctional breathing (DB) was present in 51%. HRQoL was significantly reduced in post COVID patients and positively correlated to peak exercise capacity.InterpretationHospitalized COVID-19 patients presented, 7 months after discharge, with a reduction in functional capacity and HRQoL when compared to historical controls. HRQoL were reduced and correlated with the reduced peak VO2 in our population.

Introdução: O Streptococcus pneumoniae é uma das principais bactérias associadas a coinfecções virais. Informações quanto à colonização pneumocócica e coinfecções são limitadas, incluindo uma possível associação com SARS-CoV-2. O objetivo deste estudo foi descrever as frequências de colonização de S. pneumoniae e identificação outros agentes respiratórios patogênicos comuns, durante o primeiro ano da pandemia de COVID-19. Métodos: Estudo observacional prospectivo em participantes com idade >10 anos, com sintomas respiratórios, entre maio e novembro/2020. Foi realizado um painel respiratório abrangente para detecção de agentes respiratórios por RT-PCR, e nos positivos para S. pneumoniae seguiu-se com a identificação de 21 sorotipos. Foram coletadas informações clínicas e dados sobre gravidade/hospitalização. Resultados: Foram incluídos 1.297 participantes; a idade mediana foi de 36,8 anos (IQR = 27,5-47,3). 134/1.297 (10,3%) participantes estavam colonizados por S. pneumoniae e 33/134 (26,4%) tiveram sorotipos identificados. O sorotipo 19A foi o mais prevalente (21,2%, 7/33), seguido por: 23A (15,2%, 5/33) e 6C/6D (12,1%, 4/33). Os principais patógenos respiratórios identificados foram SARS-CoV-2 (36,4%, 472/1.296), rinovírus (34,8%, 449/1.291), Mycoplasma pneumoniae (1,4%, 18/1.291), e em menor percentual coronavírus HKU1 e NL63, enterovírus, metapneumovírus, adenovírus, representando 1,9% (25/1.291). A detecção de rinovírus foi associada à não-colonização pneumocócica (p < 0,001), enquanto que nos outros patógenos detectados não houve associação significativa para colonização. Não foram detectados: Bordetella pertussis, bocavírus; coronavírus (229E e OC43); vírus influenza A (H1 e H3); vírus influenza B; vírus parainfluenza (1, 2 e 3); e vírus sincicial respiratório (A e B). Não houve associação entre gravidade clínica e colonização pneumocócica. 5,5% (71/1.297) indivíduos foram hospitalizados; 4% (46/1.297) precisaram de oxigênio suplementar e houve 1% (15/1.297) de óbitos. 14,3% (185/1.297) referiram uso de antibióticos na semana anterior à inclusão no estudo, sendo que 94% (173/185) não eram colonizados (p = 0,049). Conclusão: Não houve associação da colonização com patógenos respiratórios ou desfechos por hospitalização. O sorotipo 19A foi o mais prevalente nessa população, sendo um potencial agente de infecção invasiva. A avaliação da prevalência é fundamental para monitorar o cenário epidemiológico e orientar a tomada de decisões em saúde pública.

Introdução: Streptococcus pneumoniae é um importante colonizador nasofaríngeo, e potencial causador de infecções graves e invasivas em crianças. Desde 2010, a vacina pneumocócica conjugada 10 (PVC-10) está disponível pelo Programa Nacional de Imunizações. O objetivo deste estudo foi descrever a colonização de S. pneumoniae e identificar outros patógenos durante o primeiro ano da pandemia de COVID-19. Métodos: Foram recrutados em um estudo observacional prospectivo, crianças (≤10 anos) em dois hospitais do Sul do Brasil entre maio e novembro de 2020. A presença de sintomas respiratórios (dor de garganta, tosse e febre ≥37,8°C) foram critérios de inclusão dos participantes. Em todas as amostras coletadas foi realizado um painel para identificação de infecções respiratórias por RT-PCR. Nas amostras positivas para S. pneumoniae foi realizada a identificação dos 21 sorotipos mais prevalentes na América Latina. Foram coletadas informações clínicas e dados sobre vacinação. Resultados: Foram incluídos 347 participantes, com idade mediana de 3,6 anos (IQR: 1,5-7,2). Colonização pneumocócica foi identificada em 111 (32%) crianças. 43/111 (38.7%) tinham

OM-85 is a bacterial lysate from common respiratory tract pathogens, with an excellent safety profile, widely used to prevent recurrent respiratory tract infections. Several studies have been reporting the immunomodulating properties and antiviral roles of OM-85. The COVID-19 pandemic, originating in 2019, has presented a significant global public health crisis. While effective vaccines have been developed, vaccination rates vary considerably, and numerous concerning viral variants continue to emerge. The challenge persists in creating early interventions to halt the progression of the disease to its severe stages. To examine the therapeutic effect of OM-85 after SARS-CoV-2 infection and compared to recombinant human (rhINF-β) we collected nasopharyngeal cells from COVID-19 patients. The cells were treated ex-vivo with OM-85 or hrINF-β and the response was analyzed after 24h for gene expression by real-time PCR. We found that OM-85 decreased the SARS-CoV-2 N1 gene expression and increased RIG-I (DDX58) in these cells. The expression of ACE2 was undetected in these samples. These data support the antiviral effect of OM-85 against SARS-CoV-2.

Objective: Changes in the epidemiology of respiratory infections during the restrictions imposed as a response to the coronavirus disease 2019 (COVID-19) pandemic have been reported elsewhere. The present study's aim was to describe the prevalence of a large array of respiratory pathogens in symptomatic children and adolescents during the pandemic in Southern Brazil. Methods: Hospitalized and outpatients aged 2 months to 18 years with signs and symptoms of acute COVID-19 were prospectively enrolled in the study from May to November 2020 in two hospitals in a large metropolitan area in a Brazilian city. All participants performed a real-time PCR panel assessing 20 respiratory pathogens (three bacteria and 17 viruses). Results: 436 participants were included, with 45 of these hospitalized. Rhinovirus was the most prevalent pathogen (216/436) followed by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, 97/436), with a coinfection of these two viruses occurring in 31/436 participants. The remaining pathogens were found in 24 symptomatic participants (adenovirus, n = 6; Chlamydophila pneumoniae, n = 1; coronavirus NL63, n = 2; human enterovirus, n = 7; human metapneumovirus, n = 2; Mycoplasma pneumoniae, n = 6). Hospitalization was more common among infants (p = 0.004) and those with pathogens other than SARS-CoV-2 (p = 0.001). Conclusion: During the period of social distancing in response to COVID-19, the prevalence of most respiratory pathogens was unusually low. Rhinovirus remained as the main virus co-circulating with SARS-CoV-2. COVID-19 in symptomatic children was less associated with hospitalization than with other respiratory infections in children and adolescents.

ABSTRACT Objective: To evaluate the association between obesity and hospitalization in mild COVID-19 adult outpatients in Brazil. Subjects and methods: Adults with signs and symptoms suggestive of acute SARS-CoV-2 infection who sought treatment in two hospital (public and private) emergency departments were prospectively enrolled. Patients with confirmed COVID-19 at inclusion were followed by phone calls at days D7, D14 and D28. Multivariable logistic regression models were employed to explore the association between obesity and other potential predictors for hospitalization. Results: A total of 1,050 participants were screened, and 297 completed the 28-day follow-up and were diagnosed with COVID-19 by RT-PCR. The median age was 37.2 (IQR 29.7-44.6) years, and 179 (60.0%) were female. The duration of symptoms was 3.0 (IQR 2.0-5.0) days, and 10.0 (IQR 8.0-12.0) was the median number of symptoms at inclusion. Ninety-five (32.0%) individuals had obesity, and 233 (78.5%) had no previous medical conditions. Twenty-three participants (7.7%) required hospitalization during the follow-up period. After adjusting, obesity (BMI ≥ 30.0 kg/m2) (OR = 2.69, 95% CI 1.63-4.83, P < 0.001) and older age (OR = 1.05, 95% CI 1.01-1.09, P < 0.001) were significantly associated with higher risks of hospitalization. Conclusion: Obesity, followed by aging, was the main factor associated with hospital admission for COVID-19 in a young population in a low-middle income country. Our findings highlighted the need to promote additional protection for individuals with obesity, such as vaccination, and to encourage lifestyle changes.

Abstract Background The World Health Organization recommends tuberculosis (TB) preventive treatment (TPT) for all people living with HIV (PLH) and household contacts (HHC) of index TB patients. Tests for TB infection (TBI) or to rule out TB disease (TBD) are preferred, but if not available, this should not be a barrier if access to these tests is limited for high-risk people, such as PLH and HHC under 5 years old. There is equipoise on the need for these tests in different risk populations, especially HHC aged over 5. Methods This superiority cluster-randomized multicenter trial with three arms of equal size compares, in Benin and Brazil, three strategies for HHC investigation aged 0–50: (i) tuberculin skin testing (TST) or interferon gamma release assay (IGRA) for TBI and if positive, chest X-Ray (CXR) to rule out TBD in persons with positive TST or IGRA; (ii) same as (i) but GeneXpert (GX) replaces CXR; and (iii) no TBI testing. CXR for all; if CXR is normal, TPT is recommended. All strategies start with symptom screening. Clusters are defined as HHC members of the same index patients with newly diagnosed pulmonary TBD. The main outcome is the proportion of HHC that are TPT eligible who start TPT within 3 months of the index TB patient starting TBD treatment. Societal costs, incidence of severe adverse events, and prevalence of TBD are among secondary outcomes. Stratified analyses by age (under versus over 5) and by index patient microbiological status will be conducted. All participants provide signed informed consent. The study was approved by the Research Ethic Board of the Research Institute of the McGill University Health Centre, the Brazilian National Ethical Board CONEP, and the “Comité Local d’Éthique Pour la Recherche Biomédicale (CLERB) de l’Université de Parakou,” Benin. Findings will be submitted for publication in major medical journals and presented in conferences, to WHO and National and municipal TB programs of the involved countries. Discussion This randomized trial is meant to provide high-quality evidence to inform WHO recommendations on investigation of household contacts, as currently these are based on very low-quality evidence. Trial registration ClinicalTrials.gov NCT04528823.

Objective: to evaluate the accuracy of an antibody point-of-care lateral flow immunoassay (LFI - Wondfo Biotech Co., Guangzhou, China) in a pediatric population. Methods: children and adolescents (2 months to 18 years) with signs and symptoms suggestive of acute SARS-CoV-2 infection were prospectively investigated with nasopharyngeal RT-PCR and LFI at the emergency room. RT-PCR was performed at baseline, and LFI at the same time or scheduled for those with less than 7 days of the clinical picture. Overall accuracy, sensitivity and specificity were assessed, as well as according to the onset of symptoms (7-13 or ≥14 days) at the time of the LFI test. Results: In 175 children included, RT-PCR and LFI were positive in 51 (29.14%) and 36 (20.57%), respectively. The overall sensitivity, specificity, positive and negative predictive value was 70.6% (95%CI 56.2-82.5), 96.8% (95%CI 91.9-99.1), 90.0% (95%CI 77.2-96.0), and 88.9% (95%CI 83.9-92.5), respectively. At 7-13 and ≥14 days after the onset of symptoms, sensitivity was 60.0% (95%CI 26.2-87.8) and 73.2% (95%CI 57.1-85.8) and specificity was 97.9% (95%CI 88.7-99.9) and 96.1% (95%CI 89.0-99.2), respectively. Conclusion: Despite its high specificity, in the present study the sensitivity of LFI in children was lower (around 70%) than most reports in adults. Although a positive result is informative, a negative LFI test cannot rule out COVID-19 in children.

Children often show milder COVID-19 symptoms, but the underlying mechanistic insights are still lacking. Here the authors profile both pediatric and adult cohorts of COVID-19 patients in Brazil to find that children exhibit higher viral load but stronger and biased cellular immunity, thereby serving clues for the differential responses in children.

This is the third year of the SARS-CoV-2 pandemic, and yet most children remain unvaccinated. COVID-19 in children manifests as mostly mild or asymptomatic, however high viral titers and strong cellular and humoral responses are observed upon acute infection. It is still unclear how long these responses persist, and if they can protect from re-infection and/or disease severity. Here, we analyzed immune memory responses in a cohort of children and adults with COVID-19. Important differences between children and adults are evident in kinetics and profile of memory responses. Children develop early N-specific cytotoxic T cell responses, that rapidly expand and dominate their immune memory to the virus. Children’s anti-N, but not anti-S, antibody titers increase over time. Neutralization titers correlate with N-specific antibodies and CD8+T cells. However, antibodies generated by infection do not efficiently cross-neutralize variants Gamma or Delta. Our results indicate that mechanisms that protect from disease severity are possibly different from those that protect from reinfection, bringing novel insights for pediatric vaccine design. They also underline the importance of vaccination in children, who remain at risk for COVID-19 despite having been previously infected.

Respiratory syncytial virus (RSV) is a seasonal pathogen responsible for the highest percentage of viral bronchiolitis in pediatric patients. There are currently no vaccine available and therapeutic methods to mitigate the severity of RSV bronchiolitis are limited. OM-85, an oral standardized bacterial lysate isolated from human respiratory strains and widely used to prevent recurrent infections and/or exacerbations in populations at risk, has been shown to be effective and safe in children and adults. Here, we demonstrate that airway administration of OM-85 in Balb/c mice prior to infection prevents RSV-induced disease, resulting in inhibition of viral replication associated with less perivascular and peribronchial inflammation in the lungs. These protective effects are dose and time-dependent with complete protection using 1mg dose of OM-85 only four times intranasally. Mechanistic insights using this topical route in the airways revealed increased alveolar macrophages, a selective set of tolerogenic DCs, Treg and Th1 expansion in the lung, even in the absence of infection, contributing to a better Th1/Th2 balance and preventing ILC2 recruitment in the airways and associated inflammatory sequelae. OM-85 preventive treatment also improved antiviral response by increasing IFNβ and its responsive genes in the lung. In vitro, OM-85 protects against RSV infection in a type I interferon pathway. Our animal model data suggest that intranasal use of OM-85 should be considered as a potential prophylactic product to prevent RSV bronchiolitis once human studies confirm these findings.

Abstract Background Respiratory syncytial virus (RSV) is a global cause of severe respiratory morbidity and mortality in infants. While preventive and therapeutic interventions are being developed, including antivirals, vaccines and monoclonal antibodies, little is known about the global molecular epidemiology of RSV. INFORM is a prospective, multicenter, global clinical study performed by ReSViNET to investigate the worldwide molecular diversity of RSV isolates collected from children less than 5 years of age. Methods The INFORM study is performed in 17 countries spanning all inhabited continents and will provide insight into the molecular epidemiology of circulating RSV strains worldwide. Sequencing of > 4000 RSV-positive respiratory samples is planned to detect temporal and geographical molecular patterns on a molecular level over five consecutive years. Additionally, RSV will be cultured from a subset of samples to study the functional implications of specific mutations in the viral genome including viral fitness and susceptibility to different monoclonal antibodies. Discussion The sequencing and functional results will be used to investigate susceptibility and resistance to novel RSV preventive or therapeutic interventions. Finally, a repository of globally collected RSV strains and a database of RSV sequences will be created.

Objectives: The present study provides a comprehensive review of the recently published data on RSV epidemiology in adults and the elderly in Latin America. Methods: A systematic literature search was carried out in Medline, Scielo, Lilacs, and Cochrane Library. The search strategy aimed at retrieving studies focusing on RSV prevalence, burden, risk factors, and the routine clinical practice in the prevention and management of RSV infections in Latin American countries. Only articles published between January 2011 and December 2017 were considered. Results: Eighteen studies were included. Percentages of RSV detection varied highly across included studies for adult subjects with respiratory infections (0% to 77.9%), influenza-like illness (1.0% to 16.4%) and community-acquired pneumonia (1.3% to 13.5%). Considerable percentages of hospitalization were reported for RSV-infected adults with influenza-like illness (40.9% and 69.9%) and community-acquired pneumonia (91.7%). Conclusions: Recent RSV data regarding adult populations in Latin America are scarce. RSV was documented as a cause of illness in adults and the elderly, being identified in patients with acute respiratory infections, influenza-like illness and community-acquired pneumonia. The studies suggest that RSV infections may be a significant cause of hospitalization in adult populations in Latin America, including younger adults. Keywords: Respiratory Syncytial Virus, Burden, Adults, Latin America, Upper respiratory tract infections

Summary: Background: Gut microbiota-derived short-chain fatty-acid (SFCA) acetate protects mice against RSV A2 strain infection by increasing interferon-β production and expression of interferon-stimulated genes (ISGs). However, the role of SFCA in RSV infection using strains isolated from patients is unknown. Methods: We first used RSV clinical strains isolated from infants hospitalized with RSV bronchiolitis to investigate the effects of in vitro SCFA-acetate treatment of human pulmonary epithelial cells. We next examined whether SCFA-acetate treatment is beneficial in a mouse model of RSV infection using clinical isolates. We sought to investigate the relationship of gut microbiota and fecal acetate with disease severity among infants hospitalized with RSV bronchiolitis, and whether treating their respiratory epithelial cells with SCFA-acetate ex-vivo impacts viral load and ISG expression. We further treated epithelial cells from SARS-CoV-2 infected patients with SCFA-acetate. Findings: In vitro pre-treatment of A549 cells with SCFA-acetate reduced RSV infection with clinical isolates and increased the expression of RIG-I and ISG15. Animals treated with SCFA-acetate intranasally recovered significantly faster, with reduction in the RSV clinical isolates viral load, and increased lung expression of IFNB1 and the RIG-I. Experiments in RIG-I knockout A549 cells demonstrated that the protection relies on RIG-I presence. Gut microbial profile was associated with bronchiolitis severity and with acetate in stool. Increased SCFA-acetate levels were associated with increasing oxygen saturation at admission, and shorter duration of fever. Ex-vivo treatment of patients’ respiratory cells with SCFA-acetate reduced RSV load and increased expression of ISGs OAS1 and ISG15, and virus recognition receptors MAVS and RIG-I, but not IFNB1. These SCFA-acetate effects were not found on cells from SARS-CoV-2 infected patients. Interpretation: SCFA-acetate reduces the severity of RSV infection and RSV viral load through modulation of RIG-I expression. Funding: FAPERGS (FAPERGS/MS/CNPq/SESRS no. 03/2017 - PPSUS 17/2551-0001380-8 and COVID-19 20/2551-0000258-6); CNPq 312504/2017-9; CAPES) - Finance Code 001.

Introdução/Objetivo: Os fatores associados ao risco de hospitalização por COVID19 não são completamente conhecidos. O objetivo deste estudo foi descrever o risco de hospitalização dos participantes ambulatoriais com diagnóstico exclusivo para rinovírus, SARS-CoV-2 e codetecção entre esses dois agentes, durante a pandemia no sul do Brasil. Métodos: Participantes ambulatoriais (> 18 anos) com sinais agudos de tosse, febre ou dor de garganta foram recrutados prospectivamente nas tendas de atendimento do Hospital Moinhos de Vento e Hospital Restinga e Extremo Sul, entre maio e novembro de 2020, e foram acompanhados por 28 dias através de entrevistas telefônicas. Para a detecção de SARS-CoV-2 bem como para o painel respiratório, foi utilizada a técnica de RT-PCR. Para detecção de SARS-CoV-2 foi utilizado kit TaqManTM 2019-nCoV Assay Kit v1 (genes S, N e ORF1ab) a partir de swabs orofaríngeo e nasofaríngeo bilateral. Em coleta de outro swab nasofaríngeo foi realizado painel respiratório para detecção de: Bordetella pertussis; Chlamydophila pneumoniae; Mycoplasma pneumoniae; adenovírus; bocavírus; coronavírus tipos HKU1, 229E, NL63 e OC43; vírus influenza A tipos H1 e H3; vírus influenza B; enterovírus humano; metapneumovírus humano; vírus parainfluenza tipos 1, 2 e 3; RSV tipos A e B; e rinovírus). Todas as amostras foram analisadas no Laboratório de Biologia Molecular do Hospital Moinhos de Vento. Resultados: Foram recrutados 609 participantes, com idade mediana de 36 anos, sendo a maioria mulheres (63,2%). 282 (46,4%) participantes tiveram detectado apenas rinovírus, seguido por 234 (38,4%) com SARS-CoV-2 exclusivamente. A codetecção entre estes dois agentes ocorreu em 93 (15,3%) dos 608 participantes. Deste total, 26 (4,3%) participantes necessitaram hospitalização após a busca por atendimento ambulatorial. Participantes com codetecção viral apresentaram maior proporção de hospitalização quando comparados aos participantes com SARS-CoV-2 e rinovírus detectados como agentes únicos (9,7% (9/93) vs 6,8% (16/234) vs 0,4% (1/282), p < 0.001). Entretanto, quando comparadas as proporções de coinfecção com SARS-CoV-2 (como agente único), a diferença não é significativa (9,7% (9/93) vs 6,8% (16/234), p = 0.373). Conclusão: O rinovírus foi o principal patógeno detectado em adultos, e apesar da alta prevalência não foi associado ao aumento na hospitalização, sendo o maior risco atribuído à detecção de SARS-CoV-2 nessa população.

Introdução/Objetivo: Apesar do predomínio do SARS-CoV-2 como etiologia das infecções virais em adultos durante o ano de 2020, outros agentes infecciosos podem fazer parte do diagnóstico diferencial. O objetivo deste estudo foi descrever a prevalência dos patógenos respiratórios em adultos internados em dois hospitais no sul do Brasil durante a pandemia e comparar os desfechos de gravidade na internação entre participantes com diagnóstico de COVID-19 comparado com outros agentes infecciosos. Métodos: Participantes adultos (> 18 anos) hospitalizados com sinais agudos de tosse, febre ou dor de garganta foram recrutados prospectivamente entre maio e novembro de 2020, e seguidos até o final da internação. A técnica de RT-PCR foi utilizada para detecção de SARS-CoV-2 e demais agentes infecciosos. Para SARS-CoV-2 foram coletados swabs oro e nasofaríngeo bilateral tendo como alvos os genes S, N e ORF1ab. Outro swab nasofaríngeo foi coletado para realização de painel respiratório através sondas de expressão gênica que avaliou a presença de: Bordetella pertussis; Chlamydophila pneumoniae; Mycoplasma pneumoniae; adenovírus; bocavírus; coronavírus tipos HKU1, 229E, NL63 e OC43; vírus influenza A tipos H1 e H3; vírus influenza B; enterovírus; metapneumovírus; vírus parainfluenza tipos 1, 2 e 3; RSV tipos A e B; e rinovírus. Todas as amostras foram analisadas no Laboratório de Biologia Molecular do Hospital Moinhos de Vento. Resultados: Foram incluídos 156 participantes, sendo a maioria homens (57,1%) com idade mediana de 58 anos. A mediana de dias de sintomas foi 8 dias. O SARS-CoV-2 foi o agente mais prevalente, sendo detectado exclusivamente em 101 (65.0%) de 156 participantes, seguido pela detecção única de rinovírus (4,0%, 6/154). A codetecção desses dois agentes ocorreu em 28 (18,0%) dos 154 participantes. Os demais patógenos (adenovírus, coronavírus HKU1 e enterovírus) foram detectados em 5 participantes. A comparação dos desfechos de gravidade (uso de oxigênio suplementar, ventilação mecânica invasiva e óbito) não apresentou diferença quanto à codetecção versus detecção exclusiva de SARS-CoV-2 (60,7% (17/28) vs 62,4% (63/101), P = 1,00; 21,4% (6/28) vs 15,8% (16/101), P = 0,57; 7,1% (2/28) vs 5,9% (6/101), P = 0,68). Conclusão: O SARS-CoV-2 foi o principal patógeno detectado seguido pelo rinovírus, com uma importante queda na detecção de outros patógenos. A detecção de rinovírus simultânea ao SARS-CoV-2 não foi associada a maior gravidade.

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

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

Abstract Background Daily inhaled corticosteroids are widely recommended for mild persistent asthma. This study aimed to assess the efficacy of the intermittent use of beclomethasone as an alternative treatment for mild persistent asthma. Methods In this 16-week trial, children aged 6–18 years were evaluated. Subjects in the continuous treatment arm of the study received 500 μg/day of beclomethasone, whereas the intermittent ones were given 1000 μg/day (250 μg every 6 h) in combination with albuterol for 7 days upon exacerbations or worsening of symptoms. Primary outcome (i.e., treatment failure) was the occurrence of any asthma exacerbation requiring prednisone, and co-secondary outcomes were the mean/median differences for both, (1) the pre-bronchodilator FEV1 (% predicted) and (2) asthma control test (ACT/cACT) scores, from randomization to the last follow-up visit, and beclomethasone and albuterol consumption. Results Ninety-four subjects from each treatment arm were included. They were comparable regarding all baseline characteristics; prednisone was used by 10 (10.6%) and 7 (7.4%) patients, respectively (95% CI − 6.1 to 12.6%, for the difference; p = 0.47). Statistical analysis showed no statistically significant differences with respect to both FEV1 (p = 0.39) and ACT/cACT scores (p = 0.38). As assessed through canister weighting, children used from 0.5 to 0.7 and from 1.6 to 1.8 puffs per day of beclomethasone in the intermittent and continuous regimens, respectively. Regarding albuterol, received 0.3–0.4 (intermittent) and 0.1–0.2 (continuous) inhalations per day. There were no relevant clinical or functional differences between the two treatment regimens. Conclusion Clinicians might consider intermittent inhaled steroid therapy as a therapeutic regimen for mild persistent asthma. Trial registration The Portuguese and English versions of the study protocol were submitted, approved, and registered in the Brazilian Network Platform for Clinical Trials (http://www.ensaiosclinicos.gov.br) under the primary identifier number “RBR-3gbyhk”. This platform is part of the Primary Registries in the World Health Organization Registry Network, where the trial is registered under the following Universal Trial Number: 1111-1149-4774

The generation of memory is a cardinal feature of the adaptive immune response, involving different factors in a complex process of cellular differentiation. This process is essential for protecting the second encounter with pathogens and is the mechanism by which vaccines work. Epigenetic changes play important roles in the regulation of cell differentiation events. There are three types of epigenetic regulation: DNA methylation, histone modification, and microRNA expression. One of these epigenetic changes, DNA methylation, occurs in cytosine residues, mainly in CpG dinucleotides. This brief review aimed to analyse the literature to verify the involvement of DNA methylation during memory T and B cell development. Several studies have highlighted the importance of the DNA methyltransferases, enzymes that catalyse the methylation of DNA, during memory differentiation, maintenance, and function. The methylation profile within different subsets of naïve activated and memory cells could be an interesting tool to help monitor immune memory response.

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

Abstract Background Advances in juvenile idiopathic arthritis (JIA) treatment is promoting free disease survival. Cardiovascular disease (CVD) may emerge as an important cause of morbidity and mortality. Pulse wave velocity (PWV), a surrogate marker of arterial stiffness, and telomere length (TL) are considered as potential predictors of CVD and its outcomes. The study aim was to assess PWV, TL in a JIA population and to test its correlation. In a cross sectional study, 24 JIA patients, 21 controls for TL and 20 controls for PWV were included. PWV was assessed by an oscillometric device. TL was assessed by qPCR. JIA activity was accessed by JADAS-27. Smoking, diabetes, obesity, renal impairment, hypertension, dyslipidemia and inflammatory diseases were excluded. Findings Between cases and controls for TL, there was significant difference in age. No differences in gender, ethnics and bone mass index between JIA and control groups for PWV and TL. The JADAS-27 median was 8. TL was significantly reduced in JIA (0.85 ± 0.34 vs. 1. 67 ± 1.38, P = 0.025). When age adjusted by ANCOVA, the difference remained significant (P = 0,032). PWV was normal in all patients (5.1 ± 0.20 m/s vs. 4.98 ± 0.06 m/s, P = 0, 66). There was no correlation between TL, PWV or JADAS-27. Conclusion Compared to controls, JIA with high disease activity and no CVD risk factors have shorter telomeres and normal PWV. As far as we know, this first time this correlation is being tested in rheumatic disease and in paediatrics.

The 2010 Global Burden of Disease estimates indicate a trend toward increasing years lived with disability from chronic noncommunicable diseases (NCDs). Risk factors examined included smoking, diet, alcohol, drug abuse, and physical inactivity. By contrast, little consideration was given to accumulating evidence that exposures to environmental chemicals, psychosocial stress, and malnutrition during fetal development and across the life span also increase risk of NCDs. To address this gap, we undertook a narrative review of early-life environmental contributions to disease. We documented numerous etiologicassociations. We propose that future GBD estimates use an expanded approach for assessing etiologic contributions of environmental exposures to recognized disease risk factors. We argue that broadening the definition of environmental disease, together with improved methods of assessing early life exposures and their health outcomes across the life span, will allow better understanding of causal associations and provide the incentives required to support strategies to control avoidable exposures and reduce disease risk.

Despite overall progress toward achieving the Millennium Development Goals, large health discrepancies persist between developed and developing countries. The world is rapidly changing and the influences of societal change and climate change will disproportionately affect the world's most vulnerable populations, thus exacerbating current inequities. Current development strategies do not adequately address these disproportionate impacts of environmental exposures. The aim of this study was to propose a new framework to address the health consequences of environmental exposures beyond 2015. This framework is transdisciplinary and precautionary. It is based on identifying social and economic determinants of health, strengthening primary health systems, and improving the health of vulnerable populations. It incorporates deliberate plans for assessment and control of avoidable environmental exposures. It sets specific, measurable targets for health and environmental improvement.

Numerous preventive strategies against respiratory syncytial virus (RSV) are undergoing late stage evaluation in humans and, in addition to their intended benefit for acute illness, may impact long term consequences of infection in infants. Severe RSV infection has been repeatedly associated in the literature with long term complications, including impaired lung function, recurrent wheezing, and asthma. However, whether RSV lower respiratory tract infection (LRTI) causally affects the odds for developing wheezing and/or asthma during childhood requires further study, and the biological mechanisms underlying this hypothetical progression from viral illness to chronic lung disease are poorly characterized. In this review, we summarize the literature exploring the association between RSV LRTI in infancy and subsequent recurrent wheezing and pediatric asthma.

BackgroundAn increase in the prevalence of overweight and asthma has been observed. Both conditions affect negatively lung function in adults and children. The aim of this study was to analyze the effect of overweight and asthma on lung function in children.MethodsWe designed a case–control study of healthy and asthmatic subjects nested within an epidemiological asthma prevalence study in children between 8 and 16 years of age. The effect of asthma and overweight on lung function was assessed by impulse oscillometry and spirometry obtained at baseline and 10–15 min after salbutamol.Results188 children were recruited, 114 (61%) were asthmatics and 72 (38%) were overweight or obese. Children with asthma and overweight had a higher FVC (+1.16 z scores, p

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

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

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

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

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

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

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

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

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