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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.

BACKGROUND AND OBJECTIVE: The knowledge about the impact of the nonpharmacological measures to control the COVID-19 pandemic can give insight into ways in which they can also be applied for other respiratory diseases. To assess the impact of containment measures of the COVID-19 pandemic on pneumonia hospitalizations in children from 0 to 14 years of age in Brazil. METHODS: Data from hospital admissions for pneumonia were obtained from the Department of Informatics of Brazilian Public Health System database in the period of 2015-2020 and analyzed by macroregions and age groups. To evaluate the effect of containment measures, on the incidence of pneumonia, the absolute reduction and relative reduction were calculated by analyzing the subsets 2015-2019 vs. 2020. RESULTS: Comparing the subsets of April-August 2015-2019 vs. April-August 2020 for Brazil (total), there was an significant reduction in the average incidence of hospitalizations, with numbers ranging from -82% [IRR 0.17 (0.14-0.21)] for

Background Interventions to tackle the coronavirus disease 2019 (COVID-19) pandemic may affect the burden of other respiratory diseases. Considering the repercussions of these unique social experiences to infant health, this study aims to assess the early impact of social distancing due to the COVID-19 pandemic in hospital admissions for acute bronchiolitis. Methods Data from hospitalizations of acute bronchiolitis in infants Results There was a significant reduction in all comparisons, ranging from −78% (incidence rate ratio [IRR], 0.22 [95% confidence interval {CI}, .20–.24]) in 2016 vs 2020 to −85% (IRR, 0.15 [95% CI, .13–.16]) in 2019 vs 2020, for the data from Brazil. For analyses by macroregions, the reduction varied from −58% (IRR, 0.41 [95% CI, .37–.45]) in the Midwest in 2016 vs 2020 to −93% (IRR, 0.07 [95% CI, .06–.08]) in the South in 2019 vs 2020. Conclusions There was a significant reduction in hospitalization for acute bronchiolitis in children 70% for most analysis. Our data suggest an important impact of social distancing on reducing the transmission of viruses related to acute bronchiolitis. Such knowledge may guide strategies for prevention of viral spread.

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

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.

In 2020, a unique social experience was provided by the pandemic of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2. Interventions to tackle the pandemic may affect the burden of other respiratory diseases.This study aims to assess the impact of the COVID-19 mitigation strategies on hospitalizations for asthma in children aged between 1 and 14 years, adults aged between 20 and 59 years, and elderly older than 60 years.Data from hospital admissions for asthma were obtained from the Department of Informatics of Brazilian Public Health System database in the period between January 2016 and December 2020 and analyzed by age groups. To evaluate the effect of containment measures on the incidence of asthma and respiratory system diseases (total), the absolute reduction and relative reduction were calculated by analyzing the subsets from 2016 to 2019 versus 2020.There was a significant reduction in the average incidence of hospitalizations in 2020, with numbers ranging from -59% (incidence rate ratio, 0.41 [0.37-0.45]) for age 1 to 14 years (prepandemic 1,393.2/100,000 vs pandemic 574.9/100.000), -37% (incidence rate ratio, 0.63 [0.49-0.80]) for age 20 to 59 years (prepandemic 160.2/100,000 vs pandemic 101.1/100,000), and -60% (incidence rate ratio, 0.40 [0.33-0.47]) for older than 60 years (prepandemic 460.6/100,000 vs pandemic 185.3/100,000).Ashtma hospitalizations decreased in 2020, especially in the pediatric group and the older group during the COVID-19 pandemic, which may be associated with the reduction in the incidence of many respiratory viral infections.

Understanding the genetic underpinnings of disabling hearing loss, which affects ∼466 million people worldwide, can provide avenues for new therapeutic target development. We performed a genome-wide association meta-analysis of hearing loss with 125,749 cases and 469,497 controls across five cohorts, including UK Biobank, Geisinger DiscovEHR, the Malmö Diet and Cancer Study, Mount Sinai’s BioMe Personalized Medicine Cohort, and FinnGen. We identified 53 loci affecting hearing loss risk, 15 of which are novel, including common coding variants in COL9A3 and TMPRSS3. Through exome-sequencing of 108,415 cases and 329,581 controls from the same cohorts, we identified hearing loss associations with burden of rare coding variants in FSCN2 (odds ratio [OR] = 1.14, P = 1.9 × 10−15) and burden of predicted loss-of-function variants in KLHDC7B (OR = 2.14, P = 5.2 × 10−30). We also observed single-variant and gene-burden associations with 11 genes known to cause Mendelian forms of hearing loss, including an increased risk in heterozygous carriers of mutations in the autosomal recessive hearing loss genes GJB2 (Gly12fs; OR = 1.21, P = 4.2 × 10−11) and SLC26A5 (gene burden; OR = 1.96, P = 2.8 × 10−17). Our results suggest that loss of KLHDC7B function increases risk for hearing loss, and show that Mendelian hearing loss genes contribute to the burden of hearing loss in the adult population, suggesting a shared etiology between common and rare forms of hearing loss. This work illustrates the potential of large-scale exome sequencing to elucidate the genetic architecture of common traits in which risk is modulated by both common and rare variation.

Background: Asthma control is not well reflected by spirometry, yet this is the most frequently used measure of lung function in asthma clinics. Oscillometry is an alternative technique suitable for those with severe asthma. Objective: To investigate usefulness of oscillometry in subjects with severe asthma to determine which outcome variables best reflected asthma control. Methods: Adults with severe asthma were recruited from a severe asthma clinic in Brazil. Oscillometry (conventional multifrequency measurements between 6 and 32 Hz; intrabreath tracking at 8 Hz) and spirometry were performed. Asthma control was determined by the asthma control test. Results: A total of 60 adults were evaluated; mean age was 56.7 years. There was predominance of women (82%), and most patients (63%) reported onset of asthma symptoms in childhood or adolescence. There were no differences between controlled and uncontrolled asthma in spirometry. Uncontrolled asthma was associated with higher resistance (at 8 and 10 Hz) and more negative reactance (for 6, 8, and 10 Hz) (P < .05) on conventional oscillometry. Intrabreath oscillometry revealed significant differences between controlled and uncontrolled patients with asthma (P < .01 for changes in resistance and reactance between end expiration and end inspiration). The accuracy of the lung function tests in discriminating between controlled and uncontrolled asthma was higher for intrabreath variables (area under the curve = 0.65-0.72). Conclusion: Oscillometry, particularly the intrabreath technique, better reflected asthma control than spirometry measures. Our findings suggest that oscillometry may be a useful technique to aid management of severe asthma, with a potential to reflect loss of disease control.

Primary ciliary dyskinesia (PCD) causes cellular cilia motility alterations, leading to clinical manifestations in the upper and lower respiratory tract and situs abnormalities. The PCD diagnosis was improved after the inclusion of diagnostic tools, such as transmission electron microscopy and genetic screening; however, the PCD screening is a challenge yet. In this context, we aimed to describe the clinical, genetic, and ultra-ciliary characteristics in individuals with clinical suspicion of PCD (cPCD) from a Brazilian Tertiary Hospital. An observational study was carried out with individuals during the follow-up between 2011 and 2021. The individuals were submitted to clinical questionnaires, transmission electron microscopy, and genetic screening for pathogenic variants in PCD-related genes. Those patients were classified according to the degree of suspicion for PCD. In our study, we enrolled thirty-seven cPCD individuals; 20/37 (54.1%) had chronic rhinosinusitis, 28/37 (75.6%) had bronchiectasis, and 29/37 (78.4%) had recurrent pneumonia. A total of 17/37 (45.9%) individuals had transmission electron microscopy or genetic confirmation of PCD; 10 individuals had at least one positive pathogenic genetic variant in the PCD-related genes; however, only seven patients presented a conclusive result according to the American College of Medical Genetics and Genomics and the Association for Molecular Pathology with two pathogenic variants in homozygous or compound heterozygous. The median age at diagnosis was 13 years, and the median time between suspicion and diagnosis was four years. Sixteen patients had class I electron microscopy alterations, seven had class II alterations, and 14 had normal transmission electron microscopy according to the international consensus guideline for reporting transmission electron microscopy results in the diagnosis of PCD (BEAT-PCD TEM Criteria). Genetic screening for pathogenic variants in PCD-related genes and transmission electron microscopy can help determine the PCD diagnosis; however, they are still unavailable to all individuals with clinical suspicion in Brazil. We described ultrastructural alterations found in our population along with the identification of pathogenic variants in PCD-related genes.

Background: The knowledge about the impact of the nonpharmacological measures to control the COVID-19 pandemic can give insight to ways in which they can also be applied for other respiratory diseases and therefore possibly help to reduce the burden of respiratory conditions in health systems. To assess the impact of containment measures of the COVID-19 pandemic on pneumonia hospitalizations in children from 0 to 14 years of age in Brazil. Methods: Data from hospital admissions for pneumonia were obtained from the Department of Informatics of Brazilian Public Health System database in the period of 2015–2020 and analyzed by macro-regions and age groups. To evaluate the effect of containment measures, used in the pandemic, on the incidence of pneumonia, the absolute reduction (without - with pandemic containment measures) and relative reduction (without - with pandemic containment measures / without pandemic containment measures) were calculated by analyzing the subsets 2015-2019 vs 2020. Findings: Comparing the subsets of April-August 2015-2019 vs April-August 2020, there was an expressive reduction in the average incidence of hospitalizations, with numbers ranging from -87% [IRR 0.12 (0.10 to 0.14)] for < 4 years, -79% [IRR 0.21 (0.07 to 0.57)] for 5-9 years, -73% [IRR 0.26 (0.05 to 1.21)] for 10-14 and -86% [IRR 0.14 (0.06 to 0.29)] for

Background: Gut microbiota-derived short-chain fatty-acid (SFCA) acetate protects mice againstRSV A2 strain infection by increasing interferon-β production and expression of interferonstimulated genes (ISGs). However, the role of SFCAs 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 acetate treatment in human pulmonary epithelial cells. We next examined whether 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 acetate ex-vivo impacts upon viral load and ISG expression. We further treated epithelial cells from SARS-CoV-2 infected patients with acetate. Findings: In vitro pre-treatment of A549 cells with acetate reduced RSV load after infection with clinical isolates and increased the expression of RIG-I and ISG15. Animals treated with acetate intranasally recovered significantly faster, with reduction in the RSV clinical isolates viral load, and increased lung expression of IFNB1 and the RIG-I receptor. 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 acetate levels were associated with increasing oxygen saturation at admission, and shorter duration of fever. Ex-vivo treatment of patients’ respiratory cells with acetate reduced RSV load and increased expression of ISGs OAS1 and ISG15, and virus recognition receptors MAVS and RIG-I, but not IFNB1. These acetate effects were not found on cells from SARS-CoV-2 infected patients. Interpretation: Acetate reduces the severity of RSV infection and RSV viral load through modulation of RIG-I expression. Funding: This study was supported by Rio Grande do Sul Research Foundation FAPERGS (FAPERGS/MS/CNPq/SESRS no. 03/2017 - PPSUS 17/2551-0001380-8 and COVID-19 20/2551-0000258-6), CNPq 312504/2017-9 and by Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior - Brasil (CAPES) - Finance Code 001. P.B., C.V.B. and L.A.B. would like to acknowledge financial support given by CNPq/FAPERGS/CAPES/BNDES to the National Institute of Science and Technology on Tuberculosis (INCT-TB), Brazil [grant numbers: 421703- 2017-2/17-1265-8/14.2.0914.1). Declaration of Interest: The authors declare no competing interests. Ethical Approval: All animal procedures were performed in accordance with protocols approved by CEUA/UNICAMP (protocols 4022-1 and 4599-1).

Severe therapy-resistant asthma (STRA) is closely associated with distinct clinical and inflammatory pheno-endotypes, which may contribute to the development of age-related comorbidities. Evidence has demonstrated a contribution of accelerated telomere shortening on the poor prognosis of respiratory diseases in adults. Eotaxin-1 (CCL11) is an important chemokine for eosinophilic recruitment and the progression of asthma. In the last years has also been proposed as an age-promoting factor. This study aimed to investigate the association of relative telomere length (rTL) and eotaxin-1 in asthmatic children. Children aged 8-14 years (n=267) were classified as healthy control (HC, n=126), mild asthma (MA, n=124) or severe therapy-resistant asthma (STRA, n=17). rTL was performed by qPCR from peripheral blood. Eotaxin-1 was quantified by ELISA from fresh-frozen plasma. STRA had shorter telomeres compared to HC (p=0.02) and MA (p=0.006). Eotaxin-1 levels were up-regulated in STRA [median; IQR25-75)] [(1,190 pg/mL; 108-2,510)] compared to MA [(638 pg/mL; 134-1,460)] (p=0.03) or HC [(627 pg/mL; 108-1,750)] (p

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.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.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.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.

Background Invariant natural killer T (iNKT) cells play complex functions in the immune system, releasing both Th1 and Th2 cytokines. The role of iNKT cells in human asthma is still controversial and never described in severe therapy-resistant asthma in children. The objective of this work was to analyse iNKT frequency in peripheral blood of children with severe therapy-resistant asthma (STRA), compared to children with milder asthma and healthy controls. Methods Children with asthma ( n = 136) (non-severe and STRA) from a referral centre and healthy controls ( n = 40) were recruited. Peripheral blood mononuclear cells were isolated, stained with anti-CD3 and anti-iNKT (Vα24Jα18), and analysed through flow cytometry. Atopic status was defined by measuring specific IgE in serum. Airway inflammation was assessed by induced sputum. Results Children with asthma presented an increased frequency of CD3 + iNKT + cells (median 0.38% IQR 0.18–1.9), compared to healthy controls (median 0.26% IQR 0.10–0.43) ( p = 0.025). Children with STRA also showed an increased frequency of iNKT cells (1.5% IQR 1.05–2.73) compared to healthy controls and non-severe asthmatic children (0.35% IQR 0.15–1.6; p = 0.002). The frequency of iNKT cells was not different between atopic and non-atopic children. In addition, iNKT cells were not associated with any inflammatory pattern of induced sputum studied. Conclusion Our data suggests that iNKT cells play a role in paediatric asthma, which is also associated with the severity of disease, but independent of the atopic status.

Background Severe asthma in children is a global health problem. Severe therapy-resistant asthma (STRA) in children is a major clinical challenge due to persistent symptoms despite high doses of corticosteroids and results in high public health costs. Omalizumab (anti-IgE monoclonal antibody) has been described as an effective add-on therapy in these patients. The characteristics of children with STRA from low- and middle-income countries have scarcely been reported, and no real-life study has been published on the effects of omalizumab in this group of patients. The aim of our study is to report the first clinical real-life experiences with omalizumab in Brazilian children with STRA. Methods Children (6-18 years old) from a referral center who were diagnosed with STRA were included in this retrospective study based on our clinical databases. The included children had undergone at least 6 months of omalizumab treatment and fulfilled the following initial criteria: 1) >6 years old; 2) a positive skin-prick test for at least one aeroallergen; and 3) a serum total IgE level between 30 and 1500 IU/mL. Clinical and lung function variables were analyzed before and after treatment. Results Fourteen children (mean age: 11.9 years; percentage female: 72%) were included in this study. Omalizumab treatment significantly increased control of the disease according to a standardized questionnaire administered at every visit (P

Background It is not quite well established how immune responses differ in term and preterm infants beyond the first year of life. This study aimed to evaluate aspects of the innate and adaptive immune responses in a group of preterm infants in comparison with their term peers. Methods In this cross-sectional study peripheral blood mononuclear cells (PBMC) were isolated from preterm and term children at age three years. Innate immune response was evaluated by the analysis of TLR receptors expression on CD11c+HLADRhigh cells and inflammatory cytokine production after PBMC stimulation with Toll like receptors (TLR) ligands. Adaptive immune response was evaluated by T cells’ phenotyping and function after stimulation with polyclonal conventional T cell stimulus. Conclusion We have found that the patterns of innate and adaptive immune responses at 3 years of age were not affected by the fact of the children having being born preterm or at term.

Objective To evaluate the consequences of plasma from individuals with obesity on parameters associated with immunosenescence in unrelated healthy peripheral blood mononuclear cells (PBMC). Methods Freshly isolated PBMC were incubated in media supplemented with 10% of plasma from individuals with obesity or control subjects for the first 4 hours of 24 to 120 hours of culture. Results Plasma from individuals with obesity modulated the phenotype of healthy PBMC, leading to a higher rate of apoptosis, lower amounts of phospho-γH2AX and -p53, and mitochondrial dysfunction. After 120 hours, there was a higher secretion of inflammatory cytokines IL-1β and IL-8. CD8+ T lymphocytes presented decreased expression of CD28, which is associated with the immunosenescent phenotype. CD14+ macrophages showed increased expression of CD80 and CD206, suggesting a modulation in the activation of macrophages. Conclusions These results demonstrate that chronic systemic inflammation observed in obesity induces dysfunctional features in PBMC that are consistent with premature immunosenescence.

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.

Introduction: Severe therapy-resistant asthma (STRA) is associated with a range of pheno-endotypes and adults with STRA have higher risk for developing comorbidities. Studies investigating telomere length (TL) in adults have demonstrated telomere shortening in IPF, COPD and asthma. Eotaxin-1 (CCL11), an important modulator for eosinophilic function and chemo-attraction has also been proposed an aging factor. Aims: To investigate whether differences exist in TL and CCL11 on peripheral blood cells between age-matched severe and mild asthmatic (MA) children and healthy control (HC) subjects. Methods: Relative telomere length (T/S) was quantified by qPCR (peripheral blood) from 124 children with MA, 17 STRA and 73 age-matched HC. CCL11 was quantified by ELISA. Results: T/S analyses indicated that STRA group (median 0.818, IQR25-27 0.496–1.041) had significantly shorter telomeres when compared to MA (1.083 (0.732–1.582), P=0.043). No difference was observed between T/S ratio of MA or STRA and HC (0.998, (0.630–1.740)). Higher levels of CCL11 were found among children within STRA group (1,119 pg/mL (554 - 1,401)) when compared to MA (675 (388 - 1,015) or HC children (626 (256 - 922), P=0.023) with ordered differences among classes (P=0.021). T/S ratio of STRA was inversely correlated with CCL11 (r=-0.573, P=0.011). Conclusions: This is the first report showing a decrease in TL in children with STRA and associated with up-regulation of CCL11. This study adds new evidence to the theory of accelerated aging suggesting that, telomeres attrition and CCL11, could prematurely contribute to a senescent phenotype associated with risk for appearance of comorbidities

Background: Premature birth is a growing and serious public health problem affecting more than one of every ten infants worldwide. Bronchopulmonary dysplasia (BPD) is the most common neonatal morbidity associated with prematurity and infants with BPD suffer from increased incidence of respiratory infections, asthma, other forms of chronic lung illness, and death (Day and Ryan, Pediatr Res 81: 210-213, 2017; Isayama et la., JAMA Pediatr 171:271-279, 2017). BPD is now understood as a longitudinal disease process influenced by the intrauterine environment during gestation and modulated by gene-environment interactions throughout the neonatal and early childhood periods. Despite of this concept, there remains a paucity of multidisciplinary team-based approaches dedicated to the comprehensive study of this complex disease. Methods: The Discovery BPD (D-BPD) Program involves a cohort of infants < 1,250 g at birth prospectively followed until 6 years of age. The program integrates analysis of detailed clinical data by machine learning, genetic susceptibility and molecular translation studies. Discussion: The current gap in understanding BPD as a complex multi-trait spectrum of different disease endotypes will be addressed by a bedside-to-bench and bench-to-bedside approach in the D-BPD program. The D-BPD will provide enhanced understanding of mechanisms, evolution and consequences of lung diseases in preterm infants. The D-BPD program represents a unique opportunity to combine the expertise of biologists, neonatologists, pulmonologists, geneticists and biostatisticians to examine the disease process from multiple perspectives with a singular goal of improving outcomes of premature infants. Trial registration: Does not apply for this study. Fil: Ofman, Gaston. University of Alabama at Birmingahm; Estados Unidos Fil: Caballero, Mauricio Tomás. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Álvarez Paggi, Damián Jorge. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Marzec, Jacqui. National Institute of Environmental Health Sciences; Estados Unidos Fil: Nowogrodzki, Florencia. No especifíca; Fil: Cho, Hye Youn. National Institute of Environmental Health Sciences; Estados Unidos Fil: Sorgetti, Mariana. No especifíca; Fil: Colantonio, Guillermo. No especifíca; Fil: Bianchi, Alejandra. No especifíca; Fil: Prudent, Luis M.. Fundación para la Salud Materno Infantil; Argentina Fil: Vain, Néstor Eduardo. Fundación para la Salud Materno Infantil; Argentina. Sanatorio de la Trinidad Palermo.; Argentina Fil: Mariani, Gonzalo Luis. Hospital Italiano; Argentina Fil: Digregorio, Jorge. Sanatorio de la Trinidad Palermo.; Argentina Fil: Lopez Turconi, Elba. No especifíca; Fil: Osio, Cristina. Sanatorio "Otamendi y Miroli S. A."; Argentina Fil: Galletti, Maria Fernanda. Hospital Italiano; Argentina Fil: Quiros, Mariangeles. Clinica y Maternidad Suizo Argentina; Argentina Fil: Brum, Andrea. Sanatorio de la Trinidad Palermo.; Argentina Fil: Lopez Garcia, Santiago. No especifíca; Fil: Garcia, Silvia. Sanatorio "Otamendi y Miroli S. A."; Argentina Fil: Bell, Douglas. National Institute of Environmental Health Sciences; Estados Unidos Fil: Jones, Marcus H.. Pontificia Universidade Católica do Rio Grande do Sul; Brasil Fil: Tipple, Trent E.. University of Alabama at Birmingahm; Estados Unidos Fil: Kleeberger, Steven R.. National Institute of Environmental Health Sciences; Estados Unidos Fil: Polack, Fernando Pedro. University of Alabama at Birmingahm; Estados Unidos

Primary Ciliary Dyskinesia (PCD) is underdiagnosed in Brazil. We enrolled patients from an adult service of Bronchiectasis over a two-year period in a cross-sectional study. The inclusion criteria were laterality disorders (LD), cough with recurrent infections and the exclusion of other causes of bronchiectasis. Patients underwent at least two of the following tests: nasal nitric oxide, ciliary movement and analysis of ciliary immunofluorescence, and genetic tests (31 PCD genes + CFTR gene). The clinical characterization included the PICADAR and bronchiectasis scores, pulmonary function, chronic Pseudomonas aeruginosa (cPA) colonization, exhaled breath condensate (EBC) and mucus rheology (MR). Forty-nine of the 500 patients were diagnosed with definite (42/49), probable (5/49), and clinical (2/49) PCD. Twenty-four patients (24/47) presented bi-allelic pathogenic variants in a total of 31 screened PCD genes. A PICADAR score > 5 was found in 37/49 patients, consanguinity in 27/49, LD in 28/49, and eight PCD sibling groups. FACED diagnosed 23/49 patients with moderate or severe bronchiectasis; FEV1 ≤ 50% in 25/49 patients, eight patients had undergone lung transplantation, four had been lobectomized and cPA+ was determined in 20/49. The EBC and MR were altered in all patients. This adult PCD population was characterized by consanguinity, severe lung impairment, genetic variability, altered EBC and MR.

Probiotics have emerged as a promising intervention for the prevention of respiratory tract infections (RTIs) in children. Assess the effect of probiotics on prevention of RTIs in children and adolescents. MEDLINE, EMBASE, LILACS, SCIELO, CINAHL, SCOPUS, and Web of Science. Key words: "respiratory tract infections" AND probiotics. Randomized controlled trials RCT assessing the effect of probiotics on RTIs in children and adolescents were included. Two reviewers, working independently, to identify studies that met the eligibility criteria. Main and secondary outcomes were RTIs and adverse effects, respectively. Twenty-one trials with 6.603 participants were included. Pairwise meta-analysis suggested that Lactobacillus casei rhamnosus (LCA) was the only effective probiotic to the rate of RTIs compared to placebo (RR0.38; Crl 0.19-0.45). Network analysis showed that the LCA exhibited 54.7% probability of being classified in first, while the probability of Lactobacillus fermentum CECT5716 (LFC) being last in the ranking was 15.3%. LCA showed no better effect compared to other probiotic strains by indirect analysis. This systematic review found a lack of evidence to support the effect of probiotic on the incidence rate of respiratory infections in children and adolescents. Pediatr Pulmonol. 2017;52:833-843. © 2017 Wiley Periodicals, Inc.

Background: The goal of this systematic review and meta-analysis is to determine the effect of diet on telomere length. Methods: We searched the following databases: MEDLINE, Embase, LILACS, CINAHL, ISI Web of Science, and Scopus, as well as the Cochrane Central Register of Controlled Trials and the National Institutes of Health, from inception to December 2016. Articles that assessed effects of diet on telomere length were included. Results: A total of 2,128 studies were identified, 30 were read in full, and 7 were systematically reviewed. Five RCTs were included in the meta-analysis, covering 9 diets; a total of 533 participants were included. Study heterogeneity (I2) was 89%, and differences were not identified regarding average telomere lengths (mean difference 1.06; 95% CI –1.53 to 3.65). Conclusion: The available evidence suggests that there is no effect of diet on telomere length, but the strong heterogeneity in the type and duration of dietary interventions does not allow any final statement on the absence of an effect of diet on telomere length.

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

Highlights • Respiratory viral coinfections are common in children. • Overall pediatric respiratory viral coinfections have no impact on severity. • Prognostic role of specific viral interactions remains unclear., Background With advent of molecular diagnostic technologies, studies have reported detection of two or more respiratory viruses in about 30% of children with respiratory infections. However, prognostic role of coinfection remains unclear. Objective Evaluate relation between respiratory viral confection and illness severity in children. Study design MEDLINE (through PUBMED), EMBASE, EBSCO, LILACS databases were searched up to March 2015 by two independent reviewers. Studies assessing severity of viral coinfection in patients aged less than 18 years were included. Standardized forms were used for data extraction of population, study design, clinical syndromes, virus combinations compared and severity outcomes. Risk of bias and quality of evidence were assessed through EPHPP and GRADE. Subgroup analysis was performed according to age and viral combinations. Results Of 5218 records screened, 43 were included in analysis. Viral coinfection did not influence risks of all outcomes assessed: length of stay (mean difference in days in coinfection, −0.10 [95% confidence interval: −0.51 to 0.31]), length of supplemental oxygen (−0.42 [−1.05 to 0.20]), need of hospitalization (odds ratio of coinfection, 0.96 [95% confidence interval: 0.61–1.51]), supplemental oxygen (0.94 [0.66 to 1.34]), need of intensive care (0.99 [0.64 to 1.54]), mechanical ventilation (0.81 [0.33 to 2.01]) and death (2.22 [0.83 to 5.95]). Sub-analyses according to age and viral combinations have not shown influence of these factors in outcomes. Conclusions Respiratory viral coinfection did not increase severity in all outcomes assessed. Further studies are necessary to confirm this finding, especially regarding role of specific viral interactions.

Asthma is a highly prevalent chronic inflammatory lung disease characterized by airway hyperresponsiveness to allergens, airway edema, and increased mucus secretion. Such mucus can be liquefied by recombinant human deoxyribonuclease (rhDNase), in which efficacy of rhDNase has been well documented in patients with cystic fibrosis, but little studied in asthma. In the present study, we investigated whether rhDNase intranasal administration improved inflammation and pulmonary function in an experimental model of asthma.Mice were sensitized by two subcutaneous injections of ovalbumin (OVA), on days 0 and 7, followed by three intranasal challenges with OVA on days 14, 15, and 16. A control group, replacing OVA by DPBS, was included. On days 15 and 16, after 2 hours of OVA challenge, mice received 1 mg/mL of intranasal rhDNase.We showed that rhDNase decreased significantly the airway resistance and reduced EETs formation and globet cells hyperplasia.Our results suggest that extracellular DNA in mucus play a role in lower airways obstruction in OVA asthma protocol and that the treatment with rhDNase improved lung function and DNA extracellular traps, with no direct cellular anti-inflammatory effects.