Association of corticosteroid inhaler type with saliva microbiome in moderate-to-severe pediatric asthma Background Metered dose inhalers (MDIs) and dry powder inhalers (DPIs) are common inhaled corticosteroid (ICS) inhaler devices. The difference in formulation and administration technique of these devices may influence oral cavity microbiota composition. We aimed to compare the saliva microbiome in children with moderate-to-severe asthma using ICS via MDIs versus DPIs. Methods Saliva samples collected from 143 children (6-17 yrs) with moderate-to-severe asthma across four European countries (the Netherlands, Germany, Spain, and Slovenia) as part of the SysPharmPediA cohort were subjected to 16S rRNA sequencing. Microbiome was compared using global diversity (α and β) between two groups of participants based on inhaler devices (MDI (n=77) and DPI (n=65)) and differential abundance was compared using the Analysis of Compositions of Microbiomes with the Bias Correction (ANCOM-BC) method. Results No significant difference was observed in α-diversity between the two groups. However, β-diversity analysis revealed significant differences between groups using both Bray-Curtis and weighted UniFrac methods (Adjusted p-value=0.015 and 0.044, respectively). Significant differential abundance between groups, with higher relative abundance in the MDI group compared to the DPI group, was detected at the family level [Carnobacteriaceae (Adjusted p=0.033)] and at the genus level [ Granulicatella (Adjusted p=0.021) and Aggregatibacter (Adjusted p=0.011)]. Conclusion Types of ICS devices are associated with different saliva microbiome composition in moderate-to-severe pediatric asthma. The causal relation between inhaler types and changes in saliva microbiota composition needs to be further evaluated, as well as whether this leads to different potential adverse effects in terms of occurrence and level of severity.

Jana Eckert

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Background: Allergic diseases are the most prevalent chronic childhood diseases resulting in a massive societal and economic burden for the community and a significant reduction of health-related quality of life (HRQoL) for affected families. The project CHAMP (CHildhood Allergy and tolerance: bioMarkers and Predictors) was funded in 2017 by the German Federal Ministry for Education and Research. Methods: CHAMP investigates the determinants of different allergic diseases from birth to adolescence to identify clinically relevant biomarkers predicting onset, progression, remission and severity. Data on HRQoL and patient’s needs and requirements were collected, supported by the German Asthma and Allergy Association (DAAB). Using validated questionnaires and outpatient visits, eight subprojects analysed allergic diseases in epidemiological or clinical cohorts (more than 2500 children/adolescents), sampling numerous biomaterials to assess omics on several levels. Murine models disentangled underlying mechanisms of early tolerance, translating findings from the cohorts to models and vice versa. Results: The DAAB survey, including 851 participants, showed that 83% were interested in prediction of the course of different current allergic diseases and future manifestation. 86% of participants considered doctor’s specialized training and their education as highly important, over 70% chose research for allergy understanding and prevention as critical. CHAMP addresses these needs. Common SOPs have been established and recruitment is ongoing. Conclusion: The DAAB patient survey confirmed the critical need for translational allergy research. CHAMP envisions to predict onset, tolerance and remission of allergic diseases and to identify disease sub-phenotypes for future development of preventive strategies and novel avenues for therapeutic options.

Otto Laub

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Background: Children are affected rather mildly by the acute phase of COVID-19, but predominantly in children and youths, the potentially severe and life threatening pediatric multiorgan immune syndrome (PMIS) occurs later on. To identify children at risk early on, we searched for antibodies against SARS-CoV-2 and searched for early and mild symptoms of PMIS in those with high levels of antibodies. Methods: In a cross-sectional design, children aged 1-17 were recruited through primary care pediatricians for the study (a), if they had an appointment for a regular health check-up or (b), or if parents and children volunteered to participate in the study. Two antibody tests were performed in parallel and children with antibody levels >97th percentile (in the commercially available test) were screened for signs and symptoms of PMIS and SARS-CoV-2 neutralization tests were performed. Results: We identified antibodies against SARS-CoV-2 in 162 of 2832 eligible children (5.7%) between June and July 2020 in three, in part strongly affected regions of Bavaria. Approximately 60% of antibody positive children showed high levels of antibodies. In those who participated in the follow up screening, 30% showed some mild and minor symptoms similar to Kawasaki disease and in three children, cardiac and neuropsychological symptoms were identified. Symptoms correlated with high levels of non-neutralizing and concomitantly low levels of neutralizing antibodies and lower neutralizing capacity. Conclusions: Children exposed to SARS-CoV-2 should be screened for antibodies and those children with positive antibody responses should undergo a stepwise assessment for late COVID-19 effects.