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.

Background. The COVID-19 pandemic has spread across the world, leading to government measures associated with a negative impact on mental health. The aim of this study was to evaluate the impact of COVID-19 on depression, anxiety and resilience in Dutch people with cystic fibrosis (PwCF) or primary ciliary dyskinesia (PwPCD) and their caregivers during the pandemic. Methods. Adolescents (12-17 years), adults and caregivers of children (0-17 years) with CF or PCD completed questionnaires on depression (PHQ-9), anxiety (GAD-7) and resilience (BRS) between September 2020 and February 2021. The psychosocial impact of COVID-19 was measured by the Exposure and Family Impact Survey (CEFIS) Part 2. Mixed model analyses compared PHQ-9 and GAD-7 results to participants’ pre-pandemic scores. Results. 110 participants (10 PwCF, 31 PwPCD, 52 CF caregivers, 17 PCD caregivers) completed questionnaires during the pandemic. Pre-pandemic outcomes were available for 87 participants. The prevalence of symptoms of depression and anxiety (PHQ-9 or GAD-7 scores ≥5) in PwCF and PwPCD and their caregivers before and during the pandemic was high, with an increase in depression in PwCF (2.75; 95%-CI: 0.82 to 4.68) and increase in anxiety in CF caregivers (1.03; 0.09 to 1.96) during the pandemic. Resilience was within the normal range for all groups, CEFIS scores corresponded to a low to normal impact. Conclusion. PwCF and PwPCD and their caregivers were at high risk of increased depression and anxiety symptoms both before and during the pandemic, which emphasizes the importance of mental health screening and psychological care in CF and PCD.