Association of corticosteroid inhaler type with saliva microbiome in moderate-to-severe pediatric asthma

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Introduction: Metered dose inhalers (MDIs) and dry powder inhalers (DPIs) are common inhaled corticosteroid (ICS) inhaler devices. Differences in formulation and administration technique of these devices may influence oral cavity microbiota composition. Aim: To compare the saliva microbiome in children with moderate-to-severe asthma using ICS via a MDI or DPI. Methods: Saliva samples collected from 142 children (6-17 yrs) with moderate-severe asthma across four European countries (the Netherlands, Germany, Spain, and Slovenia) as part of SysPharmPediA cohort were subjected to 16S rRNA sequencing. Participants were divided into two groups based upon inhaler device: MDI (n=77) and DPI (n=65) and their microbiome was compared using global diversity (alpha and beta). Differential abundance was compared using Analysis of Compositions of Microbiomes with Bias Correction (ANCOM-BC) method. Results: No significant difference was observed in alpha diversity between the two groups. However, beta diversity analysis revealed significant differences between groups using both Bray-Curtis and weighted UniFrac methods (Adjusted p-value=0.015 and 0.044 respectively). 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) showed significant differential abundance between groups, with higher relative abundance in the MDI group. Conclusion: Types of ICS devices are associated with different saliva microbiome in moderate-severe pediatric asthma. The casual relation between inhaler type and changes in saliva microbiota composition needs to be established as well as whether this leads to adverse effects.

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