LAUSR

RATIONALE There is a major unmet need for improving the care of children and adolescents with severe asthma and wheeze. Identification of factors contributing to disease severity may lead to improved diagnostics, biomarkers, or therapies. The airway microbiota may be such a key factor. OBJECTIVE To compare the oropharyngeal airway microbiota of children and adolescents with severe and mild/moderate asthma/wheeze. METHODS Oropharyngeal swab samples from school-age and pre-school children in the European U-BIOPRED multicenter study of severe asthma, all receiving severity-appropriate treatment, were examined using 16S rRNA gene sequencing. Bacterial taxa were defined as Amplicon Sequence Variants (ASVs). RESULTS We analysed 241 samples from four cohorts; A) 86 school-age children with severe asthma, B) 39 school-age children with mild/moderate asthma, C) 65 pre-school children with severe wheeze and D) 51 pre-school children with mild/moderate wheeze. The most common bacteria were Streptococcus (mean relative abundance 33.5%), Veillonella (10.3%), Haemophilus (7.0%), Prevotella (5.9%) and Rothia (5.5%). Age group (school-age versus pre-school) was associated with the microbiota in beta-diversity analysis (F=3.32, p=0.011) and in a differential abundance analysis (28 significant ASVs). Among all children, we found no significant difference in the microbiota between children with severe and mild/moderate asthma/wheeze in a univariable beta-diversity analysis (F=1.99, p=0.08, n=241), but a significant difference in a multivariable model (F=2.66, p=0.035), including number of exacerbations in the previous year. Age was also significant when expressed as a Microbial Maturity Score (Spearman Rho 0.39, p=4.6e-10), however this score was not associated with asthma/wheeze severity. CONCLUSION There was a modest difference in the oropharyngeal airway microbiota between children with severe and mild/moderate asthma/wheeze across all children but not in individual age groups, and a strong association between the microbiota and age. This suggests the oropharyngeal airway microbiota as an interesting entity in studying asthma severity, but probably without the strength to serve as a biomarker for targeted intervention.