Seasonal Dynamics in Upper Airway Microbiomes Relate to Asthma Exacerbations

Seasonal variation in respiratory illnesses and exacerbations in pediatric populations with asthma is well described. We hypothesized that nasal microbiota composition is dynamic and covaries with season and respiratory events, and that discrete microbial-host interactions modify risk of asthma exacerbation in a season-specific manner. Bacterial (16S rRNA) and fungal (ITS2) biomarker sequencing was performed on longitudinally collected nasal samples from children with exacerbation-prone asthma during periods of respiratory health (Baseline; n=94 samples) and first captured respiratory illness (n=97). Paired nasal transcriptome data was examined for seasonal dynamics and integrative analyses. Exacerbation and respiratory illness events co-varied with season [Generalized Additive (Mixed) Models, estimated degrees of freedom (edf)=1.71, P=0.04; edf=3.15, P=<0.001, respectively], with increased frequency in the fall. Upper airway bacterial [edf=1.66, P=0.001 baseline; edf=1.61, P=0.02 respiratory illness] and fungal (edf=1.87, P=0.01 respiratory illness) microbiota and rhinovirus detection (edf=3.72, P=0.01 Baseline; edf=1.92, P=0.003 respiratory illness) also exhibited seasonal dynamics. In seasonally adjusted analysis, variation in baseline microbiota was related to both participant age and time to exacerbation. Respiratory illness microbiota exhibited season-specific relationships with exacerbation which were strongest in the fall. During respiratory illness events, following adjustment for age, sex and season, interactions between the exacerbation-associated epithelial SMAD3 transcriptional module and two distinct networks of upper airway bacteria significantly increased odds of subsequent exacerbation [OR=14.7(1.50, 144), P=0.02; OR=39.17(2.44-626), P=0.008]. Thus, upper airway microbiomes co-vary with seasonal trends in respiratory illnesses and asthma exacerbations, and seasonally adjusted analyses reveal microbial-host interactions during respiratory illness events that significantly increase risk of exacerbation.