McCauley KE, Flynn K, DiMassa V, LaMere B, Fadrosh DW, Lynch KV, Gill MA, Pongracic JA, Khurana Hershey GK, Kercsmar CM, Liu AH, Johnson CC, Kim H, Kattan M, O'Connor GT, Bacharier LB, Teach SJ, Gergen PJ, Wheatley LM, Togias A, LeBeau P, Calatroni A, Presnell S, Boushey HA, Busse WW, Gern JE, Jackson DJ, Altman MC, and Lynch SV. Seasonal Airway Microbiome and Transcriptome Interactions Promote Childhood Asthma Exacerbations. J Allergy Clin Immunol 2022.
The Journal of allergy and clinical immunology
BACKGROUND: Seasonal variation in respiratory illnesses and exacerbations in pediatric populations with asthma is well described, though whether upper airway microbes play season-specific roles in these events is unknown.
OBJECTIVE: We hypothesized that nasal microbiota composition is seasonally dynamic and that discrete microbial-host interactions modify risk of asthma exacerbation in a season-specific manner.
METHODS: Repeated nasal samples from children with exacerbation-prone asthma collected during periods of respiratory health (Baseline; n=181 samples) or first captured respiratory illness (n=97) across all seasons, underwent bacterial (16S rRNA gene) and fungal (ITS2) biomarker sequencing. Virus detection was performed by multiplex PCR. Paired nasal transcriptome data was examined for seasonal dynamics and integrative analyses.
RESULTS: Upper airway bacterial and fungal microbiota and rhinovirus detection exhibited significant seasonal dynamics. In seasonally-adjusted analysis, variation in both baseline and respiratory illness microbiota related to subsequent exacerbation. Specifically in the fall, when respiratory illness and exacerbation events were most frequent, several Moraxella and Haemophilus members were enriched both in viral positive respiratory illnesses and those that progressed to exacerbations. The abundance of two discrete bacterial networks, characteristically comprising either Streptococcus or Staphylococcus exhibited opposing interactions with an exacerbation-associated SMAD3 nasal epithelial transcriptional module to significantly increase odds of subsequent exacerbation [OR=14.7, 95% CI: 1.50-144, P=0.02; OR=39.17, 95% CI: 2.44-626, P=0.008, respectively].
CONCLUSIONS: Upper airway microbiomes co-vary with season and with seasonal trends in respiratory illnesses and asthma exacerbations. Seasonally-adjusted analyses reveal specific bacterial-host interactions that significantly increase risk of asthma exacerbation in these children.
ePub ahead of print