Postnatal risk factors for childhood asthma include developing lung microbiota, early allergen sensitization and recurrent viral respiratory infections. Immune dysfunction in early-life increases lower respiratory infections likelihood, promotes allergic sensitization and persistent airway inflammation. Children raised on dairy farms are less prone to allergies and asthma. 

Our data shows inhaled lyophilized microbes from farm dust protect neonatal mice from allergic airways disease triggered by HDM or recurrent viral infections. We also identified 3 distinct nasal phenotypes (E1, E2, E3 nasotypes), associated with specific expression profiles, in asthmatic children. E2 was prominent in asthmatic children, while wheezers showed a distinct E1/E3 signature switching to E2 at age 4. Early E1 nasotype deficiency correlated with persistent disease.

Our project aims to investigate the impact of farm environment exposures on airway epithelial phenotype ex vivo and uncover mechanisms underlying protection from allergen and viral-induced early-life asthma in vivo. We will investigate altered epithelial phenotype and function ex vivo, and downstream immune cell changes in vivo (spec. neutrophils) using transcriptomics, epigenetics, secretomics, etc. Using our established in vivo neonatal allergic and viral airways disease murine models and ex vivo nasal brushings from allergic rhinitis/asthma patients following treatment with farm dust extract, we will delineate molecular and cellular mechanisms mediated by protective farm environment exposures rescuing the dominant type 2 phenotype.