Functional immunophenotyping of children with critical status asthmaticus identifies differential gene expression responses in neutrophils exposed to a poly(I:C) stimulus

The host immune response to a viral immune stimulus has not been examined in children during a life-threatening asthma attack. We determined whether we could identify clusters of children with critical asthma by functional immunophenotyping using an intracellular viral analog stimulus. We performed a single-center, prospective, observational cohort study of 43 children ages 6–17 years admitted to a pediatric intensive care unit for an asthma attack between July 2019 to February 2021. Neutrophils were isolated from children, stimulated overnight with LyoVec poly(I:C), and mRNA was analyzed using a targeted Nanostring immunology array. Network analysis of the differentially expressed transcripts for the paired LyoVec poly(I:C) samples was performed. We identified two clusters by functional immunophenotyping that differed by the Asthma Control Test score. Cluster 1 (n = 23) had a higher proportion of children with uncontrolled asthma in the four weeks prior to PICU admission compared with cluster 2 (n = 20). Pathways up-regulated in cluster 1 versus cluster 2 included chemokine receptor/chemokines, interleukin-10 (IL-10), IL-4, and IL-13 signaling. Larger validation studies and clinical phenotyping of children with critical asthma are needed to determine the predictive utility of these clusters in a larger clinical setting.