Background: Inflammatory responses in acute exacerbation in children remain poorly understood.

Objective: Examine inflammatory responses during acute asthma exacerbation in children. 

Methods: We evaluated cytokine and gene expression profiles in pediatric patients admitted to tertiary pediatric hospital with acute exacerbation.  Viral PCR was done to differentiate between viral or non-viral induced exacerbations. RNA-sequencing was performed on whole blood using the Illumina NovaSeq 6000 and data analyzed using Bioconductor.

Result: After informed consent, blood was obtained from 19 children admitted for asthma exacerbation and from 14 age-matched healthy controls. Mean age 11.4 ± 3.7. Eleven had positive nasopharyngeal PCR for viral infection (9 Rhino and 2 RSV). Eight were in PICU. Mean IgE in IU/ml was 925 ± 672.  Mean days on systemic corticosteroids before blood draw was 2.5 ± 1.6. Cytokine analysis revealed non-detectable levels of Th cytokines IL-4, IL-5, IL-13, IL-17A, and IFN-?. Compared to controls, IL-1RA and IL-10 levels were significantly increased (p<0.05) in asthma subjects. We found 890 differentially expressed genes (log2 FC|>1.5| and FDR <0.05) in asthma subjects. Pathway analyses on increased genes showed enrichment for cytokine signaling (CSF2RB, IL18R1) and pyroptosis (CASP5, IL1R1, NLRP6). Significantly reduced genes were involved in T helper cell differentiation and signaling. There were no significant differences in cytokine or gene expression between viral and non-viral exacerbations.  

Conclusion: In acute asthma, T helper cell adaptive immune responses are blunted while innate immune responses remained increased, independent of trigger or severity of symptoms.