Upper Airway Cell Transcriptomics Identify a Major New Immunological Phenotype with Strong Clinical Correlates in Young Children with Acute Wheezing

Abstract

Asthma exacerbations are triggered by rhinovirus infections. We employed a systems biology approach to delineate upper-airway gene network patterns underlying asthma exacerbation phenotypes in children. Cluster analysis unveiled distinct IRF7^hi versus IRF7^lo molecular phenotypes, the former exhibiting robust upregulation of Th1/type I IFN responses and the latter an alternative signature marked by upregulation of cytokine and growth factor signaling and downregulation of IFN-γ. The two phenotypes also produced distinct clinical phenotypes. For IRF7^lo children, symptom duration prior to hospital presentation was more than twice as long from initial symptoms (<i>p</i> = 0.011) and nearly three times as long for cough (<i>p</i> < 0.001), the odds ratio of admission to hospital was increased more than 4-fold (<i>p</i> = 0.018), and time to recurrence was shorter (<i>p</i> = 0.015). In summary, our findings demonstrate that asthma exacerbations in children can be divided into IRF7^hi versus IRF7^lo phenotypes with associated differences in clinical phenotypes.