| Title | Upper Airway Cell Transcriptomics Identify a Major New Immunological Phenotype with Strong Clinical Correlates in Young Children with Acute Wheezing. | ||
| Author | Khoo, Siew-Kim; Read, James; Franks, Kimberley; Zhang, Guicheng; Bizzintino, Joelene; Coleman, Laura; McCrae, Christopher; Oberg, Lisa; Troy, Niamh M; Prastanti, Franciska; Everard, Janet; Oo, Stephen; Borland, Meredith L; Maciewicz, Rose A; Le Souef, Peter N; Laing, Ingrid A; Bosco, Anthony | ||
| Journal | J Immunol | Publication Year/Month | 2019-Mar |
| PMID | 30745463 | PMCID | -N/A- |
| Affiliation + expend | 1.Division of Cardiovascular and Respiratory Sciences, The University of Western Australia, Perth, Western Australia 6009, Australia. | ||
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-gamma. 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 (p = 0.011) and nearly three times as long for cough (p < 0.001), the odds ratio of admission to hospital was increased more than 4-fold (p = 0.018), and time to recurrence was shorter (p = 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.