Upper airway cell transcriptomics identify a major new immunological phenotype with strong clinical correlates in young children with acute wheezing

Siew Kim Khoo, James Read, Kimberley Franks, Guicheng Zhang, Joelene Bizzintino, Laura Coleman, Christopher McCrae, Lisa Öberg, Niamh M. Troy, Franciska Prastanti, Janet Everard, Stephen Oo, Meredith L. Borland, Rose A. Maciewicz, Peter N. Le Souëf, Ingrid A. Laing, Anthony Bosco

Research output: Contribution to journalArticle

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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 IRF7hi 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 (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 IRF7hi versus IRF7 lo phenotypes with associated differences in clinical phenotypes.

Original languageEnglish
Pages (from-to)1845-1858
Number of pages14
JournalJournal of Immunology
Volume202
Issue number6
DOIs
Publication statusPublished - 1 Jan 2019

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Respiratory Sounds
Phenotype
Asthma
Up-Regulation
Rhinovirus
Systems Biology
Gene Regulatory Networks
Cough
Cluster Analysis
Intercellular Signaling Peptides and Proteins
Down-Regulation
Odds Ratio
Cytokines
Recurrence
Infection

Cite this

Khoo, Siew Kim ; Read, James ; Franks, Kimberley ; Zhang, Guicheng ; Bizzintino, Joelene ; Coleman, Laura ; McCrae, Christopher ; Öberg, Lisa ; Troy, Niamh M. ; Prastanti, Franciska ; Everard, Janet ; Oo, Stephen ; Borland, Meredith L. ; Maciewicz, Rose A. ; Le Souëf, Peter N. ; Laing, Ingrid A. ; Bosco, Anthony. / Upper airway cell transcriptomics identify a major new immunological phenotype with strong clinical correlates in young children with acute wheezing. In: Journal of Immunology. 2019 ; Vol. 202, No. 6. pp. 1845-1858.
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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 IRF7hi 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 (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 IRF7hi versus IRF7 lo phenotypes with associated differences in clinical phenotypes.",
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Upper airway cell transcriptomics identify a major new immunological phenotype with strong clinical correlates in young children with acute wheezing. / Khoo, Siew Kim; Read, James; Franks, Kimberley; Zhang, Guicheng; Bizzintino, Joelene; Coleman, Laura; McCrae, Christopher; Öberg, Lisa; Troy, Niamh M.; Prastanti, Franciska; Everard, Janet; Oo, Stephen; Borland, Meredith L.; Maciewicz, Rose A.; Le Souëf, Peter N.; Laing, Ingrid A.; Bosco, Anthony.

In: Journal of Immunology, Vol. 202, No. 6, 01.01.2019, p. 1845-1858.

Research output: Contribution to journalArticle

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AU - Khoo, Siew Kim

AU - Read, James

AU - Franks, Kimberley

AU - Zhang, Guicheng

AU - Bizzintino, Joelene

AU - Coleman, Laura

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AU - Öberg, Lisa

AU - Troy, Niamh M.

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AU - Oo, Stephen

AU - Borland, Meredith L.

AU - Maciewicz, Rose A.

AU - Le Souëf, Peter N.

AU - Laing, Ingrid A.

AU - Bosco, Anthony

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