An Exaggerated type i interferon antiviral response is associated with exacerbations in pediatric asthma
Swanson CL, Babineau D, Whalen E, Gill MA, Shao B, Liu AH, Jepson B, Gruchalla RS, O'Connor GT, Pongracic JA, Kercsmar CM, Khurana Hershey GK, Zoratti EM, Johnson CC, Teach SJ, Kattan M, Bacharier LB, Beigelman A, Sigelman SM, Gergen PJ, Wheatley LM, Presnell S, Togias A, Busse WW, Jackson DJ, and Altman MC. An Exaggerated type i interferon antiviral response is associated with exacerbations in pediatric asthma. J Allergy Clin Immunol 2018; 141(2 Suppl S):AB116.
J Allergy Clin Immunol
RATIONALE: Type-I interferon responses are critical to controlling viral upper respiratory tract infections (URIs), but excessive antiviral responses can have detrimental effects on the airway. We investigated the peripheral blood and upper airway gene expression responses to URIs in children with difficult-to-control asthma to determine differences in type-I interferon responses associated with exacerbations in vivo. METHODS: 106 children with exacerbation prone asthma and peripheral blood eosinophils ≥150 /mm3 were enrolled. Peripheral blood and nasal samples were collected at baseline and within 72 hours of URI onset (prior to any systemic corticosteroid use). Gene expression was determined by RNAsequencing and virus infection by PCR. Differential gene expression was assessed by modular analysis coupled with multivariable linear modeling. RESULTS: URIs for which a virus was detected had significantly elevated expression of multiple interferon-associated modules in both the upper airway and peripheral blood compared to baseline samples and compared to URIs without a detectable virus (fold changes 1.3-2.1, p
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