Recommended Citation
Altman MC, 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, and Jackson DJ. Coordinated epithelial and eosinophil inflammatory pathways underpin upper respiratory tract viral infection (URI) triggered asthma exacerbations. J Allergy Clin Immunol 2018; 141(2 Suppl S):AB110.
Document Type
Conference Proceeding
Publication Date
2-2018
Publication Title
J Allergy Clin Immunol
Abstract
RATIONALE: Upper respiratory infections (URIs) are the primary cause of asthma exacerbations in children. Understanding the molecular mechanisms by which URIs lead to exacerbations is crucial to better management and prevention.
METHODS: Children with exacerbation prone asthma and blood eosinophils >150/mm3 were enrolled and nasal lavage samples collected within 72 hours of initial URI symptoms. Nasal cell differentials were determined by cytospin and nasal gene expression assessed by RNAsequencing. 145 URIs from 104 distinct individuals were analyzed; URIs leading to asthma exacerbation (n545) were compared to URIs that resolved without exacerbation (n5100). Differential gene expression was assessed by cell deconvolution and modular analysis coupled with linear mixed effects modeling.
RESULTS: URIs that led to an exacerbation demonstrated differential expression of 11 gene set modules (false discovery rate<0.05) representing multiple interconnected molecular pathways. Nine were increased with exacerbation, 2 were decreased. Detectable effect sizes ranged from 1.15 to 1.53. Five of the increased modules were associated with epithelial cells and represent important epithelial functions including TGFB response and EGFR signaling. Two modules were associated with eosinophils and represent eosinophil-epithelial interaction and Th2-type inflammation. The magnitude of expression change in 5 of these modules was significantly correlated with decline in lung function during the exacerbation suggesting these findings are integrally connected with exacerbation pathogenesis.
CONCLUSIONS: We identified a network of interconnected molecular pathways activated during URIs that lead to exacerbation in children with severe asthma. This systems scale platform for monitoring immune responses in pediatric asthma can be used to directly investigate mechanisms of therapeutic interventions.
Volume
141
Issue
2 Suppl S
First Page
AB110
