Airway and Systemic Dysregulation of Interferon Responses Promote Asthma Exacerbations in Urban Children
Recommended Citation
Gaberino C, Altman M, Gill M, Bacharier L, Gruchalla R, O'Connor G, Pongracic J, Khurana Hershey G, Kattan M, Liu A, Teach S, Zoratti EM, Gergen P, Visness C, Busse W, Jackson D. Airway and Systemic Dysregulation of Interferon Responses Promote Asthma Exacerbations in Urban Children. J Allergy Clin Immunol 2024; 153(2):AB253.
Document Type
Conference Proceeding
Publication Date
2-1-2024
Publication Title
J Allergy Clin Immunol
Abstract
Rationale: To understand the molecular pathways that differ during colds that progress to asthma exacerbation versus resolve without intervention, we compared differential gene expression in peripheral blood and airway samples during illnesses. Methods: 208 urban children (6-17 years) with exacerbation-prone asthma and blood eosinophils ≥150/microliter were prospectively monitored for cold symptoms. Exacerbation illnesses (Ex+), defined as colds leading to an asthma exacerbation requiring systemic corticosteroid use within 10 days, were compared to colds that resolved without exacerbation (Ex-). Participants had blood and nasal lavage samples collected after cold symptom onset. RNA sequencing of blood and nasal airway samples and differential gene expression analysis were performed comparing Ex+ versus Ex- illnesses using mixed effects modeling. Results: 106 participants were evaluated during 153 colds [46 Ex+ (33 virus-positive) and 107 Ex- (69 virus-positive)]. Significant differentially expressed genes comparing Ex+ to Ex- illnesses included: blood (502 total: 433 up-regulated, 69 down-regulated), airway (3144 total: 1712 up-regulated, 1432 down-regulated) [FDR<0.05]. Blood and airway samples had 252 overlapping significant differentially expressed genes. Gene set enrichment analysis identified interferon pathways (including CXCL10, IRF7, IFIT2, STAT1) as the most significantly up-regulated pathways in both blood and airway samples during illnesses resulting in exacerbation [FDR<0.05] (Hallmark/C2 Pathways). Conclusions: While viral infections exist in both Ex+ and Ex- illnesses, illnesses that resulted in asthma exacerbations exhibited significantly greater up-regulation of interferon pathways in both peripheral blood and airway samples. These results suggest that both local and systemic dysregulation of interferon responses play an important role in asthma exacerbations in urban children.
Volume
153
Issue
2
First Page
AB253
