Very Low Childhood Opportunity Index is associated with increased epithelial inflammation but decreased T2 and Th17 pathway expression in children with Asthma

Document Type

Conference Proceeding

Publication Date

2-1-2025

Publication Title

J Allergy Clin Immunol

Abstract

Rationale: The Child Opportunity Index (COI), a nationally available measure of relative educational, health/environmental, and social/economic opportunity, has been associated with asthma incidence. We sought to determine the association of COI to airway gene expression patterns. Methods: Analysis included a subset of 220 children with exacerbation-prone asthma in urban neighborhoods enrolled in the MUPPITS-2 clinical trial. We dichotomized census tract-level COI at the median COI of 8 into low (L, n=123) and very low (VL, n=97) groups. Baseline gene expression modules previously defined by weighted gene correlation network analysis (WGCNA) were summarized for each participant, and differential module enrichment was compared in children from L versus VL COI census tracts. Further, differential biological pathway enrichment analyses were performed using Gene Set Enrichment Analysis (GSEA). Results: The participants averaged 10.9 years of age and 44.5% were female. There were fewer Hispanic and White participants in the VL group, but no differences in sex, age, or BMI between groups. There were 722 differentially expressed genes. WCGNA-derived modules associated with TGFb/ SMAD3 mediated epithelial remodeling, squamous epithelium, and IL-33 responses were positively enriched in VL COI. Positive enrichment of ciliary, and reactome pathways and negative enrichment of immune-associated pathways (IL-4, IL-5, IL-6, and IL-17) were detected by GSEA in the VL COI group. Conclusions: Very low COI scores in urban children with exacerbation-prone asthma were associated with epithelial remodeling, and comparatively less Th2 and Th17 enrichment. These patterns of airway gene expression may reflect adverse effects of environmental exposures, such as pollution, in these neighborhoods.

Volume

155

Issue

2

First Page

AB188

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