Long-Term PM Exposure and Upregulation of Expression in Nasal Epithelium from Youth with Asthma.

Little is known about long-term particulate matter 92.5 μm in aerodynamic diameter (PM) exposure and airway epithelial gene expression. To test for association between long-term PM exposure and nasal epithelial gene expression in youth with asthma. Transcriptome-wide association study (TWAS) of long-term PM in nasal epithelium from youth aged 6-20 years in the ) Epigenetic Variation and Childhood Asthma in Puerto Ricans study ( = 182), ) Vitamin D Kids Asthma Study ( = 58), and ) Stress and Treatment Response in Puerto Rican and African American Children with Asthma study ( = 81). Satellite hybrid models were used to estimate PM exposure in the prior year at each participant's residence. Multivariable negative binomial regression was used for each TWAS, adjusting for age, sex, and other covariates. A meta-analysis of all TWAS results was then conducted using an inverse variance-weighted average approach. Most participants (∼95%) in the meta-analysis of TWAS for PM exposure identified as Puerto Rican or Black. Long-term PM was associated with ) upregulated expression of (calcium-activated chloride channel regulator 1; false discovery rate-adjusted [FDR-P] = 0.008), (synaptonemal complex protein 2; FDR-P = 0.01), and (cytochrome p450 family 2 subfamily A member 6; FDR-P = 0.02); and ) downregulated expression of (ectodysplasin A receptor; FDR-P = 0.01). In a meta-analysis, upregulation was associated with one or more positive allergen-specific IgE (FDR-P < 0.001) and increased blood eosinophils (FDR-P < 0.001) and total IgE (FDR-P < 0.001). In a meta-analysis of TWASs in predominantly Puerto Rican and Black youth with asthma, long-term PM exposure was associated with upregulated airway epithelial expression, in turn linked to biomarkers of T2-high immunity.