0016 Diurnal Nasal Gene Expression in Children

Abstract Introduction Nasal symptoms of rhinitis and inflammation increased in the evening and overnight. However, the molecular basis for increased nasal mucus production and rhinitis symptoms has not been explored. We hypothesized that nasal gene expression would show diurnal variation that correlates with symptoms of rhinitis and is altered in the setting of pediatric obstructive sleep apnea (OSA). Methods Nasal swabs were obtained at the start and end of diagnostic polysomnography (PSG) in children referred for PSG from a single pediatric sleep center. Children were classified as healthy if AHI on PSG was < 1.5/hr, mild OSA for AHI 1.5-4.9/hr, moderate OSA 5-10/hr, and severe >10/hr. RNA was isolated on swabs from 6 healthy children and 22 children with OSA (1 mild, 4 moderate, 4 severe) and analyzed using RNA-sequencing. Limma was used to identify genes with differential expression based on time of sample (PM for pre-PSG or AM for post-PSG) or for diagnosis of OSA. Weighted gene co-expression network analysis (WGCNA) identified 4 modules of gene expression that were analyzed using fgsea for enriched molecular pathways. Results We identified 4,569 with differential gene expression in the morning vs evening in both healthy children and children with OSA. Analysis for an interaction effect, identified 80 genes differentially expressed in the morning in children with OSA as compared to children without OSA. Modular analysis of gene expression identified 2 modules with increased expression in the morning and 2 modules with increased expression in the evening. Modules with increased expression in the evening included genes related to protein translation, oxidative phosphorylation, ribosomal RNA processing, and mucus production. Modules with increased expression in the morning included genes related to inflammatory signaling, immune cell chemotaxis, and olfactory receptor signaling. Increasing severity of OSA was associated with diminished diurnal differences in gene expression as compared to samples from those without OSA. Conclusion Time of day alters nasal gene expression with increased expression of immune signaling and chemotaxis genes in the morning and increased expression of metabolism, protein translation, and protein secretion genes in the evening. Support (if any) SRS (WTP), Parker B Francis Fellowship (WTP), NIH K08HL179396 (WTP), NIH K24AI150991 (JSD)