Abstract
BackgroundThe combination of the antihistamine azelastine (AZE) with the corticosteroid fluticasone propionate (FP) in a single spray, has been reported to be significantly more effective at reducing allergic rhinitis (AR) symptoms than treatment with either corticosteroid or antihistamine monotherapy. However, the biological basis for enhanced symptom relief is not known. This study aimed to compare gene expression profiles (760 immune genes, performed with the NanoString nCounter) from peripheral blood and nasal brushing/lavage lysate samples in response to nasal spray treatment.MethodsModerate/severe persistent dust mite AR sufferers received either AZE (125 μg/spray) nasal spray (n = 16), FP (50 μg/spray) nasal spray (n = 14) or combination spray AZE/FP (125 μg AZE and 50 μg FP/spray) (n = 14) for 7 days, twice daily. Self‐reported symptom questionnaires were completed daily for the study duration. Gene expression analysis (760 immune genes) was performed with the NanoString nCounter on purified RNA from peripheral blood and nasal brushing/lavage lysate samples.ResultsIn nasal samples, 206 genes were significantly differentially expressed following FP treatment; 182 genes downregulated (−2.57 to −0.45 Log2 fold change [FC]), 24 genes upregulated (0.49–1.40 Log2 FC). In response to AZE/FP, only 16 genes were significantly differentially expressed; 10 genes downregulated (−1.53 to −0.58 Log2 FC), six genes upregulated (1.07–1.62 Log2 FC). Following AZE treatment only five genes were significantly differentially expressed; one gene downregulated (−1.68 Log2 FC), four genes upregulated (0.59–1.19 Log2 FC). Immune gene changes in peripheral blood samples following treatment were minimal. AR symptoms improved under all treatments, but improvements were less pronounced following AZE treatment.ConclusionAZE/FP, FP, and AZE had diverse effects on immune gene expression profiles in nasal mucosa samples. The moderate number of genes modulated by AZE/FP indicates alternative pathways in reducing AR symptoms whilst avoiding extensive local immune suppression.
Highlights
Allergic rhinitis (AR) is associated with significant global medical and economic burden.[1,2,3] Intranasal antihistamines and corticosteroids are first‐line treatments for allergic rhinitis (AR) management
The purpose of this study was to investigate the potential mechanisms through which antihistamine and corticosteroid nasal sprays provide relief from AR symptoms and to determine if combining an antihistamine and corticosteroid provides any synergistic effects on gene expression profiles in the nasal mucosa and blood samples
The current study used a parallel‐group design to compare the immune gene expression profiles of nasal lysate samples from AR sufferers following administration with azelastine/fluticasone propionate “Dymista ®” group (AZE/fluticasone propionate (FP)) formulated together in comparison to products formulated with a single active ingredient as control groups
Summary
Allergic rhinitis (AR) is associated with significant global medical and economic burden.[1,2,3] Intranasal antihistamines and corticosteroids are first‐line treatments for AR management. The purpose of this study was to investigate the potential mechanisms through which antihistamine and corticosteroid nasal sprays provide relief from AR symptoms and to determine if combining an antihistamine and corticosteroid provides any synergistic effects on gene expression profiles in the nasal mucosa and blood samples. The combination of the antihistamine azelastine (AZE) with the corticosteroid fluticasone propionate (FP) in a single spray, has been reported to be significantly more effective at reducing allergic rhinitis (AR) symptoms than treatment with either corticosteroid or antihistamine monotherapy. This study aimed to compare gene expression profiles (760 immune genes, performed with the NanoString nCounter) from peripheral blood and nasal brushing/lavage lysate samples in response to nasal spray treatment.
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