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Mometasone furoate and fluticasone furoate are equally effective in restoring nasal epithelial barrier dysfunction in allergic rhinitis.

ABSTRACT: Tight junction defects (TJ) have been associated with a defective epithelial barrier function in allergic rhinitis (AR). Intranasal corticosteroids are potent drugs frequently used to treat AR and are shown to restore epithelial integrity by acting on TJs and by reducing type 2 cytokine production. However, the effect of different classes of intranasal corticosteroids on the epithelial barrier has not been studied. Therefore, we compared the effect of 2 intranasal corticosteroids, ie, fluticasone furoate (FF) and mometasone furoate (MF) on epithelial barrier function. Both FF and MF similarly increased trans-epithelial electrical resistance of primary nasal epithelial cell cultures from AR patients. In a house dust mite-induced allergic asthma mouse model, FF and MF had similar beneficial effects on fluorescein isothiocyanate-dextran 4 kDa mucosal permeability, eosinophilic infiltration and IL-13 levels. Both molecules increased mRNA expression of the TJ proteins occludin and zonula occludens-1, thereby restoring epithelial barrier function. Lastly, we showed that long-term FF treatment also increased expression of occludin in AR patients compared to controls. In conclusion, both FF and MF effectively restore epithelial barrier function by increasing expression of TJ proteins in AR patients.

SUBMITTER: Doulaptsi M

PROVIDER: S-EPMC8436167 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature

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Mometasone furoate and fluticasone furoate are equally effective in restoring nasal epithelial barrier dysfunction in allergic rhinitis.

Doulaptsi Maria M Wils Tine T Hellings Peter W PW Martens Katleen K Farré Ricard R Vicario Maria M Fokkens Wytske W Prokopakis Emmanuel E Steelant Brecht B

The World Allergy Organization journal 20210911 9

Tight junction defects (TJ) have been associated with a defective epithelial barrier function in allergic rhinitis (AR). Intranasal corticosteroids are potent drugs frequently used to treat AR and are shown to restore epithelial integrity by acting on TJs and by reducing type 2 cytokine production. However, the effect of different classes of intranasal corticosteroids on the epithelial barrier has not been studied. Therefore, we compared the effect of 2 intranasal corticosteroids, ie, fluticason ...[more]

PMID: 34567350

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Project description:BackgroundIntranasal corticosteroids are the most efficacious anti-inflammatory medications for allergic rhinitis (AR). However, the efficacy and safety of intranasal corticosteroids in children have not yet been subject to specific research in China. The aim of this study was to investigate the efficacy and safety of fluticasone furoate nasal spray (FFNS) in a Chinese pediatric population.MethodsIn this phase 4 randomized, double-blind, placebo-controlled, multicenter study, pediatric AR patients aged 2-12 years were randomized 1:1:1, receiving either FFNS 55 µg or 110 µg or placebo. Electronic diary cards were completed to record symptoms, rescue medication use, and treatment compliance. Anterior rhinoscopy and overall response to therapy were evaluated and recorded.ResultsPatients treated with FFNS at either dose experienced a significantly greater reduction in daily reflective total nasal symptom score compared with placebo. This was maintained in a younger subset of patients (2-6 years). Drug-related adverse events occurred in <20% of patients in all groups. FFNS was well tolerated at both doses.ConclusionsThis study demonstrates favorable efficacy and safety profiles for FFNS 55 µg or 110 µg in Chinese pediatric populations (2-12 years), supporting its use in clinical treatment for AR children, including younger children aged 2-6 years.ImpactThe aim of this study was to investigate the efficacy and safety of intranasal fluticasone furoate in Chinese pediatric allergic rhinitis. This research not only addresses the deficiency in efficacy and safety data for intranasal corticosteroids in very young patients (aged 2-6 years) worldwide but also demonstrates that fluticasone furoate nasal spray shows a favorable benefit/risk profile at different dose levels. Our data will be of interest to the broad readership of Pediatric Research and will positively contribute to the dialog regarding the treatment of allergic rhinitis in children aged 2-6 years.

Project description:IntroductionThe safety and efficacy of fluticasone furoate nasal spray (FFNS) for the symptoms of seasonal and perennial allergic rhinitis have been previously demonstrated in several clinical studies. The objective of this pilot study was to compare the efficacy and safety of FFNS 110 mcg once daily with placebo in patients with irritant (non-allergic) rhinitis triggered predominantly by air pollution.MethodsThis was a randomized, double-blind, placebo-controlled, 4-week study of subjects in Thailand with irritant rhinitis who received either FFNS 110 mcg (N=53) or placebo (N=49) once-daily. Subjects with a ≥2 year history of air pollution as their predominant rhinitis trigger, negative skin test to local seasonal/perennial allergens, positive histamine skin test, and normal sinus radiograph were enrolled if they met minimum reflective total nasal symptom score (rTNSS) ≥4.5 (maximum=9) and a nasal congestion score of ≥2 (maximum =3). All were assessed for nasal eosinophilia at study entry and completion. Air quality was monitored throughout the study. The primary efficacy endpoint was the mean change from baseline over the treatment period in daily rTNSS, the average of the morning and evening rTNSS. The key secondary measure was the mean change from baseline over the entire treatment period in morning pre-dose instantaneous total nasal symptom score (iTNSS).ResultsThe Air Quality Index (AQI) during the study generally did not reach unhealthy levels. Baseline daily rTNSS scores were similar between treatment groups (FFNS=6.7; placebo=6.4). The least square mean change from baseline in rTNSS was -2.17 and -2.10 for FFNS and placebo, respectively, with a difference of -0.065 (p=0.845). Gradual improvements were seen in both treatment groups for iTNSS; however, the treatment difference (-0.075) was not statistically significant (p=0.827). Additionally, there were no statistically significant differences between treatment groups for AM and PM rTNSS, individual nasal symptoms, daily reflective, AM and PM reflective and AM pre-dose instantaneous total ocular symptom scores (TOSS) or individual ocular symptom scores. Nasal cytology at baseline found more than two-thirds of subjects had <20% eosinophils. Adverse events were few and similar between groups and noted as mild in intensity.ConclusionSubjects receiving FFNS had similar improvement to placebo in their rhinitis symptoms. The lack of a treatment effect may be in part due to the overall good air quality present throughout the study or an insufficient dose or duration of FFNS. The safety findings showed FFNS 110 mcg once daily to be well tolerated.

Dataset Information

Mometasone furoate and fluticasone furoate are equally effective in restoring nasal epithelial barrier dysfunction in allergic rhinitis.

Publications

Mometasone furoate and fluticasone furoate are equally effective in restoring nasal epithelial barrier dysfunction in allergic rhinitis.

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