Effect of an Intranasal Corticosteroid on Quality of Life and Local Microbiome in Young Children With Chronic Rhinosinusitis: A Randomized Clinical Trial

Abstract

Importance: Intranasal corticosteroids (INCs) remain the first-line treatment of chronic rhinosinusitis (CRS) in both adults and children, despite the lack of evidence regarding their efficacy in the pediatric population. Similarly, their effect on the sinonasal microbiome has not been well documented.

Objective: To assess the clinical, immunological, and microbiological effects of 12 weeks of an INC in young children with CRS.

Design, setting, and participants: This open-label randomized clinical trial was performed in a pediatric allergy outpatient clinic in 2017 and 2018. Children aged 4 to 8 years with CRS diagnosed by a specialist were included. Data were analyzed from January 2022 to June 2022.

Interventions: Patients were randomized to receive intranasal mometasone in an atomizer for 12 weeks (1 application per nostril, once per day) and supplemental 3-mL sodium chloride (NaCl), 0.9%, solution in a nasal nebulizer once a day for 12 weeks (INC group) or 3-mL NaCl, 0.9%, solution in a nasal nebulizer once a day for 12 weeks (control group).

Main outcomes and measures: Measures taken both before and after treatment included the Sinus and Nasal Quality of Life Survey (SN-5), a nasopharynx swab for microbiome analysis by next-generation sequencing methods, and nasal mucosa sampling for occurrence of innate lymphoid cells (ILCs).

Results: Of the 66 children enrolled, 63 completed the study. The mean (SD) age of the cohort was 6.1 (1.3) years; 38 participants (60.3%) were male and 25 (39.7%) were female. The clinical improvement reflected by reduction in SN-5 score was significantly higher in the INC group compared with the control group (INC group score before and after treatment, 3.6 and 3.1, respectively; control group score before and after treatment, 3.4 and 3.8, respectively; mean between-group difference, -0.58; 95% CI, -1.31 to -0.19; P = .009). The INC group had a greater increase in nasopharyngeal microbiome richness and larger decrease in nasal ILC3 abundance compared with the control group. A significant interaction was observed between change in microbiome richness and the INC intervention on the prediction of significant clinical improvement (odds ratio, 1.09; 95% CI, 1.01-1.19; P = .03).

Conclusions and relevance: This randomized clinical trial demonstrated that treatment with an INC improved the quality of life of children with CRS and had a significant effect on increasing sinonasal biodiversity. Although further investigation is needed of the long-term efficacy and safety of INCs, these data may reinforce the recommendation of using INCs as a first-line treatment of CRS in children.

Trial registration: ClinicalTrials.gov Identifier: NCT03011632.

Figure 1.. Consolidated Standards of Reporting Trials (CONSORT) Flow Diagram

Figure 2.. Change From Baseline in Clinical Presentation of Chronic Rhinosinusitis by Study Group

Change from baseline was determined by subtracting each before-treatment value from the after-treatment value. A, Correlation between change from baseline in SN-5 score and change from baseline in nasopharynx microbiome richness (P = .02). The dashed line indicates the minimal clinically important difference in SN-5 score (−0.5). Increased OTU value indicates greater richness. B, Change from baseline in nasopharynx microbiome richness (P = .04). C, Change from baseline in nasopharynx microbiome diversity as measured by Shannon index (P = .14). D, Change from baseline in nasal abundance of ILC1 (P = .22). E, Change from baseline in nasal ILC3 abundance (P = .03). In the box plots, the top and bottom of each box indicates the IQR; internal horizontal line, median; dots, individual values; whiskers, full range of values. ILC indicates innate lymphoid cell; INC, intranasal corticosteroid; OTUs, operational taxonomic units; SN-5, Sinus and Nasal Quality of Life Survey.