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

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.

Upper-airway dysbiosis related to frequent sweets consumption increases the risk of asthma in children with chronic rhinosinusitis.

BACKGROUND: Innate immunity response to local dysbiosis seems to be one of the most important immunologic backgrounds of chronic rhinosinusitis (CRS) and concomitant asthma. We aimed to assess clinical determinants of upper-airway dysbiosis and its effect on nasal inflammatory profile and asthma risk in young children with CRS. METHODS: We recruited one hundred and thirty-three children, aged 4-8 years with doctor-diagnosed CRS with or without asthma. The following procedures were performed in all participants: face-to-face standardized Sinus and Nasal Quality of Life questionnaire, skin prick test, taste perception testing, nasopharynx swab, and sampling of the nasal mucosa. Upper-airway dysbiosis was defined separately by asthma-specific microbiome composition and reduced biodiversity. Multivariate methods were used to define the risk factors for asthma and upper-airway dysbiosis and their specific inflammatory profile of nasal mucosa. RESULTS: The asthma-specific upper-airway microbiome composition reflected by the decreased ratio of Patescibacteria/Actinobacteria independently of atopy increased the risk of asthma (OR:8.32; 95%CI: 2.93-23.6). This asthma-specific microbiome composition was associated with ≥ 7/week sweet consumption (OR:2.64; 95%C:1.11-6.28), reduced biodiversity (OR:3.83; 95%CI:1.65-8.87), the presence of Staphylococcus strains in the nasopharynx (OR:4.25; 95%CI:1.12-16.1), and lower expression of beta-defensin 2, IL-5, and IL-13 in the nasal mucosa. The reduced biodiversity was associated with frequent antibiotic use and with a higher nasal expression of IL-17 and T1R3 (sweet taste receptor). In asthmatic children, reduced sweet taste perception was observed. CONCLUSIONS: Specific upper-airway dysbiosis related to frequent sweet consumption, frequent antibiotic courses, and altered nasal immune function increases the risk of asthma in young children with CRS.