Endotypes of chronic rhinosinusitis in children

Currently, there are no sensitive markers with sufficient specificity to diagnose endotypes of chronic rhinosinusitis in children which would allow to identify targets for biological therapy. Objective. To identify diagnostic biomarkers of chronic rhinosinusitis endotypes in children. Patients and methods. The study included 160 children with chronic rhinosinusitis aged from 5 to 17 years, who were divided into five groups by disease’s phenotype: without polyps and comorbid background, with polyps, with allergic rhinitis, with bronchial asthma and with pharyngeal lymphoid ring hypertrophy. The control group consisted of 30 healthy children. All patients underwent a full clinical, endoscopic examination, computed tomography of sinuses and detection of inflammatory biomarkers in blood serum: IL-5, IFN-γ, IL-17α, TNF-α, IL-22; IL-6, IL-33, IL-35, eosinophil cationic peptide (ECP), myeloperoxidase (MPO), TGF-β1, total IgE. Results. A number of clusters equal 5 were identified by clustering method. Based on the association data between phenotypes and endotypes of chronic rhinosinusitis, 5 endotypes with significant association were identified (c2 (Yates)=270.6; p<0.0001). The two endotypes (without polyps and with hypertrophy of the pharyngeal lymphoid ring) had the greatest agreement with phenotype. Endotype ranking revealed diagnostically significant biomarkers. Conclusion. Diagnostic serum biomarkers for endotype of rhinosinusitis with polyps are IL-17α, IL-22, TNF-α, IL-33 and a decrease in IL-35 level; for rhinosinusitis endotype in combination with allergic rhinitis — an increase in the levels of total IgE, IL-5 and ECP; for endotype of rhinosinusitis in combination with bronchial asthma — reduced IL-35 level; for endotype without polyps — increased levels of TGF-β1 and IFN-γ; for endotype in combination with pharyngeal lymphoid ring hypertrophy — increased levels of MPO, TGF-β1 and IL-35.