Study On The Heterogeneity Of Early Diagnosis And Oral Glucocorticoid Efficacy In Patients With Chronic Sinusitis With Intrinsic Nasal Polyp

Objective:Chronic rhinosinusitis with nasal polyps(CRSwNP)is a heterogeneous disease with different clinical characteristics and different treatment responsiveness.The aims of this study were to compare the nasal fluid cytology and cytokines between eosinophilic CRSwNP(eCRSwNP)and non-eosinophilic CRSwNP(neCRSwNP)and establish a new multivariate model to predict eCRSwNP before surgery to improve personalized treatment for CRSwNP patients.Methods:Eighty-six consecutive patients with CRSwNP and sixteen healthy controls were recruited in this study.Nasal fluid(NF)was collected from all subjects and nasal polyp tissue was collected during the surgery.The differential cell counts and concentrations of IL-6,IL-8,TNF-α and IL-10 in NF were measured.Univariate and multivariate logistic regression analysis was used to identify predictors for eCRSwNP.Results:There were more inflammatory cells in NF of CRSwNP than controls.The eosinophil percentage was significantly higher in eCRSwNP than neCRSwNP and controls.The concentration of IL-8 was significantly higher in neCRSwNP than in eCRSwNP and controls.Blood eosinophilia,nasal fluid eosinophilia,higher total ethmoid score/total maxillary score(E/M)ratio and higher visual analogue scale(VAS)score were associated with eCRSwNP,the area under receiver operating characteristic curve(AUC)was 0.800,0.755,0.703 and 0.648,respectively.Using the coefficients of multivariate regression,we set up a scoring system to predict eCRSwNP with three of the variates and the AUC was 0.883.Conclusion:ECRSwNP,neCRSwNP and healthy controls demonstrated different cytology and cytokine profiles in NF.A new preoperational multivariate prediction model for eCRSwNP with NF eosinophilia,blood eosinophilia and higher E/M ratio was established.Objective:The mechanisms underlying different responses of chronic rhinosinusitis with nasal polyps(CRSwNP)patients to oral glucocorticoids(GC)are unclear.The major aims of this study were to explore the transcriptomic and oxidative lipidomic signatures and the effects of GC in patients with different clinical responses,and screen candidate biomarkers predicting clinical responses.Methods:Nasal polyp biopsies were obtained before and after 14-day oral GC treatment from 16 patients with CRSwNP,and normal nasal mucosa specimens were collected from 12 control subjects.RNA sequencing and oxidative lipidomics were performed,and differential gene expression analysis was conducted in the Responder and Non-responder groups at baseline and after treatment.Results:In the Responder group,GC significantly improved clinical symptoms and reduced tissue eosinophil infiltration.Meanwhile,GC led to a pronounced transcriptomic reversion with robust suppression of inflammatory responses and abnormal metabolism of extracellular matrix,as well as restoration of cilia function.However,non-responders were mainly characterized by epithelial hyperplasia and keratinization,with much less transcriptomic improvement after GC treatment.Higher expression of type 2 inflammatory molecules(CCL13,IGHE,CCL18,CCL23,CCR3 and CLC)with lower levels of LACRT,PPDPFL,DES,C6,MUC5B and SCGB3A1 were related to a stronger clinical response to GC.Besides decreased prostaglandins and increased leukotrienes,increased dysregulation in other oxylipid mediators derived from polyunsaturated fatty acids was determined in nasal polyps,which was ameliorated by GC treatment.Conclusions:Systemic GC exert anti-inflammatory effects,improve tissue remodeling,restore cilia function,and ameliorate dysregulation of oxylipid mediator pathway in CRSwNP.GC-responders exhibited different transcriptomic signatures from nonresponders.