Role Of Nasal Nitric Oxide In Diagnosis And Phenotypes Of Chronic Sinusitis

BackgroundChronic sinusitis(CRS)is a common chronic inflammatory disease in the nose.Nitric oxide is considered as a marker of respiratory tract inflammation.In the upper respiratory tract,nasal nitric oxide(nNO)is mainly produced by the mucosa of the nasal cavity and sinus.Therefore,nNO has certain clinical significance for the diagnosis of CRS disease.EPOS2020 divides CRS into type 1,type 2 and type 3 according to the type of inflammatory immune response.The immune inflammation type of type 2 was mainly characterized by increased eosinophils.It was found that the degree of tissue eosinophil infiltration and inflammatory response was closely related to the severity and prognosis of CRS disease.In addition,some studies have found that type 2 immune-mediated inflammation leads to epithelial barrier dysfunction,which is characterized by the reduction of epithelial cell diversity caused by basal cell differentiation.Our team study found that nasal polyp epithelial tissue remodeled mainly manifested in three types:epithelial hyperplasia,goblet cell hyperplasia and epithelial squamous cell metaplasia.Therefore,the study of nNO level in the clinical diagnosis of chronic sinusitis and the correlation between intrinsic type and epithelial tissue remodeling type is of certain significance for the accurate diagnosis of CRS.ObjectiveTo investigate the clinical value of nasal nitric oxide(nNO)in the diagnosis of chronic sinusitis(CRS)Research methodsThe clinical characteristics of 135 CRS patients and 40 non-CRS patients were retrospectively analyzed,including patients’ age,BMI,peripheral blood eosinophils,E/M ratio,CT Lund-Mackay score,pathological epithelial type,and nNO level.Participating cases will be used for group analysis based on clinical characteristics and laboratory examination.CRS patients were classified as chronic sinusitis without nasal polyps group and chronic sinusitis with nasal polyps group;CRSsNP and CRSwNP patients were divided into allergic and unallergic groups;CRSwNP is classified into eosinophilic sinusitis with nasal polyps group and non-eosinophilic sinusitis with nasal polyps group,according to the epithelial remodeling situation,it is divided into epithelial hyperplasia group,goblet cell hyperplasia group and squamous cell metaplasia group.The difference of nNO level among each group and the correlation of clinical data were analyzed.The diagnostic value of nNO in CRS was analyzed by ROC curve and Logistic regression model.Results1.The level of nNO in CRS CRSsNP and CRSwNP patients was significantly lower than in non-CRS patients(P<0.001);The level of nNO in CRSwNP patients was significantly lower than in CRSsNP patients(P<0.001).The level of nNO in the eCRSwNP patients was significantly lower than in the non-eCRSwNP patients(P<0.001).The level of nNO in CRSwNP epithelial hyperplasia group and goblet cell hyperplasia group was significantly lower than that in squamous metaplasia group(P<0.05).2.In CRS and CRSwNP groups,the nNO levels were significantly negatively correlated with E/M ratio and Lund-Mackay score(r=-0.423,P<0.001;r=-0.650,P<0.001;r=-0.434,P＜0.001;r=-0.608,P<0.001,respectively).The levels of nNO in CRSwNP with allergy and CRSwNP without allergy were significantly negatively correlated with E/M ratio and Lund-Mackay score(r=-0.503,P<0.05;r=-0.632,P<0.01;r=-0.400,P<0.01;r=-0.608,P<0.001,respectively).The levels of nNO in non-eCRSwNP and eCRSwNP groups were significantly negatively correlated with E/M ratio and Lund-Mackay score(r=-0.512,P<0.01;r=-0.624,P<0.01;r=-0.288,P<0.01;r--0.532,P<0.01,respectively).The levels of nNO were negatively correlated with E/M ratio and Lund-Mackay score in both epithelial hyperplasia and goblet cell hyperplasia groups(r=-0.518,P<0.05;r=-0.640,P<0.01;r=-0.421,P<0.01;r=-0.599,P<0.001,respectively).3.Multivariate Logistic regression analysis found a significant correlation between nNO level and CRS typing(P<0.01).4.In distinguishing non-CRS from CRS CRSsNP and CRSwNP,nNO had moderate predictive value(AUC=0.849,P<0.001;AUC=0.771,P<0.001;AUC=0.894,P<0.001,respectively).In distinguishing CRSsNP from CRSwNP,nNO had moderate predictive value(AUC=0.776,P<0.01).In distinguishing non-CRS from non-eCRSwNP,nNO had moderate predictive value(AUC=0.861,P<0.001)and had high predictive value from eCRSwNP(AUC=0.910,P<0.001).In distinguishing non-CRS from epithelial hyperplasia,goblet cell hyperplasia and squamous cell metaplasia,nNO had moderate predictive value(AUC=0.898,P<0.001;AUC=0.882,P<0.001;AUC=0.720,P=0.025,respectively).ConclusionThe nNO has clinical application value in the preliminary diagnosis of CRS,distinguish CRSsNP and CRSwNP,predict eCRSwNP and non-eCRSwNP,as well as the prediction of nasal polyp lesion scope and epithelial tissue remodeling type.