Extra-esophageal Pepsin From Stomach Refluxate Promoted The Formation Of Vocal Fold Polyps

Objective:To explore the relationship between gastroesophageal reflux diease(GERD)and vocal fold polyps(VFP),and study its possible pathogenesis.Materials and Method:27 patients with VFP and 20 controls without VFP were recruited between May 2018 and October 2018.All the subjects complete saliva pepsin test,GerdQ questionnaire,45 subjects finished24-hour multichannel intraluminal impedance and PH(24h MII-pH)monitoring,and 25 resection specimens of VFP for immunohistochemical(IHC)and double immunofluorescence(IF)staining.Result:The incidence of GERD in the VFP group was significantly higher than the control group(?~2=8.82,p=0.003).Patients with VFP had higher GerdQ score,pepsin concentraion and positive rate,and the difference is statistically significant(p<0.05).Moreover,the acid reflux parameter values,number of proximal reflux and upright reflux were higher in the VFP group,and the difference is statistically significant(p<0.05).To analyze the correlation between salivary pepsin concentration and pepsin in tissue,we found that pepsin concentration in saliva were significantlypositivelycorrelatedwithpepsinlevelsin tissue(r~2=0.50,p=0.011).Pepsin and TGF-?1-positive cells were colocalized with CD45RO-positive cells.The IHC staining result shows that the majority of VFP patients had a positive expression of pepsin(20/25,80%),and the pepsin-positive cells were found both in the squamous epithelium and mesenchyme.The IHC staining of TGF-1 in VFP revealed a similar area to pepsin staining in VFP.Conclusion:The laryngeal inflammation caused by pepsin may promote the formation of vocal fold polyps,this may suggested a potential pathogenesis of VFP.Pepsin from extro-esophageal refluxate is significantly associated with VFP.In addition,we found that based on IHC for VFP as a diagnosis standard,salivary pepsin test was a reliable method to diagnose extra-esophageal reflux.