| BackgroundThe prevalence of laryngopharyngeal reflux disease(LPRD)is increasing in recent years.It is estimated that 10%of patients visiting otolaryngology clinics have reflux-attributed disease.Reflux of gastric contents into the laryngopharynx and injury to the mucous membranes is another important factor which contributes to several otolaryngology specific diseases.However,there are many problems in the pathogenesis,diagnosis and treatment of LPRD.The degree of LPRD is related to the composition,the frequency,and the duration of reflux.As the relevant normal reference range for pH monitoring parameters or expression of pepsin in the laryngopharynx is not clear,what level of laryngopharyngeal environment pH,the number of reflux expisodes or pepsin amount contributes to pathological changes is no uniform standard and objective evidence.Tweenty four-hour pharyngeal pH monitoring is a clinically recognized highly sensitive method for diagnosing reflux diseases.At present the pH monitoring parameters of diagnosing gastroesophageal reflux disease(GERD)was used to diagnose LPRD.However,GERD and LPRD are not exactly the same in clinical symptoms,pathophysiology,and clinical sequelae.It will underestimate the number of reflux episodes and result in a higher rate of missed diagnosis when using the diagnostic criteria for gastroesophageal reflux exposure events or focusing only on monitoring parameters with a pH of less than 4.The oropharyngeal Dx-pH monitorin,a device specially designed for the detection of laryngopharyngeal reflux and different from the previous esophageal pH monitoring,has attracted more and more attention of scholars.It has a high sensitivity and the patient is well tolerated.However,there is controversy about whether there is a physiological pH<4 acid reflux exposure in the normal environment of the laryngopharynx and the number of reflux expisodes and the normal range of percent time at different baseline pH is not yet clear basing on this test systom.As an important injury factor of reflux disease,pepsin enters into the saliva as it reaches laryngophraryx with reflux.Different methods have been used to detect the concentration of pepsin in saliva samples from patients with LPRD and healthy volunteers in many studyies.The results of these studies show that the detection of pepsin concentration in saliva is a simple,non-invasive,and cost-effective means of diagnosing LPRD.However,there is still controversy about whether there is pepsin in the saliva of healthy people.The normal concentration value of pepsin in saliva is not exact.Therefore,when the laryngopharynx mucosa suffered pathological injury,what the concentration of pepsin in saliva is can not be defined.Histopathological examination is a direct qualitative diagnosis and often hailed as a "gold standard".Detection of pepsin in tissue by immunohistochemical staining is a reliable and special method to diagnose LPRD,while it is controversial whether there is pepsin in the laryngopharyngeal tissue of healthy people.Normal range of pepsin expression level in laryngopharyngeal tissue among the healthy subjects is not clear.Thus,the pathological diagnostic criteria for pepsin expression in laryngopharygeal mucosa are not consistent.In addition,the studies on the pH of the laryngopharyx among the healthy population,the range of pepsin concentration in the saliva at different time,and the expression of pepsin in the normal laryngeal mucosa are all based on different populations at present.There are no studies on the normal values of the three diagnostic methods based on the same population..The purpose of this study was to investigate the normal oropharyngeal pH value and related pH monitoring parameters by the oropharyngeal Dx-pH monitoring system,and to use an enzyme-linked immunosorbent assay(ELISA)to investigate the 24-hour saliva pepsin concentration in the normal population and the change,and to study the level of pepsin expression through immunohistochemical techniques in the normal population and its significance,and to explore the larygopharyngeal reflux score range of the normal population and the significance based on the same population.It is expected that the results of this study will provide normal data reference for subsequent studies in the development of diagnostic criteria for LPRD.Materials and MethodsThis study was conducted from September 2016 to December 2017 at local Hospital.When meeting the inclusion and exclusion criteria,the volunteers will be recruited and then complete the required clinical and experimental test items,including questionnaires,physical examination,electronic nasopharyngoscopy,oropharyngeal Dx-pH monitoring,salivary pepsin detection and pathological examination of pepsin in ventricle mucosal tissue.The obtained experimental data was statistically analyzed by SPSS23.0 statistical software package.The test level P<0.05 was statistically significant.Result1.The average oropharyngeal pH was 6.59±0.34 in the 107 healthy volunteers.Acidic reflux didn't find in the subjects with pH less than 4,and the percentage of time when the pH was higher than 6.5 was less than that reported in the Literature.During the total time of 24 hours and upright or supine position,the Dx-pH monitoring parameters in the pH baseline lower than 6.5,6.0,5.5,5.0 were higher than those reported in the literature.2.The concentration of pepsin in salivary pepsin concentration was different at different time(P=0.004).The concentration of pepsin in saliva was the highest upon waking at morning 6.19(0,12.42)ng/ml,and the concentration of pepsin in saliva was the lowest at one hour after dinner 0(0,0).3.Immunohistochemical staining of pepsin in the ventricular mucosa:6 cases were positive(6.8%),51 cases were weak positive(58%)and 31 cases were negative(35.2%)in the 88 healthy volunteers.Pepsin is mainly detected in the cytoplasm of squamous epithelial mucosa and stroma.4.There was no gender difference in pepsin concentration at different time and pepsin immunohistochemistry staining scores,and no significant correlation with age and BMI.5.The healthy subjects' RFS score,with an average RFS of 7.1±2.6,followed a normal distribution.The mean RFS scores of male and female volunteers were 8.3±2.5 and 6.1±2.3,respectively,which was statistically significant(P<0.001),suggesting males had higher RFS scores than female.Conclusion1.The average pH value of the pharyngeal environment in normal population was 6.59±0.34.The 95-percentile of the Dx-pH monitoring parameters at different pH baselines could be used as a diagnostic reference value for diagnosing the pharyngeal reflux to improve the specificity of oropharynx Dx-pH monitoring and diagnosis.2.Pepsin could be used as a marker of reflux to the mucous membranes of the pharynx.The recommended normal range of salivary pepsin concentration in the morning upon waking was 0 to 55.39 ng/ml.3.Physiological reflux existed in the larynx and pharynx of some healthy subjects.4.There is a gender difference in RFS scores among healthy people.It was recommended that the normal reference range of RFS scores was 0 to 12 in male subjects and 0 to 9 in female subjects. |
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