Objective: To investigate the effect of gastroesophageal reflux disease (GERD) on the clinical characteristics of patients with laryngopharyngeal reflux disease(LPRD). Methods: The data of 141 patients with symptoms of LPRD, who were admitted to the Department of Pharyngology, Laryngology& Phonosurgery at the Sixth Medical Center of the PLA General Hospital from November 2020 to October 2021, were retrospectively analyzed.There were 118 males and 23 females, aged 28-75 (56.72±10.04) years old. The included patients underwent simultaneous 24-hour hypopharyngeal and esophageal multichannel intraluminal impedance pH monitoring (24h-HEMII-pH), salivary pepsin test at multiple times, Reflux Symptom Index (RSI), and Reflux Finding Score (RFS). One laryngopharyngeal reflux event on 24 h-HEMII-pH monitoring results was used as a diagnostic criterion for LPRD. And the duration of lower esophageal pH<4.0>4.0% at 24 h or DeMeester score>14.7 were used as diagnostic criteria for GERD. Among them, patients with both positive LPRD and GERD were classified as L&G group, patients with positive LPRD and negative GERD were classified as IL group, patients with negative LPRD and positive GERD were classified as IG group, and patients with both negative LPRD and GERD were classified as N group. The differences in the clinical characteristics of reflux and salivary pepsin assay in each group were statistically analyzed. SPSS 23.0 software was applied for statistical analysis. Results: According to the 24 h-HEMII-pH results, 116 (82.3%) patients were diagnosed with LPRD and 45 (31.9%) with GERD, including 82 (58.2%) in the IL group, 34 (24.1%) in the L&G group, 11 (7.8%) in the IG group, and 14 (9.9%) in the N group. Based on the salivary pepsin test, a total of 106 patients had positive results, and the L&G group had a significantly higher rate of positive total salivary pepsin test (94.1%) and positive morning test (70.6%) than the IL group (75.6%, 26.8%), IG group (63.6%, 27.3%) and N group (35.7%, 28.6%), with chi-square values of 19.01 and 20.81, both with P<0.001. The patients in the L&G group had a significantly higher RSI score (14.0) than the IL group (7.0), IG group (1.0) and N group (0), H=52.26,P<0.001. The difference in RFS between the L&G and IL groups was not statistically significant (Z=-0.92,P>0.05). Conclusion: Combined with GERD, LPRD patients have more obvious clinical symptoms and higher positive rate of pepsin test in saliva.
Aged ; Female ; Humans ; Male ; Middle Aged ; Esophageal pH Monitoring ; Hypopharynx ; Laryngopharyngeal Reflux ; Pepsin A ; Retrospective Studies ; Adult

Objective: To investigate the possible pathophysiological mechanism of laryngopharyngeal reflux (LPR) in the development of lingual tonsil hypertrophy (LTH). Methods: The lingual tonsil tissues were collected from 73 patients [48 males and 25 females, aged from 24 to 76 (52.86±12.04) years] who underwent surgery for laryngopharyngeal diseases at the Department of Otolaryngology and Head and Neck Surgery, Southern Hospital of Southern Medical University from October 2019 to December 2020, and the lingual tonsil grade (LTG), reflux symptom index (RSI) and reflux finding score (RFS) were assessed. The expression of pepsin in LTH was detected by immunohistochemistry. The coexpression of pepsin and macrophages were detected by immunohistofluorescence. In vitro, cytological experiments and pathway assays were performed on macrophages stimulated by pepsin. Pathway alterations of macrophages in pepsin-positive high-grade LTH were detected by double-fluorescence immunohistochemistry. Data were analyzed by SPSS 20.0 software. Results: There were 44 clinically significant LPRD patients with LTG 3 and 4, and the pepsin positive rate was 88.6% (39/44). While, the pepsin positive rate of LTG 1 and 2 was 48.3% (14/29). LTG was significantly positively correlated with RFS/RSI positive rate(χ²=23.01/19.62, P<0.001/0.001; r=0.54/0.51, P<0.001/0.001) and pepsin tissue staining intensity (H=21.58, P<0.001; r=0.53, P<0.001), respectively. Pepsin and macrophages were clearly colocalized in high grade LTH. In vitro, pepsin promoted macrophage proliferation (P<0.05) and production of IL-6/IL-8 (P<0.05). Pepsin significantly up-regulated the p38/JNK MAPK pathway in macrophages (P<0.05). Pepsin up-regulated the expression of IL-6 and IL-8 of macrophages by activating the p38 MAPK pathway (P<0.05), and up-regulated the expression of IL-8 by activating the JNK pathway (P<0.05). The p38/JNK MAPK pathways were highly expressed in macrophages of pepsin-positive LTH (P<0.05). Conclusions: LPR is an important pathogenic factor in LTH. Macrophages may mediate pepsin-induced inflammation and the pathogenesis of LTH.
Female ; Male ; Humans ; Palatine Tonsil ; Pepsin A ; Interleukin-6 ; Interleukin-8 ; Hypertrophy ; Macrophages ; Laryngopharyngeal Reflux

Ascorbic acid is one of the most well-known nutritional supplement and antioxidant found in fruits and vegetables. Calcium ascorbate has been developed to mitigate the gastric irritation caused by the acidity of ascorbic acid. The aim of this study was to compare calcium ascorbate and ascorbic acid, focusing on their antioxidant activity and effects on gastric juice pH, total acid output, and pepsin secretion in an in vivo rat model, as well as pharmacokinetic parameters. Calcium ascorbate and ascorbic acid had similar antioxidant activity. However, the gastric fluid pH was increased by calcium ascorbate, whereas total acid output was increased by ascorbic acid. In the rat pylorus ligation-induced ulcer model, calcium ascorbate increased the gastric fluid pH without changing the total acid output. Administration of calcium ascorbate to rats given a single oral dose of 100 mg/kg as ascorbic acid resulted in higher plasma concentrations than that from ascorbic acid alone. The area under the curve (AUC) values of calcium ascorbate were 1.5-fold higher than those of ascorbic acid, and the C(max) value of calcium ascorbate (91.0 ng/ml) was higher than that of ascorbic acid (74.8 ng/ml). However, their T(max) values were similar. Thus, although calcium ascorbate showed equivalent antioxidant activity to ascorbic acid, it could attenuate the gastric high acidity caused by ascorbic acid, making it suitable for consideration of use to improve the side effects of ascorbic acid. Furthermore, calcium ascorbate could be an appropriate antioxidant substrate, with increased oral bioavailability, for patients with gastrointestinal disorders.
Animals ; Ascorbic Acid ; Biological Availability ; Calcium* ; Fruit ; Gastric Juice ; Humans ; Hydrogen-Ion Concentration ; In Vitro Techniques* ; Models, Animal ; Pepsin A ; Plasma ; Pylorus ; Rats ; Ulcer ; Vegetables

OBJECTIVES: To investigate the content of pepsin in salivary, and to assess the laryngophargeal lesions based on the reflux founding score (RFS) scale in asymptomatic volunteers, in order to provide a reference for the diagnosis of laryngopharyngeal reflux. METHODS: A total of 91 asymptomatic subjects were recruited in this study. Participants provided a fasting saliva specimen for pepsin measurement using enzyme-linked immunoadsorbent assay, completed the reflux symptom index (RSI) assessment and underwent laryngostroboscopic examination using a rigid endoscope. Their RFS were graded according to the laryngeal findings. RESULTS: The median concentration of pepsin in 91 asymptomatic volunteers was 55.5 μg/L (range 3.53-191.64 μg/L). The mean individuals RSI was 2.24±2.34, and the mean individuals RFS was 5.78±1.74. CONCLUSIONS Our data demonstrate that certain concentration of pepsin was detected and showed a higher RFS score in asymptomatic volunteers.
Humans ; Laryngopharyngeal Reflux ; diagnosis ; Laryngoscopy ; Pepsin A ; analysis ; Saliva ; chemistry ; Volunteers

BACKGROUND/AIMS: Increased salivary pepsin could indicate an increase in gastro-esophageal reflux, however, previous studies failed to demonstrate a correlation between salivary pepsin concentrations and 24-hour esophageal acid exposure. This study aims to detect the salivary pepsin and to evaluate the relationship between salivary pepsin concentrations and intercellular spaces (IS) in different gastroesophageal reflux disease phenotypes in patients. METHODS: A total of 45 patients and 11 healthy volunteers were included in this study. All subjects underwent upper gastrointestinal endoscopy, 24-hour ambulatory multichannel impedance-pH (MII-pH) monitoring, and salivary sampling at 3-time points during the 24-hour MII-pH monitoring. IS were measured by transmission electron microscopy, and salivary pepsin concentrations were determined by enzyme-linked immunosorbent assay. RESULTS: The IS measurements were greater in the esophagitis (EE), non-erosive reflux disease (NERD), and hypersensitive esophagus (HO) groups than in the functional heartburn (FH) and healthy volunteer groups, and significant differences were indicated. Patients with NERD and HO had higher average pepsin concentrations compared with FH patients. A weak correlation was determined between IS and salivary pepsin among patients with NERD (r = 0.669, P = 0.035). CONCLUSIONS: We confirmed the presence of a higher level of salivary pepsin in patients with NERD than in patients with FH. Salivary pepsin concentrations correlated with severity of mucosal integrity impairment in the NERD group. We suggest that in patients with NERD, low levels of salivary pepsin can help identify patients with FH, in addition the higher the pepsin concentration, the more likely the severity of dilated IS.
Endoscopy, Gastrointestinal ; Enzyme-Linked Immunosorbent Assay ; Esophagitis ; Esophagus ; Extracellular Space ; Gastroesophageal Reflux* ; Healthy Volunteers ; Heartburn ; Humans ; Microscopy, Electron, Transmission ; Pepsin A* ; Phenotype

BACKGROUND AND OBJECTIVES: To compare the simple spitting method and the Salivette® method of collecting saliva for detecting pepsin in patients with laryngopharyngeal reflux disease (LPRD). SUBJECTS AND METHOD: Thirty-two patients diagnosed with LPRD by 24 hour multichannel intraluminal impedance and pH monitoring were enrolled prospectively. The amounts of pepsin in saliva determined by the simple spitting method and the Salivette® method were compared. RESULTS: Simple spitting showed higher sensitivity, specificity, accuracy, positive predictive value and negative predictive value. There was no statistically significant difference between the amount of pepsin detected by simple spitting (10.07±11.68 ng/mL) versus that detected using the Salivette® method (7.09±7.27 ng/mL) (p=0.258). CONCLUSIONS: The simple spitting method has higher sensitivity, specificity and accuracy than the Salivette® method for detecting pepsin in patients with LPRD.
Electric Impedance ; Humans ; Hydrogen-Ion Concentration ; Laryngopharyngeal Reflux* ; Methods* ; Pepsin A* ; Prospective Studies ; Saliva* ; Sensitivity and Specificity

Acute non-variceal upper gastrointestinal bleeding, the most common etiology of which is peptic ulcer disease, remains a persistent challenge despite a reduction in both its incidence and mortality. Both pharmacologic and endoscopic techniques have been developed to achieve hemostasis, with varying degrees of success. Among the pharmacologic therapies, proton pump inhibitor (PPI) remains the mainstay of treatment with potent acid suppression. Maintenance of the intragastric pH level above 6 by the administration of PPI prevents hemolysis caused by acid or pepsin and thereby promotes aggregation of platelets. Intragastric acid suppression can be achieved more effectively with continuous intravenous infusion of PPI after intravenous bolus injection. A high dose intravenous PPI is effective in reducing the risk of rebleeding, the need for surgery and repeated endoscopy. However, data regarding non-high dose intravenous PPIs are limited. In the future, novel PPIs and potassium-competitove acid blocker are in the area of interest. Combination therapy with the use of endoscopic hemostatic treatment and intravenous PPI administration is known to result in the best outcome for non-variceal upper gastrointestinal bleeding.
Endoscopy ; Hemolysis ; Hemorrhage* ; Hemostasis ; Hydrogen-Ion Concentration ; Incidence ; Infusions, Intravenous ; Mortality ; Pepsin A ; Peptic Ulcer ; Proton Therapy

Laryngopharyngeal reflux (LPR) is a very prevalent condition with a rising incidence. The diagnosis remains challenging and often controversial because the pathophysiology of LPR is often poorly understood and there is currently no diagnostic gold standard for LPR. Pepsin is produced by gastric chief cells in zymogen form as pepsinogen, and subsequently cleaved by the hydrochloric acid in the stomach, generating active pepsin protein. Pepsin is only produced in the stomach, and thus when detected in the laryngopharynx, it can be used as a specific marker for reflux. The carcinogenic properties of the gastric contents may also lead to cancer in target organs especially considering that they do not have intrinsic protective mechanisms as found in the esophagus. Many studies have demonstrated a high prevalence of LPR in patients with laryngeal cancer, but these studies are confounded by the cofactor such as smoking and alcohol consumption. This review focuses on the current studies about pepsin as a specific marker for LPR and putative relationship between pepsin and laryngeal cancer.
Alcohol Drinking ; Carcinogenesis ; Chief Cells, Gastric ; Diagnosis ; Esophagus ; Humans ; Hydrochloric Acid ; Hypopharynx ; Incidence ; Laryngeal Neoplasms ; Laryngopharyngeal Reflux* ; Pepsin A* ; Pepsinogen A ; Prevalence ; Smoke ; Smoking ; Stomach

Adenoid hypertrophy is a disease that mostly occurs among children of 3-5 years old. It is caused by repeated inflammation and infection of nasopharynx and its adjoin parts, or the adenoid itself, which will finally leads to pathological hyperplasia of adenoid. With so much information we have acquired about this disease, its specific mechanism remains unknown. In recent years, some researches have indicated that adenoid hypertrophy may have something to do with extra-gastroesophageal reflux, in which pepsin plays a very important role, and pepsin will do a series of pathological damages to the upper airway as it reaches the upper respiratory tract. Based on relative domestic and foreign literature, this paper attempts to make a review about the relationship between gastroesophageal reflux and adenoid hypertrophy.
Adenoids ; pathology ; Child ; Gastroesophageal Reflux ; complications ; Humans ; Hypertrophy ; complications ; Nasopharynx ; pathology ; Pepsin A ; metabolism

OBJECTIVE: To analyze the role and significance of pepsin and pepsinogen in the pathogenesis of OME in children. METHOD: Pediatric patients with otitis media aged 2-8 years who enrolled in our department of the hospital from May of 2012 to December of 2012 were set as experimental group (38 cases, 48 ears) which should be underwent tympanic membrane puncture/tube insertion. Meanwhile, pediatric patients waiting for cochlear implant without otitis media (10 ears), were set as control group. Middle ear lavage fluid and plasma samples from the two groups were collected and detected using enzyme-linked immune method for pepsin and pepsinogen. RESULT: The concentrations of pepsin and pepsinogen in the middle ear lavage fluid of OME group [(48.8 ± 415.99) ng/ml and 676.32 ± 336.71)ng/ml] were significantly higher than those in the control group [(8.20 ± 4.59)ng/ml and (77.27 ± 50.33) ng/ml] (P < 0.01). Meanwhile, the concentration of pepsinogen in the middle ear lavage of OME patients was significantly higher than that of plasma (P < 0.01). The concentration of pepsin in the middle ear lavage fluid from the dry ear subgroup was lower than those in the serum ear and mucous ear subgroups (P < 0.01), but there was no significant difference about concentrations of pepsinogen among the dry ear, serum ear and mucous ear subgroups (P > 0.05). CONCLUSION Pepsin and pepsinogen in the middle ear cavity of OME patients maybe originated from laryngopharyngeal reflux (LPR), indicating that LPR is associated with the pathogenesis of OME in children.
Child ; Child, Preschool ; Ear, Middle ; metabolism ; Enzyme-Linked Immunosorbent Assay ; Humans ; Laryngopharyngeal Reflux ; physiopathology ; Otitis Media with Effusion ; metabolism ; Pepsin A ; metabolism ; Pepsinogen A ; metabolism ; Tympanic Membrane ; surgery