Pepsin Levels Research Articles

Evaluation of Salivary Pepsin Levels and Dental Erosion in Patients With Gastroesophageal Reflux Disease.

Background Gastroesophageal reflux disease (GERD) is a common gastrointestinal condition affecting many individuals worldwide. GERD is characterized by esophageal symptoms and may contribute to various extraesophageal symptoms, including dental erosion (DE). This study aimed to estimate the levels of pepsin in the saliva of GERD patients to evaluate and compare the activity of pepsin between the GERD and healthy groups and investigate the prevalence of DE in the GERD group. Methodology In this case-control study, 40 patients with GERD, diagnosed with an endoscope, and 35 healthy subjects were included.Patients and healthy individuals were subjected to the GERD questionnaire (GerdQ). A dental assessment was performed using the Basic Erosive Wear Examination (BEWE).A total score of the BEWE risk level was obtained by summing the scores obtained in each sextant (no risk = ≤2, low risk = 3-8, medium risk = 9-13, and high risk = >13). Five milliliters of unstimulated saliva were collected in a sterile tube. The salivary pepsin levels examined using the enzyme-linked immunosorbent assay were recorded for both groups. Results DE was significantly more frequent in GERD patients compared to healthy subjects. Overall, 32 (80%) GERD patients and 11(31.4%) healthy individuals had DE risk. The mean salivary pepsin was 43.60 ± 10.61 ng/mL in the GERD group and 20.60 ± 9.27 ng/mL in the healthy group. A statistically significant difference was found in pepsin levels between the two groups (p < 0.001). Conclusions The study concluded that GERD patients had a higher prevalence of DE than healthy individuals. Our findings suggest that elevated salivary pepsin levels and their role as a factor responsible for DE need further evaluationto understand the mechanisms of pepsin-mediated damage leading to DE.

THE PROGNOSTIC SIGNIFICANCE OF SALIVARY PEPSIN LEVEL IN THE DEVELOPMENT OF RECURRENT RESPIRATORY PATHOLOGY IN INFANTS WITH RUMINATION SYNDROME

Introduction. Infant rumination syndrome (IRS) is most common among infants with functional disorders of the gastrointestinal tract and can lead to the development of recurrent respiratory pathology. Pepsin is believed to play a key role in the upper airway mucosa impairment. The objective of the study was to determine the prognostic significance of salivary pepsin level in the development of recurrent respiratory pathology in infants with rumination syndrome. Materials and Methods. We analyzed the clinical and anamnestic data of 55 infants: the main group consisted of 38 children with apparent rumination syndrome, and the comparison group included 17 healthy children with no clinical manifestations of this syndrome. Salivary pepsin and IL-8 levels were measured three times a day by the enzyme-linked immunosorbent assay (Human Pepsin Elisa Kit and Human IL-8 ELISA Kit, USA). The study results were statistically processed using the Statistica v.6.1 software package. To assess the diagnostic significance of salivary pepsin level, ROC analysis was performed to determine the optimal cut-off point and calculate the area under the ROC curve (AUC) with 95% CI and operating characteristics of the criterion (sensitivity and specificity). Results and Discussion. Daily monitoring of salivary pepsin in infants showed that pepsin level was significantly higher in the main group vs. the comparison group, both for average daily values and intermediate indicators. No statistically significant difference was found between the three saliva samples and the daily average pepsin level in the main group of infants, which may be indicative of latent episodes of reflux during the day. A direct correlation was found between salivary levels of IL-8 and pepsin levels in the main group of children (r = 0.78, p &lt; 0.05). Among the potential predictors of recurrent respiratory pathology risk in infants with rumination syndrome, the following were established: fasting pepsin level &gt; 309.27 pg/ml, pepsin level in 1 hour after feeding &gt; 275.73 pg/ml, and pepsin level after regurgitation &gt; 532.31 pg/ml. Conclusions. Fasting pepsin level &gt; 309.27 pg/ml and pepsin level in 1 hour after feeding &gt; 275.73 pg/ml can be used in a multiple logistic regression model to predict the risk of recurrent respiratory pathology, taking into account other clinical, anamnestic, and laboratory data. A post-regurgitation pepsin level &gt; 532.31 pg/ml is an independent predictor and can be used alone.

SPECIFIC FEATURES OF THE ORAL MICROBIOME IN YOUNG CHILDREN WITH ARYNGOPHARYNGEAL REFLUX AND ITS ROLE THE DEVELOPMENT OF RECURRENT RESPIRATORY DISEASES.

The aim: To examine the composition of the oral microbiome in young children with laryngopharyngeal reflux (LPR) and its role the development of recurrent respiratory diseases. Materials and methods: There were examined 38 children with physiological gastroesophageal reflux (GER), 18 children with LPR who had a medical history of recurrent bronchitis and 17 healthy children (control group). The study included the collection of anamnesis, objective examination. The qualitative and quantitative microbial composition of the upper respiratory tract was performed obtained by oropharyngeal deep swab. Salivary pepsin level and IL-8 were determined by enzyme-linked immunosorbent assay. Results: This research showed significant alterations in the oral microbiome of patients with GER and LPR as compared to healthy control. We found that gram-negative microbiota such as Klebsiella pneumoniae, Escherichia coli, Proteus vulgaris, Proteus spp. and Candida albicans were identified in children with GER and LPR compared to the healthy control. At the same time, the amount of such a representative of the normal microbiome as Streptococcus viridans in children with LPR was sharply reduced. There were established a much higher mean salivary pepsin level of the patients with LPR than in the GER and control group. We found the association between high pepsin levels, saliva IL-8 levels and frequency of respiratory pathology in children with LPR. Conclusions: Our study confirms that increased levels of pepsin in saliva are a risk factor for recurrent respiratory diseases in children with LPR.

Role of Laryngopharyngeal Reflux Changes in Children with Adenoid Hypertrophy: A Randomized Controlled Prospective Study.

This prospective randomized controlled analysis aimed to assess the changes in laryngopharyngeal reflux (LPR) in children with adenoid hypertrophy (AH). Study design: a prospective, randomized, and controlled analysis. The reflux symptom index (RSI) and the reflux finding score (RFS) scores were used to evaluate the laryngopharyngeal reflux changes in children diagnosed with adenoid hypertrophy. The pepsin concentration in salivary samples was examined, and the positive pepsin was used to assess the sensitivity and specificity of RSI, RFS, and RSI combined with RFS in forecasting LPR. In 43 children with AH, the sensitivity of the RSI and RFS scale (used alone or in combination) in diagnosing pharyngeal reflux in children with adenoid hypertrophy was lower. Pepsin expression was identified in 43 items of salivary samples, with a total positive rate of 69.77%, most of which were optimistic. The expression level of pepsin was positively correlated with the grade of adenoid hypertrophy (r = 0.576, P < 0.01). Based on the positive rate of pepsin, we found that the sensitivity and specificity of RSI and RFS were 5.77%, 35.03%, and 91.74%, 55.89%. Moreover, there was a noticeable distinction in the number of acid reflux episodes between the LPR-positive and LPR-negative groups. There is a special connection between LPR change and children's AH. LPR exerts a crucial role in the progression of children's AH. Because of the low sensitivity of RSI and RFS, it is not suitable for LPR children to choose AH.

Clinical relevance of salivary pepsin detection in diagnosing gastroesophageal reflux disease subtypes.

Gastroesophageal reflux disease (GERD) is heterogeneous with a varied symptom spectrum and reflux profiles. Its definite diagnosis often requires invasive tools including endoscopy or reflux monitoring. The aim of this study was to investigate the clinical relevance of salivary pepsin detection as a non-invasive screening tool to diagnose GERD of different subtypes. A total of 77 patients with suspected GERD symptoms and 12 asymptomatic controls were analysed. All participants performed symptom evaluation, upper endoscopy, esophageal manometry, and 24-hour multichannel intraluminal impedance-dual pH probe monitoring. Saliva was self-collected across three different time points: at early fasting, postprandially, and at symptom occurrence. Salivary pepsin levels were measured via Peptest. The optimal threshold of salivary pepsin for diagnosing distal or proximal reflux was determined according to a receiver-operating characteristic curve. The average salivary pepsin concentration of suspected GERD patients was significantly higher than that of controls (100.63 [68.46, 141.38] vs 67.90 [31.60, 115.06] ng/mL, P = 0.044), although no difference was found among patients with different symptom spectrums. The distal reflux group had a higher average pepsin concentration than non-reflux patients (170.54 [106.31, 262.76] vs 91.13 [63.35, 127.63] ng/mL, P = 0.043), while no difference was observed between the distal reflux group and the proximal reflux group. The optimal cut-off value of salivary pepsin concentration for diagnosing pathological distal reflux was 157.10 ng/mL, which was higher than that for diagnosing pathological proximal reflux (122.65 ng/mL). The salivary pepsin concentration was significantly correlated with distal and proximal reflux parameters. Salivary pepsin measurement can help in identifying true GERD with pathological distal reflux or proximal reflux, regardless of different symptom spectrums. A higher threshold should be applied for diagnosing distal reflux than for proximal reflux.

Relationship Between Intra-Abdominal pressure and microaspiration of gastric contents in critically ill mechanically ventilated patients

The relationship between increased intra-abdominal pressure (IAP) and microaspiration of oro-gastric content in mechanically-ventilated patients has not yet been established. Microaspiration is proposed as one of the causes of ventilator-associated pneumonia (VAP). We aimed to investigate whether mechanically-ventilated patients with increased IAP present evidence of lung microaspiration by assessing pepsin levels in bronchial secretions and evaluated the relationship between pepsin and VAP.68 mechanically-ventilated patients and 10 control subjects were recruited from an academic ICU in Greece. IAP, pH, pepsin and total protein levels, in bronchial secretions, were assessed within 14 days. Patients underwent assessment for timely VAP diagnosis based on clinical, radiological and laboratory criteria.Pepsin and total protein levels were significantly elevated in patients compared to controls. Pepsin values correlated significantly with IAP (r = 0.61, ***p < 0.001). Multivariate regression analysis showed that IAP was an independent risk factor for increased pepsin values in bronchial secretions [OR95%CI 1.463(1.061–1.620), *p = 0.014]. Pepsin values were higher in patients with VAP, while IAP was independently associated with VAP. There was an indication towards increased VAP in patients with increased pepsin.In conclusion, our results show that pepsin in bronchial secretions may be elevated when IAP is increased, indicating microaspiration and potentially VAP.

Effect of Islamic Ramadan fasting on peptic ulcer perforation: A retrospective comparative study

Background: Fasting for extended periods of time increases gastric acid and pepsin levels and consequently the risk of peptic ulcer perforation (PUP). The effects of Ramadan fasting on PUP have not been thoroughly studied, and a few existing studies report contradictory findings. The present study compares patients with PUP operated during the Islamic Ramadan fasting to those operated outside this period and determines whether an association between Ramadan fasting and PUP exists. Patients and methods: A retrospective cross-sectional study between June 2019 and December 2020 was conducted at the Al-Nasr Hospital in the city of Ibb in Yemen. All adult patients operated for a PUP were included. Patient demographic characteristics, risk factors for peptic ulcer, ultrasound and radiological findings on admission, operative findings, postoperative complications, and outcomes were collected from the Hospital Medical Records. Patients were divided into two groups for comparison. Group A included the patients operated on during Ramadan, while Group B included patients operated on outside Ramadan. Results: A total of 40 adult patients with PUP were included. The overall mean age of the participants was 41.6 ± 8.21 years (range: 23–58 years). Most patients were men (30, 75%), and most (19, 47.5%) were admitted to the Al-Nasr Hospital between 24 and 48 hours from the start of the symptoms. History of chewing khat, consumption of nonsteroidal anti-inflammatory drugs, dyspepsia, alcohol use, and smoking were presented in 39 (97.5%), 30 (75%), 36 (90%), 6 (15%), and 35 (87.5%) patients, respectively. The most presented blood group (57.5% of patients) was O type. Most of the patients (72.5%) presented with multiple gastrointestinal symptoms such as abdominal pain, anorexia, vomiting, and constipation. An x-ray found air under the diaphragm in 85% of the patients. Ultrasonography found free fluid in 20 (50%) patients. The size of the perforated ulcer (diameter) was less than 10 mm in 65% of the patients. Postoperative complications were surgical site infection, fluid collection, need for reoperation, and intra-abdominal sepsis in 6 (15%), 4 (10%), 3 (7.5%), and 3 (7.5%) patients, respectively. Most patients (37, 92.5%) recovered well and were discharged from the hospital, and three (7.5%) patients died. The comparative analysis demonstrated a significantly younger age in those operated during Ramadan fasting (Group A) compared to those operated at other times of the year (Group B; 38.8 ± 7.42 years vs. 44.4 ± 8.17; p = 0.029). We observed a statistically significant increase in the number of patients with PUP operated on during Ramadan (p = 0.006), compared to those operated at other times of the year. There was no statistically significant difference between groups in demographic factors, radiologic findings, operative findings, or outcomes (p ≥ 0.05). During the ultrasound, ascites were more frequently diagnosed in group A patients, while acute appendicitis was generally misdiagnosed in Group B patients, a statistically significant difference (p = 0.013). Conclusions: The findings of the present study report an increase in the number of PUP operations during Ramadan fasting in Yemen, but not in postoperative complications, suggesting an association between Ramadan fasting and PUP.

Use of an innovative cuff pressure control and subglottic secretions drainage system in COVID-19 ARDS patients undergoing pronation

We conducted a proof of concept study where Anapnoguard endotracheal tubes and its control unit were used in 15 patients with COVID-19 acute respiratory distress syndrome. Anapnoguard system provides suction, venting, rinsing of subglottic space and controls cuff pressure detecting air leakage through the cuff. Alpha-amylase and pepsin levels, as oropharyngeal and gastric microaspiration markers, were assessed from 85 tracheal aspirates in the first 72 h after connection to the system. Oropharyngeal microaspiration occurred in 47 cases (55%). Episodes of gastric microaspiration were not detected. Patient positioning, either prone or supine, did not affect alpha-amylase and pepsin concentration in tracheal secretions. Ventilator-associated pneumonia (VAP) rate was 40%. The use of the AG system provided effective cuff pressure control and subglottic secretions drainage. Despite this, no reduction in the incidence of VAP has been demonstrated, compared to data reported in the current COVID-19 literature. The value of this new technology is worth of being evaluated for the prevention of ventilator-associated respiratory tract infections.

An in vitro digestion model accounting for sex differences in gastro-intestinal functions and its application to study differential protein digestibility

It is increasingly recognized that differences in gut functions govern the digestive fate of foods and oral formulations. Yet, sex-based differences are scantly addressed in food digestion research despite evidence of their implications to the performance of pharmaceutics. This work conducted a wide review and sieved 40 clinical trials to underpin sex-based differences in oral, gastric and intestinal parameters. Detailed information on identified gut function differences is detailed, for example sex-based differences in gastric pH, pepsin levels and gastric emptying as well as various intestinal parameters. In turn, quantitative parameters were applied to a computer-controlled set of bioreactors to generate an in vitro digestion model of healthy men or women. Subsequently, these models were applied to study the gastro-intestinal breakdown of lactoferrin (LF), β-lactoglobulin (β-lac), α-lactalbumin (α-lac) or whey protein concentrate (WPC) by SDS-PAGE and LC-MS/MS. This revealed specific protein regions localized to the outer rims of β-lac and α-lac were differentially degraded in men and women. Bioinformatic analysis of gastric effluents highlights possible differences in generation of bioactive peptides, such as the satiety-affecting peptides LIVTQTMKG (lacto-ghrestatin) and VAGTWY (DPP-IV inhibitor). Thus, this work details a new tool for in vitro digestion modeling which opens avenues for research towards tailoring healthier food solutions for healthy women which may be distinguishable from those offered to men. • Human trials were mined for sex-based differences in gastro-intestinal functions. • An in vitro digestion model recreating GI functions of women was developed. • Specific protein regions localized to the outer rims of whey proteins are differentially degraded. • Proteomic analyses illustrate differences in generation of bioactive peptides in men or women. • This work opens new avenues for engineering foods for women.

Peculiarities of the relationship between aggressive and protective factors of the gastric mucosa in patients with esophagogastroduodenal pathology with impaired adaptive potential and autonomic homeostasis (according to PRECISE-diagnostics)

Background. An imbalance of interaction between the sympathetic and parasympathetic links of the autonomic nervous system leads to autonomic dysregulation of the heart rate resulting in insufficient stress resistance, impaired adaptation and depletion of the protective mechanisms of the gastric mucosa. Therefore, the purpose of our research was to study adaptive potential of the body depending on the aggressive and protective factors of the gastric juice. Materials and methods. Seventy-one patients with esophagogastroduodenal pathology were examined using the method of PRECISE-diagnostics. The level of pH, pepsin, glycoproteins, fucose and sialic acids in the gastric contents was determined. The patients were divided into 3 representative groups: I— 30 individuals with hiatal hernia; II— 20 patients with achalasia cardia; III— 21 people with duodenal ulcer disease complicated by stenosis. Results. An imbalance of sympathetic and parasympathetic links of autonomic system was detected in 85.2% of patients. The sympathetic mechanisms dominated in 71.3% of cases. At the same time, most patients with achalasia cardia had vagotonia. The adaptive and compensatory mechanisms were identified after studying the relationship between the aggressive and protective factors of the gastric mucosa. When analyzing the correlation of aggressive and protective factors of gastric juice, the following adaptive and compensatory options were revealed: 1) hyperreactive, with simultaneous increase in the factors of both aggression and protection; 2)compensatory (an increase in the level of aggressive factors against the background of normal protective indicators); 3) decompensatory (an increase in the level of aggressive factors simultaneously with a decrease in protective factors). Conclusions. The adaptive potential of the body in 85.2% of surgical patients, mostly those with hiatal hernia and achalasia cardia, according to PRECISE-diagnostics was defined as reduced, in the form of impaired adaptation in decompensatory type of the relationship between aggressive and protective factors of gastric juice.

Are Cirrhotic Patients Receiving Invasive Mechanical Ventilation at Risk of Abundant Microaspiration.

Previous studies have identified cirrhosis as a risk factor for ventilator-associated pneumonia (VAP). The aim of our study was to determine the relationship between cirrhosis and abundant gastric-content microaspiration in intubated critically ill patients. We performed a matched cohort study using data from three randomized controlled trials on abundant microaspiration in patients under mechanical ventilation. Each cirrhotic patient was matched with three to four controls for gender, age ± 5 years and simplified acute physiology score II (SAPS II) ± 5 points. Abundant microaspiration was defined by significant levels of pepsin and alpha-amylase in >30% of tracheal aspirates. All tracheal aspirates were collected for the first 48 h of the study period. The percentage of patients with abundant gastric-content microaspiration was the primary outcome. The abundant microaspiration of oropharyngeal secretions, VAP incidence, the duration of mechanical ventilation, length of intensive care unit (ICU) stay and mortality were the secondary outcomes. A. total of 39 cirrhotic patients were matched to 138 controls. The percentage of patients with abundant gastric-content microaspiration did not differ between the two groups (relative risk: 0.91 (95% CI: 0.75 to 1.10)). There was no significant difference between the two groups in terms of the abundant microaspiration of oropharyngeal secretions, VAP, the duration of mechanical ventilation, the length of ICU stay and mortality. Our results suggest that cirrhosis is not associated with abundant gastric-content microaspiration.

Effects of white mustard (Sinapis alba) oil on growth performance, immune response, blood parameters, digestive and antioxidant enzyme activities in rainbow trout (Oncorhynchusmykiss)

A study was conducted to evaluate the effects of dietary supplementation of white mustard (Sinapis alba) oil (WMO) on growth performance, immune responses, digestive and antioxidant enzyme activities in juvenile rainbow trout (Oncorhynchus mykiss). For this purpose, fish (initial weight: 25.77 ± 0.13 g) were divided into four experimental groups in triplicate and fed ad libitum twice a day with diets containing WMO at 0 (control), 0.5, 1, and 1.5% of diet for 9 weeks. Three fish from each tank (n:9 per treatment) were sampled on 21st, 42nd, and 63rd days for further analyses. At the end of the feeding period, fish were challenged with Aeromonas hydrophila and Yersinia ruckeri in two separate experimental setups. Results showed that final weight, weight gain, and specific growth rate were significantly increased in all experimental groups compared to the control. Feed conversion ratio was similar among treatments. Respiratory burst and potential killing activity decreased in all experimental groups compared to the control (P < 0.05). Lysozyme and myeloperoxidase activities were elevated in all experimental groups at the end of the experiment compared to the control (P < 0.05). Cytokine gene expressions in the head kidney and intestine were elevated in all experimental groups compared to that of the control in general (P < 0.05). Hematological responses of the experimental fish groups were similar to that of the control (P > 0.05). Pepsin and trypsin levels decreased in all experimental groups (P < 0.05). In terms of antioxidant enzyme activities, significant improvement in liver superoxide dismutase, catalase, and glutathione s-transferase activities in all treatment groups were determined (P < 0.05). In addition, a significant decline in liver lipid peroxidation levels was recorded in all treated groups at all sampling times compared to the control (P < 0.05). At the end of this feeding trial, no significant differences (P > 0.05) were observed in survival against A. hydrophila among experimental groups compared to the control (P > 0.05). However, increased survival against Y. ruckeri was determined in experimental fish groups (P < 0.05). This study suggests that white mustard oil had a favorable effect on the overall health and growth of rainbow trout.

Correlation of Esophageal Mean Nocturnal Baseline Impedance With Markers of Laryngopharyngeal Reflux.

Mean nocturnal baseline impedance (MNBI) is a measure of the esophageal epithelial barrier function calculated via high-resolution impedance manometry and can be used as a diagnostic tool and treatment response predictor for gastroesophageal reflux disease (GERD). However, its utility for laryngopharyngeal reflux (LPR) has been minimally studied. We aimed to investigate the relationship of MNBI between patients with suspected LPR, healthy controls, and their 24-h multichannel intraluminal impedance-pH (MII-pH) study results. Retrospective patient series analysis was performed of patients with suspected LPR and healthy controls who underwent 24-h MII-pH monitoring. MNBI values were calculated from impedance channels at the level of the hypopharynx, proximal esophagus, and distal esophagus. We compared these MNBI values between the subject groups with secondary analysis on MII-pH results, reflux symptom index, reflux findings score, DeMeester score, and salivary pepsin levels. Twenty-three patients with suspected LPR and 14 healthy controls were enrolled. Decreased distal esophageal MNBI was found to be significantly decreased in patients with suspected LPR compared with healthy controls (p< 0.01) and in subjects with positive MII-pH studies compared to negative MII-pH studies (p< 0.01). There were no significant correlations of MNBI at the hypopharynx or proximal esophagus. Distal esophageal MNBI has significant correlations with many phenotypic and biological markers of LPR. These findings indicate that MNBI has the potential to be applied to LPR, similar to its emerging use as a diagnostic tool and treatment response predictor for GERD. 3 Laryngoscope, 133:1927-1932, 2023.

RNA-Seq Reveals Protective Mechanisms of Mongolian Medicine Molor-Dabos-4 on Acute Indomethacin-Induced Gastric Ulcers in Rats.

This study aimed to apply transcriptomics to determine how Molor-Dabos-4 (MD-4) protects healthy rats against indomethacin (IND)-induced gastric ulcers and to identify the mechanism behind this protective effect. Rats were pretreated with MD-4 (0.3, 1.5, or 3 g/kg per day) for 21 days before inducing gastric ulcers by oral administration with indomethacin (30 mg/kg). Unulcerated and untreated healthy rats were used as controls. Effects of the treatment were assessed based on the ulcer index, histological and pathological examinations, and indicators of inflammation, which were determined by enzyme-linked immunosorbent assay. Transcriptomic analysis was performed for identifying potential pharmacological mechanisms. Eventually, after identifying potential target genes, the latter were validated by quantitative reverse-transcription polymerase chain reaction (qRT-PCR). After pretreatment with MD-4, gastric ulcers, along with other histopathological features, were reduced. MD-4 significantly (p < 0.05) increased the superoxide dismutase (SOD) levels in ulcers and reduced pepsin, TNF-α, and IL-6 levels. RNA-seq analysis identified a number of target genes on which MD-4 could potentially act. Many of these genes were involved in pathways that were linked to anti-inflammatory and antioxidant responses, and other protective mechanisms for the gastric mucosa. qRT-PCR showed that altered expression of the selected genes, such as Srm, Ryr-1, Eno3, Prkag3, and Eef1a2, was consistent with the transcriptome results. MD-4 exerts protective effects against IND-induced gastric ulcers by reducing inflammatory cytokines and pepsin and increasing the expression of SOD levels. Downregulation of Srm, Ryr-1, Eno3, Prkag3, and Eef1a2 genes involved in regulating arginine and proline metabolism, calcium signaling pathway, HIF-1 signaling pathway, oxytocin signaling pathway, and legionellosis are possibly involved in MD-4-mediated protection against gastric ulcers.

Diagnostic thresholds and optimal collection protocol of salivary pepsin for gastroesophageal reflux disease.

Gastroesophageal reflux disease (GERD) is primarily diagnosed based on symptoms and response to a proton-pump inhibitor (PPI) trial. Gold standard testing requires an invasive endoscopic procedure, often with ambulatory pH monitoring. Salivary pepsin is a potential noninvasive modality for GERD diagnosis. This study aimed to assess diagnostic performance of salivary pepsin thresholds for GERD and determine optimal collection protocol of saliva in an external validation cohort. Over 10months, adults with symptoms of GERD undergoing esophagogastroduodenoscopy with wireless pH-monitoring off PPI were enrolled. Saliva was self-collected by participants over 4 days across three different time points: fasting ante meridiem (AM), post-prandial, and bedtime (PM). Pepsin levels were calculated via Peptest. Pepsin variability and agreement were determined using linear mixed effects models and intraclass correlation. Validation of diagnostic threshold and performance characteristics were evaluated by receiver-operator curve analysis. Twenty participants enrolled in the study; 50% with physiologic acid exposure (acid exposure time < 4% no GERD) and 50% with elevated acid exposure (GERD). Mean pepsin concentrations were significantly lower in the AM (22.6 ± 25.2ng/mL) compared to post-prandial (44.5 ± 36.7ng/mL) and PM (55.4 ± 47.0ng/mL). Agreement between pepsin concentrations across 3 days was substantial for AM samples (kappa 0.61), with lower agreement for post-prandial and PM samples. A single AM pepsin concentration of 25ng/mL was 67% accurate for GERD with 56% sensitivity and 78% specificity. This validation study highlights fair accuracy and performance characteristics of a single fasting AM salivary pepsin concentration for the diagnosis of GERD.

Analysis of symptoms and clinical signs of laryngopharyngeal reflux depending on pepsia in saliva

In the last fifty years, an epidemic of reflux disease has occurred as a result of poor eating habits, stress, and activities of the food industry. Part of this disease is laryngopharyngeal reflux, a disease characterized by the return of gastric contents to the throat and surrounding organs, leading to hoarseness, coughing, difficulty in swallowing and breathing, and ultimately the development of benign and malignant changes in the larynx. This study is aimed to examine the symptoms and signs of laryngopharyngeal reflux in the study group before and after therapy and to compare the concentration of pepsin in saliva with the above. The prospective longitudinal cohort study included 50 subjects, divided into two groups. The first group consisted of 25 subjects with laryngopharyngeal reflux. The second group consisted of 25 healthy subjects without symptoms and signs of laryngopharyngeal reflux. Symptoms and signs before and after therapy were collected using RSI and RFS questionnaires. Pepsin in saliva was measured with Peptest before and after therapy. The most pronounced symptoms are hoarseness, postnasal drip, and a feeling of "a lump in the throat". The median RSI score after three months of therapy was reduced from 20 to 8. From the first group, 7 subjects had measurable levels of pepsin in saliva, and none after therapy. In the control group, no subjects were found to have pepsin in their saliva. Significant improvement was observed in clinical findings (subglottic edema, posterior commissure hypertrophy, vocal cord edema, dense endolaryngeal secretion) after three months of therapy in subjects with LPR. No association of pepsin with LPR symptoms was observed but there is a significant positive association between pepsin and the clinical finding of erythema/hyperemia. In most cases, we start therapy with medication. It is, therefore, important to emphasize that laryngopharyngeal reflux treatment must always begin with a change in diet, lifestyle, and stress regulation. Treatment must be individual and should include a multidisciplinary team with a nutritionist, psychologist, and psychiatrist.

Exposure to bile and gastric juice can impact the aerodigestive microbiome in people with cystic fibrosis

Studies of microbiota reveal inter-relationships between the microbiomes of the gut and lungs. This relationship may influence the progression of lung disease, particularly in patients with cystic fibrosis (CF), who often experience extraoesophageal reflux (EOR). Despite identifying this relationship, it is not well characterised. Our hypothesis is that the gastric and lung microbiomes in CF are related, with the potential for aerodigestive pathophysiology. We evaluated gastric and sputum bacterial communities by culture and 16S rRNA gene sequencing in 13 CF patients. Impacts of varying levels of bile acids, pepsin and pH on patient isolates of Pseudomonas aeruginosa (Pa) were evaluated. Clonally related strains of Pa and NTM were identified in gastric and sputum samples from patients with symptoms of EOR. Bacterial diversity was more pronounced in sputa compared to gastric juice. Gastric and lung bile and pepsin levels were associated with Pa biofilm formation. Analysis of the aerodigestive microbiomes of CF patients with negative sputa indicates that the gut can be a reservoir of Pa and NTM. This combined with the CF patient’s symptoms of reflux and potential aspiration, highlights the possibility of communication between microorganisms of the gut and the lungs. This phenomenon merits further research.

Bronchoalveolar lavage (BAL) amylase and pepsin levels as potential biomarkers of aspiration pneumonia

Background and objectiveThere are currently no established markers for aspiration pneumonia. We hypothesized that bronchoalveolar lavage (BAL) amylase and pepsin might be candidate biomarkers for aspiration pneumonia. MethodsThis cross-sectional study reviewed consenting adults who underwent clinically-indicated bronchoscopy at Aizu Medical Center. BAL samples were obtained using standardized methods. Amylase levels were measured in our clinical laboratory, and pepsin levels were assessed by ELISA. ResultsAspiration pneumonia was clinically diagnosed based on the guidelines of the Japanese Respiratory Society in 48 of the 327 participants. Median BAL salivary amylase and pepsin levels in this group were 702.0 U/L and 12.7 ng/ml respectively, which were significantly higher than in non-aspiration pneumonia patients. BAL amylase ≥204 U/L had 77.1% sensitivity and 84.2% specificity as a diagnostic index, and the area under the receiver operating characteristic (ROC) curve was 0.859 (95% confidence interval (CI), 0.803-0.915). Similarly, BAL pepsin levels of ≥7.45 ng/ml had 87.2% sensitivity and 59.9% specificity for identifying aspiration, and the area under the ROC curve was 0.757 (95% CI, 0.688-0.826). Multivariate regression demonstrated that BAL amylase ≥204 U/L and BAL pepsin ≥7.45 ng/ml were associated with significantly higher odds for aspiration pneumonia (odds ratio (OR) 10.0, 95% CI, 4.51-22.2, and OR 8.81 95% CI, 3.32-23.4, respectively). There were no significant associations between risk factors for aspiration pneumonia and BAL amylase and pepsin levels. ConclusionBAL amylase and pepsin might be useful biomarkers for suggesting aspiration pneumonia, and could be objective markers without relying on known risk factors for aspiration.

Expression of pepsin in nasopharyngeal carcinoma and its correlation with quality of life after radiotherapy

Objective: By analyzing the expression of pepsin in nasopharyngeal carcinoma (NPC) tissues, to investigate the correlation between laryngeal reflux (LPR) and NPC, as well as the effect of LPR on the quality of life of patients with NPC after radiotherapy. Methods: A total of 133 patients with NPC who underwent radiotherapy at the Department of Otorhinolaryngology of the Affiliated Hospital of Guizhou Medical University and the Affiliated Cancer Hospital of Guizhou Medical University from 2005 to 2019 were enrolled consecutively, including 90 males and 43 females, aged (44.32±7.47) years old. At the same period, 58 patients with chronic nasopharyngitis who underwent nasopharyngeal biopsy were selected as the control group. Immunohistochemical method was used to detect the expression of pepsin in nasopharyngeal specimens of the two groups. In addition, 188 normal individuals were selected as the normal group in the same period. NPC patients before and within 6 months after radiotherapy were inverstigated by the General Information Questionnaire and the Quality of Life Scale, and the pepsin levels in saliva of NPC patients before and after radiotherapy and the individuals in normal group were measured. SPSS 21.0 software was used for statistical analysis. Results: Pepsin expression in 133 specimens of NPC patients was strongly positive in 24 cases (18.05%), positive in 21 cases (15.79%), weakly positive in 69 cases (51.88%), and negative in 19 cases (14.29%). The specimens of control group had 10 cases of weakly positive (17.24%), 48 cases of negative (82.76%), but no strong positive or positive pepsin expression. The rate of positive pepsin expression in the NPC group was higher than that in the control group, with a statistically significant (χ2=83.15, P<0.001). The pepsin content in the saliva of NPC patients after radiotherapy ((30.31±7.82) ng/ml) was higher than that before radiotherapy ((20.47±8.21) ng/ml) and the normal group (5.11±2.13) ng/ml), and the pepsin content in saliva before radiotherapy was higher than that in the normal group, and all differences were statistically significant (all P<0.05). After radiotherapy, the five functional domains of quality of life and overall quality of life of NPC patients decreased, while the related symptom scores increased (all P<0.05). Multiple linear regression analysis showed that pepsin content in saliva was the influential factor of five functional domains of quality of life, related symptoms and overall quality of life in NPC patients after radiotherapy (all P<0.05). Conclusion: The positive rate of pepsin expression in NPC tissues is high, and the pepsin in saliva before and after radiotherapy of NPC patients is significantly higher than that in normal, suggesting that LPR may be involved in the process of NPC and affect the quality of life after radiotherapy in NPC patients.

Predictive Value of Laryngeal Mucosa Pepsin in Therapeutic Response of Laryngopharyngeal Reflux

To investigate the predictive capability of pepsin level in the laryngeal mucosa to the therapeutic effect of proton-pump inhibitors in patients with suspected laryngopharyngeal reflux (LPR), so as to verify whether it can be referred to as a biomarker of LPR. Prospective case study. Sixty patients with clinical empiric LPR were enrolled, with an reflux symptom index (RSI) ≥ 13 and an reflux finding score (RFS) > 7 as screening criteria. Biopsy specimens from the interarytenoid mucosa were obtained under topical anesthesia for pepsin immunohistochemical staining. Two parameters were observed in these patients with different pepsin levels after the administration of esomeprazole for 12 weeks: the RSI and the RFS. Among the 60 cases, 35 cases were negative or weakly positive for pepsin (Pepsin(-) group), and 25 cases were moderately positive or strongly positive for pepsin (Pepsin(+) group). After therapy, the RSI significantly decreased from 17.00 (15.00, 19.00) to 6.00 (5.00, 11.00) in the Pepsin(+) group (Z=-4.38, P < 0.01), but no difference was found in the RFS (T=1.48, P > 0.05). No significant difference was observed in the RSI (T=2.01, P > 0.05) or the RFS (T=2.01, P > 0.05) in the Pepsin(-) group either before or after therapy. An improvement in the RSI ≥ 50% was taken as the standard of effective therapy. The effective rate in the Pepsin(+) group was 72.0% (18/25), while it was 14.3% (5/35) in the Pepsin(-) group. There was a significant difference in the effective rate between the two groups (χ2=20.55, P < 0.01). Proton-pump inhibitors exhibited better effects in patients with higher pepsin levels in the laryngeal mucosa. Laryngeal mucosa pepsin may serve as an ideal indicator to screen patients suitable for proton-pump inhibitor therapy and a reliable biomarker to identify patients with LPR.