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Journal of Otolaryngology - Head & Neck... Oct 2023To study the variability and diagnostic value of multiple salivary pepsin measurements in the detection of laryngopharyngeal reflux (LPR).
OBJECTIVE
To study the variability and diagnostic value of multiple salivary pepsin measurements in the detection of laryngopharyngeal reflux (LPR).
METHODS
Patients with LPR symptoms were consecutively recruited from December 2019 to Augustus 2022. Twenty-one asymptomatic individuals completed the study. The diagnostic was confirmed with hypopharyngeal-esophageal impedance-pH monitoring (HEMII-pH). Patients collected three saliva samples during the 24-h testing period. Symptoms and findings were studied with reflux symptom score-12 and reflux sign assessment. Sensitivity, specificity, positive (PPV) and negative (NPV) predictive values of pepsin measurements were calculated considering morning, post-lunch and post-dinner samples. The consistency and relationship between HEMII-pH, pepsin measurements, and clinical features were investigated.
RESULTS
Morning, post-lunch and post-dinner saliva pepsin concentrations were measured in 42 patients. Pepsin measurements were 64.9%, 59.5%, and 59.0% sensitive for morning, post-lunch and post-dinner collections at cutoff ≥ 16 ng/mL. Considering the highest concentration of the three pepsin saliva collections, the accuracy, sensitivity, specificity and PPV were 70.5%, 73.0%; 66.7% and 78.9%, respectively. Morning pepsin measurements reported higher consistency, sensitivity, and specificity than post-dinner and post-lunch pepsin measurements.
CONCLUSION
The collection of several saliva pepsin samples improves the detection rate of LPR. In case of high clinical LPR suspicion and negative pepsin test, a HEMII-pH study could provide further diagnostic information.
Topics: Humans; Laryngopharyngeal Reflux; Saliva; Pepsin A; Prospective Studies; Esophageal pH Monitoring
PubMed: 37794462
DOI: 10.1186/s40463-023-00670-5 -
Journal of Otolaryngology - Head & Neck... Oct 2023To investigate the association between obstructive sleep apnea (OSA) and laryngopharyngeal reflux (LPR) through oropharyngeal pH-monitoring and pepsin saliva...
OBJECTIVE
To investigate the association between obstructive sleep apnea (OSA) and laryngopharyngeal reflux (LPR) through oropharyngeal pH-monitoring and pepsin saliva measurements.
DESIGN
Prospective uncontrolled study.
METHODS
Patients with sleep disturbances and reflux symptoms underwent polysomnography, 24-h oropharyngeal pH-monitoring and saliva pepsin collections. The prevalence of LPR was investigated in OSA patients according to oropharyngeal pH-monitoring and pepsin measurements. A correlation analysis was performed between pH-monitoring findings, pepsin saliva levels, reflux symptom score-12 (RSS-12), reflux sign assessment (RSA), Apnea-Hypopnea Index (AHI), Epworth Sleepiness Scale, Pichot and arousal findings.
RESULTS
Thirty-seven patients completed the evaluations. LPR was detected in 34/37 (92%) and 29/34 (85%) patients at the oropharyngeal-pH monitoring and pepsin test, respectively. OSA was detected in 30 patients (81%). Among them, LPR was detected in 28/30 (93%) cases. Pharyngeal reflux events mainly occurred nighttime/supine in OSA patients. Both Ryan score and supine reflux time at pH < 6.5 were significantly associated with BMI and the RSA sub- and total scores (p < 0.02). Tongue-base hypertrophy score was positively associated with the number of micro-arousals (p = 0.027); the supine percent of pH < 6.5 (p = 0.030); morning (p = 0.030) and bedtime pepsin saliva measurements (p = 0.037). The bedtime pepsin saliva level was significantly associated with Ryan Score (p = 0.047); AHI (p = 0.017) and the sleep saturation < 90% time (p = 0.040). The saliva level of the morning pepsin was associated with a shortest paradoxical sleep phase (p = 0.013).
CONCLUSION
OSA patients may have high prevalence of pharyngeal reflux events at the oropharyngeal pH-monitoring and high pepsin saliva measurements. Oropharyngeal pH-monitoring should be useful for the correlation between reflux and sleep findings in OSA patients. Future large cohort controlled studies are needed to determine the prevalence of LPR in OSA and healthy individuals.
Topics: Humans; Saliva; Pepsin A; Prospective Studies; Laryngopharyngeal Reflux; Sleep Apnea, Obstructive; Hydrogen-Ion Concentration
PubMed: 37838710
DOI: 10.1186/s40463-023-00675-0 -
JPGN Reports Feb 2023Aspiration is common in mechanically ventilated patients and may predispose patients to aspiration pneumonia, chemical pneumonitis, and chronic lung damage. Pepsin A is...
UNLABELLED
Aspiration is common in mechanically ventilated patients and may predispose patients to aspiration pneumonia, chemical pneumonitis, and chronic lung damage. Pepsin A is a specific marker of gastric fluid aspiration and is often detected in ventilated pediatric patients. We investigated the effect of oral care and throat suctioning in the detection of pepsin A in tracheal aspirates (TAs) up to 4 hours after these procedures.
METHODS
Twelve pediatric patients between age 2 weeks to 14 years who underwent intubation for cardiac surgery were enrolled in this study. Six of the 12 patients were consented before their surgery with initial specimen collected at the time of intubation and last one shortly before extubation (intubation duration < 24 hours). The remaining 6 patients were consented after cardiac surgery. All specimens were collected per routine care per respiratory therapy protocol and shortly before extubation (intubation duration > 24 hours). Tracheal fluid aspirates were collected every 4 to 12 hours in the ventilated patients. Enzymatic assay for gastric pepsin A and protein determination were performed. The time of oral care and throat suctioning within 4 hours prior was recorded prospectively.
RESULTS
A total of 342 TA specimens were obtained from the 12 intubated pediatric patients during their course of hospitalization; 287 (83.9%) showed detectable total pepsin (pepsin A and C) enzyme activity (> 6 ng/mL) and 176 (51.5%) samples had detectable pepsin A enzyme levels (>6 ng/mL of pepsin A). Only 29 samples of 76 samples (38.2%) had evidence of microaspiration after receiving oral care, while 147 of 266 (55.3%) samples were pepsin A positive when no oral care was provided. Odds ratio is 0.50 (Cl 0.30-0.84), and the number needed to treat is 5.8 (Confidence interval 3.4-22.3). Testing air filters for pepsin was not beneficial.
CONCLUSION
Oral care is a highly effective measure to prevent microaspiration of gastric fluid in ventilated pediatric patients. The number needed to treat (5.8) suggests this is a very effective prevention strategy. Our study suggests that pepsin A is a useful and sensitive biomarker that allows identification of gastric aspiration.
PubMed: 37181916
DOI: 10.1097/PG9.0000000000000290 -
HNO Nov 2021Laryngopharyngeal reflux (LPR) is defined as backflow of gastral or gastroduodenal content into the upper aerodigestive tract and characterized by a variety of... (Review)
Review
Laryngopharyngeal reflux (LPR) is defined as backflow of gastral or gastroduodenal content into the upper aerodigestive tract and characterized by a variety of unspecific symptoms such as chronic cough, globus sensation, or mucus hypersecretion. Due to the lack of a gold standard and the heterogeneity of studies, the diagnosis of LPR is still problematic and challenging. However, in patients with characteristic symptoms and endoscopic findings, with an increased reflux symptom index, a pathologic reflux finding score (RFS), pathologic 24 h esophageal or oropharyngeal pH monitoring, and without any other underlying condition, the diagnosis of LPR is probable. In the following review, we critically discuss the abovementioned methods as well as more recent tools such as measurements of pepsin concentrations in the saliva for diagnosis of LPR.
Topics: Esophageal pH Monitoring; Humans; Laryngopharyngeal Reflux; Pepsin A; Saliva
PubMed: 33619606
DOI: 10.1007/s00106-021-01006-3 -
American Journal of Respiratory and... Dec 2022Primary graft dysfunction (PGD) is the principal cause of early morbidity and mortality after lung transplantation. The lung microbiome has been implicated in later...
Primary graft dysfunction (PGD) is the principal cause of early morbidity and mortality after lung transplantation. The lung microbiome has been implicated in later transplantation outcomes but has not been investigated in PGD. To define the peritransplant bacterial lung microbiome and relationship to host response and PGD. This was a single-center prospective cohort study. Airway lavage samples from donor lungs before organ procurement and recipient allografts immediately after implantation underwent bacterial 16S ribosomal ribonucleic acid gene sequencing. Recipient allograft samples were analyzed for cytokines by multiplex array and pepsin by ELISA. We enrolled 139 transplant subjects and obtained donor lung ( = 109) and recipient allograft ( = 136) samples. Severe PGD (persistent grade 3) developed in 15 subjects over the first 72 hours, and 40 remained without PGD (persistent grade 0). The microbiome of donor lungs differed from healthy lungs, and recipient allograft microbiomes differed from donor lungs. Development of severe PGD was associated with enrichment in the immediate postimplantation lung of oropharyngeal anaerobic taxa, particularly . Elevated pepsin, a gastric biomarker, and a hyperinflammatory cytokine profile were present in recipient allografts in severe PGD and strongly correlated with microbiome composition. Together, immediate postimplantation allograft / ratio, pepsin, and indicator cytokines were associated with development of severe PGD during the 72-hour post-transplantation period (area under the curve = 0.81). Lung allografts that develop PGD have a microbiome enriched in anaerobic oropharyngeal taxa, elevated gastric pepsin, and hyperinflammatory phenotype. These findings suggest a possible role for peritransplant aspiration in PGD, a potentially actionable mechanism that warrants further investigation.
Topics: Humans; Primary Graft Dysfunction; Pepsin A; Prospective Studies; Lung Transplantation; Cytokines; Lung; Inflammation; Allografts; Microbiota
PubMed: 36103583
DOI: 10.1164/rccm.202112-2786OC -
Journal of Agricultural and Food... Mar 2024Coffee is one of the most popular beverages around the world and its consumption contributes to the daily intake of dietary melanoidins. Despite the emerging...
Coffee is one of the most popular beverages around the world and its consumption contributes to the daily intake of dietary melanoidins. Despite the emerging physiological role of food melanoidins, their effect on digestive processes has not been studied so far. In this study, the activity of the gastrointestinal enzymes pepsin and trypsin was investigated in the presence of water-soluble coffee melanoidins. The gastric enzyme pepsin is only slightly affected, whereas the intestinal enzyme trypsin is severely inhibited by coffee melanoidins. The intestinal digestibility of casein was significantly inhibited by coffee melanoidins at a concentration achievable by regular coffee consumption. The inhibition of proteolytic enzymes by coffee melanoidins might decrease the nutritional value of dietary proteins.
Topics: Coffee; Pepsin A; Peptide Hydrolases; Trypsin; Dietary Proteins; Polymers
PubMed: 38456211
DOI: 10.1021/acs.jafc.3c09654 -
Medicine May 2021The aim of this study is to explore the relationship between gastroesophageal reflux disease (GERD) and vocal fold polyps (VFPs).This is a Case-Control study and was... (Observational Study)
Observational Study
The aim of this study is to explore the relationship between gastroesophageal reflux disease (GERD) and vocal fold polyps (VFPs).This is a Case-Control study and was performed with the help of The Second Affiliated Hospital of Chongqing Medical University.Twenty-seven patients with VFP and 20 controls without VFP were recruited between May and October 2018. All the subjects underwent a saliva pepsin test, completed the GerdQ questionnaire and 24-hour multichannel intraluminal impedance with pH (24-h MII-pH) monitoring. Twenty-five resected VFP specimens were examined with immunohistochemical (IHC) and double immunofluorescence (IF) staining.The incidence of GERD in the VFP group was significantly higher than that in the control group (P = .003). Patients with VFP had significantly higher GerdQ scores, pepsin concentrations, and pepsin-positive rates (P < .05). Moreover, the number of proximal and upright reflux events was significantly higher in the VFP group (P < .05). The pepsin concentration in saliva showed a significant positive correlation with the pepsin levels in tissues (r2 = 0.50, P = .011). Pepsin and TGF-β1-positive cells were colocalized with CD45RO-positive cells. IHC staining showed that the majority of VFP patients had a positive expression of pepsin (20/25, 80%) and pepsin-positive cells were found in both the squamous epithelium and mesenchymal tissues. IHC staining of TGF-β1 in VFP revealed findings similar to those of pepsin staining.GERD is an important risk factor for VFP. Pepsin may promote the aggregation of immune cells, increase the local cytokines, and promote inflammatory reaction, suggesting a potential new pathogenesis for VFP. The saliva pepsin test is a reliable method for GERD diagnosis.
Topics: Adult; Aged; Case-Control Studies; Esophageal pH Monitoring; Female; Gastroesophageal Reflux; Humans; Incidence; Male; Middle Aged; Pepsin A; Polyps; Prospective Studies; Respiratory Mucosa; Risk Factors; Saliva; Vocal Cords
PubMed: 34011039
DOI: 10.1097/MD.0000000000025787 -
Biosensors Nov 2022Instead of molecularly imprinting a whole protein molecule, imprinting protein epitopes is gaining popularity due to cost and solubility issues. Belonging to the matrix...
Instead of molecularly imprinting a whole protein molecule, imprinting protein epitopes is gaining popularity due to cost and solubility issues. Belonging to the matrix metalloproteinase protein family, MMP-1 is an interstitial collagenase that degrades collagen and may be involved in cell migration, cell proliferation, the pro-inflammatory effect, and cancer progression. Hence, it can serve as a disease protein biomarker and thus be useful in early diagnosis. Herein, epitopes of MMP-1 were identified by screening its crystal structure. To identify possible epitopes for imprinting, MMP-1 was cleaved in silico with trypsin, pepsin at pH = 1.3, and pepsin at pH > 2.0 using Peptide Cutter, generating peptide fragments containing 8 to 12 amino acids. Five criteria were applied to select the peptides most suitable as potential epitopes for MMP-1. The triphenylamine rhodanine-3-acetic acid (TPARA) functional monomer was synthesized to form a stable pre-polymerization complex with a selected template epitope. The complexed functional monomer was then copolymerized with 3,4-ethoxylenedioxythiophene (EDOT) using potentiodynamic electropolymerization onto indium−tin−oxide (ITO) electrodes. The composition of the molecularly imprinted poly(TPARA-co-EDOT) (MIP) was optimized by maximizing the film’s electrical conductivity. Cyclic voltammetry was used to determine MMP-1 concentration in the presence of the Fe(CN)63−/Fe(CN)64− redox probe actuating the “gate effect.” A calibration curve was constructed and used to determine the usable concentration range and the limit of detection as ca. 0.001 to 10.0 pg/mL and 0.2 fg/mL MMP-1, respectively. Finally, the MMP-1 concentration in the A549 human lung (carcinoma) culture medium was measured, and this determination accuracy was confirmed using an ELISA assay.
Topics: Humans; Molecular Imprinting; Matrix Metalloproteinase 1; Epitopes; Polymers; Pepsin A; Peptides; Poly A
PubMed: 36421137
DOI: 10.3390/bios12111018 -
Diseases of the Esophagus : Official... Apr 2021Uncertain diagnostic performance has limited clinical adoption of salivary pepsin, a noninvasive diagnostic tool for gastroesophageal reflux disease (GERD). This study...
Uncertain diagnostic performance has limited clinical adoption of salivary pepsin, a noninvasive diagnostic tool for gastroesophageal reflux disease (GERD). This study aimed to assess diagnostic performance of salivary pepsin, and test validity of thresholds in an external cohort of patients with or without GERD. This two-phase prospective study conducted at two centers enrolled adult asymptomatic volunteers, patients with symptoms of GERD undergoing reflux monitoring, and patients with Barrett's esophagus (BE). Fasting saliva samples were processed for pepsin concentration using Peptest. Phase 1 compared pepsin concentration between No GERD (volunteers/functional heartburn) and GERD (erosive reflux disease/nonerosive reflux disease (NERD)/BE). Phase 2 tested validity of the diagnostic thresholds identified from Phase 1 among external functional heartburn and NERD cohorts. Of 243 enrolled subjects, 156 met inclusion criteria. Phase 1 (n = 114): Pepsin concentrations were significantly higher in GERD (n = 84) versus No GERD (n = 30) (73.8 ng/mL vs. 21.1 ng/mL; P < 0.001). Area under the curve for pepsin concentration was 0.74 (95% CI 0.65, 0.83). A salivary pepsin threshold of 24.9 ng/mL optimized the true negative rate and 100.0 ng/mL optimized the true positive rate. Phase 2 (n = 42): Pepsin concentrations were significantly higher in NERD (n = 22) versus Functional Heartburn (n = 20) (176.0 ng/mL vs. 53.3 ng/mL, P < 0.001). Applying Phase 1 thresholds in this external cohort, salivary pepsin 24.9 ng/mL was 86% sensitive (64%, 97%) and 100.0 ng/mL was 72% specific for distinguishing NERD from functional heartburn. Given modest sensitivity and specificity for GERD, salivary pepsin may have clinical utility as a noninvasive office based diagnostic screening tool for GERD.
Topics: Adult; Gastroesophageal Reflux; Heartburn; Humans; Pepsin A; Prospective Studies; Saliva
PubMed: 33180095
DOI: 10.1093/dote/doaa117 -
Scientific Reports Aug 2017Biologically inert gases play important roles in the biological functionality of proteins. However, researchers lack a full understanding of the effects of these gases...
Biologically inert gases play important roles in the biological functionality of proteins. However, researchers lack a full understanding of the effects of these gases since they are very chemically stable only weakly absorbed by biological tissues. By combining X-ray fluorescence, particle sizing and molecular dynamics (MD) simulations, this work shows that the aggregation of these inert gases near the hydrophobic active cavity of pepsin should lead to protein deactivation. Micro X-ray fluorescence spectra show that a pepsin solution can contain a high concentration of Xe or Kr after gassing, and that the gas concentrations decrease quickly with degassing time. Biological activity experiments indicate a reversible deactivation of the protein during this gassing and degassing. Meanwhile, the nanoparticle size measurements reveal a higher number of "nanoparticles" in gas-containing pepsin solution, also supporting the possible interaction between inert gases and the protein. Further, MD simulations indicate that gas molecules can aggregate into a tiny bubble shape near the hydrophobic active cavity of pepsin, suggesting a mechanism for reducing their biological function.
Topics: Biochemical Phenomena; Enzyme Activation; Hydrophobic and Hydrophilic Interactions; Models, Molecular; Molecular Dynamics Simulation; Noble Gases; Particle Size; Pepsin A; Protein Conformation; Solutions; Spectrometry, X-Ray Emission
PubMed: 28860621
DOI: 10.1038/s41598-017-10678-3