-
American Journal of Critical Care : An... Nov 2021In patients in the intensive care unit (ICU) receiving mechanical ventilation, aspiration of gastric contents may lead to ventilator-associated events and other adverse...
BACKGROUND
In patients in the intensive care unit (ICU) receiving mechanical ventilation, aspiration of gastric contents may lead to ventilator-associated events and other adverse outcomes. Pepsin in pulmonary secretions is a biomarker of microaspiration of gastric contents.
OBJECTIVES
To evaluate the association between tracheal pepsin A and clinical outcomes related to ventilator use.
METHODS
A subset of 297 patients from a larger clinical trial on aspiration of oral secretions in adults receiving mechanical ventilation consented to have pepsin A measured in their tracheal aspirate samples. A concentration ≥6.25 ng/mL indicated a positive result. Abundant microaspiration was defined as pepsin A in ≥30% of samples. Statistical analyses included analysis of variance, analysis of covariance, and χ2 tests.
RESULTS
Most patients were White men, mean age 59.7 (SD, 18.8) years. Microaspiration was found in 43.8% of patients (n = 130), with abundant microaspiration detected in 17.5% (n = 52). After acuity was controlled for, patients with tracheal pepsin A had a longer mechanical ventilation duration (155 vs 104 hours, P < .001) and ICU stay (9.9 vs 8.2 days, P = .04), but not a longer hospital stay.
CONCLUSIONS
Microaspiration of gastric contents occurred in nearly half of patients and was associated with a longer duration of mechanical ventilation and a longer stay in the ICU. Additional preventative interventions beyond backrest elevation, oropharyngeal suctioning, and management of endotracheal tube cuff pressure may be needed. Also, the timing of pepsin measurements to capture all microaspiration events requires additional exploration.
Topics: Adult; Humans; Intensive Care Units; Intubation, Intratracheal; Male; Middle Aged; Pepsin A; Respiration, Artificial; Trachea
PubMed: 34719715
DOI: 10.4037/ajcc2021528 -
Applied Nursing Research : ANR Oct 2022This study explored relationships between enteral feeding and tracheal pepsin A.
AIM
This study explored relationships between enteral feeding and tracheal pepsin A.
BACKGROUND
Mechanically ventilated (MV) patients receiving enteral feeding are at risk for microaspiration. Tracheal pepsin A, an enzyme specific to gastric cells, was a proxy for microaspiration of gastric secretions.
METHODS
Secondary analysis of RCT data from critically ill, MV adults was conducted. Microaspiration prevention included elevated head of bed, endotracheal tube cuff pressure management, and regular oral care. Tracheal secretions for pepsin A were collected every 12 h. Microaspiration was defined as pepsin A ≥ 6.25 ng/mL. Positive pepsin A in >30 % of individual tracheal samples was defined as abundant microaspiration (frequent aspirator). Chi-squared, Fisher's Exact test, and generalized linear model (GLM) were used.
RESULTS
Tracheal pepsin A was present in 111/283 (39 %) mechanically ventilated patients and 48 (17 %) had abundant microaspiration. Enteral feeding was associated with tracheal pepsin A, which occurred within 24 h of enteral feeding. Of the patients who aspirated, the majority received some enteral feeding 96/111 (86 %), compared to only 15/111 (14 %) who received no feeding. A greater number of positive pepsin A events occurred with post-pyloric feeding tube location (55.6 %) vs. gastric (48.6 %), although significant only at the event-level. Frequent aspirators (abundant pepsin A) had higher pepsin A levels compared to infrequent aspirators.
CONCLUSIONS
Our findings confirmed the stomach as the microaspiration source. Contrary to other studies, distal feeding tube location did not mitigate microaspiration. Timing for first positive pepsin A should be studied for possible association with enteral feeding intolerance.
Topics: Adult; Bodily Secretions; Critical Illness; Enteral Nutrition; Humans; Infant, Newborn; Intubation, Intratracheal; Pepsin A; Respiratory Aspiration of Gastric Contents; Trachea
PubMed: 36116866
DOI: 10.1016/j.apnr.2022.151611 -
Current Gastroenterology Reports Aug 2016In the otolaryngology practice, there is a rising concern with the current diagnosis and management of laryngopharyngeal reflux (LPR). The implication of LPR in many... (Review)
Review
In the otolaryngology practice, there is a rising concern with the current diagnosis and management of laryngopharyngeal reflux (LPR). The implication of LPR in many common head and neck symptoms, along with the rising cost of empiric therapy and no overall improvement in patient symptoms, has established a need to review what are indeed laryngopharyngeal complaints secondary to reflux and what are not. This article reviews the otolaryngologist's approach to LPR, the various ways diagnosis is made, and the guidelines that inform the current trends in otolaryngology management of LPR. The goal of this article is to recognize that reflux can be the cause of a variety of laryngopharyngeal complaints seen within an otolaryngology practice, but when empiric therapy does not improve symptoms, consideration should be given to other non-reflux causes.
Topics: Esophageal pH Monitoring; Humans; Laryngopharyngeal Reflux; Laryngoscopy; Pepsin A; Practice Guidelines as Topic; Practice Patterns, Physicians'; Proton Pump Inhibitors
PubMed: 27417389
DOI: 10.1007/s11894-016-0515-z -
The Laryngoscope Jan 2023At the conclusion of this presentation, participants should better understand the carcinogenic potential of pepsin and proton pump expression in Barrett's esophagus.
EDUCATIONAL OBJECTIVE
At the conclusion of this presentation, participants should better understand the carcinogenic potential of pepsin and proton pump expression in Barrett's esophagus.
OBJECTIVE
Barrett's esophagus (BE) is a well-known risk factor for esophageal adenocarcinoma (EAC). Gastric H /K ATPase proton pump and pepsin expression has been demonstrated in some cases of BE; however, the contribution of local pepsin and proton pump expression to carcinogenesis is unknown. In this study, RNA sequencing was used to examine global transcriptomic changes in a BE cell line ectopically expressing pepsinogen and/or gastric H /K ATPase proton pumps.
STUDY DESIGN
In vitro translational.
METHODS
BAR-T, a human BE cell line devoid of expression of pepsinogen or proton pumps, was transduced by lentivirus-encoding pepsinogen (PGA5) and/or gastric proton pump subunits (ATP4A, ATP4B). Changes relative to the parental line were assessed by RNA sequencing.
RESULTS
Top canonical pathways associated with protein-coding genes differentially expressed in pepsinogen and/or proton pump expressing BAR-T cells included those involved in the tumor microenvironment and epithelial-mesenchymal transition. Top upstream regulators of coding transcripts included TGFB1 and ERBB2, which are associated with the pathogenesis and prognosis of BE and EAC. Top upstream regulators of noncoding transcripts included p300-CBP, I-BET-151, and CD93, which have previously described associations with EAC or carcinogenesis. The top associated disease of both coding and noncoding transcripts was cancer.
CONCLUSIONS
These data support the carcinogenic potential of pepsin and proton pump expression in BE and reveal molecular pathways affected by their expression. Further study is warranted to investigate the role of these pathways in carcinogenesis associated with BE.
LEVEL OF EVIDENCE
NA Laryngoscope, 133:59-69, 2023.
Topics: Humans; Proton Pumps; Pepsinogen A; Proton Pump Inhibitors; Barrett Esophagus; Esophageal Neoplasms; Pepsin A; Carcinogenesis; Adenosine Triphosphatases; Tumor Microenvironment
PubMed: 35315085
DOI: 10.1002/lary.30109 -
Food & Function May 2021Enzyme-catalysed hydrolysis is important in protein digestion. Protein hydrolysis is initiated by pepsin at low pH in the stomach. However, pepsin action and...
Enzyme-catalysed hydrolysis is important in protein digestion. Protein hydrolysis is initiated by pepsin at low pH in the stomach. However, pepsin action and acidification happen simultaneously to gastric emptying, especially for liquid meals. Therefore, different extents of exposure to the gastric environment change the composition of the chyme that is emptied from the stomach into the small intestine over time. We assessed the susceptibility of a protein to trypsin-catalysed hydrolysis in the small intestine, depending on its pH and hydrolysis history, simulating chyme at different times after the onset of gastric emptying. Isothermal titration calorimetry was used to study the kinetics of pepsin and trypsin-catalysed hydrolysis. Bovine serum albumin (BSA) that was acidified and hydrolysed with pepsin, showed the highest extent and most efficient hydrolysis by trypsin. BSA in the chyme that would be first emptied from the stomach, virtually bypassing gastric acidity and peptic action, reduced trypsin-catalysed hydrolysis by up to 58% compared to the acidified, intact protein, and 77% less than the acidified, pepsin-hydrolysate. The least efficient substrate for trypsin-catalysed hydrolysis was the acidified, intact protein with a specificity constant (k/K) nearly five times lower than that of the acidified, pepsin-hydrolysate. Our results illustrate the synergy between pepsin and trypsin hydrolysis, and indicate that gastric hydrolysis increases the efficiency of the subsequent trypsin-catalysed hydrolysis of a model protein in the small intestine.
Topics: Calorimetry; Catalysis; Digestion; Gastric Emptying; Hydrogen-Ion Concentration; Hydrolysis; Pepsin A; Protein Conformation; Serum Albumin, Bovine; Stomach; Trypsin
PubMed: 33908536
DOI: 10.1039/d1fo00413a -
Journal of Chemical Information and... Feb 2022The flexibility of β hairpin structure known as the flap plays a key role in catalytic activity and substrate intake in pepsin-like aspartic proteases. Most of these...
The flexibility of β hairpin structure known as the flap plays a key role in catalytic activity and substrate intake in pepsin-like aspartic proteases. Most of these enzymes share structural and sequential similarity. In this study, we have used apo Plm-II and BACE-1 as model systems. In the apo form of the proteases, a conserved tyrosine residue in the flap region remains in a dynamic equilibrium between the normal and flipped states through rotation of the χ and χ angles. Independent MD simulations of Plm-II and BACE-1 remained stuck either in the normal or flipped state. Metadynamics simulations using side-chain torsion angles (χ and χ of tyrosine) as collective variables sampled the transition between the normal and flipped states. Qualitatively, the two states were predicted to be equally populated. The normal and flipped states were stabilized by H-bond interactions to a tryptophan residue and to the catalytic aspartate, respectively. Further, mutation of tyrosine to an amino-acid with smaller side-chain, such as alanine, reduced the flexibility of the flap and resulted in a flap collapse (flap loses flexibility and remains stuck in a particular state). This is in accordance with previous experimental studies, which showed that mutation to alanine resulted in loss of activity in pepsin-like aspartic proteases. Our results suggest that the ring flipping associated with the tyrosine side-chain is the key order parameter that governs flap dynamics and opening of the binding pocket in most pepsin-like aspartic proteases.
Topics: Aspartic Acid Endopeptidases; Catalysis; Pepsin A
PubMed: 35138093
DOI: 10.1021/acs.jcim.1c00840 -
American Journal of Respiratory and... Dec 2022
Topics: Humans; Pepsin A; Primary Graft Dysfunction; Lung Transplantation; Lung; Inflammation; Allografts; Microbiota
PubMed: 36222878
DOI: 10.1164/rccm.202210-1873ED -
Molecules (Basel, Switzerland) Apr 2023Skin aging represents a health and aesthetic problem that could result in infections and skin diseases. Bioactive peptides can potentially be used in skin aging...
Skin aging represents a health and aesthetic problem that could result in infections and skin diseases. Bioactive peptides can potentially be used in skin aging regulation. Chickpea ( L.) selenoproteins were obtained from germination with 2 mg NaSeO/100 g of seeds for 2 days. Alcalase, pepsin, and trypsin were used as hydrolyzers, and a membrane < 10 kDa was used to fractionate the hydrolysate. Se content, antioxidant capacity, elastase and collagen inhibition, functional stability, and preventative capacity were analyzed. Significant increases in Se content were found in germinated chickpea flour and protein related to the control. An increase of 38% in protein was observed in the selenized flour related to the control. A band (600-550 cm) observed in the selenized hydrolysates suggested the insertion of Se into the protein. Hydrolysates from pepsin and trypsin had the highest antioxidant potential. Se enhanced the stability of total protein and protein hydrolysates through time and increased their antioxidant capacity. Hydrolysates > 10 kDa had higher elastase and collagenase inhibition than the total protein and hydrolysates < 10 kDa. Protein hydrolysates < 10 kDa 6 h before UVA radiation had the highest inhibition of collagen degradation. Selenized protein hydrolysates showed promising antioxidant effects that could be related to skin anti-aging effects.
Topics: Antioxidants; Cicer; Protein Hydrolysates; Pepsin A; Trypsin; Pancreatic Elastase
PubMed: 37110634
DOI: 10.3390/molecules28083402 -
The Laryngoscope Feb 2022Otitis media (OM) is a common inflammatory disease spectrum. Cytokine signaling, neutrophil activity, and mucin hypersecretion during recurrent and chronic OM contribute...
OBJECTIVE
Otitis media (OM) is a common inflammatory disease spectrum. Cytokine signaling, neutrophil activity, and mucin hypersecretion during recurrent and chronic OM contribute to persistent, viscous middle ear (ME) effusions, hearing loss, and potential for developmental delay. Extraesophageal reflux (EER), specifically pepsin, triggers inflammatory signaling in respiratory mucosa and is associated with OM. The objective of this study was to investigate the association of pepsin with ME inflammatory signaling and the outcomes and examine causality in vitro.
STUDY DESIGN
Cross-sectional study.
METHODS
ME fluid (MEF) and preoperative audiometric data were collected from 30 pediatric subjects undergoing tympanostomy tube placement for recurrent OM or OM with effusion. MEF viscosity was characterized by the surgeon. Pepsin, inflammatory molecules, and mucin were assayed by enzyme-linked immunosorbent assay (ELISA). ME epithelial primary culture was exposed to 0.1 to 1 mg/ml pepsin at pH 5, 6, and 7 for 30 minutes, and cytokine expression was assayed via qPCR.
RESULTS
Pepsin was observed in the MEF of 77% of patients (range 71-2,734 ng/ml). Pepsin correlated with effusion viscosity, interleukins -6 and -8, neutrophil elastase, and mucin 5B (P < .05). Pepsin-negative MEF was more frequently absent of interleukin 8 or mucin 5B (P < .05). Weak acid was generally insufficient to elicit cytokine expression in ME cells in vitro, however, pepsin induced IL6, IL8, and TNF at pH 7 (P < .05) and weak acid (pH 6) facilitated a response at lower pepsin concentration.
CONCLUSIONS
Pepsin may contribute to inflammatory signaling, persistent viscous effusion, and poorer OM outcomes.
LEVEL OF EVIDENCE
4 Laryngoscope, 132:470-477, 2022.
Topics: Child; Child, Preschool; Cross-Sectional Studies; Female; Humans; Infant; Male; Otitis Media with Effusion; Pepsin A; Viscosity
PubMed: 34272879
DOI: 10.1002/lary.29749 -
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