Peptest Studies

  • Ears, Nose & Throat (ENT) Papers

  • Gastroenterology Papers

  • Respiratory Papers

  • Basic Science

Ears, Nose & Throat (ENT)

2021: Diagnostic Value of the PeptestTM in Detecting Laryngopharyngeal Reflux

Author(s):Karol Zeleník, Viktória Hránková, Adéla Vrtková, Lucia Staníková, Pavel Komínek and Martin Formánek

Overview: The aim of this study was to investigate the diagnostic value of the Peptest in detecting LPR based on 24-hr multichannel intraluminal impedance-pH (MII-pH) monitoring using several hypopharyngeal reflux episodes as criterion for LPR.

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2020: Laryngopharyngeal Reflux: Symptoms, Signs, and Presence of Pepsin in Saliva - A Reliable Diagnostic Triad

Author(s):Shilpa Divakaran, Sivaa Rajendran, Roshan Marie Thomas, Jaise Jacob and Mary Kurien

Overview: This study evaluates the predictive value of salivary pepsin in diagnosing laryngopharyngeal reflux (LPR) as suggested by the results of reflux symptom index  (RSI > 13), reflux finding score (RFS > 7), and positive response to treatment with a 4-week course of proton-pump inhibitors.

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2020: Pepsin as a biomarker of reflux in patients presenting at a UK ENT voice clinic

Author(s):Peter W. Dettmar, Katie H. A. Boulton, Andrew D. Woodcock, Rhianna K. Lenham, Mark Watson

Overview: The aim of this study was to evaluate pepsin as a biomarker of reflux in symptomatic patients presenting at a secondary referral ENT voice clinic.

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2020: Diagnostic Utility of Salivary Pepsin as Compared With 24-Hour Dual pH/Impedance Probe in Laryngopharyngeal Reflux

Author(s):Michael Zhang, Clemente Chia, Claire Stanley, Debra J. Phyland and Paul M. Paddle

Overview: This study assesses the diagnostic utility of salivary pepsin (Peptest) at different thresholds and during symptomatic periods as compared with the 24h-HEMII-pH probe in diagnosing LPR.

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2020: Pepsin as a Biomarker for Self-Diagnosing Reflux Associated Symptoms

Author(s):Katie H A Boulton*, Jeanine Fisher, Andrew D Woodcock and Peter W Dettmar

Overview: The aim of the study was to show how pepsin can be used as a biomarker for reflux, using the noninvasive diagnostic Peptest for the self-diagnosis of reflux related symptoms.

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2020: Tooth erosion and the role of pepsin reflux

Author(s):Jeanine Fisher, Graham Porter, Stuart Graham, Christos Ziaras, Andrew D Woodcock and Peter W Dettmar

Overview: The purpose of the study was to evaluate if there is a link between salivary pepsin levels and tooth erosion. Also, to determine if gastroesophageal reflux disease (GERD) is responsible for much of the tooth erosion seen by dentists.

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2020: Evidence of Pepsin-Related Ocular Surface Damage and Dry Eye (PROD Syndrome) in Patients with Laryngopharyngeal Reflux

Author(s):Rocco Plateroti, Marta Sacchetti, Giuseppe Magliulo, Andrea Maria Plateroti, Annalisa Pace, Antonietta Moramarco, Alessandro Lambiase and Alice Bruscolini

Overview: Laryngeal reflux (LPR) showed detectable levels of tear pepsin that explain the nasolacrimal obstruction. The purpose of this study was to determine whether patients with LPR show ocular surface changes and to investigate the relationship between lacrimal pepsin concentration and ocular alterations.

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2019: Utility of Salivary Pepsin in Patients With Reflux Related Chronic Cough

Author(s):María Luisa Nieto Cabrera, Juan José Soler-Cataluña, Clara Rodrigo Nieto, Begoña Capella Soriano, Fernando Sánchez-Toril, María José Lorenzo Dus

Overview: La tos crónica (TC) asociada a reflujo es muy frecuente en la práctica clínica, pero su diagnóstico no siempre es sencillo. La determinación de pepsina en saliva es un método novedoso, sencillo y no invasivo para el estudio de reflujo

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2019: Pepsin & Oropharyngeal pH Monitoring to Diagnose Patients With Laryngopharyngeal Reflux

Author(s):Michael Weitzendorfer, Stavros A. Antoniou, Philipp Schredl, Kai Witzel, Isabella C. Weitzendorfer, Alexandra Majerus, Klaus Emmanuel, Oliver O. Koch

Overview: The aim of this study was to compare the diagnostic accuracy of salivary pepsin with oropharyngeal pH monitoring using the Restech measurement system (Dx-pH) for the diagnosis of laryngopharyngeal reflux (LPR).

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2019: Laryngopharyngeal Reflux (LPR)

Author(s):Krzysztof Nowak, Saurabh Sharma, and Subhash Kini

Overview: Laryngopharyngeal reflux (LPR) can be defined as influx of stomach contents into the upper airway, especially the laryngopharynx and posterior nasopharynx. As a result, affected individuals complain of various laryngopharyngeal and respiratory symptoms caused by the damage to the upper airway epithelium. The aim of this chapter is to give a succinct overview of the current understanding of LPR.

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2019: A pilot study demonstrating the evidence for reflux disease in patients presenting with non-allergic rhinitis (NAR)

Author(s):Qiuping Wang, Rhianna K. Lenham, Xiu Wang, Yifei Li, Manjie Jiang, Wei Chen, Li Xu, Changqing Yang, Andrew D. Woodcock, Peter W. Dettmar

Overview: To overcome the misdiagnosis of reflux disease and provide subjects with the appropriate treatment determine the link between non-allergic rhinitis (NAR) and reflux disease through analyzing pepsin concentration in patients presenting with NAR using the reflux diagnostic test, Peptest.

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2018: Chronic pharyngitis and the association with pepsin detection and reflux disease

Author(s):Peter W. Dettmar, Qiuping Wang, Rachel M. Hodgson, Xiu Wang, Yifei Li, Manjie Jiang, Li Xu, Yu Lan, Andrew D. Woodcock

Overview: Pepsin is a biomarker for reflux disease and a major etiological factor in laryngopharyngeal reflux (LPR). Do chronic pharyngitis patients have significant concentrations of pepsin present in saliva samples indicating the presence of reflux disease?

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2018: Pepsin: biomarker, mediator, and therapeutic target for reflux and aspiration

Author(s):Nikki Johnston, Peter W. Dettmar, Frank G. Ondrey, Rahul Nanchal, Sang-Hyuk Lee, and Jonathan M. Bock

Overview: Extra-esophageal reflux is suspected to cause a wide range of clinical symptoms in the upper airways. Diagnosis and treatment has focused on acid, but realization of the role of nonacid reflux has resulted in research investigating the use of pepsin as a biomarker for gastric reflux and aspiration.

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2018: Laryngopharyngeal reflux disease: clinical presentation, diagnosis and therapeutic challenges in 2018

Author(s):Jerome R. Lechien, Sven Saussez and Petros D. Karkos

Overview: The purpose of this article is to review the recent literature on clinical presentation, diagnosis and treatment and to propose a complete management algorithm of LPR.

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2018: The Diagnostic Usefulness of the Salivary Pepsin Test in Symptomatic Laryngopharyngeal Reflux

Author(s):Luz Barona-Lleo, Rafael Barona-De Guzman, and Claudio Krstulovic

Overview: The aim of the study was to determine the sensitivity, specificity, positive and negative Likelihood Ratio (LR) of the salivary pepsin assay (PEP-test, RD Biomed, Hull, UK) as diagnostic tool of LPR.

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2018: The Upper Esophageal Sphincter Assist Device Is Associated With Symptom Response in Reflux-Associated Laryngeal Symptoms

Author(s):Rena Yadlapati, Jenna Craft, Christopher J. Adkins and John E. Pandolfino

Overview: This study aimed to assess the therapeutic efficacy of the upper esophageal sphincter assist device in a pragmatic clinical setting, and to identify factors associated with symptom response among patients with suspected Reflux-associated laryngeal symptoms.

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2018: Saliva Pepsin Detection and Proton Pump Inhibitor Response in Suspected Laryngopharyngeal Reflux

Author(s):Ching-Ping Wang, Chen-Chi Wang, Han-Chung Lien, Wen-Jiun Lin, Shang-Heng Wu, Kai-Li Liang, Shih-An Liu

Overview: To evaluate the prediction value of saliva pepsin detection for an 8-week proton pump inhibitor (PPI) response in patients with a Reflux Symptoms Index (RSI) score 3, which indicates possible laryngopharyngeal reflux.

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2018: Chronic pharyngitis and the association with pepsin detection and reflux disease

Author(s):Peter W. Dettmar, Qiuping Wang, Rachel M. Hodgson, Xiu Wang, Yifei Li, Manjie Jiang, Li Xu, Yu Lan, Andrew D. Woodcock

Overview: Pepsin is a biomarker for reflux disease and a major etiological factor in laryngopharyngeal reflux (LPR). Do chronic pharyngitis patients have significant concentrations of pepsin present in saliva samples indicating the presence of reflux disease?

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2018: The Upper Esophageal Sphincter Assist Device Is Associated With Symptom Response in Reflux-Associated Laryngeal Symptoms

Author(s):Rena Yadlapati, Jenna Craft, Christopher J. Adkins and John E. Pandolfino

Overview: This study aimed to assess the therapeutic efficacy of the upper esophageal sphincter assist device in a pragmatic clinical setting, and to identify factors associated with symptom response among patients with suspected reflux-associated laryngeal symptoms.

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2017: Clinical-Diagnostic Correlations in Laryngopharyngeal Reflux (LPR). The Role of Peptest

Author(s):Gelardi M, Eplite A, Mezzina A, Taliente S, Plantone F, Dettmar PW, Quaranta N

Overview: The aim of the present study was to correlate the qualitativequantitative values of salivary pepsin (using PeptestTM) with symptoms and signs obtained from RSI and RFS. The final goal is to validate this enzyme immunoassay method using LPR diagnostic tools.

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2017: Role of Pepsin and Oropharyngeal pH-Monitoring to Assess the Postoperative Outcome of Patients with Laryngopharyngeal Reflux: Results of a Pilot Trial

Author(s):Michael Weitzendorfer, Richard Pfandner, Stavros A. Antoniou, Werner Langsteger, Kai Witzel, Klaus Emmanuel,and Oliver O. Koch

Overview: The aim of this study was to evaluate the value of salivary pepsin and oropharyngeal pHmonitoring to assess the surgical outcome of patients with laryngopharyngeal reflux (LPR).

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2017: Laryngopharyngeal Reflux Disease – LPRD

Author(s):Nizama Salihefendic, Muharem Zildzic, Emir Cabric

Overview: This paper is written with the intention to assess the frequency of symptoms of LPR in family medicine, possible diagnostics and adequate treatment in primary health care.

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2017: Salivary Pepsin Test: Useful and Simple Tool for the Laryngopharyngeal Reflux Diagnosis

Author(s):Luz Barona-Lleó, Claudia Duval, Rafael Barona-de Guzmána

Overview: The aim of the study is to describe the findings obtained by applying the salivary pepsin test in a sample of patients with the clinical suspicion of Laryngopharyngeal reflux (LPR)

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2017: Is Pepsin a Reliable Marker of Laryngopharyngeal Reflux? A Systematic Review

Author(s):Christian Calvo-Henriquez, Alberto Ruano-Ravina, Pedro Vaamonde, Gabriel Martinez-Capoccioni, and Carlos Martin-Martın

Overview: The objective of the present research is to analyze the existing literature using pepsin as a diagnostic tool of LPR through a systematic review of Laryngopharyngeal reflux (LPR)

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2016: Laryngopharyngeal reflux: diagnosis, treatment and latest research

Author(s):G. L. Falk and S. J. Vivian

Overview: A review of the recent changes in understanding of laryngopharyngeal and extra-oesophageal reflux symptoms.

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2016: The Role of Pepsin in LPR: Will It Change Our Diagnostic and Therapeutic Approach to the Disease?

Author(s):Kendra E. Luebke, Tina L. Samuels & Nikki Johnston

Overview: Research is needed to elucidate the exact role that pepsin plays in inflammatory and neoplastic diseases of the laryngopharynx and to develop pharmacologic agents targeting pepsin.

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2016: Association between 24-hour combined multichannel intraluminal impedance-pH monitoring and symptoms or quality of life in patients with laryngopharyngeal reflux

Author(s):Kim, S.I., Kwon, O.E., Na, S.Y., Lee, Y.C., Park, J.M. & Eun, Y.G.

Overview: To evaluate the association between the parameters of 24-hour multichannel intraluminal impedance (MII)-pHmonitoring and the symptoms or quality of life (QoL) in laryngopharyngeal reflux (LPR) patients.

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2015: Diagnosis of extraesophageal reflux in children with chronic otitis media with effusion using Peptest

Author(s):Martin Formanek, Karol Zelenık, Pavel Komınek, Petr Matousek

Overview: The aim of the study was to investigate whether Peptest, an immunoassay used to detect pepsin, could be used to diagnose extraesophageal reflux (EER) in children with chronic otitis media with effusion (OME). The results obtained using this fast, simple and non-expensive method were compared with the results of previous studies.

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2015: Salivary Pepsin Concentrations are Higher for Patients with Reflux Associated Laryngeal Symptoms: A Prospective Pilot Study

Author(s):Christopher Adkins, Rena Yadlapati, Diana Jaiyeola, Andrew J. Gawron, Michael I. Ellenbogen, Bruce K. Tan, Stephanie Shintani-Smith, Michiel Bove, Caroline Price, Alcina K. Lidder, John E. Pandolfino

Overview: The aim of this study was to assess for differences in salivary pepsin for patients with LPR and gastroesophageal reflux disease (GERD) symptoms compared to controls.

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2015: Salivary pepsin assay as a diagnostic test for laryngopharyngeal reflux

Author(s):Stapleton et al

Overview: This study demonstrates that salivary pepsin assay has an excellent specificity and positive predictive value in diagnosing laryngopharyngeal reflux.

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2015: Detecting laryngopharyngeal reflux in patients with upper airways symptoms: Symptoms, signs or salivary pepsin?

Author(s):Alexander Spyridoulias, Siobhan Lillie, Aashish Vyas, Stephen J. Fowler

Overview: We compared symptoms, laryngeal signs and salivary pepsin as potential diagnostic methods for identifying LPR in patients with upper airway symptoms.

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2015: Immunoserologic Pepsin Detection in The Saliva as a Non-Invasive Rapid Diagnostic Test for Laryngopharyngeal Reflux

Author(s):Emre Ocak, Gözde Kubat, İrfan Yorulmaz

Overview: To evaluate the accuracy of immunoserologic pepsin detection in the saliva for the diagnosis of LPR.

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2014: Objective detection of esophagopharyngeal reflux in patients with hoarseness and endoscopic signs of laryngeal inflammation

Author(s):Hayat JO, Yazaki E, Moore AT, Hicklin L, Dettmar P3, Kang JY, Sifrim D.

Overview: This paper aimed to quantify pharyngeal exposure to gastric contents in patients diagnosed with reflux-related hoarseness and healthy controls using new diagnostic techniques.

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2013: Pepsin detection despite the use of acid suppressant medication in patients with airway reflux related chronic cough

Author(s):Gemma L Crossfield, Warren Jackson, Jennifer Burke, Andrew D Woodcock, Vicki Strugala, Chris Ward, Jeffrey P Pearson, Peter W Dettmar, Alyn H Morice

Overview: The following study assessed pepsin identification in chronic cough patients as a marker of airway reflux on proton pump inhibitor (PPI) medication.

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2013: Laryngopharyngeal reflux and GERD

Author(s):Nikki Johnston, Peter W. Dettmar, Vicki Strugala, Jacqui E. Allen, and Walter W. Chan

Overview: This paper on on laryngopharyngeal reflux includes commentaries on the use of patient-completed questionaires and anti-human pepsin antibodies and other non-invasive tests in diagnosis; the role of pepsin and acid in the etiologies of laryngeal cancers; and the application of proton pump inhibitor (PPI) therapy for the treatment of LPR.

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2012: Do Patients With Hoarseness and Endoscopic Signs of LPR Have Abnormal Esophago-Pharyngeal Reflux?

Author(s):Jamal O. Hayat, Jin-Yong Kang, Peter W. Dettmar, Andrew T. Moore, Lucy C. Hicklin, Etsuro Yazaki, Daniel Sifrim

Overview: It is proposed that hoarseness can be induced by abnormal exposure of the vocal cords to gastric contents. In these patients, laryngoscopy may show non-specific inflammatory signs, generally attributed to LPR. New methods are proposed to assess pharyngeal exposure to gastric contents.

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2012: Novel Techniques For Assessing Oesophago-Pharyngeal Reflux in Patients

Author(s):J. O. Hayat, E. Yazaki, A. T. Moore, L. A. C. Hicklin, P. W. Dettmar, J.-Y. Kang, D. Sifrim

Overview: It is suggested that hoarseness along with typical signs on laryngoscopy can be caused by oesophagopharyngeal reflux, often referred to as LPR. New methods are proposed to assess pharyngeal exposure to gastric contents. They are suggested to measure 1) liquid or mixed gas-liquid acid and non-acid reflux (HMII-pH), 2) aerosolized acid reflux (Dx-pH measuring system, Restech), and 3) presence of pepsin in saliva. We aimed to quantify pharyngeal exposure to gastric contents in patients with hoarseness and healthy controls using the above techniques.

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2012: New Developments in Extraesophageal Reflux Disease

Author(s):Elif Saritas Yuksel and Michael F. Vaezi

Overview: This paper discusses recent developments in extraesophageal reflux disease with special emphasis on new diagnostic modalities and treatment options.

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2012: Laryngopharyngeal pepsin reflux in patients with upper airway symptoms

Author(s):A Spyridoulias, S Lillie, A Vyas, SJ Fowler

Overview: We investigated: (a) the prevalence of pepsin reflux in respiratory patients requiring nasendoscopy for the investigation of upper airway symptoms; (b) the performance of commonly used clinical LPR-diagnostic tools in predicting the presence of salivary pepsin

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2011: Pepsin detection in patients with laryngopharyngeal reflux before and after fundoplication

Author(s):Eelco Wassenaar, Nikki Johnston, Albert Merati, Martin Montenovo, Rebecca Petersen, Roger Tatum, Carlos Pellegrini, Brant Oelschlager

Overview: Some patients with gastroesophageal reflux disease (GERD) suffer from laryngopharyngeal reflux (LPR). There is no reliable diagnostic test for LPR as there is for GERD. We hypothesized that detection of pepsin (a molecule only made in the stomach) in laryngeal epithelium or sputum should provide evidence for reflux of gastric contents to the larynx, and be diagnostic of LPR.

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2011: Laryngopharyngeal reflux-the ear, nose and throat patient

Overview:We investigated: (a) the prevalence of pepsin reflux in respiratory patients requiring nasendoscopy for the investigation of upper airway symptoms; (b) the performance of commonly used clinical LPR-diagnostic tools in predicting the presence of salivary pepsin.

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2011: The prevalence of laryngopharyngeal reflux in the English population

Author(s): Tawakir Kamani, Susannah Penney, Indu Mitra, Vijay Pothula

Overview: Although symptoms of laryngopharyngealreflux (LPR) symptoms are commonly seen in the ENTclinic, their aetiology and prevalence in the population remain unknown.

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2011: Review article: reflux and its consequences

Author(s): P.W. Dettmar, D.O. Castell and R.C. Heading

Overview: The ‘Reflux and its consequences’ conference was held in Hull in 2010 and brought together a multidisciplinary group of experts all with a common interest in the many manifestations of reflux disease to present recent research and clinical progress in GERD and EERD.

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2008: Use of a Non-Invasive Pepsin Diagnostic Test for Reflux: a series of case studies

Author(s):Strugala, McGlashan, Morice, Dettmar

Overview:  A non-invasive diagnostic test in the form of a lateral flow test (LFT) specific for pepsin has been shown to be of benefit in the diagnosis of extraoesophageal reflux (EOR). This test is able to detect pepsin, as a marker of prior reflux, in the sputum of a patient, particular if experiencing symptoms.

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2007: Evaluation of a non-invasive pepsin dipstick test for the diagnosis of extra-oesophageal reflux

Author(s):Strugala, McGlashan, Watson, Morice, Calderone, Dettmar

Overview: Here we present data from a multi-centre pilot study the primary outcome of which was to establish whether a non-invasive in vitro test was capable of diagnosing patients with EOR by detection of the presence of gastric enzyme pepsin in sputum/saliva.

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2007: Detection of pepsin using a non-invasive lateral flow test for the diagnosis of extra-oesophageal reflux

Author(s):Strugala, McGlashan, Watson, Morice, Granier, Dettmar

Overview: Diagnosis of extra-oesophageal reflux (EOR) remains difficult. 24hr pHmetry or impedance monitoring are invasive and insufficiently sensitive enough for use in EOR and the laryngoscopic signs of EOR can be non-specific. An objective, noninvasive test for the presence of EOR is warranted.

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Gastroenterology

2021: Peptest and soft tissue lesions of the oral cavity

Author(s):Gaetano Isola, Simona Santonocito, Grazia Fichera, Calogero Grillo, Antonino Maniaci, Paola Campagna, Caterina Maria GrilloOverview:The aim of the study is to evaluate the correlation between the presence of pepsin in saliva and soft tissue lesions of the oral cavity in patients with GERD.

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2021: Pepsin and pH of Gastric Juice in Patients With Gastrointestinal Reflux Disease and Subgroups

Author(s):Pelin Ergün, Sezgi Kipcak, Peter W Dettmar, Jeanine Fisher, Andrew Woodcock, Serhat BorOverview:The aim of this study was to investigate the pepsin values and pH results of gastric juice among the subtypes of gastroesophageal reflux disease (GERD) and functional heartburn.

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2021: Pepsin properties, structure, and its accurate measurement: a narrative review

Author(s):Kyle J. Stanforth, Matthew D. Wilcox, Peter I. Chater, Iain A. Brownlee, Maria I. Zakhour, Katherine M. R. M. Banecki, Jeffery P. Pearson

Overview:This review deals with several studies where pepsin quantitation is attempted, and their measurement techniques assessed.

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2021: Association between gastroesophageal reflux disease and vocal fold polyps

Author(s):Yazhu Zou, Dan Deng, Xia Li, Zhaoxia Yang

Overview:The aim of this study is to explore the relationship between gastroesophageal reflux disease (GERD) and vocal fold polyps (VFPs).

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2020: Pepsin as a biomarker for self-diagnosing reflux associated symptoms in UK and USA individuals

Author(s):Katie H. A. Boulton, Jeanine Fisher, Andrew D. Woodcock, Peter W. DettmarOverview:The aim of this study was to show how pepsin can be used as a biomarker for reflux, using Peptest for the self-diagnosis of reflux related symptoms.

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2020: Pepsin as a Biomarker for Self-Diagnosing Reflux Associated Symptoms

Author(s):Katie H A Boulton*, Jeanine Fisher, Andrew D Woodcock and Peter W Dettmar

Overview:The aim of the study was to show how pepsin can be used as a biomarker for reflux, using the noninvasive diagnostic Peptest for the self-diagnosis of reflux related symptoms.

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2020: The Association of Pepsin and Reflux in US Individuals Self-diagnosing their Reflux like Symptoms

Author(s):Katie H A Boulton*, Jeanine Fisher, Andrew D Woodcock, Peter W Dettmar

Overview:Diagnosis of GERD like symptoms is not straight forward and many individuals do not have a diagnosis with current tests being invasive, expensive and often with low patient compliance

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2020: A narrative review of the prevalence of gastroesophageal reflux disease (GERD)

Author(s):Katie H. A. Boulton, Peter W. Dettmar

Overview:This review takes a historical look into gastroesophageal reflux disease with the first references dating back to the 1400s.

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2020: Diagnostic performance of salivary pepsin for gastroesophageal reflux disease

Author(s):Rena Yadlapati, Alexander Kaizer, Madeline Greytak, Eze Ezekewe, Violette Simon, Sachin Wani 
Overview: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

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2019: Salivary Pepsin for Diagnosis of Sub-types of Gastroesophageal Reflux Disease

Author(s):Yan-Jun Wang, Xiu-Qiong Lang, Dan Wu, Yu-Qin He, Chun-Hui Lan, Xiao-Xiao, Bin Wang, Duo-Wu Zou, Ji-Min Wu, Yong-Bin Zhao, Peter W Dettmar, Dong-Feng Chen and Min Yang

Overview:To determine the value of salivary pepsin in discriminating sub-types of gastroesophageal reflux disease (GERD) and GERD-related disorders.

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2019: High prevalence of gastroesophageal reflux in vocal opera students. A case-control type study

Author(s):Alexandra Corojan Loor, Sebastian Nedelcuț, Dan Lucian Dumitraşcu

Overview:Opera singers are at risk to develop gastroesophageal reflux, because of the vocational challenges during singing. The singers are reluctant to be submitted to pH-metry fearing throat injuries. We evaluated the gastroesophageal reflux in vocal opera students using a non-invasive salivary test

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2019: Clinical utility of salivary pepsin measurement in patients with proton pump inhibitor‑refractory gastroesophageal refux disease symptoms: a prospective comparative study

Author(s):Tomoaki Matsumura, Makoto Arai, Takeshi Suzuki, Toshitaka Hoppo, Yosuke Seki, Shingo Kasamatsu, Hideaki Ishigami, Kentaro Ishikawa, Kenichiro Okimoto, Naoki Akizue, Daisuke Maruoka, Tomoo Nakagawa, Takeo Odaka, Yoshitak Okamoto, Naoya Kato

Overview:Salivary pepsin measurement has been reported to be useful for diagnosing gastroesophageal refux disease (GERD). This study aimed to clarify the usefulness of salivary pepsin measurement in patients with proton pump inhibitor (PPI)-refractory GERD symptoms without erosive esophagitis.

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2019: Validation in China of a non-invasive salivary pepsin biomarker containing two unique human pepsin monoclonal antibodies to diagnose gastroesophageal reflux disease

Author(s):Yong Feng Wang, Chang Qing Yang, Ying Xuan Chen, Ai Ping Cao, Xiao Feng Yu, Yang Yu, Zi Yan Zhang, Xi Zhong Shen, Fei Liu, Lan Zhong, Ying Xin Wang, Zhan Ju Liu, Yan Hong Shi, Jie Zhong, Jing Nan Li, Yu Lan9, Rhianna K. Lenham, Andrew D. Woodcock, Peter W. Dettmar, Jing-Yuan Fang

Overview:The primary aim of this multicentre clinical study was to validate the efficacy of Peptest in patients diagnosed with gastroesophageal reflux and healthy controls in China.

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2019: Extraoesophageal Reflux Manifestations of Gastro-oesophageal Reflux Disease

Author(s):Berit Schneider-Stickler

Overview:Gastro-oesophageal reflux disease (GERD) is defined as a condition when the reflux of gastric content causes troublesome symptoms or complications. Gastro-oesophageal reflux is associated with numerous pathologic conditions of the upper aerodigestive tract. GERD can be subclassified into oesophageal and extraoesophageal syndromes. Extraoesophageal manifestations can be either pulmonary or otorhinolaryngological. This review provides an overview of most important extra-oesophageal reflux manifestations in GERD patients.

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2017: Testing placement of gastric feeding tubes in infants

Author(s):Norma A. Metheny, Ann Pawluszka, Melanie Lulic, Leslie J. Hinyard and Kathleen L. Meert

Overview:To determine the efficacy of a rapid pepsin assay in distinguishing between tracheal aspirates and gastric aspirates at 4 gastric pH cut points

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2017: The diagnostic value of pepsin detection in saliva for gastro-esophageal reflux disease: a preliminary study from China

Author(s):Xing Du, Feng Wang, Zhiwei Hu, Jimin Wu, Zhonggao Wang, Chao Yan, Chao Zhang and Juan Tan

Overview:None of current diagnostic methods has been proven to be a reliable tool for gastro-esophageal reflu disease (GERD). Pepsin in saliva has been proposed as a promising diagnostic biomarker for gastro-esophageal reflux. We aimed to determine the diagnostic value of salivary pepsin detection for GERD.

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2017: Salivary pepsin detection as a gastroesophageal reflux disease marker in pediatric population

Author(s):Andres Bodas et al

Overview:The aim of this paper is to establish test sensitivity, specificity, predictive value and its validation in the pediatric population.

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2015: Optimisation of the Peptest diagnostic test for detection of GORD using pepsin as a marker

Author(s):V. Strugala, P.W. Dettmar, K.D. Bardhan

Overview:A study into the ability of Peptest to detect patients with GORD was performed. The optimal sampling strategy to give the highest diagnostic yield was investigated.

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2015: Esophageal testing: What we have so far

Author(s):Nicola de Bortoli, Irene Martinucci, Lorenzo Bertani, Salvatore Russo, Riccardo Franchi, Manuele Furnari, Salvatore Tolone, Giorgia Bodini, Valeria Bolognesi, Massimo Bellini, Vincenzo Savarino, Santino Marchi, Edoardo Vincenzo Savarino

Overview:In the coming years, laryngopharyngeal symptoms could be evaluated with up and coming non-invasive or minimally invasive techniques, such as pepsin detection in saliva or pharyngeal pH-metry.

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2015: Pepsin in saliva for the diagnosis of gastro-oesophageal reflux disease

Author(s):Tina Samuels, Craig Hoekzema, Jon Gould, Matthew Goldblatt, Matthew Frelich, Matthew Bosler, Sang-Hyuk Lee and Nikki Johnston

Overview:The aims of this study were to establish normal values of salivary pepsin in healthy asymptomatic subjects and to determine its value to discriminate patients with refluxrelated symptoms (GORD, hypersensitive oesophagus (HO)) from functional heartburn (FH).

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2015: Local Synthesis of Pepsin in Barrett's Esophagus and the Role of Pepsin in Esophageal Adenocarcinoma

Author(s):Tina Samuels, Craig Hoekzema, Jon Gould, Matthew Goldblatt, Matthew Frelich, Matthew Bosler, Sang-Hyuk Lee and Nikki Johnston

Overview:Given the carcinogenic potential of pepsin and inefficacy of PPIs to prevent EAC, the presence and effect of pepsin in the esophagus should be investigated.

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2015: Does salivary pepsin measurement change diagnostic outcome in patients investigated by 24-pH monitoring?

Author(s):A. M. P. Rasijeff, W. Jackson, J.M. Burke, P.W. Dettmar

Overview:In contrast to routine diagnostic methods, quantification of salivary pepsin is rapid and noninvasive. Furthermore, 24h pH-monitoring has limited sensitivity. We aimed to evaluate the impact of salivary pepsin measurement on diagnosis of GORD in patients undergoing 24h pH-monitoring.

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2013: Pepsin in saliva and gastroesophageal reflux monitoring in healthy subjects and patients with heartburn/regurgitation

Author(s): Hayat, Gabieta-Gomez, Yazaki, Kang, Woodcock, Dettmar, Mabary, SifrimO

verview:The aim of this study was to measure pepsin in saliva with objective assessment of GOR by impedance-pH (MII-pH) in a cohort of asymptomatic subjects and consecutive patients with clinically significant heartburn (according to the Montreal definition of GORD).

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2012: Validation of peptest a new non-invasive technology for the diagnosis of LPR

Author(s):Bor, Capanoglu, Yildirim, Vardar, Woodcock, Dettmar

Overview:The study was designed to validate the reliability of a non-invasive lateral flow device (LFD) PeptestTM for pepsin determination following reflux symptoms during intraesophageal impedance measurement (MII-pH)

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2012: Rapid Salivary Pepsin Test: Blinded Assessment of Test Performance in Gastroesophageal Reflux Disease

Author(s):Elif Saritas Yuksel, MD; Shih-Kuang S. Hong, MD, MSCI; Vicki Strugala, PhD; James C. Slaughter, DrPH; Marion Goutte, BS; C. Gaelyn Garrett, MD; Peter W. Dettmar, PhD; Michael F. Vaezi, MD, PhD

Overview:Pepsin lateral flow device (LFD) is a rapid noninvasive test to detect salivary pepsin as a surrogate marker for gastroesophageal reflux disease (GERD). We aimed to establish the test sensitivity, specificity, positive and negative predictive values (PPV, NPV) in patients with symptomatic and objective evidence of GERD compared to healthy controls.

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2012: Use of a non-invasive pepsin diagnostic test to detect GERD

Author(s): Bortoli, Savarino et al

Overview:The aim was to evaluate the accuracy of PEP-Test in diagnosing GERD using MII-pH monitoring as reference standard

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2010: Reflux and its Consequences - the Laryngeal, Pulmonary and Oesophageal Manifestations

Author(s):P. W. Dettmar, D. O. Castell and R. C. Heading

Overview:The ‘Reflux and its consequences’ conference was held in Hull in 2010 and brought together a multidisciplinary group of experts all with a common interest in the many manifestations of reflux disease to present recent research and clinical progress in GERD and EERD. In particular new techniques for diagnosing reflux were showcased at the conference.

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Respiratory

2021: A narrative review of the potential role of microaspiration and a dysregulated aerodigestive microbiome in lung disease

Author(s):Abdullah Althuwaybi, Amal Alamer, Melissa J. McDonnell, Michelle Brennan, Robert M. Rutherford, Matthew Wilcox, Peter Chater, Jeffrey Pearson, Chris Ward

Overview:  This review therefore discusses interconnections in the human microbiome, with a focus on the potential for aerodigestive pathophysiology and microaspiration.

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2020:The Association of Pepsin and Reflux in US Individuals Self-diagnosing their Reflux like Symptoms.

Author(s): Katie H A Boulton*, Jeanine Fisher, Andrew D Woodcock, Peter W Dettmar

Overview:  Diagnosis of GERD like symptoms is not straight forward and many individuals do not have a diagnosis with current tests being invasive, expensive and often with low patient compliance.

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2020: Pepsin as a Marker of Reflux Aspiration in Children With Esophageal Atresia: A Pilot Study

Author(s):MS Nootigattu, RA Evans, MC Steiner, NJ Greening

Overview:  Reflux aspiration secondary to gastroesophageal reflux disease (GERD) is one of the causes of chronic gastrointestinal and respiratory morbidity in children with esophageal atresia (EA). Currently there are no simple, validated non-invasive tests for the diagnosis of reflux aspiration in children

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2019: Using salivary pepsin and the reflux symptom index as objective markers of gastrooesophageal reflux to predict exacerbations of COPD

Author(s):MS Nootigattu, RA Evans, MC Steiner, NJ Greening

Overview:  We aimed to determine the prevalence of objectively assessed measures of GORD and LPR, using salivary pepsin (a non-invasive biomarker of GORD, including silent reflux disease) and the Reflux Symptom Index (RSI) respectively, and whether these were associated with exacerbations of COPD.

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2018: Airway reflux: an emerging topic in respiratory medicine

Author(s):Adalberto Pacheco, Christian Domingo

Overview:  The relationship between airway reflux and airway diseases is still developing: epidemiological evidence of this association is undeniable, but the cause–effect relationship remains unclear.

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2016: Bronchial reacutization and gastroesophageal reflux: is there a potential clinical correlation?

Author(s):Carlo Pomari, Luisa Mauroner, Simona Paiano, Luca Rosario Assante, Luca Bertolaccini, Giacomo Ruffo, Paride Mainardi, Paolo Bocus, Andrea Geccherle, Sergio Ivan Albanese, Stefano Ciaffoni

Overview:  Pepsin plays a role in gastroesophageal reflux (GER). Aims of this study were to verify if pepsin could be the cause of frequent bronchial exacerbations and to check if the persistence of chronic respiratory symptoms were correlated with pre-existing respiratory diseases.

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2015: Use of pepsin detection to identify airways reflux in a range of pulmonary diseases

Author(s):V. Strugala

Overview:  In this pilot investigation, Peptest was used in patients presenting to the department of Pneumology and Physiology at a teaching hospital in the Czech Republic.

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2015: Detection of pepsin in sputum: a rapid and objective measure of airways reflux

Author(s):V. Strugala

Overview:  We hypothesised that Peptest could provide simple objective confirmation of airways reflux in unselected patients with chronic cough.

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2015: Diagnosis of extraesophageal reflux in children with chronic otitis media with effusion using Peptest

Author(s):Martin Formanek, Karol Zelenik, Pavel Kominek, Petr Matousek

Overview:  The aim of the study was to investigate whether Peptest, an immunoassay used to detect pepsin, could be used to diagnose extraesophageal reflux (EER) in children with chronic otitis media wit effusion (OME).

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2014: Detection of pepsin as a marker of reflux in the coughed-up saliva samples of COPD patients.

Author(s):Strugala V, Hill L, Miles J, Bardhan KD, Dettmar PW

Overview:The aim of this cohort study was to objectively identify reflux in general COPD patient population by rapid detection of pepsin in expectorated saliva.

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2013: Pepsin detection in expectorated saliva: a useful marker for airway reflux?

Author(s):Shoaib Faruqi, Andrew D. Woodcock, Peter W. Dettmar, Alyn H. Morice

Overview:  The presence of pepsin in the oesophagus, or more proximally in the pharynx or the airways, suggest GOR. The aim of this study was to study the diagnostic utility of measuring pepsin in expectorated saliva in unselected patients presenting with chronic cough.

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2013: Pepsin as a biomarker of airway reflux in idiopathic pulmonary fibrosis - An observational study

Author(s):Dudziak, Crooks, Woodcock, Dettmar, Morice, Hart

Overview: Current understanding of IPF proposes repetitive pulmonary epithelial injury with aberrant healing as a principal mechanism. Gastro-oesophageal reflux (GOR) and micro-aspiration of gastric contents may cause lung injury with subsequent fibrosis. GOR is known to be prevalent in IPF patients. We assessed the feasibility of salivary pepsin measurement in IPF patients and investigated the temporal variability and relationship between salivary pepsin and symptoms.

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2012: Pepsin detection despite the use of acid suppressant medication in patients with airway reflux related chronic cough

Author(s): Gemma L Crossfield, Warren Jackson, Jennifer Burke, Andrew D Woodcock, Vicki Strugala, Chris Ward, Jeffrey P Pearson, Peter W Dettmar, Alyn H Morice

Overview:Airway reflux is a common cause of unexplained chronic cough and proton pump inhibitor (PPI) medication is commonly prescribed as initial therapy. The following study assessed pepsin identification in Chronic Cough patients as a marker of airway reflux on PPI.

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2011: Reflux and asthma-mechanisms of interaction and asthma outcomes

Author(s):S. M. Harding

Overview: Oesophageal contents can alter lung function and impact airway inflammation. Reflux treatment improves asthma outcomes in selected asthmatics.

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2011: Reflux in cough and airway disease

Author(s): A H Morice

Overview:A new technology, including airway pH and exhaled breath condensate pepsin levels provide supporting evidence for the hypothesis that chronic cough is really a single diagnosis which has been termed the cough hypersensitivity syndrome.

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2009: Detection of pepsin in sputum and exhaled breath condensate: could it be a useful marker for reflux-related respiratory disease?

Author(s):Strugala,  Faruqi, Dettmar, Morice

Overview:We present data utilising sputum/saliva or exhaled breath condensate (EBC) of patients with chronic cough with and without recent symptoms.

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Basic Science

2020: In vitro modelling of the mucosa of the oesophagus and upper digestive tract

Authors:Kyle Stanforth, Peter Chater, Iain Brownlee, Matthew Wilcox, Chris Ward, Jeffrey Pearson

Overview:This review discusses the utility and limitations of model gut systems in accurately modelling the mucosa of the digestive tract from both an anatomical and functional perspective, with a particular focus on the oesophagus and the upper digestive tract, and what this means for effective in vitro modelling of oesophageal pathology.

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2019: Damage to the Upper Gastrointestinal Tract - The Role of Pepsin

Authors:Rhianna K Lenham, Jeanine Fisher and Peter W Dettmar

Overview: This review explores contemporary literature comprising of books, articles and conference presentations reporting on all roles of pepsin and the damage it can cause to the upper gastrointestinal tract.

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2017: Pepsin and pH Levels of Human Gastric Juices in Gastroesophageal Reflux Disease Subgroups and Functional Heartburn.

Authors:P. Ergun, S. Kipcak, P. Dettmar, A. Woodcock, S. Bor

Overview: The aim of this paper is to draw the key evidence together and to raise awareness of EER amongst gastroenterologists, who today are increasingly invited by ENT and respiratory specialists to help investigate patients in whom this condition is suspected.

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2017: The characteristics of salivary pepsin in patients with severemotor and intellectual disabilities

Authors:Naoki Hashizumea, Suguru Fukahoria, Kimio Asagiria, Shinji Ishiia,Nobuyuki Saikusaa, Naruki Higashidatea, Motomu Yoshidaa, Daisuke Masuia, Saki Sakamotoa, Yoshiaki Tanakaa, Minoru Yagia, Yushiro Yamashita

Overview: The aim of the present study was to determine the utility of measuring the salivary pepsin level (SPL) as an objectiveassessment of gastroesophageal reflux disease (GERD) in severe motor and intellectual disabilities (SMID) patients.

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2014: Chronic pepsin exposure promotes anchorage-independent growth, and migration of a hypopharyngeal squamous cell line

Author(s):Elizabeth A. Kelly, Tina L. Samuels and Nikki Johnston

Overview: Hypopharyngeal squamous cell line chronically exposed to pepsin demonstrated increased cell migration, and colony forming ability relative to control cells. These experiments indicate that chronic pepsin exposure acts as a promoter of tumorigenesis and metastasis of airway epithelium, suggesting a role for pepsin in laryngopharyngeal carcinogenesis attributed to gastric reflux.

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2012: Reflux Revisited - Advancing the Role of Pepsin

Authors: Bardhan, Strugala, and Dettmar

Overview: The aim of this paper is to draw the key evidence together and to raise awareness of EER amongst gastroenterologists, who today are increasingly invited by ENT and respiratory specialists to help investigate patients in whom this condition is suspected.

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2011: Nature and properties of gastro-oesophageal and extra-oesophageal refluxate

Author(s):J. P. Pearson & S. Parikh

Overview: Gastric juice contains many damaging agents against which the stomach has effective defences including a mucus bilayer which generates an unstirred layer which supports surface neutralisation of acid and forms a diffusion barrier to pepsin.

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2011: Uptake of pepsin at pH 7 -in non-acid reflux- causes inflammatory, and perhaps even neoplastic, changes in the laryngopharynx.

Author(s):N. Johnston

Overview: Pepsin has been previously assumed to cause damage by its proteolytic activity alone, but our discovery that pepsin is taken up by laryngeal epithelial cells by receptormediated endocytosis opens the door to a new mechanism for cell damage, and downstream, the development of new therapies for reflux disease – receptor antagonists and ⁄ or pepsin inhibitors.

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