Abstract
Background: The history of pepsin dates back to 1836, when it was discovered by Theodor Schwann. In 1938 Herriott studied the conversion of pepsinogen to pepsin, which is now known to be most aggressive proteolytic enzyme in gastric refluxate. Pepsin has been identified as a biomarker of gastric reflux into the esophagus, the airways and the lungs. Peptest was developed as a non-invasive, sensitive and specific diagnostic test to rapidly identify reflux in patients presenting with a range of symptoms and introduced on to the UK market in August 2010.
Methods: Patients diagnosed with the symptoms of gastro esophageal reflux disease (GERD), extra esophageal reflux (EER), laryngopharyngeal reflux (LPR) and various respiratory diseases were tested for the presence of reflux by Peptest. The reflux diagnostic test is based on lateral flow technology and contains two unique anti-pepsin human monoclonal antibodies; one to detect and one to capture pepsin within a clinical sample. The intensity of the pepsin ‘test’ line within the window of the lateral flow device is measured using a Peptest cube reader and the intensity automatically converts to a concentration of pepsin (ng/ml).
Results: There are over 100 publications describing the reflux diagnostic activity of Peptest across upper gastrointestinal and airway/lung diseases. Compared to healthy asymptomatic control subjects patients presenting with heartburn were shown to have a significantly higher prevalence of salivary pepsin. There is growing evidence that pepsin is a major aetiological factor in LPR and Peptest is routinely used in many ENT clinics. Key respiratory centres in the UK and the Czech Republic demonstrated similar pepsin positivity in patients presenting with a range of respiratory diseases.
Conclusions: Peptest as a marker of prior reflux improves the accuracy of reflux diagnosis in order to better tailor appropriate treatments in patients presenting across a range of upper gastrointestinal, airway and respiratory diseases. Therefore reducing the use and dependency on invasive and expensive diagnostic tests.
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References
Gelardi M, Eplite A, Mezzina A, Taliente S, Plantone F, Dettmar PW, Quaranta N. Clinical-diagnostic correlations in laryngopharyngeal reflux (LPR). The role of peptest. Int J Open Access Otolaryngol. 2017;1:1–8.
Bredenoord AJ, Pandolfino JE, Smout AJPM. Gastro-oesophageal reflux disease. Lancet. 2013;381:1933–42.
Eren E, Arslanoğlu S, Aktaş A, Kopar A, Ciğer E, Önal K, Katilmiş H. Factors confusing the diagnosis of laryngopharyngeal reflux: the role of allergic rhinitis and inter-rater variability of laryngeal findings. Eur Arch Otorhinolayngol. 2014;271:743–7.
Lowden M, McGlashan JA, Steel A, Strugala V, Dettmar PW. Prevalence of symptoms suggestive of extra-oesophageal reflux in a general practice population in the UK. Logoped Phoniatr Vocol. 2009;34:32–5.
Reulbach TR, Belafsky PC, Blalock PD, Koufman JA, Postma GN. Occultlaryngeal pathology in a community-based cohort. Otolaryngol Head Neck Surg. 2001;124:448–50.
Fruton JS. A history of pepsin and related enzymes. Q Rev Biol. 2002;77:127–47.
Fruton JS. Aspartyl proteinases. In: Neuberger A, Brocklehurst K, editors. Hydrolytic enzymes. New York: Elsevier; 1988. p. 1–37.
Taylor WH. The proteolytic activity of human gastric juice and pig and calf gastric mucosal extracts below pH 5, studies on gastric proteolysis. Biochem J. 1959;71:73–83.
Taylor WH. The nature of the enzyme-substrate interaction responsible for gastric Proteolytic pH-activity curves with two maxima, studies on gastric proteolysis. Biochem J. 1959;71(2):373–83.
Fujinaga M, Chernaia MM, Tarasova NI, Mosimann SC, James MNG. Crystal structure of human pepsin and its complex with pepstatin. Protein Sci. 1995;4:960–72.
Luebke KE, Samuels TL, Johnston N. The role of pepsin in LPR: will it change our diagnostic and therapeutic approaches to the disease. Curr Otorhinolaryngol Rep. 2016;4:55–62.
Taylor WH. Proteinases of the stomach in health and disease. Physiol Rev. 1962;42:519–53.
Roberts NB. Human pepsins – their multiplicity, function and role in reflux disease. Aliment Pharmacol Ther. 2006;24(Suppl. 2):2–9.
Strugala V, Avis J, Jolliffe IG, Johnstone LM, Dettmar PW. The role of an alginate suspension on pepsin and bile acids – key aggressors in the gastric refluxate. Does this have implications for the treatment of gastro-oesophageal reflux disease? J Pharm Pharmacol. 2009;61:1021–8.
Strugala V, Pearson JP, Panetti M, Koufman JA, Dettmar PW. Considering the still potent enzymatic activity of gastric juice at high pH values, what should be the threshold to consider above the UES? In: Giuli R, Scarpignato C, Collard J-M, Richter JE, editors. The duodenogastroesophageal reflux. Paris: Pub John Libbey; 2006. p. 181.
Etherington DJ, Taylor WH. Nomenclature of the pepsins. Nature. 1967;216:219–80.
Dent J, Vakil N, Jones R, et al. Accuracy of the diagnosis of GORD by questionnaire, physicians and a trial of proton pump inhibitor treatment: the diamond study. Gut. 2010;59:714–21.
Bytzer P, Jones R, Vakil N, et al. Limited ability of the proton-pump inhibitor test to identify patients with gastroesophageal reflux disease. Clin Gastroenterol. 2012;10:1360–6.
Vakil NB, Halling K, Becher A, et al. Systematic review of patient-reported outcome instruments for gastroesophageal reflux disease symptoms. Eur J Gastroenterol Hepatol. 2013;25:2–14.
Savarino E, Zentilin P, Masracci L, et al. Microscopic esophagitis distinguishes patients with non-erosive reflux disease from those with functional heartburn. J Gastroenterol. 2013;48:473–82.
Bardhan KD, Strugala V, Dettmar PW. Reflux revisited: advancing the role of pepsin. Int J Otolaryngol. 2012;2012:646901. https://doi.org/10.1155/2012/646901.
Bortoli N, Savarino E, Furnari M, Matrinucci I, Zentilin P, Bertani L, Franchi R, Bellini M, Savarino V, Marchi S. Use of a non-invasive pepsin diagnostic test to detect GERD: correlation with MII-pH evaluation in a series of suspected NERD patients. A pilot study. Gastroenterology. 2013;144(5 Suppl 1):S118.
Hayat JO, Gabieta-Somnez S, Yazaki E, Kang J-Y, Woodcock A, Dettmar P, Mabary J, Knowles CH, Sifrim D. Pepsin in saliva for the diagnosis of gastro-oesophageal reflux disease. Gut. 2015;64:373–80.
Hayat JO, Gabieta S, Woodcock A, Dettmar PW, Mabary J, Yazaki E, Kang J-Y, Sifrim D. Postprandial pepsin saliva in healthy subjects and patients with GERD. Relationship with postprandial reflux. Gastroenterology. 2014;146(5 Suppl 1):S751.
Barona-Lleo L, Duval C, Barona-de Guzman R. Salivary pepsin test: useful and simple tool for the laryngopharangeal reflux diagnosis. Acta Otorrinolaringol Esp. 2018;69(2):80–5.
Stapleton E, Watson M, Strugala V, Dettmar P. Salivary pepsin assay as a diagnostic test for laryngopharyngeal reflux. In: 15th British Academic Conference in Otolaryngology and ENT Expo; 2015.
Strugala V, Dettmar PW, Bittenglova R, Fremundova L, Peŝek M. Use of pepsin detection to identify airways reflux in a range of pulmonary diseases. Clin Respir J. 2017;11(5):666–7.
Pesek M, Fremundova L, Bittenglova R, Turkova-Sedlackova T, Dettmar PW. Report on the first results of pepsin positivity in upper airway secretions in patients with chronic bronchial and lung diseases. Stud Pneumol Phthiseol. 2014;74(4):143–9.
Pesek M, Bittenglova R, Fremundova L, Turkova-Sedlackova T, Dettmar PW. Detection of pepsin in airway secretions in interstitial lung disease. Stud Pneumol Phthiseol. 2014;74(5):168–73.
Strugala V, Woodcock AD, Dettmar PW, Faruqi S, Morice AH. Detection of pepsin in sputum: a rapid and objective measure of airways reflux. Eur Respir J. 2016;47(1):339–41.
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Dettmar, P.W., Lenham, R.K., Parkinson, A.J., Woodcock, A.D. (2018). Pepsin Detection as a Diagnostic Test for Reflux Disease. In: Morice, A., Dettmar, P. (eds) Reflux Aspiration and Lung Disease. Springer, Cham. https://doi.org/10.1007/978-3-319-90525-9_8
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