Pepsin Detection as a Diagnostic Test for Reflux Disease

  • Peter W. DettmarEmail author
  • Rhianna K. Lenham
  • Adrian J. Parkinson
  • Andrew D. Woodcock


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.


Peptest Reflux disease Diagnostic tests Salivary pepsin Gastro-esophageal reflux disease Laryngopharyngeal reflux Respiratory diseases Lateral flow teat Unique pepsin monoclonal antibodies 


  1. 1.
    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.Google Scholar
  2. 2.
    Bredenoord AJ, Pandolfino JE, Smout AJPM. Gastro-oesophageal reflux disease. Lancet. 2013;381:1933–42.CrossRefPubMedGoogle Scholar
  3. 3.
    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.CrossRefGoogle Scholar
  4. 4.
    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.CrossRefPubMedGoogle Scholar
  5. 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.CrossRefPubMedGoogle Scholar
  6. 6.
    Fruton JS. A history of pepsin and related enzymes. Q Rev Biol. 2002;77:127–47.CrossRefPubMedGoogle Scholar
  7. 7.
    Fruton JS. Aspartyl proteinases. In: Neuberger A, Brocklehurst K, editors. Hydrolytic enzymes. New York: Elsevier; 1988. p. 1–37.Google Scholar
  8. 8.
    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.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    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.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    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.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    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.CrossRefGoogle Scholar
  12. 12.
    Taylor WH. Proteinases of the stomach in health and disease. Physiol Rev. 1962;42:519–53.CrossRefPubMedGoogle Scholar
  13. 13.
    Roberts NB. Human pepsins – their multiplicity, function and role in reflux disease. Aliment Pharmacol Ther. 2006;24(Suppl. 2):2–9.CrossRefPubMedGoogle Scholar
  14. 14.
    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.CrossRefPubMedGoogle Scholar
  15. 15.
    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.Google Scholar
  16. 16.
    Etherington DJ, Taylor WH. Nomenclature of the pepsins. Nature. 1967;216:219–80.CrossRefGoogle Scholar
  17. 17.
    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.CrossRefPubMedGoogle Scholar
  18. 18.
    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.CrossRefGoogle Scholar
  19. 19.
    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.CrossRefPubMedGoogle Scholar
  20. 20.
    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.CrossRefPubMedGoogle Scholar
  21. 21.
    Bardhan KD, Strugala V, Dettmar PW. Reflux revisited: advancing the role of pepsin. Int J Otolaryngol. 2012;2012:646901. Scholar
  22. 22.
    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.CrossRefGoogle Scholar
  23. 23.
    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.CrossRefPubMedGoogle Scholar
  24. 24.
    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.CrossRefGoogle Scholar
  25. 25.
    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.CrossRefPubMedGoogle Scholar
  26. 26.
    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.Google Scholar
  27. 27.
    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.CrossRefPubMedGoogle Scholar
  28. 28.
    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.Google Scholar
  29. 29.
    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.Google Scholar
  30. 30.
    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.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Peter W. Dettmar
    • 1
    Email author
  • Rhianna K. Lenham
    • 1
  • Adrian J. Parkinson
    • 1
  • Andrew D. Woodcock
    • 1
  1. 1.RD Biomed LimitedCastle Hill HospitalCottinghamUK

Personalised recommendations