Skip to main content

Advertisement

Log in

Usefulness of pepsin saliva measurement for the detection of primary burning mouth syndrome related to reflux

  • Laryngology
  • Published:
European Archives of Oto-Rhino-Laryngology Aims and scope Submit manuscript

Abstract

Objectives

To study the diagnostic value of salivary pepsin tests for detecting laryngopharyngeal reflux (LPR) in patients with primary burning mouth syndrome (BMS).

Methods

Patients with BMS and asymptomatic individuals were consecutively recruited from September 2018 to June 2023. Patients underwent hypopharyngeal-esophageal impedance pH-monitoring (HEMII-pH) and saliva collections to measure pepsin. Stomatology evaluation was carried out to exclude other causes of BMS. Oral, pharyngeal and laryngeal signs and symptoms were evaluated with Reflux Sign Assessment (RSA) and Reflux Symptom Score (RSS). Sensitivity, specificity, positive (PPV) and negative (NPV) predictive values of pepsin test were calculated considering the highest values of pepsin tests at ≥ 16, ≥ 36, and ≥ 100 ng/mL cutoffs. Receiver operating characteristic curve (ROC) was evaluated.

Results

Forty-nine patients with both BMS and LPR at the HEMII-pH and 21 asymptomatic individuals were recruited. Pepsin test was 83.7%, 79.6%, and 71.4% sensitive at cutoffs ≥ 16, ≥ 36, and ≥ 100 ng/mL, respectively. The ROC analysis reported that a threshold of ≥ 21.5 ng/mL was associated with sensitivity, specificity, PPV and NPV of 81.6%, 81.0%, 90.1% and 65.4%, respectively. The severity score of burning mouth symptom was significantly associated with the saliva pepsin concentration (rs = 0.263; p = 0.029) and the oral RSA (rs = 0.474; p = 0.007).

Conclusion

Pepsin test is a valuable diagnostic approach for detecting LPR in patients with BMS. Patients with high level of saliva pepsin reported more severe burning mouth symptoms. Future studies are needed to confirm the role of LPR in the primary BMS.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

Data availability

Data are available on request.

References

  1. Ritchie A, Kramer JM (2018) Recent advances in the etiology and treatment of burning mouth syndrome. J Dent Res 97(11):1193–1199. https://doi.org/10.1177/0022034518782462

    Article  CAS  PubMed  Google Scholar 

  2. Alvarenga-Brant R, Costa FO, Mattos-Pereira G, Esteves-Lima RP, Belém FV, Lai H, Ge L, Gomez RS, Martins CC (2023) Treatments for burning mouth syndrome: a network meta-analysis. J Dent Res 102(2):135–145. https://doi.org/10.1177/00220345221130025

    Article  CAS  PubMed  Google Scholar 

  3. Eli I, Kleinhauz M, Baht R, Littner M (1994) Antecedents of burning mouth syndrome (glossodynia)–recent life events vs psychopathologic aspects. J Dent Res 73(2):567–572. https://doi.org/10.1177/00220345940730021301

    Article  CAS  PubMed  Google Scholar 

  4. Adamo D, Calabria E, Canfora F, Coppola N, Pecoraro G, D’Aniello L, Aria M, Mignogna MD, Leuci S (2023) Burning mouth syndrome: analysis of diagnostic delay in 500 patients. Oral Dis. https://doi.org/10.1111/odi.14553

    Article  PubMed  Google Scholar 

  5. Lechien JR, Akst LM, Hamdan AL et al (2019) Evaluation and management of laryngopharyngeal reflux disease: state of the art review. Otolaryngol Head Neck Surg 160(5):762–782. https://doi.org/10.1177/0194599819827488

    Article  PubMed  Google Scholar 

  6. Lechien JR, Hans S, De Marrez LG, Dequanter D, Rodriguez A, Muls V, Ben Abdelouahed F, Evrard L, Maniaci A, Saussez S, Bobin F (2021) Prevalence and features of laryngopharyngeal reflux in patients with primary burning mouth syndrome. Laryngoscope 131(10):E2627–E2633. https://doi.org/10.1002/lary.29604

    Article  CAS  PubMed  Google Scholar 

  7. Johnston N, Wells CW, Samuels TL, Blumin JH (2009) Pepsin in nonacidic refluxate can damage hypopharyngeal epithelial cells. Ann Otol Rhinol Laryngol 118(9):677–685. https://doi.org/10.1177/000348940911800913

    Article  PubMed  Google Scholar 

  8. Calvo-Henríquez C, Ruano-Ravina A, Vaamonde P, Martínez-Capoccioni G, Martín-Martín C (2017) Is pepsin a reliable marker of laryngopharyngeal reflux? A systematic review. Otolaryngol Head Neck Surg 157(3):385–391. https://doi.org/10.1177/0194599817709430.RSS

    Article  PubMed  Google Scholar 

  9. Lechien JR, Bobin F, Muls V, Thill MP, Horoi M, Ostermann K, Huet K, Harmegnies B, Dequanter D, Dapri G, Maréchal MT, Finck C, Rodriguez Ruiz A, Saussez S (2020) Validity and reliability of the reflux symptom score. Laryngoscope 130(3):E98–E107. https://doi.org/10.1002/lary.28017

    Article  CAS  PubMed  Google Scholar 

  10. Lechien JR, Vaezi MF, Chan WW et al. (2023) The Dubai definition and diagnostic criteria of laryngopharyngeal reflux: the IFOS consensus. Laryngoscope

  11. Gyawali CP, Kahrilas PJ, Savarino E, Zerbib F, Mion F, Smout AJPM, Vaezi M, Sifrim D, Fox MR, Vela MF, Tutuian R, Tack J, Bredenoord AJ, Pandolfino J, Roman S (2018) Modern diagnosis of GERD: the Lyon consensus. Gut 67(7):1351–1362. https://doi.org/10.1136/gutjnl-2017-314722

    Article  PubMed  Google Scholar 

  12. Lechien JR, Bobin F, Muls V et al (2019) Validity and reliability of the reflux sign assessment (RSA). Ann Otol Rhinol Laryngol. https://doi.org/10.1177/0003489419888947

    Article  PubMed  Google Scholar 

  13. Hakeem A, Fitzpatrick SG, Bhattacharyya I, Islam MN, Cohen DM (2018) Clinical characterization and treatment outcome of patients with burning mouthsyndrome. Gen Dent 66(3):41–47

    PubMed  Google Scholar 

  14. Becker S, Schmidt C, Berghaus A, Tschiesner U, Olzowy B, Reichel O (2011) Does laryngopharyngeal reflux cause intraoral burning sensations? A preliminary study. Eur Arch Otorhinolaryngol 268(9):1375–1381. https://doi.org/10.1007/s00405-011-1543-9

    Article  PubMed  Google Scholar 

  15. Aframian DJ, Ofir M, Benoliel R (2010) Comparison of oral mucosal pH values in bulimia nervosa, GERD, BMS patients and healthy population. Oral Dis 16(8):807–811. https://doi.org/10.1111/j.1601-0825.2010.01692.x

    Article  CAS  PubMed  Google Scholar 

  16. Campisi G, Lo Russo L, Di Liberto C, Di Nicola F, Butera D, Vigneri S, Compilato D, Lo Muzio L, Di Fede O (2008) Saliva variations in gastro-oesophageal reflux disease. J Dent 36(4):268–271. https://doi.org/10.1016/j.jdent.2008.01.003

    Article  CAS  PubMed  Google Scholar 

  17. Di Fede O, Di Liberto C, Occhipinti G, Vigneri S, Lo Russo L, Fedele S, Lo Muzio L, Campisi G (2008) Oral manifestations in patients with gastro-oesophageal reflux disease: a single-center case-control study. J Oral Pathol Med 37(6):336–340. https://doi.org/10.1111/j.1600-0714.2008.00646.x

    Article  PubMed  Google Scholar 

  18. Katz J, Shenkman A, Stavropoulos F, Melzer E (2003) Oral signs and symptoms in relation to disease activity and site of involvement in patients with inflammatory bowel disease. Oral Dis 9(1):34–40. https://doi.org/10.1034/j.1601-0825.2003.00879.x

    Article  CAS  PubMed  Google Scholar 

  19. Lechien JR (2022) Clinical update findings about pH-impedance monitoring features in laryngopharyngeal reflux patients. J Clin Med 11(11):3158. https://doi.org/10.3390/jcm11113158

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Pearson JP, Parikh S, Orlando RC, Johnston N, Allen J, Tinling SP et al (2011) Review article: reflux and its consequences–the laryngeal, pulmonary and oesophageal manifestations. Conference held in conjunction with the 9th International Symposium on Human Pepsin (ISHP) Kingston-upon-Hull, UK, 21–23 April 2010. Aliment Pharmacol Ther 33(Suppl 1):1–71. https://doi.org/10.1111/j.1365-2036.2011.04581.x

    Article  PubMed  Google Scholar 

  21. Lechien JR, Chan WW, Akst LM, Hoppo T, Jobe BA, Chiesa-Estomba CM, Muls V, Bobin F, Saussez S, Carroll TL, Vaezi MF, Bock JM (2022) Normative ambulatory reflux monitoring metrics for laryngopharyngeal reflux: a systematic review of 720 healthy individuals. Otolaryngol Head Neck Surg 166(5):802–819. https://doi.org/10.1177/01945998211029831.Wang

    Article  PubMed  Google Scholar 

  22. Zeleník K, Hránková V, Vrtková A, Staníková L, Komínek P, Formánek M (2021) Diagnostic value of the Peptest™ in detecting laryngopharyngeal reflux. J Clin Med 10(13):2996. https://doi.org/10.3390/jcm10132996

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Zhang M, Chia C, Stanley C, Phyland DJ, Paddle PM (2021) Diagnostic utility of salivary pepsin as compared with 24-hour dual pH/impedance probe in laryngopharyngeal reflux. Otolaryngol Head Neck Surg 164(2):375–380. https://doi.org/10.1177/0194599820951183

    Article  PubMed  Google Scholar 

  24. Wang J, Li J, Nie Q, Zhang R (2022) Are multiple tests necessary for salivary pepsin detection in the diagnosis of laryngopharyngeal reflux? Otolaryngol Head Neck Surg 166(3):477–481. https://doi.org/10.1177/01945998211026837

    Article  PubMed  Google Scholar 

  25. Hayat JO, Gabieta-Somnez S, Yazaki E, Kang JY, Woodcock A, Dettmar P, Mabary J, Knowles CH, Sifrim D (2015) Pepsin in saliva for the diagnosis of gastro-oesophageal reflux disease. Gut 64(3):373–380. https://doi.org/10.1136/gutjnl-2014-307049.LechienJVoice

    Article  CAS  PubMed  Google Scholar 

  26. Samuels TL, Pearson AC, Wells CW, Stoner GD, Johnston N (2013) Curcumin and anthocyanin inhibit pepsin-mediated cell damage and carcinogenic changes in airway epithelial cells. Ann Otol Rhinol Laryngol 122(10):632–641

    Article  PubMed  Google Scholar 

  27. Lechien JR, De Vos N, Everard A, Saussez S (2021) Laryngopharyngeal reflux: the microbiota theory. Med Hypotheses 146:110460. https://doi.org/10.1016/j.mehy.2020.110460

    Article  PubMed  Google Scholar 

Download references

Funding

None.

Author information

Authors and Affiliations

Authors

Contributions

Study concept and design: JRL, LAV, FB. Acquisition, analysis, or interpretation of data: JRL, FB. Drafting of the manuscript: JRL. Critical revision of the manuscript for important intellectual content: LAV, FB.

Corresponding author

Correspondence to Jérôme R. Lechien.

Ethics declarations

Conflict of interest

Authors have no conflict of interest.

Informed consent

Patients consented to the study.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lechien, J.R., Bobin, F. & Vaira, L.A. Usefulness of pepsin saliva measurement for the detection of primary burning mouth syndrome related to reflux. Eur Arch Otorhinolaryngol 281, 827–833 (2024). https://doi.org/10.1007/s00405-023-08317-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00405-023-08317-x

Keywords

Navigation