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Review
. 2020 Dec;28(6):401-409.
doi: 10.1097/MOO.0000000000000664.

Pepsin in gastroesophageal and extraesophageal reflux: molecular pathophysiology and diagnostic utility

Tina L Samuels  1 , Nikki Johnston
Affiliations
Review

Pepsin in gastroesophageal and extraesophageal reflux: molecular pathophysiology and diagnostic utility

Tina L Samuels et al. Curr Opin Otolaryngol Head Neck Surg. 2020 Dec.

Abstract

Purpose of review: Gastroesophageal and extraesophageal reflux are prevalent and costly diseases. Recognition of the pathogenicity of nonacid reflux has stimulated interest in alternatives to acid-targeting diagnostics and therapeutics. Pepsin is the most deleterious enzyme in refluxate, eliciting inflammatory and carcinogenic effects irrespective of acid. Its presence in all refluxate and detection in saliva have situated pepsin as the most widely researched biomarker for reflux today. This review summarizes emerging findings regarding pepsin-mediated damage during reflux and developments in pepsin-targeting diagnostics.

Recent findings: New evidence supports a role for pepsin in epithelial--mesenchymal transition, an important process in carcinogenesis and fibrosis. The first global transcriptomic analysis of pepsin-exposed laryngeal cells was described, yielding evidence of a putative airway pepsin receptor. Evaluation of pepsin diagnostics highlighted the need for rigorous validation in which pepsin concentrations are corroborated by a secondary quantitative assay, and reflux is confirmed or excluded by multichannel intraluminal impedance pH testing. Standards for sample collection and storage, and normative and pathological values are lacking.

Summary: Progress continues to be made in our understanding of pepsin-mediated damage with implications for novel therapeutic strategies. Salivary pepsin diagnostics continue to garner interest; however, further work appears necessary to improve their accuracy and reproducibility.

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References

    1. Delshad SD, Almario CV, Chey WD, Spiegel BMR. Prevalence of gastroesophageal reflux disease and proton pump inhibitor-refractory symptoms. Gastroenterology 2020; 158:1250.e2–1261.e2.
    1. Yamasaki T, Hemond C, Eisa M, et al. The changing epidemiology of gastroesophageal reflux disease: are patients getting younger? J Neurogastroenterol Motil 2018; 24:559–569.
    1. Johnston N, Ondrey F, Rosen R, et al. Airway reflux. Ann N Y Acad Sci 2016; 1381:5–13.
    1. Johnston N, Dettmar PW, Bishwokarma B, et al. Activity/stability of human pepsin: implications for reflux attributed laryngeal disease. Laryngoscope 2007; 117:1036–1039.
    1. Johnston N, Wells CW, Samuels TL, Blumin JH. Rationale for targeting pepsin in the treatment of reflux disease. Ann Otol Rhinol Laryngol 2010; 119:547–558.

MeSH terms