Is pepsin in the foreground of extraesophageal reflux management yet?

PURPOSE OF REVIEW: The objective of this article is to summarize recent advances in research regarding the pathophysiology of pepsin in EER and emerging technologies for EER management. RECENT FINDINGS: Recent research adds mechanistic support for pepsin-mediated injury during EER, including an emerging role in chronic pulmonary fibrotic diseases. Innovative diagnostics aim to measure pepsin activity and endocytosis, while novel biomarkers of gastroduodenal reflux highlight opportunities for multiplex diagnostic assays and personalized treatment approaches. Preclinical studies increasingly support direct pepsin inhibition by HIV protease inhibitors leading to an ongoing clinical trial to evaluate fosamprenavir for LPR. SUMMARY: Research continues to make strides towards EER-specific diagnostics and therapeutics. Areas of critical need remain, such as ICD-10-CM diagnostic codes for EER/LPR, a fit-for-purpose outcomes tool for regulatory approval of novel treatments, and drug delivery platforms such as a laryngopharyngeal inhaler to target EER disease sites.