Faculty Collaboration Database

Association of Pepsin With Inflammatory Signaling and Effusion Viscosity in Pediatric Otitis Media. Laryngoscope 2022 Feb;132(2):470-477

Date

07/18/2021

Pubmed ID

34272879

DOI

10.1002/lary.29749

Scopus ID

2-s2.0-85110911486 (requires institutional sign-in at Scopus site)   7 Citations

Abstract

OBJECTIVE: Otitis media (OM) is a common inflammatory disease spectrum. Cytokine signaling, neutrophil activity, and mucin hypersecretion during recurrent and chronic OM contribute to persistent, viscous middle ear (ME) effusions, hearing loss, and potential for developmental delay. Extraesophageal reflux (EER), specifically pepsin, triggers inflammatory signaling in respiratory mucosa and is associated with OM. The objective of this study was to investigate the association of pepsin with ME inflammatory signaling and the outcomes and examine causality in vitro.

STUDY DESIGN: Cross-sectional study.

METHODS: ME fluid (MEF) and preoperative audiometric data were collected from 30 pediatric subjects undergoing tympanostomy tube placement for recurrent OM or OM with effusion. MEF viscosity was characterized by the surgeon. Pepsin, inflammatory molecules, and mucin were assayed by enzyme-linked immunosorbent assay (ELISA). ME epithelial primary culture was exposed to 0.1 to 1 mg/ml pepsin at pH 5, 6, and 7 for 30 minutes, and cytokine expression was assayed via qPCR.

RESULTS: Pepsin was observed in the MEF of 77% of patients (range 71-2,734 ng/ml). Pepsin correlated with effusion viscosity, interleukins -6 and -8, neutrophil elastase, and mucin 5B (P < .05). Pepsin-negative MEF was more frequently absent of interleukin 8 or mucin 5B (P < .05). Weak acid was generally insufficient to elicit cytokine expression in ME cells in vitro, however, pepsin induced IL6, IL8, and TNF at pH 7 (P < .05) and weak acid (pH 6) facilitated a response at lower pepsin concentration.

CONCLUSIONS: Pepsin may contribute to inflammatory signaling, persistent viscous effusion, and poorer OM outcomes.

LEVEL OF EVIDENCE: 4 Laryngoscope, 132:470-477, 2022.

Author List

Samuels TL, Khampang P, Espahbodi M, McCormick CA, Chun RH, McCormick ME, Yan K, Kerschner JE, Johnston N

Authors

Robert H. Chun MD Professor in the Otolaryngology department at Medical College of Wisconsin
Nikki Johnston PhD Professor in the Otolaryngology department at Medical College of Wisconsin
Michael E. McCormick MD Associate Professor in the Otolaryngology department at Medical College of Wisconsin
Ke Yan PhD Associate Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Child
Child, Preschool
Cross-Sectional Studies
Female
Humans
Infant
Male
Otitis Media with Effusion
Pepsin A
Viscosity