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Association of Pepsin With Inflammatory Signaling and Effusion Viscosity in Pediatric Otitis Media
Tina L Samuels1, Pawjai Khampang1, Mana Espahbodi1
1Department of Otolaryngology and Communication Sciences, Medical College of Wisconsin, Milwaukee, Wisconsin, U.S.A.
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.
Insights
Pepsin in middle ear fluid correlates with effusion viscosity and inflammation in otitis media (OM). This enzyme may worsen OM outcomes, even at neutral pH.
Area of Science:
- Otolaryngology
- Pediatric Medicine
- Gastroenterology
Background:
- Otitis media (OM) involves inflammation and viscous middle ear effusions, potentially causing hearing loss.
- Extraesophageal reflux (EER), particularly pepsin, is linked to respiratory inflammation and OM.
- Understanding pepsin's role in OM is crucial for managing persistent middle ear effusions.
Purpose of the Study:
- To investigate the association between pepsin and inflammatory signaling in middle ear effusions (MEF).
- To examine the impact of pepsin on OM outcomes.
- To evaluate the causal role of pepsin in vitro.
Main Methods:
- Collected MEF and audiometric data from 30 pediatric patients with recurrent OM.
- Assayed MEF for pepsin, inflammatory molecules, and mucin using ELISA.
- Exposed primary middle ear epithelial cultures to pepsin in vitro and measured cytokine expression via qPCR.
Main Results:
- Pepsin was detected in 77% of MEF samples and correlated with effusion viscosity, IL-6, IL-8, neutrophil elastase, and Mucin 5B.
- Pepsin-negative MEF showed less frequent presence of IL-8 or Mucin 5B.
- In vitro, pepsin induced IL-6, IL-8, and TNF at neutral pH, with weak acid facilitating response at lower pepsin concentrations.
Conclusions:
- Pepsin may contribute to the inflammatory signaling observed in otitis media.
- The presence of pepsin is associated with increased effusion viscosity and inflammatory markers.
- Pepsin could play a role in the development of persistent, viscous middle ear effusions and poorer OM outcomes.
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