Role of pepsin and pepsinogen: linking laryngopharyngeal reflux with otitis media with effusion in children

Abstract

Objectives/hypothesis: To analyze the relationship between laryngopharyngeal reflux (LPR) represented by pepsin and pepsinogen, and pathogenesis of otitis media with effusion (OME).

Study design: Prospective case-control study.

Methods: Children with OME who required adenoidectomy and tympanostomy/tympanostomy tubes placement were enrolled in OME group, whereas children with adenoid hypertrophy (AH) who required adenoidectomy and individuals who required cochlear implantation (CI) were enrolled in AH and CI groups, respectively. Pepsinogen mRNA and protein levels were assessed by real-time fluorescence-based quantitative polymerase chain reaction and immunohistochemistry in adenoid specimens from the OME and AH groups. Pepsin and pepsinogen concentrations were evaluated by enzyme-linked immunosorbent assay in middle ear fluid and plasma from the OME and CI groups.

Results: The levels of pepsinogen protein expressed in cytoplasm of epithelial cells and clearance under epithelial cells in adenoid specimens from the OME group were significantly higher than those in the AH group. Furthermore, the concentrations of pepsin and pepsinogen in the OME group were 51.93±11.58 ng/mL and 728±342.6 ng/mL, respectively, which were significantly higher than those in the CI group (P<.001). In addition, the concentrations of pepsin in dry ears were significantly lower than those in serous and mucus ears in the OME group (F=22.77, P<.001).Finally, the concentration of pepsinogen in middle ear effusion was positively correlated with the expression intensity of pepsinogen protein in cytoplasm of epithelial cells (r=0.73, P<.05) in the OME group.

Conclusions: Pepsin and pepsinogen in middle ear effusion are probably caused by LPR and may be involved in the pathogenesis of OME.

Level of evidence: 3b.

Keywords: Otitis media with effusion; laryngopharyngeal reflux; pepsin; pepsinogen.