The Role of Gastric Pepsin in the Inflammatory Cascade of Pediatric Otitis Media

Abstract

Recurrent acute otitis media and otitis media with effusion are exceptionally common in the pediatric population.¹ It has been suggested that extraesophageal reflux is one of the pathophysiologic mechanisms that appears to drive middle ear disease in children.^2-7 Direct evidence of aspirating gastric contents into the middle ear was demonstrated by the detection of gastric pepsin A.^8-12 Pepsin is produced by the chief cells of the stomach as the gastric proteolytic proenzyme pepsinogen, which has no enzymatic activity at a neutral pH level and is converted to active pepsin at a pH level lower than 4.0. At least 7 proteolytic pepsin isoforms are produced in the human stomach; pepsin A is the predominating isoform and also the gastric specific form of pepsin. Pepsin and its inactive form pepsinogen in effusion samples of children with otitis media was reported to correlate with the number of pharyngeal reflux episodes, measured by pH monitoring.^4,13,14 Our first study found that almost 15% of the middle ear samples from children with otitis media were positive for pepsin.¹⁰ Later, we evaluated a large cohort of patients with otitis media and a control group without otitis media.¹⁵ Pepsin was detected in the middle ear cleft of 20% of patients with otitis media undergoing tympanostomy tube placement, compared with 1.4% of controls.¹⁵ In addition, there was a significant association of the prevalence of pepsin in the middle ear with mucoid effusion, particularly purulent effusion, and younger age. Absence of gastric pepsin in control patients without otitis media provides compelling evidence that reflux plays a pathophysiologic role in the disease.¹⁵ A recent study also found that pepsin levels were significantly higher in children with otitis media compared with those without the disease.¹⁶