title: The role of gastric pepsin in the inflammatory cascade of pediatric otitis media.
abstract: OBJECTIVE
  Otitis media is characterized as an ongoing inflammation with accumulation of an effusion in the middle ear cleft. The molecular mechanisms underlying the pathogenesis, particularly the inflammatory response, remain largely unknown. We hypothesize that aspiration of gastric contents into the nasopharynx may be responsible for the initiation of the inflammatory process or aggravate a preexisting condition.
  
  
  OBJECTIVE
  To investigate the correlation of gastric pepsin A with inflammatory cytokines, bacterial infection, and clinical outcomes.
  
  
  METHODS
  Prospective study of 129 pediatric patients undergoing myringotomy with tube placement for otitis media at a tertiary care pediatric hospital.
  
  
  METHODS
  Ear samples were tested for pepsin A; cytokines interleukin (IL)-6, IL-8, and tumor necrosis factor; and bacterial culture inoculation. Data were analyzed by descriptive statistics and regression analysis to identify risk factors for the presence of pepsin A and to correlate pepsin A levels with cytokine levels, infection status, and clinical outcomes.
  
  
  RESULTS
  Of the 129 patients, 199 ear samples were obtained; 82 samples (41%) and 64 patients (50%) were positive for pepsin A as measured by immunoassay. Pepsin A positivity correlated with age younger than 3.0 years (mean [SD], 2.3 [2.1] years in the positive group vs 3.3 [3.0] years in the negative group) and with all 3 cytokine levels (mean [SD] tumor necrosis factor, 29.5 [45.9] pg/mL in the positive group vs 13.2 [21.6] pg/mL in the negative group; IL-6, 6791.7 [9389.1] pg/mL in the positive group vs 2849.9 [4066.3] pg/mL in the negative group; and IL-8, 6828.2 [8122.3] pg/mL in the positive group vs 2925.1 [3364.5] pg/mL in the negative group [all P < .05]); however, logistic regression analysis showed that only IL-8 (odds ratio, 3.96; 95% CI, 1.3-12.0; P = .02) and age (odds ratio, 3.83; 95% CI, 1.2-12.7; P = .03) were significant independent variables. No statistically significant association was found with other parameters. Multiple linear regressions revealed that the levels of pepsin A were correlated with IL-8 levels (R2 = 0.248; P < .001) and the need for second or third tubes 6 to 12 months after the first (R2 = 0.102; P = .006). The presence of pepsin A in the middle ear was not associated with increased bacterial infection. Interleukin 8 was independent and significantly associated with both pepsin A levels and bacterial infection (R2 = 0.144 and 0.263, respectively; P = .001 for both).
  
  
  CONCLUSIONS
  Extraesophageal reflux as indicated by the presence of pepsin A is closely involved in the middle ear inflammatory process and may worsen the disease in some children; however, a proof of cause and effect between extraesophageal reflux and middle ear inflammation requires further investigation.
authors: Division of Pediatric Otolaryngology, Nemours/Alfred I. duPont Hospital for Children, Wilmington, Delaware.
authors: Robert C
authors: RC
authors: O'Reilly
authors: Department of Biomedical Research, Nemours/Alfred I. duPont Hospital for Children, Wilmington, Delaware.
authors: Sam
authors: S
authors: Soundar
authors: Department of Biomedical Research, Nemours/Alfred I. duPont Hospital for Children, Wilmington, Delaware.
authors: Dalal
authors: D
authors: Tonb
authors: Department of Biomedical Research, Nemours/Alfred I. duPont Hospital for Children, Wilmington, Delaware.
authors: Laura
authors: L
authors: Bolling
authors: Division of Pediatric Otolaryngology, Nemours/Alfred I. duPont Hospital for Children, Wilmington, Delaware3Center for Ear, Nose & Throat, Lanham, Maryland.
authors: Estelle
authors: E
authors: Yoo
authors: Department of Biomedical Research, Nemours/Alfred I. duPont Hospital for Children, Wilmington, Delaware.
authors: Tracey
authors: T
authors: Nadal
authors: Division of Pediatric Otolaryngology, Nemours/Alfred I. duPont Hospital for Children, Wilmington, Delaware4Connecticut Children's Medical Center, Division of Otolaryngology, University of Connecticut School of Medicine, Hartford.
authors: Christopher
authors: C
authors: Grindle
authors: Division of Pediatric Otolaryngology, Nemours/Alfred I. duPont Hospital for Children, Wilmington, Delaware.
authors: Erin
authors: E
authors: Field
authors: Department of Biomedical Research, Nemours/Alfred I. duPont Hospital for Children, Wilmington, Delaware.
authors: Zhaoping
authors: Z
authors: He
mesh_terms: D002648:Child; D002675:Child, Preschool; D005260:Female; D005764:Gastroesophageal Reflux / Q000150:complications; D006193:Haemophilus influenzae / Q000302:isolation & purification; D006801:Humans; D007223:Infant; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D008297:Male; D008876:Middle Ear Ventilation; D001936:Moraxella catarrhalis / Q000302:isolation & purification; D010034:Otitis Media with Effusion / Q000209:etiology / Q000378:metabolism* / Q000601:surgery; D010035:Otitis Media, Suppurative / Q000209:etiology / Q000378:metabolism* / Q000601:surgery; D010434:Pepsin A / Q000378:metabolism*; D011446:Prospective Studies; D012307:Risk Factors; D013296:Streptococcus pneumoniae / Q000302:isolation & purification; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D015850:Interleukin-6; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D010434:Pepsin A