title: Longitudinal Evaluation of Noninvasive Biomarkers for Eosinophilic Esophagitis.
abstract: BACKGROUND
  The diagnosis and management of eosinophilic esophagitis (EoE) often requires multiple endoscopies. Serum biomarkers can be elevated in EoE patients, but their clinical utility in diagnosis and assessing response to treatment is not well established.
  
  
  OBJECTIVE
  To evaluate serum biomarkers in EoE subjects compared with controls and assess longitudinally in response to treatment.
  
  
  METHODS
  We conducted a prospective cohort study of children and adults undergoing esophagogastroduodenoscopy for suspected EoE. After completing an 8-week course of proton-pump inhibitor therapy, esophageal mucosal biopsies were obtained, as well as, serum analysis of absolute eosinophil count (AEC), eotaxin-3, eosinophil-derived neurotoxin (EDN), eosinophil cationic protein (ECP) and interleukin-5. Subjects with normal endoscopic and histologic findings constituted controls. Those meeting criteria for EoE underwent repeat esophagogastroduodenoscopy and biomarker measurements following treatment with topical steroids for 8 weeks.
  
  
  RESULTS
  Median levels of AEC (263.50 vs. 102 cu/mm, P<0.001), ECP (26.98 vs. 5.20 ng/mL, P<0.001) and EDN (31.70 vs. 14.18 ng/mL, P=0.004) were significantly elevated in EoE subjects compared with controls and correlated with esophageal eosinophilia. Levels of AEC (odds ratio, 1.79; 95% confidence interval, 1.28-2.64) and ECP (odds ratio, 1.61; 95% confidence interval, 1.23-2.36) were associated with a diagnosis of EoE. Among the 5 biomarkers evaluated, only AEC significantly predicted esophageal eosinophilia following topical steroid therapy in EoE subjects (P=0.006).
  
  
  CONCLUSIONS
  AEC, ECP, and EDN were higher in EoE subjects compared with controls and correlated with degree of esophageal eosinophilia. Furthermore, AEC predicted post-treatment eosinophilia, suggesting a potential role in monitoring EoE disease activity.
authors.affiliation: Departments of *Pediatrics §Medicine, Gastroenterology Service ∥Research Programs, Walter Reed National Military Medical Center Departments of †Pediatrics ¶Medicine, Uniformed Services University of the Health Sciences, Bethesda ‡Joint Pathology Center, Defense Health Agency, Silver Spring, MD.
authors.forename: Steve B
authors.initials: SB
authors.lastname: Min
authors.forename: Cade M
authors.initials: CM
authors.lastname: Nylund
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Baker
authors.forename: Mazer
authors.initials: M
authors.lastname: Ally
authors.forename: Brian
authors.initials: B
authors.lastname: Reinhardt
authors.forename: Yen-Ju
authors.initials: YJ
authors.lastname: Chen
authors.forename: Luz
authors.initials: L
authors.lastname: Nazareno
authors.forename: Fouad J
authors.initials: FJ
authors.lastname: Moawad
mesh_terms: D000287:Administration, Topical; D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000032:analysis; D001706:Biopsy; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D004359:Drug Therapy, Combination; D016145:Endoscopy, Digestive System; D047150:Eosinophil Cationic Protein / Q000097:blood*; D047208:Eosinophil-Derived Neurotoxin / Q000097:blood*; D057765:Eosinophilic Esophagitis / Q000097:blood* / Q000188:drug therapy* / Q000473:pathology; D004804:Eosinophils; D000071041:Esophageal Mucosa / Q000473:pathology; D005260:Female; D006801:Humans; D007223:Infant; D007958:Leukocyte Count; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011446:Prospective Studies; D054328:Proton Pump Inhibitors / Q000627:therapeutic use; D012720:Severity of Illness Index; D013256:Steroids / Q000008:administration & dosage*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D015415:Biomarkers; D054328:Proton Pump Inhibitors; D013256:Steroids; D047208:Eosinophil-Derived Neurotoxin; D047150:Eosinophil Cationic Protein