title: Histological Response to Fluticasone Propionate in Patients With Eosinophilic Esophagitis Is Associated With Improved Functional Esophageal Mucosal Integrity.
abstract: OBJECTIVE
  The esophageal mucosal integrity is impaired in patients with eosinophilic esophagitis (EoE). We aimed to evaluate the effect of fluticasone propionate on inflammation and functional and structural markers of esophageal mucosal barrier integrity in adult patients with EoE.
  
  
  METHODS
  In this prospective study, we included 15 EoE patients (median age (IQR), 43 (30-45) years). Patients underwent upper endoscopy before and after an 8-week course of swallowed fluticasone propionate 500 μg BID. Several parameters of esophageal mucosal barrier integrity were evaluated: esophageal electrical tissue impedance in vivo during endoscopy, transepithelial electrical resistance (TER) and transepithelial molecule flux in Ussing chambers using esophageal biopsy specimens, and intercellular spaces as a structural marker of permeability using electron microscopy. Esophageal eosinophils and mast cells were counted, and expression of inflammatory cytokines and barrier integrity proteins was investigated using qPCR. Esophageal symptoms and signs were also assessed.
  
  
  RESULTS
  Peak eosinophil and mast cell counts decreased significantly after fluticasone propionate treatment. The esophageal mucosal integrity increased substantially during treatment, as shown by increased extracellular impedance and TER (both P<0.01) and decreased transepithelial molecule flux in Ussing chambers (P<0.05). Whereas expression of genes encoding for inflammatory cytokines (IL5, IL13, eotaxin-3, periostin, TSLP) decreased after treatment, expression of genes encoding for barrier integrity proteins (filaggrin and desmoglein-1) increased.
  
  
  CONCLUSIONS
  Fluticasone propionate treatment decreases eosinophilic inflammation and improves the esophageal mucosal barrier integrity in adult EoE patients. Improvement of the mucosal barrier integrity correlates with normalization of expression of desmoglein-1 and filaggrin marker genes.
authors: Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands.|Tytgat Institute for Liver and GI Research, Academic Medical Center, Amsterdam, The Netherlands.
authors: Bram D
authors: BD
authors: van Rhijn
authors: Department of Pathology, Academic Medical Center, Amsterdam, The Netherlands.
authors: Joanne
authors: J
authors: Verheij
authors: Department of Pathology, Academic Medical Center, Amsterdam, The Netherlands.
authors: Marius A
authors: MA
authors: van den Bergh Weerman
authors: Tytgat Institute for Liver and GI Research, Academic Medical Center, Amsterdam, The Netherlands.
authors: Caroline
authors: C
authors: Verseijden
authors: Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands.|Tytgat Institute for Liver and GI Research, Academic Medical Center, Amsterdam, The Netherlands.
authors: René M J G J
authors: RM
authors: van den Wijngaard
authors: Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands.|Tytgat Institute for Liver and GI Research, Academic Medical Center, Amsterdam, The Netherlands.
authors: Wouter J
authors: WJ
authors: de Jonge
authors: Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands.
authors: Andreas J P M
authors: AJ
authors: Smout
authors: Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands.
authors: Albert J
authors: AJ
authors: Bredenoord
mesh_terms: D000328:Adult; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage; D001706:Biopsy; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D003679:Deglutition / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D017097:Electric Impedance; D057765:Eosinophilic Esophagitis / Q000188:drug therapy / Q000473:pathology* / Q000503:physiopathology; D004804:Eosinophils / Q000187:drug effects / Q000473:pathology*; D004945:Esophagoscopy; D005260:Female; D000091344:Filaggrin Proteins; D000068298:Fluticasone / Q000008:administration & dosage*; D005500:Follow-Up Studies; D005786:Gene Expression Regulation; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism / Q000503:physiopathology / Q000648:ultrastructure*; D007958:Leukocyte Count; D008297:Male; D008854:Microscopy, Electron; D008875:Middle Aged; D011446:Prospective Studies; D012313:RNA / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020127:Recovery of Function; D016896:Treatment Outcome
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D012313:RNA; D000068298:Fluticasone