BACKGROUND: The molecular basis and effects of proton pump inhibitor (PPI) therapy on PPI-responsive oesophageal eosinophilia (PPI-REE) and eosinophilic oesophagitis (EoE) remain unknown. AIM: To compare symptom-histological and cytokine gene expression in PPI-REE and EoE patients, at baseline and after specific treatment. METHODS: In consecutive adult patients with an EoE phenotype (dysphagia/food impaction, typical endoscopic findings and > 15 eos/HPF), gene expression of eotaxin-3, IL-13, and IL-5 were determined in distal and proximal oesophagus, at baseline and after omeprazole 40 mg b.d. for 8 weeks. PPI-REE was defined by clinicohistological response. PPI nonresponders (EoE) were offered treatment with topical steroids. RESULTS: Fifty three patients were re-evaluated on PPI therapy. 23 patients (43%) had PPI-REE and 30 patients (57%) had EoE. At baseline, eotaxin-3/IL-13/IL-5 gene expression was indistinguishable between EoE and PPI-REE, excepting increased IL-5 expression in proximal oesophagus (12.54 vs. 57, P = 0.029). PPI therapy significantly decreased eotaxin-3/IL-13 in PPI-REE, at both oesophageal sites (P ≤ 0.008), and IL-5 in distal (P = 0.016), but not in proximal oesophagus. Patients with steroid-responsive EoE also showed a significant decrease in eotaxin-3/IL-5 expression at both oesophageal sites. In EoE patients, initial PPI trial significantly decreased distal oesophageal eosinophilia (63.78 to 41.79 eos/HPF, P = 0.025) and led to symptom remission in 16%, but did not influence Th2 markers. CONCLUSIONS: Baseline cytokine gene expression in PPI-REE was nearly indistinguishable from EoE. PPI therapy significantly downregulated oesophageal eotaxin-3/Th2-cytokine gene expression in PPI-REE, similarly to that seen in steroid-responsive EoE. A subset of EoE patients showed clinicohistological improvement on PPI therapy.
BACKGROUND: The molecular basis and effects of proton pump inhibitor (PPI) therapy on PPI-responsive oesophageal eosinophilia (PPI-REE) and eosinophilic oesophagitis (EoE) remain unknown. AIM: To compare symptom-histological and cytokine gene expression in PPI-REE and EoE patients, at baseline and after specific treatment. METHODS: In consecutive adult patients with an EoE phenotype (dysphagia/food impaction, typical endoscopic findings and > 15 eos/HPF), gene expression of eotaxin-3, IL-13, and IL-5 were determined in distal and proximal oesophagus, at baseline and after omeprazole 40 mg b.d. for 8 weeks. PPI-REE was defined by clinicohistological response. PPI nonresponders (EoE) were offered treatment with topical steroids. RESULTS: Fifty three patients were re-evaluated on PPI therapy. 23 patients (43%) had PPI-REE and 30 patients (57%) had EoE. At baseline, eotaxin-3/IL-13/IL-5 gene expression was indistinguishable between EoE and PPI-REE, excepting increased IL-5 expression in proximal oesophagus (12.54 vs. 57, P = 0.029). PPI therapy significantly decreased eotaxin-3/IL-13 in PPI-REE, at both oesophageal sites (P ≤ 0.008), and IL-5 in distal (P = 0.016), but not in proximal oesophagus. Patients with steroid-responsive EoE also showed a significant decrease in eotaxin-3/IL-5 expression at both oesophageal sites. In EoE patients, initial PPI trial significantly decreased distal oesophageal eosinophilia (63.78 to 41.79 eos/HPF, P = 0.025) and led to symptom remission in 16%, but did not influence Th2 markers. CONCLUSIONS: Baseline cytokine gene expression in PPI-REE was nearly indistinguishable from EoE. PPI therapy significantly downregulated oesophageal eotaxin-3/Th2-cytokine gene expression in PPI-REE, similarly to that seen in steroid-responsive EoE. A subset of EoE patients showed clinicohistological improvement on PPI therapy.
Authors: Evan S Dellon; Chris A Liacouras; Javier Molina-Infante; Glenn T Furuta; Jonathan M Spergel; Noam Zevit; Stuart J Spechler; Stephen E Attwood; Alex Straumann; Seema S Aceves; Jeffrey A Alexander; Dan Atkins; Nicoleta C Arva; Carine Blanchard; Peter A Bonis; Wendy M Book; Kelley E Capocelli; Mirna Chehade; Edaire Cheng; Margaret H Collins; Carla M Davis; Jorge A Dias; Carlo Di Lorenzo; Ranjan Dohil; Christophe Dupont; Gary W Falk; Cristina T Ferreira; Adam Fox; Nirmala P Gonsalves; Sandeep K Gupta; David A Katzka; Yoshikazu Kinoshita; Calies Menard-Katcher; Ellyn Kodroff; David C Metz; Stephan Miehlke; Amanda B Muir; Vincent A Mukkada; Simon Murch; Samuel Nurko; Yoshikazu Ohtsuka; Rok Orel; Alexandra Papadopoulou; Kathryn A Peterson; Hamish Philpott; Philip E Putnam; Joel E Richter; Rachel Rosen; Marc E Rothenberg; Alain Schoepfer; Melissa M Scott; Neil Shah; Javed Sheikh; Rhonda F Souza; Mary J Strobel; Nicholas J Talley; Michael F Vaezi; Yvan Vandenplas; Mario C Vieira; Marjorie M Walker; Joshua B Wechsler; Barry K Wershil; Ting Wen; Guang-Yu Yang; Ikuo Hirano; Albert J Bredenoord Journal: Gastroenterology Date: 2018-09-06 Impact factor: 22.682
Authors: Girish S Hiremath; Fatimah Hameed; Ann Pacheco; Anthony Olive; Carla M Davis; Robert J Shulman Journal: Dig Dis Sci Date: 2015-06-12 Impact factor: 3.199
Authors: E S Dellon; L L Higgins; R Beitia; S Rusin; J T Woosley; R Veerappan; S R Selitsky; J S Parker; R M Genta; R H Lash; R Aranda; R J Peach; M Grimm Journal: Aliment Pharmacol Ther Date: 2016-05-18 Impact factor: 8.171