ArticlePloS one2014
Proton pump inhibitors decrease eotaxin-3 expression in the proximal esophagus of children with esophageal eosinophilia.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03781596 (Randomized Controlled Trial Comparing Fluticasone Plus Omeprazole With Fluticasone Alone for Eosinophilic Esophagitis), which is not on this map. Cited by 28 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Randomized Controlled Trial Comparing Fluticasone Plus Omeprazole With Fluticasone Alone for Eosinophilic Esophagitis
Who cites it
28 citing papers in PubMed, 1 synthesis or guideline pooled it, 49 citations in OpenAlex.
- Guideline
- Downregulation of MUC6 improves esophageal epithelial barrier dysfunction and inhibits epithelial-mesenchymal transition in reflux esophagitis.BMC gastroenterology · 2026Article
- Article
- Relationship between proton pump inhibitor prescription and asthma exacerbation among adult patients: a self-controlled case series study.Internal and emergency medicine · 2024Article
- Regulatory T cells Are Increased and Correlate With Mast Cells in Eosinophilic Esophagitis.Journal of neurogastroenterology and motility · 2024Article
- Pathogenesis of Nasal Polyposis: Current Trends.Indian journal of otolaryngology and head and neck surgery : official publication of the Association of Otolaryngologists of India · 2023Article
- Esophageal Mucosal Permeability as a Surrogate Measure of Cure in Eosinophilic Esophagitis.Journal of clinical medicine · 2022Article
- Proton Pump Inhibitor Therapy for Eosinophilic Esophagitis: History, Mechanisms, Efficacy, and Future Directions.Journal of asthma and allergy · 2022Review
- Pharmacogenomics fail to explain proton pump inhibitor refractory esophagitis in pediatric esophageal atresia.Neurogastroenterology and motility · 2022Article
- Proton Pump Inhibitors in Children: the Good, the Bad, and the Ugly.Current allergy and asthma reports · 2020Review
- CYP2C19 and STAT6 Variants Influence the Outcome of Proton Pump Inhibitor Therapy in Pediatric Eosinophilic Esophagitis.Journal of pediatric gastroenterology and nutrition · 2019Article
- Eosinophilic esophagitis in pediatric age, state of the art and review of the literature.Acta bio-medica : Atenei Parmensis · 2018Review
- Eosinophilic Esophagitis: an Important Comorbid Condition of Asthma?Clinical reviews in allergy & immunology · 2018Review
- Biological therapies for eosinophilic gastrointestinal diseases.The Journal of allergy and clinical immunology · 2018Review
- Eosinophilic Esophagitis Is an Underlying Cause for Gastrointestinal Concerns in Children.Frontiers in pediatrics · 2018Review
- The Role of Proton Pump Inhibitors in the Management of Pediatric Eosinophilic Esophagitis.Frontiers in pediatrics · 2018Review
- Eosinophilic esophagitis: current understanding and evolving concepts.Asia Pacific allergy · 2017Review
- Proton pump inhibitors decrease eotaxin-3/CCL26 expression in patients with chronic rhinosinusitis with nasal polyps: Possible role of the nongastric H,K-ATPase.The Journal of allergy and clinical immunology · 2017Article
- GPR84 and TREM-1 Signaling Contribute to the Pathogenesis of Reflux Esophagitis.Molecular medicine (Cambridge, Mass.) · 2016Article
- Recent discoveries and emerging therapeutics in eosinophilic esophagitis.World journal of gastrointestinal pharmacology and therapeutics · 2016Review
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 1 country.
Funding
Abstract
objectiveBesides reducing gastric acid secretion, proton pump inhibitors (PPIs) suppress Th2-cytokine-stimulated expression of an eosinophil chemoattractant (eotaxin-3) by esophageal epithelial cells through acid-independent, anti-inflammatory mechanisms. To explore acid-inhibitory and acid-independent, anti-inflammatory PPI effects in reducing esophageal eosinophilia, we studied eotaxin-3 expression by the proximal and distal esophagus of children with esophageal eosinophilia before and after PPI therapy. In vitro, we studied acid and bile salt effects on IL-13-stimulated eotaxin-3 expression by esophageal epithelial cells.
designAmong 264 children with esophageal eosinophilia seen at a tertiary pediatric hospital from 2008 through 2012, we identified 10 with esophageal biopsies before and after PPI treatment alone. We correlated epithelial cell eotaxin-3 immunostaining with eosinophil numbers in those biopsies. In vitro, we measured eotaxin-3 protein secretion by esophageal squamous cells stimulated with IL-13 and exposed to acid and/or bile salt media, with or without omeprazole.
resultsThere was strong correlation between peak eosinophil numbers and peak eotaxin-3-positive epithelial cell numbers in esophageal biopsies. Eotaxin-3 expression decreased significantly with PPIs only in the proximal esophagus. In esophageal cells, exposure to acid-bile salt medium significantly suppressed IL-13-induced eotaxin-3 secretion; omeprazole added to the acid-bile salt medium further suppressed that eotaxin-3 secretion, but not as profoundly as at pH-neutral conditions.
conclusionIn children with esophageal eosinophilia, PPIs significantly decrease eotaxin-3 expression in the proximal but not the distal esophagus. In esophageal squamous cells, acid and bile salts decrease Th2 cytokine-stimulated eotaxin-3 secretion profoundly, possibly explaining the disparate PPI effects on the proximal and distal esophagus. In the distal esophagus, where acid reflux is greatest, a PPI-induced reduction in acid reflux (an effect that could increase eotaxin-3 secretion induced by Th2 cytokines) might mask the acid-independent, anti-inflammatory PPI effect of decreasing cytokine-stimulated eotaxin-3 secretion.
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