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A new paradigm for GERD pathogenesis. Not acid injury, but cytokine-mediated inflammation driven by HIF-2?: a potential role for targeting HIF-2? to prevent and treat reflux esophagitis.

ABSTRACT: Traditionally, reflux esophagitis was assumed to develop as a caustic, chemical injury inflicted by refluxed acid. Recently, however, studies in rats and humans suggest that reflux esophagitis develops as a cytokine-mediated inflammatory injury, with hypoxia inducible factor (HIF)-2? playing a major role. In response to the reflux of acid and bile, HIF-2? in esophageal epithelial cells becomes stabilized, thereby increasing production of pro-inflammatory cytokines that attract T lymphocytes and other inflammatory cells to damage the esophagus. Recent studies have identified small molecule inhibitors of HIF-2? that demonstrate exquisite isoform selectivity, and clinical trials for treatment of HIF-2?-driven kidney cancers are ongoing. It is conceivable that a HIF-2?-directed therapy might be a novel approach to prevention and treatment of reflux esophagitis.

SUBMITTER: Souza RF

PROVIDER: S-EPMC5922421 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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A new paradigm for GERD pathogenesis. Not acid injury, but cytokine-mediated inflammation driven by HIF-2α: a potential role for targeting HIF-2α to prevent and treat reflux esophagitis.

Souza Rhonda F RF Bayeh Liela L Spechler Stuart J SJ Tambar Uttam K UK Bruick Richard K RK

Current opinion in pharmacology 20171105

Traditionally, reflux esophagitis was assumed to develop as a caustic, chemical injury inflicted by refluxed acid. Recently, however, studies in rats and humans suggest that reflux esophagitis develops as a cytokine-mediated inflammatory injury, with hypoxia inducible factor (HIF)-2α playing a major role. In response to the reflux of acid and bile, HIF-2α in esophageal epithelial cells becomes stabilized, thereby increasing production of pro-inflammatory cytokines that attract T lymphocytes and ...[more]

PMID: 29112883

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Project description:BackgroundGastroesophageal reflux disease (GERD) affects a significant proportion of individuals, with life stress being a contributing factor. This study aimed to investigate the correlation between psychosomatic evaluations, heart rate variability (HRV), and GERD in a cohort of individuals. Additionally, the study aimed to analyze the sequencing changes following proton pump inhibitor (PPI) treatment and identify predictive factors associated with refractory GERD.MethodsA prospective cohort of 105 individuals with reflux esophagitis and a control group of 50 participants without acid reflux symptoms were enrolled. Psychosomatic evaluations, including GERDQ, GERDQLQ, RSI, BAI, BDI, and SSS-8, were assessed at baseline and during treatment. HRV parameters were also evaluated. Multivariate analysis was used to identify predictive factors for refractory GERD. PPIs were administered regularly for the initial 2 months and then used on-demand. Refractory GERD was defined as less than 50% improvement in symptom relief or GERDQLQ score ≥ 20 after 8 weeks of PPI treatment.ResultsThe GERD group had higher scores in all psychosomatic evaluations compared to the control group (all p-values < 0.001). There were no significant changes in any parameters of HRV before and after treatment in the GERD group. Strong and consistent correlations were observed between GERD symptoms and psychological scores (BAI, BDI, and SSS-8) across all time points (W0, W4, and W8). Sequential reductions in GERD symptom scores and psychosomatic evaluations were observed during the initial eight weeks of treatment. Higher GERDQ (≥10) and SSS-8 (≥12) scores were predictive of refractory GERD (p = 0.004 and p = 0.009, respectively).ConclusionsThis study emphasizes the importance of considering physiological and psychological factors in the management of GERD. Psychosomatic evaluations provide valuable insights for assessing and treating GERD patients. Integrating stress management and comprehensive assessments into personalized treatment strategies is crucial.

Dataset Information

A new paradigm for GERD pathogenesis. Not acid injury, but cytokine-mediated inflammation driven by HIF-2?: a potential role for targeting HIF-2? to prevent and treat reflux esophagitis.

Publications

A new paradigm for GERD pathogenesis. Not acid injury, but cytokine-mediated inflammation driven by HIF-2α: a potential role for targeting HIF-2α to prevent and treat reflux esophagitis.

Similar Datasets

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