Angelika Zalewski

Esophageal microbiome in eosinophilic esophagitis

Objective The microbiome has been implicated in the pathogenesis of a number of allergic and inflammatory diseases. The mucosa affected by eosinophilic esophagitis (EoE) is composed of a stratified squamous epithelia and contains intraepithelial eosinophils. To date, no studies have identified the esophageal microbiome in patients with EoE or the impact of treatment on these organisms. The aim of this study was to identify the esophageal microbiome in EoE and determine whether treatments change this profile. We hypothesized that clinically relevant alterations in bacterial populations are present in different forms of esophagitis. Design In this prospective study, secretions from the esophageal mucosa were collected from children and adults with EoE, Gastroesophageal Reflux Disease (GERD) and normal mucosa using the Esophageal String Test (EST). Bacterial load was determined using quantitative PCR. Bacterial communities, determined by 16S rRNA gene amplification and 454 pyrosequencing, were compared between health and disease. Results Samples from a total of 70 children and adult subjects were examined. Bacterial load was increased in both EoE and GERD relative to normal subjects. In subjects with EoE, load was increased regardless of treatment status or degree of mucosal eosinophilia compared with normal. Haemophilus was significantly increased in untreated EoE subjects as compared with normal subjects. Streptococcus was decreased in GERD subjects on proton pump inhibition as compared with normal subjects. Conclusions Diseases associated with mucosal eosinophilia are characterized by a different microbiome from that found in the normal mucosa. Microbiota may contribute to esophageal inflammation in EoE and GERD.

Evaluation of esophageal distensibility in eosinophilic esophagitis: an update and comparison of functional lumen imaging probe analytic methods

Distensibility evaluation of the esophageal body using the functional lumen imaging probe (FLIP) offers an objective measure to characterize patients with eosinophilic esophagitis (EoE), though this analysis may be limited by unrecognized catheter movement and esophageal contractility. The aims of this study were to report novel FLIP analytic methods of esophageal distensibility measurement in EoE and to assess the effect of contractility.

877 Prospective Trial of Four Food Elimination Diet Demonstrates Comparable Effectiveness in the Treatment of Adult and Pediatric Eosinophilic Esophagitis

DI-metrics derived from FLIP data acquisition of simultaneous cross-sectional area and distention pressure. The line plot of the smallest CSA versus intrabag pressure for an EoE patient is illustrated to highlight the metrics of distensibility: distensibility slope (DS), distensibility plateau (DP) and plateau onset pressure (POP). Note the insets of the realtime FLIP data approximating the POP at approximately 22 mmHg and the distensibility along the DP at 58 mmHg. There is little overall change in the smallest esophageal CSA along the length of the esophageal body despite a change in pressure once the plateau is reached.

Prospective assessment of the diagnostic utility of esophageal brushings in adults with eosinophilic esophagitis

Patients with eosinophilic esophagitis (EoE) undergo multiple endoscopies with biopsy for both diagnosis and assessment of treatment response, which is inconvenient and costly. Brush cytology has been examined in Barretts esophagus to reduce the need for repeated endoscopic biopsies. The aim of this pilot study was to evaluate the ability of brush cytology to detect mucosal eosinophilia in patients with EoE. This prospective study included adults with untreated and treated esophageal eosinophilia undergoing endoscopy at a tertiary care center. Patients received paired brushings and biopsies at the proximal and distal esophagus. A blinded pathologist quantified the number of eosinophils and epithelial cells per high-power field (hpf) on the cytology slides. The ratio of eosinophils/epithelial cells was used to normalize the cytology specimens for density of cells collected. The main outcome measures were sensitivity and specificity of brush cytology, and correlation between cytology and histology. Twenty-eight patients enrolled. The average age of the cohort was 37.7 ± 10.4 years; 75% of subjects were male. The sensitivity of cytology was 67-69% at the proximal esophagus and 70-72% at the distal esophagus. The specificity was 61-67% proximally and 70-75% distally. Histology was not significantly correlated with the max ratio of eosinophils/epithelial cells per hpf or the absolute number of eosinophils on cytology slides. Cytology using esophageal brushing has limited sensitivity and specificity for the detection of esophageal mucosal eosinophilia. The presence of exudates on endoscopy increased the detection of eosinophilia, which could make cytology useful in pediatric EoE, which often has a more exudative presentation. Diagnostic yield may improve with alternative acquisition techniques or the incorporation of eosinophil degranulation proteins.

Improvement in Esophageal Distensibility in Response to Medical and Diet Therapy in Eosinophilic Esophagitis

Objectives:We aimed to evaluate the effect of medical and diet therapies on esophageal distensibility assessed using the functional lumen imaging probe (FLIP) and the association of changes in esophageal distensibility with clinical outcomes in eosinophilic esophagitis (EoE).Methods:Patients with EoE were evaluated with FLIP during endoscopy at baseline and following therapy without interval dilatation. Evaluation also included a validated patient-reported outcome (PRO; a positive PRO was considered at a 30% score improvement), mucosal biopsies, and scoring of endoscopic features of EoE. FLIP data were analyzed to calculate the distensibility plateau (DP).Results:In all, 18 patients (ages 19–54 years; 4 female) treated with topical steroid (8), elimination diet (6), and/or proton-pump inhibitor (4 only treated with proton-pump inhibitor) were included. Follow-up testing occurred at a mean (range) of 14.6 (8–28) weeks. Improvement was observed in DP (13.9 (12.2–19.2) to 16.8 mm (15.8–19.2), P=0.007) and peak eosinophil count (45 (29–65) to 23 per high-power field (h.p.f.) (5–53), P=0.042). Nine patients had a positive symptomatic outcome. Six of 8 (75%) patients with a DP increase ≥2 mm had a positive PRO (P=0.077), while 2 of 7 (29%) patients that achieved an eosinophil count <15/h.p.f. had a positive PRO (P=0.167).Conclusions:Improvement in esophageal body distensibility can be achieved with medical and diet therapies without dilation in EoE. Improved DP appeared to be better indicator of symptomatic improvement than eosinophil count, supporting FLIP as a valuable outcome measure in EoE.

Dysregulation of the Wnt pathway in adult eosinophilic esophagitis

Eosinophilic esophagitis (EoE) is a chronic inflammatory disease characterized pathologically by eosinophil infiltration. In addition to loss of barrier integrity, a dominant T Helper 2-associated immune response and strong allergic connection, the esophagus tissue undergoes dramatic changes, with frequent presence of mucosal rings, strictures, linear furrows, and trachealization. Although the inflammatory mechanisms behind this disease are being increasingly well understood, the structural features remain unexplained. We examined the expression of key members of the Wnt-signaling pathway in biopsies from patients with EoE. This pathway has been shown to be critically important in regulating cellular homeostasis, growth, and differentiation and to be dysregulated in several disease conditions. Biopsies from adult EoE patients were collected by endoscopy and mRNA extracted. After cDNA synthesis, the relative gene expression from key upstream (secreted frizzled-related protein 1) and downstream (c-myc and Cyclin D1) molecules in the Wnt pathway, as well as several Wnt pathway members (Wnt1, Axin1, low-density lipoprotein receptor-related protein 6, glycogen synthase kinase 3 beta, and β-catenin), were determined. Biopsies from patients with EoE displayed significantly higher expression of secreted frizzed-related protein 1 than controls, as well as reductions in Cyclin D1 and c-myc. In contrast, there were no differences in the Wnt pathway molecules. The levels of expression of Cyclin D1 and c-myc, as well as β-catenin, in EoE patients showed strong correlations with the frequency of esophageal eosinophils. Our findings suggest that although there are no changes in the overall levels of key Wnt pathway genes in adult EoE, there is evidence for dysregulation of upstream and downstream regulators of Wnt signaling. Importantly, the associations with eosinophilia suggest that these may participate in the pathogenesis of this disease and be markers of disease severity.

Assessing Adherence and Barriers to Long-Term Elimination Diet Therapy in Adults with Eosinophilic Esophagitis

BackgroundThe six-food elimination diet (SFED) is an effective treatment approach for eosinophilic esophagitis (EoE), but it can be challenging and affect patients’ quality of life.AimAssess patients’ long-term adherence to SFED and potential factors influencing adherence.MethodsEoE patients were recruited online via multiple platforms. Patients were classified as reaching the maintenance stage if they responded to SFED and identified specific trigger foods by reintroduction. Maintenance stage patients were categorized into those actively following the elimination diet (ACTIVE) and those no longer on their prescribed diet (FORMER). Participants completed a study-specific questionnaire assessing patient experiences related to SFED use.ResultsForty-two participants were identified as having reached the SFED’s maintenance stage. 57% (24/42) of the maintenance stage patients were ACTIVE users. FORMER users rated the SFED’s effectiveness at treating symptoms (5.45 ± 3.96, 10 max.) lower than ACTIVE users (8.29 ± 2.76, p = .02). A greater percentage of FORMER users (100%) agreed social situations create challenges in following the diet compared to ACTIVE users (67%, p < .05). Anxiety related to SFED was also higher among FORMER users (64%) compared to ACTIVE users (21%, p < .01). Both ACTIVE (95.8%) and FORMER (81.8%, NSS) users would recommend the elimination diet to other EoE patients.ConclusionsUnderstanding SFED adherence is multifactorial and complex. Factors influencing SFED adherence during long-term maintenance with diet therapy include diet effectiveness, social situations, and diet-related anxiety. Despite a lower than expected long-term adherence to maintenance of an elimination diet, the majority would recommend diet therapy as a treatment to other EoE patients.

Gender-specific differences in the molecular signatures of adult Eosinophilic Oesophagitis

The influence of gender on the prevalence, presentation and pathogenesis of allergic diseases is being increasingly recognized [1]. Eosinophilic Eosophagitis (EoE) is a chronic inflammatory disorder of the esophagus, seen in both children and adults, and is 3-4 times more common in males than females [2]. Diagnosis of EoE has relied on quantification of eosophageal eosinophils by biopsy and patient-reported symptoms but recent studies have supported the use of tissue-based molecular biomarker assessment, based on gene expression signatures [3], aiding patient diagnosis [4]. This article is protected by copyright. All rights reserved.

879 The Esophageal String Test (EST) Quantifies Luminal Eosinophil and Chemokine Biomarkers Reflective of Esophageal Inflammation in Adults With Eosinophilic Esophagitis (EoE)

DI-metrics derived from FLIP data acquisition of simultaneous cross-sectional area and distention pressure. The line plot of the smallest CSA versus intrabag pressure for an EoE patient is illustrated to highlight the metrics of distensibility: distensibility slope (DS), distensibility plateau (DP) and plateau onset pressure (POP). Note the insets of the realtime FLIP data approximating the POP at approximately 22 mmHg and the distensibility along the DP at 58 mmHg. There is little overall change in the smallest esophageal CSA along the length of the esophageal body despite a change in pressure once the plateau is reached.