Prognostic Value of Colonic Tissue and Blood Eosinophils in Ulcerative Colitis.

BACKGROUND It has been suggested that eosinophils may be a prognostic marker of disease outcome in ulcerative colitis (UC), but conflicting data exist. The objective was to investigate the extent of mucosal eosinophils and peripheral blood eosinophil count in newly diagnosed UC patients and to investigate its predictive value in short- and long-term disease outcomes. METHODS The degree of eosinophilia in baseline colonic biopsies and blood of newly diagnosed UC patients was retrospectively analyzed. It was investigated if tissue and blood eosinophilia could be a marker of a severe phenotype of UC, defined as the need for corticosteroids or immunomodulators in the first year or treatment with therapeutic monoclonal antibodies or colectomy during follow-up. Time to therapeutic monoclonal antibodies and time to colectomy were also evaluated as outcomes. RESULTS There were 103 UC patients (median age 26 years) included. Median tissue peak eosinophil count (PEC) was 70.0 and median peripheral blood eosinophil count was 0.3 × 109/L at diagnosis. Tissue PEC (r = -0.161, P = .104) and blood eosinophil count (r = 0.022, P = .877) were not correlated with the severity of histologic inflammation. Logistic regression analyses did not identify PEC and blood eosinophil count as predictors of more severe disease outcomes. Tissue PEC and peripheral blood eosinophil count did not predict the time the initiation of therapeutic monoclonal antibodies or colectomy. CONCLUSION Baseline tissue or peripheral blood eosinophils are not markers of disease activity and cannot be used as a predictor of severe disease outcomes in both adults and children with UC

The Habitual Diet of Dutch Adult Patients with Eosinophilic Esophagitis Has Pro-Inflammatory Properties and Low Diet Quality Scores

We determined the nutritional adequacy and overall quality of the diets of adult patients with eosinophilic esophagitis (EoE). Dietary intakes stratified by sex and age were compared to Dietary Reference Values (DRV). Overall diet quality was assessed by two independent Diet-Quality-Indices scores, the PANDiet and DHD-index, and compared to age- and gender-matched subjects from the general population. Lastly, food and nutrient intakes of EoE patients were compared to intakes of the general population. Saturated fat intake was significantly higher and dietary fiber intake significantly lower than the DRV in both males and females. In males, the DRV were not reached for potassium, magnesium, selenium, and vitamins A and D. In females, the DRV were not reached for iron, sodium, potassium, selenium, and vitamins A, B2, C and D. EoE patients had a significantly lower PANDiet and DHD-index compared to the general population, although the relative intake (per 1000 kcal) of vegetables/fruits/olives was significantly higher (yet still up to 65% below the recommended daily amounts) and alcohol intake was significantly lower compared to the general Dutch population. In conclusion, the composition of the habitual diet of adult EoE patients has several pro-inflammatory and thus unfavorable immunomodulatory properties, just as the general Dutch population, and EoE patients had lower overall diet quality scores than the general population. Due to the observational character of this study, further research is needed to explore whether this contributes to the development and progression of EoE

Advances in the physiological assessment and diagnosis of GERD

Abstract GERD is a common condition worldwide. Key mechanisms of disease include abnormal oesophagogastric junction structure and function, and impaired oesophageal clearance. A therapeutic trial of acid-suppressive PPI therapy is often the initial management, with endoscopy performed in the setting of alarm symptoms and to exclude other conditions. If symptoms persist and endoscopy does not reveal evidence of GERD, oesophageal function tests are performed, including oesophageal manometry and ambulatory reflux monitoring. However, reflux episodes can be physiological, and some findings on endoscopy and manometry can be encountered in asymptomatic individuals without GERD symptoms. The diagnosis of GERD on the basis of functional oesophageal testing has been previously reported, but no updated expert recommendations on indications and the interpretation of oesophageal function testing in GERD has been made since the Porto consensus over a decade ago. In this Consensus Statement, we aim to describe modern oesophageal physiological tests and their analysis with an emphasis on establishing indications and consensus on interpretation parameters of oesophageal function testing for the evaluation of GERD in clinical practice. This document reflects the collective conclusions of the international GERD working group, incorporating existing data with expert consensus opinion

Transcriptomic profiling of the acute mucosal response to local food injections in adults with eosinophilic esophagitis

Background: Exposure of the esophageal mucosa to food allergens can cause acute mucosal responses in patients with eosinophilic esophagitis (EoE), but the underlying local immune mechanisms driving these acute responses are not well understood. Objective: We sought to gain insight into the early transcriptomic changes that occur during an acute mucosal response to food allergens in EoE. Methods: Bulk RNA sequencing was performed on esophageal biopsy specimens from adult patients with EoE (n = 5) collected before and 20 minutes after intramucosal injection of various food extracts in the esophagus. Baseline biopsy specimens from control subjects without EoE (n = 5) were also included. Results: At baseline, the transcriptome of the patients with EoE showed increased expression of genes related to an EoE signature. After local food injection, we identified 40 genes with a potential role in the early immune response to food allergens (most notably CEBPB, IL1B, TNFSF18, PHLDA2, and SLC15A3). These 40 genes were enriched in processes related to immune activation, such as the acute-phase response, cellular responses to external stimuli, and cell population proliferation. TNFSF18 (also called GITRL), a member of the TNF superfamily that is best studied for its costimulatory effect on T cells, was the most dysregulated early EoE gene, showing a 12-fold increase compared with baseline and an 18-fold increase compared with a negative visual response. Further experiments showed that the esophageal epithelium may be an important source of TNFSF18 in EoE, which was rapidly induced by costimulating esophageal epithelial cells with the EoE-relevant cytokines IL-13 and TNF-α. Conclusions: Our data provide unprecedented insight into the transcriptomic changes that mediate the acute mucosal immune response to food allergens in EoE and suggest that TNFSF18 may be an important effector molecule in this response

Improving Care in Eosinophil-Associated Diseases: A Charter.

Eosinophil-associated diseases (EADs) are a range of heterogeneous conditions in which eosinophils are believed to play a critical pathological role. EADs include common illnesses such as eosinophilic asthma and chronic rhinosinusitis and rare conditions such as hypereosinophilic syndromes (HES) and eosinophilic gastrointestinal disorders (EGIDs). EADs are associated with substantial burdens for the patient, including chronic, debilitating symptoms, increased financial burden, decreased health-related quality of life, and the need for repeated visits to multiple different healthcare professionals (HCPs), emergency departments, and/or hospitals. Poor EAD recognition by HCPs often contributes to delayed diagnoses, which further delays patient access to appropriate care and effective treatments, contributing to poor health outcomes. The objective of this charter is to outline key patient rights and expectations with respect to the management of their condition(s) and to set forth an ambitious action plan to improve health outcomes for patients with EADs: (1) people with EADs, their caretakers, HCPs, and the public must have greater awareness and education about EADs; (2) people with EADs must receive a timely, accurate diagnosis; (3) all people with EADs must have access to an appropriate multidisciplinary team, when necessary; and (4) people with EADs must have access to safe and effective treatment options without unnecessary regulatory delays. The principles described in this charter demonstrate the core elements of quality care that people with EADs must receive, and they represent clear steps by which to reduce patient and caregiver burden and improve patient outcomes. We urge HCPs, healthcare systems, and policymakers worldwide to swiftly adopt these principles to ensure patients with EADs have an accurate diagnosis in a timely manner and access to high-level care and treatment in an appropriate setting

Plain Language Summary of principles for improving the care of people with eosinophil-associated diseases.

Eosinophil-associated diseases (EADs) are a group of conditions in which eosinophils (a type of white blood cell) are thought to play a key role in the disease and how it develops. Some EADs are common, such as atopic dermatitis (also called eczema) and a subtype of asthma called eosinophilic asthma, while others are rare, such as hypereosinophilic syndrome (a condition in which a person has a very high number of eosinophils in both the blood and one or more organs). People with EADs face many problems related to their conditions. Symptoms such as severe abdominal pain, itch, or shortness of breath impact both the patient as well as their friends and family. Patients with EADs also experience delays to diagnosis and treatment as well as financial barriers. Healthcare professionals sometimes fail to recognize the complex set of symptoms that characterize an EAD, and this may cause delays in reaching a correct diagnosis. As a result, it may take longer for a patient to get the best care and the most effective treatments, which may contribute to poor health. The goal of this charter is to describe the key elements of good quality care, which all people with EADs deserve, as well as to present an action plan to improve health and overall well-being for people with EADs. Proposed use of this patient charter: The principles described in this charter (a written guide to achieve an outcome) show the core elements of quality care that people with EADs must receive. They also describe clear steps to reduce the burden on patients and their caregivers and to improve patient health outcomes. We urge healthcare professionals, hospitals, and policymakers around the world to adopt these principles quickly. By doing this, people with EADs will be more likely to receive an accurate and timely diagnosis and have access to quality care and treatment in the right setting

Systematic Review of Outcome Measures Used in Observational Studies of Adults with Eosinophilic Esophagitis.

BACKGROUND Over the last 20 years, diverse outcome measures have been used to evaluate the effectiveness of therapies for eosinophilic esophagitis (EoE). This systematic review aims to identify the readouts used in observational studies of topical corticosteroids, diet, and dilation in adult EoE patients. METHODS We searched MEDLINE and Embase for prospective and retrospective studies (cohorts/case series, randomized open-label, and case-control) evaluating the use of diets, dilation, and topical corticosteroids in adults with EoE. Two authors independently assessed the articles and extracted information about histologic, endoscopic, and patient-reported outcomes and tools used to assess treatment effects. RESULTS We included 69 studies that met inclusion criteria. EoE-associated endoscopic findings (assessed either as absence/presence or using Endoscopic Reference Score) were evaluated in 24/35, 11/17, and 9/17 studies of topical corticosteroids, diet, and dilation, respectively. Esophageal eosinophil density was recorded in 32/35, 17/17, and 11/17 studies of topical corticosteroids, diet, and dilation, respectively. Patient-reported outcomes were not uniformly used (only in 14, 8, and 3 studies of topical corticosteroids, diet, and dilation, respectively), and most tools were not validated for use in adults with EoE. CONCLUSIONS Despite the lack of an agreed set of core outcomes that should be recorded and reported in studies in adult EoE patients, endoscopic EoE-associated findings and esophageal eosinophil density are commonly used to assess disease activity in observational studies. Standardization of outcomes and data supporting the use of outcomes are needed to facilitate interpretation of evidence, its synthesis, and comparisons of interventions in meta-analyses of therapeutic trials in adults with EoE

Budesonide orodispersible tablets for induction of remission in patients with active eosinophilic oesophagitis: A 6-week open-label trial of the EOS-2 Programme

BACKGROUND A novel budesonide orodispersible tablet (BOT) has been proven effective in adult patients with active eosinophilic oesophagitis (EoE) in a 6-week placebo-controlled trial (EOS-1). AIMS To report the efficacy of an open-label induction treatment with BOT in a large prospective cohort of EoE patients within the EOS-2 study. METHODS Patients with clinico-histological active EoE were treated with BOT 1 mg BID for 6 weeks. The primary endpoint was clinico-histological remission (≤2 points on numerical rating scales [0-10] each for dysphagia and odynophagia, and peak eosinophil count <16 eos/mm$^{2}$ hpf (corresponds to <5 eos/hpf)). Further study endpoints included clinical and histological remission rates, change in the EEsAI-PRO score, change in peak eosinophil counts, and deep endoscopic remission using a modified Endoscopic Reference Score. RESULTS Among 181 patients enrolled, 126 (69.6%) achieved clinico-histological remission (histological remission 90.1%, clinical remission 75.1%). The mean peak eosinophil counts decreased by 283 eos/mm$^{2}$ hpf (i.e., by 89.0%). Mean EEsAI-PRO score decreased from baseline by 29 points and deep endoscopic remission was achieved in 97 (53.6%) patients. The majority of patients judged tolerability as good or very good (85.6%) and compliance was high (96.5%). Local candidiasis was suspected in 8.3% of patients; all were of mild severity, resolved with treatment and none led to premature withdrawal from the study. CONCLUSIONS In this large prospective trial, a 6-week open-label treatment with BOT 1 mg BID was highly effective and safe in achieving clinico-histological remission of active EoE and confirmed the results of the placebo-controlled EOS-1 trial

Dietary composition of adult eosinophilic esophagitis patients is related to disease severity

Background: In addition to the elimination diet, dietary composition may influence disease severity in patients with eosinophilic esophagitis (EoE) through modulation of the immune response. Aim: To explore the immunomodulatory role of nutrition before and during elimination diet in adult EoE patients. Methods: Nutritional intake was assessed in 39 Dutch adult EoE patients participating in the Supplemental Elemental Trial (Dutch trial registry NL6014, NTR6778) using 3-day food diaries. In this randomized controlled trial, diagnosed patients received either a four-food elimination diet alone (FFED) or FFED with addition of an amino acid-based formula for 6 weeks. Multiple linear regression analyses were performed to assess associations between the intake of nutrients and food groups per 1000 kCal and peak eosinophil count/high power field (PEC), both at baseline and after 6 weeks. Results: At baseline, we found a statistically significant negative (thus favorable) relationship between the intake of protein, total fat, phosphorus, zinc, vitamin B12, folate, and milk products and PEC (p <.05), while calcium (p =.058) and full-fat cheese/curd (p =.056) were borderline (favorably) significant. In contrast, total carbohydrates, prepacked fruit juice, and white bread were significantly positively (unfavorable) related to PEC (p <.05), while ultra-processed meals (p =.059) were borderline (unfavorably) significant. After dietary intervention, coffee/tea were significantly negatively (favorably) related to PEC, hummus/legumes were significantly positively (unfavorably) related with PEC, while peanuts were borderline significantly positively related (p =.058). Conclusion: Dietary composition may be related to inflammation in adult EoE patients. High-quality and anti-inflammatory diets may be a promising adjuvant therapy in the dietary management of EoE

Mast cells disrupt the function of the esophageal epithelial barrier

Mast cells (MCs) accumulate in the epithelium of patients with eosinophilic esophagitis (EoE), an inflammatory disorder characterized by extensive esophageal eosinophilic infiltration. Esophageal barrier dysfunction plays an important role in the pathophysiology of EoE. We hypothesized that MCs contribute to the observed impaired esophageal epithelial barrier. Herein, we demonstrate that coculture of differentiated esophageal epithelial cells with immunoglobulin E-activated MCs significanly decreased epithelial resistance by 30% and increased permeability by 22% compared with non-activated MCs. These changes were associated with decreased messenger RNA expression of barrier proteins filaggrin, desmoglein-1 and involucrin, and antiprotease serine peptidase inhibitor kazal type 7. Using targeted proteomics, we detected various cytokines in coculture supernatants, most notably granulocyte-macrophage colony-stimulating factor and oncostatin M (OSM). OSM expression was increased by 12-fold in active EoE and associated with MC marker genes. Furthermore, OSM receptor-expressing esophageal epithelial cells were found in the esophageal tissue of patients with EoE, suggesting that the epithelial cells may respond to OSM. Stimulation of esophageal epithelial cells with OSM resulted in a dose-dependent decrease in barrier function and expression of filaggrin and desmoglein-1 and an increase in protease calpain-14. Taken together, these data suggest a role for MCs in decreasing esophageal epithelial barrier function in EoE, which may in part be mediated by OSM