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Background: The demographic characteristics of patients with eosinophilic gastrointestinal diseases (EGIDs) are poorly understood. Population-based assessments of EGID demographics may indicate health disparities in diagnosis., Objectives: We aimed to characterize the demographic distribution of EGIDs and evaluate the potential for bias in reporting patient characteristics., Methods: We conducted a systematic review, extracting data on age, sex, gender, race, ethnicity, body mass index, insurance, and urban/rural residence on EGID patients and the source population. Differences in proportions were assessed by chi-square tests. Demographic reporting was compared to recent guidelines., Results: Among 50 studies that met inclusion/exclusion criteria, 12 reported ≥1 demographic feature in both EGID and source populations. Except for age and sex or gender, demographics were rarely described (race = 4, ethnicity = 1, insurance = 1) or were not described (body mass index, urban/rural residence). A higher proportion of male subjects was observed for EoE or esophageal eosinophilia relative to the source population, but no difference in gender or sex distribution was observed for other EGIDs. "Sex" and "gender" were used interchangeably, and frequently only the male proportion was reported. Reporting of race and ethnicity was inconsistent with guidelines., Conclusion: Current data support a male predominance for EoE only. Evidence was insufficient to support enrichment of EGIDs in any particular racial, ethnic, or other demographic group. Population-based studies presenting demographics on both cases and source populations are needed. Implementation of guidelines for more inclusive reporting of demographic characteristics is crucial to prevent disparities in timely diagnosis and management of patients with EGIDs., Competing Interests: Supported by U54AI117804 (Consortium of Eosinophilic Gastrointestinal Disease Researchers), which is part of the Rare Disease Clinical Research Network, an initiative of the Office of Rare Disease Research, National Center for Advancing Translational Sciences (NCATS), and is funded through collaboration between the National Institute of Allergy and Infectious Diseases (NIAID), the National Institute of Diabetes and Digestive and Kidney Diseases, NCATS, and patient advocacy groups including the American Partnership for Eosinophilic Disorders, Campaign Urging Research for Eosinophilic Disease (CURED), and Eosinophilic Family Coalition (EFC). This work was also funded in part by the Division of Intramural Research, NIAID, National Institutes of Health. Disclosure of potential conflict of interest: M. Chehade served as consultant for Regeneron, Allakos, Adare/Ellodi, Shire/Takeda, AstraZeneca, Sanofi, Bristol Myers Squibb, Phathom, Recludix Pharma, and Nexstone Immunology; and received research funding from Regeneron, Allakos, Shire/Takeda, AstraZeneca, Adare/Ellodi, Danone, and Bristol Myers Squibb. A. B. Muir has served on medical advisory board for Bristol Myers Squibb and Nexstone Immunology; and has received research funding from Morphic. M. H. Collins has received research funding from AstraZeneca, Ception, GSK, Meritage Pharma Inc, Receptos/Celgene/BMS, Regeneron Pharmaceuticals and Shire, a Takeda company; and is consultant for Allakos, Arena Pharmaceuticals, AstraZeneca, Calypso Biotech, EsoCap Biotech, GlaxoSmithKline, Receptos/Celgene/BMS, Regeneron Pharmaceuticals, Robarts Clinical Trials Inc/Alimentiv Inc and Shire, a Takeda company. C. M. Davis has received research funding from the National Institutes of Health/National Institute of Allergy and Infectious Disease (Consortium of Food Allergy Research/Consortium of Eosinophilic Gastrointestinal Researchers), DBV Technologies, DBV, Aimmune Therapeutics, Regeneron Pharmaceuticals, and Allergenis. G. T. Furuta is chief medical officer at EnteroTrack; consultant for Shire/Takeda; and has received grant funding from Arena and Holoclara. S. Gupta is consultant/data safety and monitoring board member or author for Adare, BMS, QOL, Takeda, MedScape, PVI, ViaSkin, and UpToDate; and has received research support from Allakos, Ellodi, and AstraZeneca. P. Khoury has received research funding from American Partnership for Eosinophilic Disorders. K. A. Peterson is consultant or served as advisor for AGA, Alladapt, AstraZeneca, Allakos, Bristol Meyers Squibb, Ellodi, Lucid, Nexstone, Peerview, Regeneron, Takeda, and WebMD; has received research support from AstraZeneca, Allakos, Adare, Regeneron-Sanofi, and Revolo; served as speaker for AGA, Regeneron, Peerview, Takeda, Allakos, and WebMD; received grant support (unrestricted) from Allakos and Chobani; and holds equity in Nexeos Bio. E. T. Jensen has received consultant fees from Regeneron, Jazz Pharmaceuticals, and TARGET-RWE. The rest of the authors declare that they have no relevant conflicts of interest., (© 2024 The Author(s).)

Introduction: Eosinophilic esophagitis (EoE) is a chronic, inflammatory, antigen-driven disease of the esophagus. Tissue EoE pathology has previously been extensively characterized by novel transcriptomics and proteomic platforms, however the majority of surface marker determination and screening has been performed in blood due to mucosal tissue size limitations. While eosinophils, CD4 + T cells, mast cells and natural killer (NK) T cells were previously investigated in the context of EoE, an accurate picture of the composition of peripheral blood mononuclear cells (PBMC) and their activation is missing., Methods: In this study, we aimed to comprehensively analyze the composition of peripheral blood mononuclear cells and their activation using surface marker measurements with multicolor flow cytometry simultaneously in both blood and mucosal tissue of patients with active EoE, inactive EoE, patients with gastroesophageal reflux disease (GERD) and controls. Moreover, we set out to validate our data in co-cultures of PBMC with human primary esophageal epithelial cells and in a novel inducible mouse model of eosinophilic esophagitis, characterized by extensive IL-33 secretion in the esophagus., Results: Our results indicate that specific PBMC populations are enriched, and that they alter their surface expression of activation markers in mucosal tissue of active EoE. In particular, we observed upregulation of the immunomodulatory molecule CD38 on CD4 + T cells and on myeloid cells in biopsies of active EoE. Moreover, we observed significant upregulation of PD-1 on CD4 + and myeloid cells, which was even more prominent after corticosteroid treatment. With co-culture experiments we could demonstrate that direct cell contact is needed for PD-1 upregulation on CD4 + T cells. Finally, we validated our findings of PD-1 and CD38 upregulation in an inducible mouse model of EoE., Discussion: Herein we show significant alterations in the PBMC activation profile of patients with active EoE in comparison to inactive EoE, GERD and controls, which could have potential implications for treatment. To our knowledge, this study is the first of its kind expanding the multi-color flow cytometry approach in different patient groups using in vitro and in vivo translational models., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Gruden, Kienzl, Ristic, Kindler, Kaspret, Schmid, Kargl, Sturm, Doyle, Wright, Baumann-Durchschein, Konrad, Blesl, Schlager and Schicho.)

Despite the high incidence of COVID-19 worldwide, clinical experience with severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) in inborn errors of immunity remains limited. Recent studies have shown that patients with defects in type 1 interferon (IFN)-related pathways or those with autoantibodies against type 1 IFNs develop severe COVID-19. We reported the clinical course of 22 patients with CTLA-4 insufficiency and COVID-19 and retrospectively examined autoantibodies against type 1 IFNs at baseline. Data were obtained from the patient interviews and chart reviews. Screening for anti-IFN autoantibodies was performed using a multiplex particle-based assay. Student t test, Mann Whitney, analysis of variance, or χ2 tests were used where appropriate. Twenty-two patients aged from 8 months to 54 years, with genetically confirmed CLTA-4 insufficiency, developed COVID-19 from 2020 to 2022. The most common symptoms were fever, cough, and nasal congestion, and the median duration of illness was 7.5 days. Twenty patients (91%) developed mild COVID-19 and were treated as outpatients. Two patients were hospitalized because of COVID-19 pneumonia but did not require mechanical ventilation. Ten (45%) patients were vaccinated at the time of their first COVID-19 infection. Eleven patients received outpatient treatment with monoclonal antibodies against the SARS-CoV-2 spike protein. During the study period, 17 patients were vaccinated against SARS-CoV-2, with no severe vaccine-related adverse effects. Although median anti-S titers following vaccination or infection were lower in patients receiving immunoglobulin replacement therapy (IGRT) (349 IU/dL) than in those not receiving IGRT (2594 IU/dL; P = .15); 3 of 9 patients on IGRT developed titers >2000 IU/dL. All patients tested negative for autoantibodies against IFN-α, IFN-β, and IFN-ω at baseline. Most patients with CTLA-4 insufficiency and COVID-19 had nonsevere disease, lacked autoantibodies against type 1 IFNs, and tolerated messenger RNA vaccines with few adverse effects. Whether our findings can be extrapolated to patients receiving CTLA-4-targeting checkpoint inhibitors requires further studies.

In response to the social inequities that exist in health care, the NIH-funded Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR) recently formed a diversity committee to examine systemic racism and implicit bias in the care and research of eosinophilic gastrointestinal diseases (EGIDs). Herein, we describe our process, highlighting milestones and issues addressed since the committee's inception, which we hope will inspire other researchers to enhance diversity, equity, inclusion, and accessibility (DEIA) in their fields. Our journey began by establishing mission and vision statements to define the purpose of the committee. Regular discussion of diversity-related topics was incorporated into existing meetings and web-based materials were shared. This was followed by educational initiatives, including establishing a library of relevant publications and a speaker series to address DEIA topics. We then established a research agenda focused on the following actionable items: (1) to define what is known about the demographics of EGIDs by systematic review of population-based studies; (2) to develop a practical tool for reporting participant demographics to reduce bias in EGID literature; (3) to examine health disparities in the care of individuals with eosinophilic esophagitis who present to the emergency department with an esophageal food impaction; (4) to examine how access to a gastroenterologist affects the conclusions of published research examining the prevalence of pediatric eosinophilic esophagitis; and (5) to develop a model for examining the dimensions of diversity, and provide a framework for CEGIR's ongoing projects and data capture. In addition to promoting consciousness of DEIA, this initiative has fostered inclusivity among CEGIR members and will continue to inspire positive changes in EGID care and research., Competing Interests: MC received consultant fees from Regeneron, Adare/Ellodi, AstraZeneca, Sanofi, Bristol Myers Squibb, Recludix Pharma, Allakos, Shire/Takeda, Phathom, and received research funding from Regeneron, Allakos, Shire/Takeda, AstraZeneca, Adare/Ellodi, Danone. GFuruta serves as CMO for EnteroTrack and received research funding from Arena/Pfizer, Holoclara, and NIH. JPA received payment or honoraria for lectures from Takeda Global Research and Development, participated on a Data Safety Monitoring Board for OctaPharma USA, Inc., and received grants or contracts from Cures Within Reach and Celgene. SA received consultant fees for Regeneron, AstraZeneca, Bristol Meyers Squibb, research funding from Implicit Biosciences, is co-inventor of oral viscous budesonide UCSD patent Takeda license, and received educational speaker fees from Sanofi/Genzyme, Regeneron. MHC received research funding from AstraZeneca, Ception, GlaxoSithKline, Meritage Pharma Inc., Receptos/Celgene/BMS, Regeneron Pharmaceuticals and Shire, a Takeda company, and is a consultant for Allakos, Arena Pharmaceuticals, AstraZeneca, Calypso Biotech, EsoCap Biotech, GlaxoSmithKline, Receptos/Celgene/BMS, Regeneron Pharmaceuticals, Robarts Clinical Trials Inc./Alimentiv, Inc. and Shire, a Takeda company. ESD received research funding from Adare/Ellodi, Allakos, Arena, AstraZeneca, GSK, Meritage, Miraca, Nutricia, Celgene/Receptos/BMS, Regeneron, Revolo, Shire/Takeda, consultant fees from Abbott, Abbvie, Adare/ Ellodi, Aimmune, Akesobio, Alfasigma, ALK, Allakos, Amgen, Aqilion, Arena/Pfizer, Aslan, AstraZeneca, Avir, Biorasi, Calypso, Celgene/Receptos/BMS, Celldex, Eli Lilly, EsoCap, Eupraxia, Ferring, GSK, Gossamer Bio, Holoclara, Invea, Landos, LucidDx, Morphic, Nexstone Immunology, Nutricia, Parexel/Calyx, Phathom, Regeneron, Revolo, Robarts/Alimentiv, Salix, Sanofi, Shire/Takeda, Target RWE, Upstream Bio, and educational grants from Allakos, Holoclara, Invea. GFalk received consultant fees for Adare/Ellodi, Allakos, Bristol Myers Squibb/Celgene, Lucid, Nexstone, Phathom, Regeneron/Sanofi, Shire/Takeda, Upstream Bio, and research support from Adare/Ellodi, Allakos, Arena/Pfizer, Bristol Myers Squibb/Celgene, Lucid, Nexteos, Regeneron/Sanofi, Shire/Takeda. SG is a Consultant/DSMB member/author for Adare, BMS, QOL, Takeda, MedScape, PVI, ViaSkin, and UpToDate, and received research support from Allakos, Ellodi, AstraZeneca. ETJ received consulting fees for Regeneron Pharmaceuticals and Jazz Pharmaceuticals. PK received funding from APFED. DM has received past honoraria from GSK for awareness activities unrelated to this publication and/or disease state. MR is a consultant for Pulm One, Spoon Guru, ClostraBio, Serpin Pharm, Allakos, Celldex, Nextstone One, Bristol Myers Squibb, Astra Zeneca, Ellodi Pharma, GlaxoSmith Kline, Regeneron/Sanofi, Revolo Biotherapeutics, and Guidepoint and has an equity interest in the first seven listed, and royalties from reslizumab (Teva Pharmaceuticals), PEESSv2 (Mapi Research Trust) and UpToDate. MR is an inventor of patents owned by Cincinnati Children’s Hospital. JS received grant support from Regeneron/Sanofi, Novartis, NIH, FARE, consulting fees from Regeneron, Sanofi, Alladapt, Readysetfood, ARS Pharmacy, and royalties from Uptodate. ABM received research funding from Morphic and served on medical advisory board for Bristol Myers Squib and Nextone Immunology. VM received consultant fees from Allakos, Regeneron, Sanofi, and Shire/Takeda, and served on an adjudication board for Alladapt. CD received research funding from DBV Technologies, Food Allergy Research and Education, Allergenis, Regeneron Pharmaceuticals, Pfizer, and consultant or advisory board fees for Aimmune Therapeutics. JBW has received consultant fees from Allakos, Ellodi, Regeneron, Sanofi/Genzyme, AstraZeneca, and Invea Therapeutics, and clinical trial/research funding from Allakos, Invea Therapeutics, and Sanofi-Regeneron. BLW, DDB, AK, GE, GH, KK, EK, SKyle, PM, PM-K, CS, MJS, G-YY, KS, NM, SKesh, PB, MS, AZ, AP, AH, and GF have no conflicts of interest to declare., (© The Author(s), 2023.)

Eosinophilic esophagitis (EoE) is a chronic allergy-mediated condition with an increasing incidence in both children and adults. Despite EoE's strong impact on human health and welfare, there is a large unmet need for treatments with only one recently FDA-approved medication for EoE. The goal of this study was to establish swine as a relevant large animal model for translational biomedical research in EoE with the potential to facilitate development of therapeutics. We recently showed that after intraperitoneal sensitization and oral challenge with the food allergen hen egg white protein (HEWP), swine develop esophageal eosinophilia-a hallmark of human EoE. Herein, we used a similar sensitization and challenge treatment and evaluated immunological and pathological markers associated with human EoE. Our data demonstrate that the incorporated sensitization and challenge treatment induces (i) a systemic T-helper 2 and IgE response, (ii) a local expression of eotaxin-1 and other allergy-related immune markers, (iii) esophageal eosinophilia (>15 eosinophils/0.24 mm 2 ), and (iv) esophageal endoscopic findings including linear furrows and white exudates. Thereby, we demonstrate that our sensitization and oral challenge protocol not only induces the underlying immune markers but also the micro- and macro-pathological hallmarks of human EoE. This swine model for EoE represents a novel relevant large animal model that can drive translational biomedical research to develop urgently needed treatment strategies for EoE., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2022 Cortes, Brodsky, Chen, Pridgen, Odle, Snider, Cruse, Putikova, Masuda, Doyle, Wright, Dawson, Blikslager, Dellon, Laster and Käser.)

Background & Aims: Substantial heterogeneity in terminology used for eosinophilic gastrointestinal diseases (EGIDs), particularly the catchall term "eosinophilic gastroenteritis," limits clinical and research advances. We aimed to achieve an international consensus for standardized EGID nomenclature., Methods: This consensus process utilized Delphi methodology. An initial naming framework was proposed and refined in iterative fashion, then assessed in a first round of Delphi voting. Results were discussed in 2 consensus meetings, and the framework was updated and reassessed in a second Delphi vote, with a 70% threshold set for agreement., Results: Of 91 experts participating, 85 (93%) completed the first and 82 (90%) completed the second Delphi surveys. Consensus was reached on all but 2 statements. "EGID" was the preferred umbrella term for disorders of gastrointestinal (GI) tract eosinophilic inflammation in the absence of secondary causes (100% agreement). Involved GI tract segments will be named specifically and use an "Eo" abbreviation convention: eosinophilic gastritis (now abbreviated EoG), eosinophilic enteritis (EoN), and eosinophilic colitis (EoC). The term "eosinophilic gastroenteritis" is no longer preferred as the overall name (96% agreement). When >2 GI tract areas are involved, the name should reflect all of the involved areas., Conclusions: This international process resulted in consensus for updated EGID nomenclature for both clinical and research use. EGID will be the umbrella term, rather than "eosinophilic gastroenteritis," and specific naming conventions by location of GI tract involvement are recommended. As more data are developed, this framework can be updated to reflect best practices and the underlying science., (Copyright © 2022. Published by Elsevier Inc.)

Introduction: We aimed to assess the diagnostic utility of eosinophil peroxidase (EPX) staining on Cytosponge (CS) samples in eosinophilic esophagitis (EoE)., Methods: Esophageal biopsy (BX) samples from adult subjects with EoE were assessed using peak eosinophils per high-power field (eos/hpf), EPX, and the EoE histologic scoring system. EPX staining and eos/hpf were compared (BX vs CS)., Results: CS EPX positivity correlated with eos/hpf (CS [ r = 0.82, P < 0.0001]; BX [ r = 0.65, P < 0.0001]) and EoE histologic scoring system (grade [ r = 0.62, P < 0.00001]; stage [ r = 0.61, P < 0.0001]). CS EPX identified subjects with active EoE (area under the curve = 0.86, P < 0.0001)., Discussion: The correlation of CS EPX with eosinophilic inflammation and histologic disease severity supports its diagnostic utility in EoE., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Background & Aims: Gastrointestinal side effects are common during oral immunotherapy (OIT) and eosinophilic esophagitis (EoE) is a potential complication. We aimed to characterize eosinophilic gastrointestinal responses to peanut OIT, in which peanut protein is given orally, with incremental increases in dose over time., Methods: Twenty adults with IgE-mediated peanut allergy were randomly assigned to groups given peanut OIT (n = 15) or placebo (n = 5); 1 additional subject withdrew before randomization. Serial gastrointestinal biopsies were collected at baseline (n = 21, 0 weeks), following dose escalation (n = 10, 52 weeks), and during the maintenance phase (n = 11, 104 weeks). Endoscopic findings were characterized using the EoE endoscopic reference score. Biopsies were assessed for eosinophils per high-power field (eos/hpf) and other pathology features using EoE histologic scoring system scores. We performed immunohistochemical analyses of eosinophil peroxidase deposition, quantified using automated image analysis., Results: At baseline, no subjects reported current gastrointestinal symptoms. However, 3 of the 21 subjects (14%) had esophageal peak eosinophil counts ≥15 eos/hpf and all subjects had dilated intercellular spaces (DIS). OIT induced or exacerbated esophageal eosinophilia (EE) at 52 weeks in most subjects (peak eosinophil counts >5 eos/hpf in 6 of 7 patients [86%]; peak eosinophil counts ≥15 eos/hpf in 4 of 7 patients [57%]). One subject met clinicopathologic criteria for EoE and withdrew; no significant changes in esophageal peak eosinophil counts were observed in the placebo group. EE in the OIT group corresponded with significant increases in EoE histologic scoring system scores and deposition of eosinophil peroxidase. In 4 of 6 participants (67%), OIT-induced EE and gastrointestinal eosinophilia resolved by the end of the maintenance phase. Gastrointestinal symptoms were not clearly associated with EE or gastrointestinal eosinophilia., Conclusions: In this pilot study, we found that peanut OIT-induced EE and gastrointestinal eosinophilia are usually transient and are not always associated with gastrointestinal symptoms. Clinicaltrials.gov no: NCT02103270., (Copyright © 2021 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Food protein-induced enterocolitis syndrome (FPIES) is a non-immunoglobulin E mediated food allergy that typically presents with repetitive emesis and may be associated with lethargy, marked pallor, hypotension, hypothermia, and/or diarrhea. Although many foods are known to cause FPIES, peanut-triggered FPIES is emerging due to changes in the feeding practice guidelines, which recommends early peanut introduction in infants., Objective: We aimed to characterize peanut-triggered acute FPIES cases in our pediatric population and to describe their attributes, treatment, and outcomes. We hypothesized that increases in the incidence of peanut-triggered FPIES coincided with implementation of the guidelines for early peanut introduction., Methods: A retrospective chart review was conducted of pediatric patients who presented to Phoenix Children's Hospital Emergency Department and subspecialty clinics during a 6-year period (January 2013 to September 2019)., Results: Thirty-three cases of patients with acute FPIES were identified, five of which were peanut triggered. In those patients with peanut-triggered FPIES, the median age for peanut introduction was 7 months (range, 5-24 months). Two patients had positive peanut skin-prick test results. All five cases were identified in the past 2 years (2018 to 2019). No peanut-triggered reactions were documented in the preceding 4-year period (2013 to 2017)., Conclusion: Peanut may be an emerging trigger of acute FPIES, coinciding with an earlier introduction of peanut in the infant diet after implementation of the new addendum guidelines for the prevention of peanut allergy. Oats and rice were the most common triggers of acute FPIES in our cohort. Further study will help clarify the significance and reproducibility of these findings., Competing Interests: The authors have no conflicts of interest to declare pertaining to this article. Catherine M. Freeman and Juan Carlos Murillo are co-first authors, (Copyright © 2021, The Author(s). Published by OceanSide Publications, Inc., U.S.A.)

Eosinophilic esophagitis (EoE) is an antigen-driven disease associated with epithelial barrier dysfunction and chronic type 2 inflammation. Eosinophils are the defining feature of EoE histopathology but relatively little is known about their role in disease onset and progression. Classically defined as destructive, end-stage effector cells, eosinophils (a resident leukocyte in most of the GI tract) are increasingly understood to play roles in local immunity, tissue homeostasis, remodeling, and repair. Indeed, asymptomatic esophageal eosinophilia is observed in IgE-mediated food allergy. Interestingly, EoE is a potential complication of oral immunotherapy (OIT) for food allergy. However, we recently found that patients with peanut allergy may have asymptomatic esophageal eosinophilia at baseline and that peanut OIT induces transient esophageal eosinophilia in most subjects. This is seemingly at odds with multiple studies which have shown that EoE disease severity correlates with tissue eosinophilia. Herein, we review the potential role of eosinophils in EoE at different stages of disease pathogenesis. Based on current literature we suggest the following: (1) eosinophils are recruited to the esophagus as a homeostatic response to epithelial barrier disruption; (2) eosinophils mediate barrier-protective activities including local antibody production, mucus production and epithelial turnover; and (3) when type 2 inflammation persists, eosinophils promote fibrosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Doyle, Masuda, Kita and Wright.)

Objectives: Dietary elimination for treatment of eosinophilic esophagitis (EoE) is limited by lack of accuracy in current allergy tests. We aimed to develop an immunologic approach to identify dietary triggers and prospectively test allergen-specific immune signature-guided dietary elimination therapy., Methods: In the first phase, we developed and assessed 2 methods for determining selected food triggers using samples from 24 adults with EoE: a CD4+ T-cell proliferation assay in peripheral blood and food-specific tissue IgG4 levels in esophageal biopsies. In the second phase, we clinically tested elimination diets created from these methods in a prospective cohort treated for 6 weeks (NCT02722148). Outcomes included peak eosinophil counts (eos/hpf), endoscopic findings (measured by the EoE Endoscopic Reference Score), and symptoms (measured by the EoE Symptom Activity Index)., Results: Parameters were optimized with a positive test on either assay, yielding agreements of 60%, 75%, 53%, 58%, and 53% between predicted and known triggers of peanut, egg, soy, wheat, and milk, respectively. In clinical testing, the mean number of foods eliminated based on the assays was 3.4, and 19 of 22 subjects were compliant with treatment. After treatment, median peak eosinophil counts decreased from 75 to 35 (P = 0.007); there were 4 histologic responders (21%). The EoE Endoscopic Reference Score and EoE Symptom Activity Index score also decreased after treatment (4.6 vs 3.0; P = 0.002; and 32.5 vs 25.0; P = 0.06, respectively)., Discussion: We successfully developed a new testing approach using CD4 T-cell proliferation and esophageal food-specific IgG4 levels, with promising accuracy rates. In clinical testing, this led to improvement in eosinophil counts, endoscopic severity, and symptoms of dysphagia, but a smaller than expected number of patients achieved histologic remission.

The inflammatory responses in chronic airway diseases leading to emphysema are not fully defined. We hypothesised that lung eosinophilia contributes to airspace enlargement in a mouse model and to emphysema in patients with chronic obstructive pulmonary disease (COPD).A transgenic mouse model of chronic type 2 pulmonary inflammation (I5/hE2) was used to examine eosinophil-dependent mechanisms leading to airspace enlargement. Human sputum samples were collected for translational studies examining eosinophilia and matrix metalloprotease (MMP)-12 levels in patients with chronic airways disease.Airspace enlargement was identified in I5/hE2 mice and was dependent on eosinophils. Examination of I5/hE2 bronchoalveolar lavage identified elevated MMP-12, a mediator of emphysema. We showed, in vitro , that eosinophil-derived interleukin (IL)-13 promoted alveolar macrophage MMP-12 production. Airspace enlargement in I5/hE2 mice was dependent on MMP-12 and eosinophil-derived IL-4/13. Consistent with this, MMP-12 was elevated in patients with sputum eosinophilia and computed tomography evidence of emphysema, and also negatively correlated with forced expiratory volume in 1 s.A mouse model of chronic type 2 pulmonary inflammation exhibited airspace enlargement dependent on MMP-12 and eosinophil-derived IL-4/13. In chronic airways disease patients, lung eosinophilia was associated with elevated MMP-12 levels, which was a predictor of emphysema. These findings suggest an underappreciated mechanism by which eosinophils contribute to the pathologies associated with asthma and COPD., Competing Interests: Conflict of interest: A.D. Doyle reports grants from NIH (F31HL124959), donor money paid to the Mayo Clinic from Donald R. Levin Family Foundation, and a scholarship at the Mayo Clinic from Mayo Clinic Sidney Luckman Family Predoctoral Fellowship, during the conduct of the study. Conflict of interest: M. Mukherjee has nothing to disclose. Conflict of interest: W.E. LeSuer has nothing to disclose. Conflict of interest: T.B. Bittner has nothing to disclose. Conflict of interest: S.M. Pasha has nothing to disclose. Conflict of interest: J.J. Frere has nothing to disclose. Conflict of interest: J.L. Neely has nothing to disclose. Conflict of interest: J.A. Kloeber has nothing to disclose. Conflict of interest: K.P. Shim has nothing to disclose. Conflict of interest: S.I. Ochkur has nothing to disclose. Conflict of interest: T. Ho has nothing to disclose. Conflict of interest: S. Svenningsen has nothing to disclose. Conflict of interest: B.L. Wright reports donor money paid to the Mayo Clinic from Donald R. Levin Family Foundation, during the conduct of the study. Conflict of interest: M.A. Rank has nothing to disclose. Conflict of interest: J.J. Lee received grants from NIH (HL058723), NIH NCRR (K26 RR0109709) and the Mayo Foundation for Medical Education and Research, during the conduct of this study; J.J. Lee is deceased and this statement was made on behalf of the author by the corresponding author. Conflict of interest: P. Nair reports grants and personal fees for consultancy and lecturing from AstraZeneca and Teva, grants from Boehringer Ingelheim, grants and personal fees for lecturing from Novartis, grants and personal fees for consultancy from Sanofi and GSK, and personal fees for consultancy from Theravance and Knopp, outside the submitted work. Conflict of interest: E.A. Jacobsen reports grants from NIH (HL065228), and donor money paid to the Mayo Clinic from Donald R. Levin Family Foundation, during the conduct of the study., (Copyright ©ERS 2019.)

There is an increasing prevalence of esophageal diseases but intact human tissue platforms to study esophageal function, disease mechanisms, and the interactions between cell types in situ are lacking. To address this, we utilized full thickness human donor esophagi to create and validate the ex vivo function of mucosa and smooth muscle (n = 25). Explanted tissue was tested for contractile responses to carbachol and histamine. We then treated ex vivo human esophageal mucosa with a cytokine cocktail to closely mimic the Th2 and inflammatory milieu of eosinophilic esophagitis (EoE) and assessed alterations in smooth muscle and extracellular matrix function and stiffening. We found that full thickness human esophagus as well as the individual layers of circular and longitudinal muscularis propria developed tension in response to carbachol ex vivo and that mucosa demonstrated squamous cell differentiation. Treatment of mucosa with Th2 and fibrotic cytokines recapitulated the majority of the clinical Eosinophilic Esophagitis Diagnostic Profile (EDP) on fluidic transcriptional microarray. Transforming growth factor-beta-1 (TGFβ1) increased gene expression of fibronectin, smooth muscle actin, and phospholamban (p < 0.001). The EoE cocktail also increased stiffness and decreased mucosal compliance, akin to the functional alterations in EoE (p = 0.001). This work establishes a new, transcriptionally intact and physiologically functional human platform to model esophageal tissue responses in EoE.

Rationale: Oral immunotherapy (OIT) is an emerging treatment for food allergy. While desensitization is achieved in most subjects, many experience gastrointestinal symptoms and few develop eosinophilic gastrointestinal disease. It is unclear whether these subjects have subclinical gastrointestinal eosinophilia (GE) at baseline. We aimed to evaluate the presence of GE in subjects with food allergy before peanut OIT. Methods: We performed baseline esophagogastroduodenoscopies on 21 adults before undergoing peanut OIT. Subjects completed a detailed gastrointestinal symptom questionnaire. Endoscopic findings were assessed using the Eosinophilic Esophagitis (EoE) Endoscopic Reference Score (EREFS) and biopsies were obtained from the esophagus, gastric antrum, and duodenum. Esophageal biopsies were evaluated using the EoE Histologic Scoring System. Immunohistochemical staining for eosinophil peroxidase (EPX) was also performed. Hematoxylin and eosin and EPX stains of each biopsy were assessed for eosinophil density and EPX/mm 2 was quantified using automated image analysis. Results: All subjects were asymptomatic. Pre-existing esophageal eosinophilia (>5 eosinophils per high-power field [eos/hpf]) was present in five participants (24%), three (14%) of whom had >15 eos/hpf associated with mild endoscopic findings (edema, linear furrowing, or rings; median EREFS = 0, IQR 0-0.25). Some subjects also demonstrated basal cell hyperplasia, dilated intercellular spaces, and lamina propria fibrosis. Increased eosinophils were noted in the gastric antrum (>12 eos/hpf) or duodenum (>26 eos/hpf) in 9 subjects (43%). EPX/mm 2 correlated strongly with eosinophil counts ( r = 0.71, p < 0.0001). Conclusions: Pre-existing GE is common in adults with IgE-mediated peanut allergy. Eosinophilic inflammation (EI) in these subjects may be accompanied by mild endoscopic and histologic findings. Longitudinal data collection during OIT is ongoing.

Food allergies have increased in prevalence over the past 20 years, now becoming an important public health concern. Although there are no therapies currently available for routine clinical care, recent reports have indicated that immunotherapies targeting the mucosal immune system may be effective. Oral immunotherapy is conducted by administering small, increasing amounts of food allergen; it has shown promise for desensitizing individuals with peanut, egg, or milk allergies. Sublingual immunotherapy also desensitizes allergic patients to foods-2 major studies have examined the effects of sublingual immunotherapy in subjects with peanut allergies. We review the complex nature of IgE-mediated food allergies and the therapies being evaluated in clinical trials. We focus on the diagnosis and management of food allergies and investigational therapies., (Copyright © 2015. Published by Elsevier Inc.)

Background: Existing sexual health programs have not significantly reduced teen pregnancies or sexually transmitted diseases. A more creative approach is needed., Methods: An assessment of 539 teens in one Ontario city was conducted to identify knowledge about and use of birth control, comfort in discussing sexual health, and preferred sites, providers and methods of service delivery., Results: Knowledge of, and comfort discussing, birth control was not associated with frequency of use but was associated with grade. Adolescents were less comfortable discussing sexual health with teachers than health professionals. Over time, comfort increased with health professionals, but not teachers. Sexually active teens reported willingness to attend mall-based clinics., Conclusions: Using birth control appears to be maturational given its association with grade. Since teens were consistently less comfortable with teachers, providing sexual health services in schools is likely ineffective. Teens may respond to clinics in creative settings such as malls.