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The Consortium of Eosinophilic Gastrointestinal disease Researchers (CEGIR) and The International Gastrointestinal Eosinophil Researchers (TIGERS) organized a day-long symposium at the 2024 Annual Meeting of the American Academy of Allergy, Asthma & Immunology. The symposium featured new discoveries in basic and translational research and debates on the mechanisms and management of eosinophilic gastrointestinal diseases (EGIDs). Updates on recent clinical trials and consensus guidelines were also presented. Herein, we summarize the updates on EGIDs presented at the symposium.
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BACKGROUND & AIMS: Achalasia has been assumed to be an autoimmune disease targeting esophageal myenteric neurons. Recently, we proposed an alternative hypothesis that achalasia sometimes might be allergy-driven, caused by a form of eosinophilic esophagitis (EoE) in which activated eosinophils and/or mast cells infiltrating esophageal muscle release products that disrupt motility and damage myenteric neurons. To seek epidemiologic support for this hypothesis, we identified patients with achalasia in the Utah Population Database, and explored their frequency of having EoE and other allergic disorders. METHODS: We used International Classification of Diseases codes to identify patients with achalasia and allergic disorders including EoE, asthma, atopic dermatitis, contact dermatitis, allergic rhinitis, allergic conjunctivitis, hives/urticaria, and anaphylaxis. We calculated relative risk (RR) for each allergic disorder by comparing the number observed in patients with achalasia with the expected number in individuals matched for birthyear and sex, and we performed subanalyses for patients age ≤40 versus age >40 years. RESULTS: Among 844 patients with achalasia identified (55% female; median age at diagnosis, 58 years), 402 (47.6%) had ≥1 allergic disorder. Fifty-five patients with achalasia (6.5%) had EoE (1.67 EoE cases expected), for a RR of 32.9 (95% confidence interval, 24.8-42.8; P < .001). In 208 patients with achalasia age ≤40 years, the RR for EoE was 69.6 (95% confidence interval, 46.6-100.0; P < .001). RR also was increased significantly for all other allergic disorders evaluated (all greater than 3-fold higher than population rates). CONCLUSIONS: Achalasia is strongly associated with EoE and other allergic disorders. These data support the hypothesis that achalasia sometimes might have an allergic etiology.
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Asma , Esofagite Eosinofílica , Acalasia Esofágica , Humanos , Feminino , Pessoa de Meia-Idade , Adulto , Masculino , Esofagite Eosinofílica/complicações , Esofagite Eosinofílica/epidemiologia , Esofagite Eosinofílica/diagnóstico , Acalasia Esofágica/complicações , Acalasia Esofágica/epidemiologia , Asma/complicações , EosinófilosRESUMO
A preliminary report from the recent phase 3 trial of benralizumab, a monoclonal antibody that binds to interleukin-5 receptor alpha (IL5Rα), in patients with EoE revealed that medication use led to tissue eosinophil eradication but did not meet the clinical endpoint of symptom resolution. Here, we characterized the clinical, endoscopic, histologic, and transcriptional changes in patients with active EoE following benralizumab treatment. We retrospectively examined patients with EoE treated with benralizumab at the University of Utah (n = 11) and reviewed reported clinical symptoms, circulating and tissue eosinophilia, and endoscopic and histologic scores. Gene expression profiles from available esophageal tissue from benralizumab-treated patients were compared to those from patients with remission EoE (n = 5), active EoE (n = 10), and controls (n = 22). Benralizumab treatment resulted in partial symptom improvement and significant reduction in tissue eosinophilia, and endoscopic and histologic disease scoring (P < 0.01). Histologic score reductions were driven by eosinophil feature scores, while scores for epithelial features (basal cell hyperplasia and dilated intercellular spaces) were similar to those in active EoE. The gene signatures in benralizumab-treated patients mimicked those of active EoE (e.g. upregulation of POSTN, CDH26, CCL26, and downregulation of DSG1). RNA profiles and pathways support histologic findings of impaired epithelial function that persists despite benralizumab treatment. In conclusion, despite eosinophil eradication, patients treated with benralizumab had persistent epithelial injury at the histologic and transcriptional level. In this cohort, benralizumab therapy failed to eradicate inflammation and epithelial dysfunction showing that interleukin-5 receptor alpha blockade monotherapy is insufficient to control EoE.
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BACKGROUND: Inflammatory diseases have been associated with an increased cardiovascular risk. However, data on incident major adverse cardiovascular events (MACE) from large population-based cohorts of patients with eosinophilic esophagitis (EoE) is lacking. METHODS: This study included all Swedish adults with EoE without a record of previous cardiovascular disease (CVD) (1990-2017, N = 1546) with follow-up until 2019. Individuals with EoE were identified from prospectively recorded histopathology reports from all Swedish pathology departments (n = 28). EoE patients were matched at index date for age, sex, calendar year and county with up to five general population reference individuals (N = 7281) without EoE or CVD. Multivariable-adjusted hazard ratios (aHRs) for MACE (ischemic heart disease, congestive heart failure, stroke and cardiovascular mortality) were calculated using Cox proportional hazards models. Full sibling comparisons and adjustment for cardiovascular medication were performed. RESULTS: During a median follow-up of 6.0 years, we observed 65 incident MACE in patients with EoE (6.4/1000 person-years (PY)) and 225 in reference individuals (4.7/1000 PY). EoE was not associated with a higher risk of MACE (aHR = 1.14, 95% CI = 0.86-1.51) or any of its components. No differences between age, sex and follow-up time were observed. The results remained stable in sensitivity analyses, including when adjusting for relevant cardiovascular medications and a full sibling comparison. CONCLUSIONS: In this large population-based cohort study, patients with EoE had no increased risk of MACE compared to reference individuals and full siblings. The results are reassuring for patients with EoE.
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Doenças Cardiovasculares , Esofagite Eosinofílica , Humanos , Esofagite Eosinofílica/epidemiologia , Esofagite Eosinofílica/complicações , Feminino , Masculino , Suécia/epidemiologia , Pessoa de Meia-Idade , Adulto , Doenças Cardiovasculares/epidemiologia , Incidência , Modelos de Riscos Proporcionais , Estudos de Coortes , Fatores de Risco , Idoso , Estudos ProspectivosRESUMO
INTRODUCTION: There are limited data on the familial risk of distal eosinophilic gastrointestinal diseases (EGIDs) in patients with eosinophilic esophagitis (EoE). We analyzed the risk of eosinophilic gastritis/gastroenteritis (EG/EGE) and eosinophilic colitis (EC) as forms of distal EGIDs using International Disease Classification-9/10 codes in subjects with EoE and their relatives. METHODS: The Utah Population Database is a resource that links genealogy information and medical records in Utah. We identified EGIDs in probands and their first-degree (FDRs), second-degree (SDRs), and third-degree (TDRs) relatives in the Utah Population Database. Relative risk and 95% confidence intervals were estimated. All individuals with inflammatory bowel disorder were eliminated to avoid misdiagnosis with EGIDs. RESULTS: We included 8,455 subjects with EoE, 396 with EG/EGE, and 172 with EC. Probands with EoE were at increased risk of EG/EGE and EC. Risks of EG/EGE were increased among FDRs and SDRs of probands with EoE , even without concomitant EoE in the relatives. Increased risk of EG/EGE in FDRs and SDRs was also present for EoE probands without EG/EGE or EC. We observed no isolated familial aggregation of EG/EGE after excluding cases with comorbid EoE. EC probands without EoE were at increased risk of EG/EGE, but no evidence of familial risk of EC was observed. DISCUSSION: The relative risk of EG/EGE is significant among relatives of patients with EoE, suggesting that shared genetic factors exist among these EGIDs. EG/EGE and EC showed limited familial clustering, although sample sizes were small.
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Colite Microscópica , Enterite , Esofagite Eosinofílica , Gastrite , Gastroenterite , Humanos , Esofagite Eosinofílica/epidemiologia , Esofagite Eosinofílica/diagnóstico , Predisposição Genética para Doença , Enterite/epidemiologia , Enterite/diagnóstico , Gastrite/diagnóstico , Gastroenterite/complicaçõesRESUMO
Women physicians are promoted less often, more likely to experience harassment and bias, and paid less than their male peers. Although many institutions have developed initiatives to help women physicians overcome these professional hurdles, few are specifically geared toward physicians-in-training. The Women in Medicine Trainees' Council (WIMTC) was created in 2015 to support the professional advancement of women physicians-in-training in the Massachusetts General Hospital Department of Medicine (MGH-DOM). In a 2021 survey, the majority of respondents agreed that the WIMTC ameliorated the challenges of being a woman physician-in-training and contributed positively to overall wellness. Nearly all agreed that they would advise other training programs to implement a similar program. We present our model for women-trainee support to further the collective advancement of women physicians.
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Internato e Residência , Médicas , Médicos , Humanos , Masculino , Feminino , Medicina Interna/educação , Inquéritos e Questionários , Competência ClínicaRESUMO
BACKGROUND: Eosinophilic esophagitis (EoE) is a chronic inflammatory condition of the esophagus associated with dysphagia and esophageal fibrosis. The incidence of EoE is not precisely known, and significant heterogeneity in study design and disease definition have led to widely variable estimates. Through the ESPRESSO (Epidemiology Strengthened by histoPathology Reports in Sweden) study we performed a nationwide population-based study to estimate the incidence and temporal patterns of biopsy-verified EoE. METHODS: Between October 2015 and April 2017, we contacted all pathology departments in Sweden (n = 28) to obtain biopsy report data on EoE. To assure a high degree of completeness, we restricted the study to 2004-2015. We then calculated age-specific and age-standardized incidence rates. RESULTS: We identified 1412 incident EoE cases between 2004-2015. The overall age-standardized incidence rates of EoE in Sweden was 1.22 per 100,000 person-years. During the study period, there was a significant increase of 33% [95%CI = 31-36%] (P < 0.001) per year in EoE incidence, and in the last 3 years of follow-up (2013-2015) the incidence was 2.79 per 100,000 person-years. This corresponds to a lifetime risk of biopsy-verified EoE for men of 0.33% (1 in 295 men) and for women 0.12% (1 in 813 women). We observed an early peak of EoE disgnosed at age 15-19 years for both males and females, and a second peak in the late 30 s for males, and early 40 s for females. We noted a 3:1 male-to-female predominance, which did not significantly vary over time. CONCLUSIONS: EoE seems to be increasing in Sweden, with an overall age-standardized incidence of EoE of 1.22 per 100,000 person-years in the last decade.
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Transtornos de Deglutição , Esofagite Eosinofílica , Adolescente , Adulto , Transtornos de Deglutição/etiologia , Esofagite Eosinofílica/complicações , Esofagite Eosinofílica/epidemiologia , Feminino , Humanos , Incidência , Masculino , Suécia/epidemiologia , Adulto JovemRESUMO
BACKGROUND AND AIMS: Eosinophilic esophagitis (EoE) is an emerging, chronic immune-mediated disease for which swallowed topical steroids and proton pump inhibitors (PPIs) represent first-line treatments. Immune-mediated diseases, steroids, and PPI use have been linked to osteoporosis. We assessed the risk of fractures in patients with EoE and determined whether the most commonly used treatments for EoE were associated with increased fracture risk. METHODS: We followed a nationwide cohort of 1263 individuals in Sweden with biopsy-verified EoE diagnosed between 2005 and 2016 for first-time fracture of any type. Age- and sex-matched reference individuals were retrieved from the Total Population Register (n = 5164). We estimated hazard ratios (HRs) for fracture in relation to EoE diagnosis, steroid exposure, and PPI use. In a separate analysis, we compared fracture risk among individuals with EoE to their siblings (n = 1394). RESULTS: During 4521 person-years of follow-up, 69 individuals with EoE experienced a first-time fracture (15.3/1000 person-years) compared with 234 reference individuals (12.6/1000 person-years). After adjusting for age, sex, birth year, and county of residence, EoE was not associated with a statistically significantly increased risk of fractures (HR = 1.2, 95% CI = 0.9-1.6). Among EoE individuals, exposure to PPIs and swallowed steroids did not modify the risk of fracture (p for heterogeneity 0.20 and 0.07 respectively). There was no increased risk of fractures in EoE compared to EoE-free siblings. CONCLUSION: The risk of fracture in EoE was not statistically significantly elevated compared to non-EoE reference individuals. Fracture risk in EoE was not modified by PPIs or steroid use.
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Esofagite Eosinofílica , Biópsia/efeitos adversos , Estudos de Coortes , Enterite , Eosinofilia , Esofagite Eosinofílica/complicações , Esofagite Eosinofílica/epidemiologia , Gastrite , Humanos , Inibidores da Bomba de Prótons/efeitos adversosRESUMO
This JAMA Insights Clinical Update discusses the symptoms, diagnosis, and management of eosinophilic gastrointestinal diseases.
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Eosinofilia , Gastroenterite , Humanos , Enterite , Eosinofilia/diagnóstico , Eosinofilia/etiologia , Eosinofilia/fisiopatologia , Gastrite/diagnóstico , Gastrite/etiologia , Gastrite/fisiopatologia , Esofagite Eosinofílica/diagnóstico , Esofagite Eosinofílica/etiologia , Esofagite Eosinofílica/fisiopatologia , Gastroenterite/diagnóstico , Gastroenterite/etiologia , Gastroenterite/fisiopatologiaAssuntos
Hemorragia Gastrointestinal/etiologia , Hemangiossarcoma/diagnóstico , Neoplasias Hepáticas/diagnóstico , Reto , Biópsia , Hemorragia Gastrointestinal/sangue , Hemangiossarcoma/sangue , Hemangiossarcoma/complicações , Hemangiossarcoma/patologia , Humanos , Fígado/diagnóstico por imagem , Fígado/patologia , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/patologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: Earlier studies on the possible association between eosinophilic esophagitis (EoE) and inflammatory bowel disease (IBD) have been contradictory. METHODS: Patients with biopsy-verified EoE diagnosed between 1990 and 2017 in Sweden (n = 1587) were age- and sex-matched with up to five general population reference individuals (n = 7808). EoE was defined using pathology reports from all 28 pathology centers in Sweden (the ESPRESSO study). Multivariate Cox regression then estimated hazard ratios for future IBD. IBD was defined based on the international classification of disease codes and histopathology codes. In secondary analyses, sibling comparators were used to further reduce potential familial confounding. Additionally, we performed logistic regression examining earlier IBD in EoE. RESULTS: During follow-up until 2020, 16 (0.01%) EoE patients and 21 (0.003%) general population reference individuals diagnosed with IBD, corresponding to a 3.5-fold increased risk of future IBD (aHR = 3.56; 95% CI 1.79-7.11). EoE was linked to Crohn's disease (aHR = 3.39 [95% CI 1.02-9.60]) but not to ulcerative colitis (aHR = 1.37; 95% CI 0.38-4.86). Compared to their siblings, patients with EoE were at a 2.48-fold increased risk of IBD (aHR = 2.48; 95% CI 0.92-6.70). Earlier IBD was 15 times more likely in EoE patients than in matched reference individuals (odds ratio, 15.39; 95% CI 7.68-33.59). CONCLUSION: In this nationwide cohort study, EoE was associated with a 3.5-fold increased risk of later IBD diagnosis. This risk increase may be due to shared genetic or early environmental risk factors, but also surveillance bias could play a role.
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Doença de Crohn , Esofagite Eosinofílica , Doenças Inflamatórias Intestinais , Humanos , Suécia/epidemiologia , Estudos de Coortes , Esofagite Eosinofílica/epidemiologia , Doenças Inflamatórias Intestinais/epidemiologia , Doença de Crohn/diagnóstico , Doença de Crohn/epidemiologiaRESUMO
Eosinophilic esophagitis is an increasingly common inflammatory allergic disease of the esophagus characterized by esophageal eosinophilia and symptoms of esophageal dysfunction. The therapeutic landscape has rapidly evolved for this emerging type 2 inflammatory disorder. We review traditional therapies including updates and expert opinions in addition to promising therapies on the horizon and the history of therapies that failed to meet end points and highlight knowledge gaps for future investigations.
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Esofagite Eosinofílica , Humanos , Esofagite Eosinofílica/terapia , Esofagite Eosinofílica/diagnósticoRESUMO
Introduction: Eosinophilic esophagitis (EoE) is a chronic, allergic inflammatory disease of the esophagus. It has a peak incidence in the 2nd and 3rd decades of life. Despite this, little is known about pregnancy outcomes in patients with EoE. Methods: Using a validated histopathologic and nationwide population-based cohort for the diagnosis of EoE, we examined maternal and fetal outcomes, with preterm birth as the primary outcome, in females with EoE compared to matched controls. Odds ratios (ORs) were calculated using logistic regression. Results: Between 1992 and 2016, we identified 19 females with EoE who gave birth to 23 children (reference births: n = 115). There was 1 (4.3%) preterm birth in the EoE cohort versus 8 (7.0%) in the reference cohort (OR = 0.60; 95% CI = 0.07-5.14). Secondary fetal outcomes included stillbirth, neonatal death, small for gestational age, low birth weight (LBW), and low Apgar score. Of these, LBW (<2,500 g) in patients with EoE compared to controls correlated to an OR of 12.42 (95% CI = 1.26-122.42); however, this finding was based on very low numbers. The remaining fetal outcomes were not significantly different between females with EoE and controls. Secondary pregnancy and maternal outcomes including induction of labor, instrumental delivery, gestational diabetes, or pre-eclampsia were not significantly different between patients with EoE and controls. Discussion/Conclusion: Overall in this nationwide cohort study, we did not find increased association of preterm birth in patients with EoE.
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BACKGROUND AND AIMS: Informed consent should allow patients the appropriate time and conditions to make decisions about their care. However, consent is often obtained immediately prior to a colonoscopy. We conducted a quality improvement study to assess how a preprocedure consent video 2 days prior to an outpatient colonoscopy impacts patient satisfaction. METHODS: Patients undergoing outpatient colonoscopy at a large academic medical center opted in to a text messaging platform for procedural information. Our intervention was an informed consent video 2 days before the colonoscopy. Our primary outcome was a composite patient satisfaction score. Pre and postintervention scores were compared using ordinal or multinomial logistic models to calculate odds ratios (OR) or relative risk ratios and 95% confidence intervals (CI), adjusting for age and sex. RESULTS: 1109 and 1452 patients completed ≥1 survey question in the pre and postintervention phases, respectively. Overall patient satisfaction did not differ between groups [OR for a 1-point increment in satisfaction score between post- vs pre-intervention groups = 1.05; 95% CI: 0.90-1.22; P = .51]. Compared to preintervention, postintervention respondents were more likely to report higher satisfaction with time available to talk with their physician (OR of a 1-point increase in individual question response = 1.29; 95% CI: 1.09-1.54; P = .004). Compared to preintervention, more physicians in the postintervention phase rated satisfaction with consent process efficiency as "very satisfied" or "satisfied" (P < .001). CONCLUSION: An informed consent video prior to colonoscopy resulted in similar overall patient satisfaction. However, post-intervention, patients were more likely to report sufficient time to talk with their physician, and physicians reported higher satisfaction with consent efficiency.
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BACKGROUND AND AIMS: Eosinophilic esophagitis (EoE) is an increasingly common, largely food allergen-driven disease characterized by dysphagia. Prior infections are known to associate with other loss of tolerance diseases such as autoimmunity. We aimed to determine if antecedent infection was associated with later EoE development. METHODS: We performed a case-control study of all patients with biopsy-verified EoE diagnosed between 2000 and 2017 in Sweden (n = 1587) and matched to 5 general population controls (n = 7660). Cases were identified using histopathology codes from the Epidemiology Strengthened by histopathology Reports in Sweden study, a validated cohort of gastrointestinal pathology reports from all 28 pathology centers in Sweden. We used logistic regression to estimate odds ratios (ORs) and 95% confidence intervals for antecedent infections from patients seen at hospital-based outpatient clinics or inpatients. In secondary analyses, we compared EoE patients with their full siblings to further reduce residual confounding. RESULTS: 564 (35.7%) EoE patients and 1793 (23.4%) matched controls had an earlier record of infection. This corresponded to a 2-fold increased risk of infections in EoE patients (OR 2.01; 95%CI: 1.78-2.27). ORs for earlier gastrointestinal or respiratory infection were 2.73 (n = 128 EoE, 268 control; 95%CI: 2.17-3.41) and 1.89 (n = 305 EoE, 960 control; 95%CI: 1.63-2.20), respectively. Having an EoE diagnosis was linked to a 3.39-fold increased odds of sepsis (n = 14 EoE, 21 control; 95%CI: 1.68-6.65). Individuals with EoE were also more likely to have had an infection compared to their non-EoE siblings (n = 427 EoE, 593 control; OR = 1.57; 95%CI = 1.30-1.89). CONCLUSION: In this nationwide cohort study, prior infection, was associated with subsequent EoE. Risks were particularly high after sepsis, and gastrointestinal or respiratory infections.
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Hospitais , Humanos , Estudos de Casos e Controles , Estudos de Coortes , Suécia/epidemiologiaRESUMO
Eosinophilic esophagitis (EoE) is an increasingly common food allergy disease of the esophagus that received its medical designation code in 2008. Despite this recency, great strides have been made in the understanding of EoE pathophysiology and type 2 immunity through basic and translational scientific investigations conducted at the bench. These advances have been critical to our understanding of disease mechanisms and generating new hypotheses, however, there currently is only one very recently approved FDA-approved therapy for EoE, leaving a great deal to be uncovered for patients with this disease. Here we review some of the innovative methods, models and tools that have contributed to the advances in EoE discovery and suggest future directions of investigation to expand upon this foundation.
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Esofagite Eosinofílica , Hipersensibilidade Alimentar , Alérgenos , Esofagite Eosinofílica/diagnóstico , Esofagite Eosinofílica/etiologia , Esofagite Eosinofílica/terapia , Alimentos , Hipersensibilidade Alimentar/diagnóstico , Hipersensibilidade Alimentar/terapia , HumanosRESUMO
Objective: Eosinophils are hallmarks in allergic type 2 inflammation and are known to release cytotoxic granule proteins that contribute to inflammation. Eosinophils develop in the bone marrow from hematopoietic stem cells and once mature, have a limited lifespan in culture, making them difficult to study ex vivo. IL-33 has increasingly been shown as a key regulator of type 2 inflammation via signaling through its receptor, ST2. The present study was conducted to detail a method of eosinophil differentiation from hematopoietic stem cells and determine the response to IL-33. Methods: CD34+ and CD14+ cells were isolated from donor apheresis cones and differentiated into eosinophils or macrophage controls, respectively. Morphologic, transcriptional and protein analyses were performed to validate this method of eosinophil differentiation. The effect of IL-33 on differentiated eosinophils was assessed using qPCR, immunofluorescence, and multiplex cytokine array. Results: CD34 differentiated eosinophils appear morphologically similar by H&E and express eosinophil peroxidase (EPX) protein as well as the conventional eosinophil transcripts EPX, CLC, and MBP. In addition, differentiated eosinophils expressed both isoforms of the IL-33 receptor, ST2L and sST2 throughout the differentiation process. Transcript levels of both IL-33 receptors were up-regulated by treatment with IL-33 at earlier timepoints in the differentiation. These cells also expressed IL-4 and IL-13 mRNA which were up-regulated by IL-33 as well. Notably, IL-13 expression was significantly higher with IL-33 treatment compared to media control at every timepoint measured. IL-33 significantly increased cellular secretion of IL-13 protein at most timepoints throughout differentiation. IL-8, LIF, CCL1, CCL5, CCL7, and CCL8 were also significantly secreted after IL-33 stimulation. Conclusions: Our findings suggest that CD34 differentiated eosinophils are morphologically and phenotypically similar to peripheral eosinophils. The release of specific cytokines in direct response to IL-33 may contribute to the pathogenesis of type 2 inflammation and facilitates new avenues for studying eosinophils as effector cells in vitro.