2024 HOPE APFED/AAAAI Grant Award

We are pleased to announce that at the meeting, the 2024 HOPE APFED/AAAAI Grant Award was presented to Maureen Bauer, MD, Associate Professor of Pediatrics Section of Pediatric Allergy & Immunology, Children’s Hospital Colorado and University of Colorado School of Medicine (pictured below).

Dr. Bauer is the recipient of a $140,000 grant over a two-year term for her promising research study titled “Improving Outcomes and Equity through Targeted Screening for Eosinophilic Esophagitis­­­­.” The grant is funded equally between APFED and the AAAAI.

With this research grant, Dr. Bauer will use the esophageal string test to see how well it can detect EoE in children who have other allergic conditions. Her study will also help determine patient and provider acceptability of using the esophageal string test to screen for EoE.

APFED Best Oral Abstract on EGID Awards

At the meeting, two abstracts were awarded with “Best Oral Abstract on EGID” which were sponsored by APFED donors. These monetary awards ($750) helped offset travel costs for the researchers to be able to present their findings. We are pleased to congratulate the winners this year:

• Edsel M. Abud, MD, PhD, FAAAAI, Scripps Clinic

“Dysregulated Adenosine Pathway Decreases Fibroblast Homeostatic Function in Eosinophilic Esophagitis”

Fibroblasts in the esophagus play a role in inflammation and scarring, but their behavior in EoE is not well understood. This study investigated the role of CD73, an enzyme involved in the adenosine pathway, in EoE fibroblasts. Fibroblasts were collected from EoE patients and healthy donors. EoE fibroblasts showed lower levels of CD73 and reduced enzyme activity compared to healthy fibroblasts. They also demonstrated increased movement and faster healing of wounds. Blocking CD73 activity in healthy fibroblasts increased their movement, while adding adenosine, a product of CD73, normalized the movement of EoE fibroblasts. The researchers concluded that EoE fibroblasts have altered CD73 expression and activity, contributing to their increased movement and potential role in EoE pathology.

• Nicole L. Wolfset, MD, Children’s Hospital of Philadelphia

“Dupilumab Reduces T-cell Antigen-Specific Response in Eosinophilic Esophagitis”

Dupilumab, an FDA-approved treatment for Eosinophilic Esophagitis (EoE), was investigated to understand its long-term impact on memory T cell responses in patients. The study involved EoE patients aged 6 to 25 who received dupilumab alongside standard EoE therapies and then reintroduced EoE-causing foods in a controlled manner. Blood samples were taken before and after dupilumab treatment and food reintroduction, and T cell responses to milk proteins were analyzed.

The results showed that dupilumab treatment led to a decrease in the proliferation of memory T cells in response to milk proteins compared to before treatment. There was also a trend towards reduced production of IL4, a marker of inflammation, in response to milk proteins. These findings suggest that dupilumab might dampen memory T cell responses to specific food antigens over time. However, more research is needed to confirm this effect and better understand its implications.

APFED Board Member Recognized with Lifetime Contribution to the AAAAI and A/I Specialty Award

Dr. William Busse, pictured below, was recognized by AAAAI for his leadership, service, research, clinical care and mentorship. Dr. Busse has served as president to AAAAI, has led a number of committees and divisions, and helped to establish the AAAAI Foundation to support junior investigators with research funding. You may learn more about Dr. Busse’s contributions in this interview with AAAAI. Congratulations, Dr. Busse!

AAAAI’s Annual Meeting included a number of special sessions and lectures specific to eosinophilic GI disease. Below are some of the sessions that were offered:

Advances and Ongoing Challenges in Eosinophilic Gastrointestinal Disorders

This special day-long symposium was organized by the Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR) and the International Gastrointestinal Eosinophil Researchers (TIGERS).

Those who attended this symposium learned about cellular mechanisms of EoE, and about advances in research, diagnostics treatments. Sessions included the esophageal microbiome in EoE; addressing diversity, equity, inclusion, and accessibility in EGIDs; and non-EoE nomenclature and progress toward guidelines for these subsets of eosinophilic GI disease.

Breakout sessions enabled attendees to discuss shared decision making, dietary therapy, and considerations in the management of EoE for adults versus children.

Advances and Ongoing Challenges in Eosinophilic Gastrointestinal Disorders Symposium organizers Dr. Benjamin Wright and Dr. Robbie Pesek.

Multidisciplinary Approach to Assessing Infants and Toddlers with Feeding Difficulties at Risk for Eosinophilic Esophagitis (EoE)
Attendees had the opportunity to learn about the prevalence and underlying etiology of feeding disorders in young children and learned ways to identify these problems in young children likely due to EoE.

Advances in Eosinophilic Gastrointestinal Diseases
This session included a series of oral research abstracts related to eosinophilic esophagitis (see our Research Abstract summaries).

Eosinophilic Diseases: Around the Horn Round-Table
This interactive session highlighted controversies in, and approaches to, caring for patients with eosinophilic disease.

How Do We Get our Treatments to Stick: Maximizing Adherence in Eosinophilic Esophagitis (EoE)
Healthcare providers discussed obstacles related to adherence to EoE therapy and discussed ways to improve adherence.

Breakthroughs in Epithelial Barrier Dysfunction and Eosinophilic Esophagitis (EoE)
This special session was designed to evaluate the role of detergents as a potential environmental factor that initiates dysfunction in the esophageal mucosal barrier and to highlight recent breakthroughs that help researchers to understand mechanisms underlying EoE.

Shared Decision-Making in Eosinophilic Esophagitis (EoE): Helping Your Patient Digest the Latest Information Efficiently
This pre-recorded session was made available to attendees to showcase the latest in treatments for EoE and ways to optimize shared decision making with EoE patients.

2024 Abstracts from J Allergy Clin Immunol, Vol. 153, No. 2 may be found here.

Eosinophilic Granulomatosis with Polyangiitis

• Comorbidities in patients with eosinophilic granulomatosis with polyangiitis and severe uncontrolled asthma: a retrospective analysis of US health insurance claims data. Researchers concluded that “Comorbidity and symptom burdens differed between patients with EGPA versus SUA alone. The comorbidity burden in SUA was respiratory-related, and in EGPA it was ENT-, ocular- and renal related.” See abstract 164 on page 53.
• Patient perspectives on the burden of eosinophilic granulomatosis with polyangiitis. EGPA patients enrolled in the MANDARA study undergoing treatment with glucocorticoids and immunosuppressants, comparing benralizumab with mepolizumab, were interviewed. Patients were interviewed twice, focusing on symptoms, treatment expectations, and impacts. Initial results from 9 patients aged 40-70 showed various bothersome symptoms including difficulty breathing, coughing, fatigue, and nasal issues. EGPA affected their work, exercise, sleep, and social activities. These findings underscore the significant burden of EGPA and emphasize the urgent need for more effective treatments to enhance patients’ quality of life. See abstract 165 on page 54.
• Healthcare resource utilization and costs in patients with eosinophilic granulomatosis with polyangiitis versus severe uncontrolled asthma: a retrospective analysis of US health insurance claims data. Real-world data on eosinophilic granulomatosis with polyangiitis (EGPA) are limited. This study used US health insurance claims data to compare the impact of EGPA and severe uncontrolled asthma (SUA) on healthcare resource use and costs. Patients newly diagnosed with EGPA between 2017 and 2021 were matched with those with SUA. EGPA patients had more hospital stays, outpatient visits, and pharmacy claims compared to SUA patients. EGPA also resulted in significantly higher healthcare costs, particularly due to expenses related to hospital stays, outpatient visits, doctor’s office visits, and pharmacy costs. This indicates that EGPA imposes a greater economic burden on patients and the healthcare system compared to SUA. See abstract 638 on page 54.

Hypereosinophilic Syndrome

• Dupilumab Use in Patients with Hypereosinophilic Syndrome: A Multi-Center Case Series. This study examines the use of dupilumab in patients with Hypereosinophilic Syndrome (HES). HES involves high levels of eosinophils in the blood or tissues, leading to various symptoms like severe asthma, dermatitis, or sinus issues. Dupilumab is approved for treating these conditions but can temporarily increase eosinophil levels, potentially causing complications in HES patients. The study looked at 25 HES patients treated with dupilumab. Most patients (80%) showed significant improvement, primarily those with chronic sinus issues. However, around half of the patients experienced worsened eosinophil levels while on dupilumab alone, and some had eosinophil-related side effects. Patients already on another medication to lower eosinophils didn’t experience these issues when dupilumab was added. In summary, while dupilumab was effective for HES, it may lead to eosinophil-related complications. Combining it with other eosinophil-lowering therapies could help mitigate these risks. See abstract 188 on page 61.
• A pilot phase 2 study of ruxolitinib for the treatment of steroid-refractory hypereosinophilic syndrome. In this study, 22 adult patients with PDGFR mutation-negative, steroid-resistant HES were given ruxolitinib in a clinical trial. The main goal was to reduce eosinophil count by 30% within 3 months. All participants saw improvement by 3 months, especially those with higher baseline eosinophil counts. Some patients continued ruxolitinib for up to 8 years. Though a few stopped due to various reasons, none were related to side effects. Fifteen patients are still using ruxolitinib for 1-53 months. The drug seemed to work by inhibiting STAT5b phosphorylation, although it didn’t affect lymphocyte numbers. In conclusion, ruxolitinib shows promise in treating steroid-resistant HES, offering hope for those who don’t respond to conventional therapies. See abstract 195 on page 64.
• Long-term Efficacy and Safety of Benralizumab Treatment for PDGFRA-negative Hypereosinophilic Syndrome. Current treatments for hypereosinophilic syndromes (HES) often have varying effectiveness and side effects. Benralizumab is a type of antibody that targets eosinophils, which are involved in HES. In this study, 20 HES patients were treated with benralizumab in a controlled trial, and 14 of them continued the treatment for over 5 years. Most patients experienced ongoing suppression of eosinophil levels. Some patients tried to reduce the frequency of injections, but a few had to resume monthly doses due to increased symptoms. Serious side effects were rare, with only a few cases of mild reactions at the injection site reported. There were no new infections or cancers detected, and immune system levels remained stable. In conclusion, long-term treatment with benralizumab appears effective and safe for HES patients, offering a promising option for managing the condition. See abstract 196 on page 64.
• Single Center Off-Label Benralizumab use for Refractory Hypereosinophilic Syndrome Demonstrates Satisfactory Safety and Efficacy. Hypereosinophilic syndrome (HES) involves high levels of eosinophils damaging organs. Medications targeting interleukin-5 (IL-5) are used for eosinophil-related diseases. Mepolizumab is currently approved for HES, but benralizumab, which blocks IL5R, shows promise. This study looked at 15 patients with severe HES or who couldn’t reduce steroid use, treated with compassionate need benralizumab. Patients received benralizumab at our center and most saw a significant decrease in eosinophils after just one dose. Nearly all were able to stop using steroids completely. Symptoms improved for most, and no serious side effects occurred. In conclusion, our study suggests benralizumab is safe and effective for HES, reducing eosinophils, reversing organ damage, and minimizing steroid use in most patients with few side effects. See abstract 197 on page 64.
• Development of a prediction model for hypereosinophilic syndrome using real-world data. A prediction model was developed using healthcare databases from May 2017 to December 2021. Adults with high levels of eosinophils in their blood and at least one HES diagnosis code were considered HES patients, while those without HES codes served as controls. The model used various factors such as demographics, medical history, medications, and healthcare usage to predict HES diagnosis. It identified several key predictors of HES, including bone marrow biopsy, specific levels of blood eosinophils, and certain autoimmune diseases. The model demonstrated good performance in predicting HES indicating its potential to identify undiagnosed HES patients and provide a more accurate understanding of the condition’s burden in real-world settings. See abstract 667 on page 64.

Eosinophilic Gastrointestinal Disorders

• Clinical Characteristics and Treatment Responses of Oral Immunotherapy-Associated Eosinophilic Esophagitis. Eosinophilic esophagitis (EoE) can develop as a complication of oral immunotherapy (OIT), leading to OIT discontinuation. However, some patients manage to achieve EoE remission by continuing OIT with medical treatment. Researchers examined the progress and outcomes of patients who developed OIT-associated EoE at their medical center and identified 14 out of 712 patients who were diagnosed with EoE during OIT. Symptoms typically began during OIT build-up, but diagnosis often occurred later, during OIT maintenance. Symptoms included vomiting, abdominal pain, dysphagia, and food aversion. Interestingly, many patients had EoE-like symptoms before starting OIT. Among those who had follow-up exams, some achieved EoE remission after stopping OIT, while others managed to continue OIT and achieve remission with medical treatment. In conclusion, EoE symptoms can appear before starting OIT, and diagnosis may be delayed until later stages of OIT. While stopping OIT can lead to EoE remission, some patients can manage EoE while continuing OIT with medication. See abstract 376 on page 55.
• Eosinophilic Esophagitis Incidence in Sublingual Immunotherapy Tablet Clinical Trials is Similar to the Background Incidence in the General Population. Sublingual immunotherapy (SLIT) is a successful treatment for allergic rhinitis, with few reports of SLIT-linked EoE. This study aimed to assess the occurrence of EoE in SLIT-tablet trials. EoE cases were examined from 5 SLIT-tablet trials involving house dust mite and ragweed allergens. Among 2,906 participants, only 2 EoE cases were found, resulting in an incidence of 6.0 cases per 100,000 treatment-years. Symptoms included difficulty swallowing and vomiting. Both cases were identified through biopsy. In conclusion, the incidence of EoE in SLIT-tablet trials mirrors that in the general population. While SLIT-tablet safety is continually monitored, the small number of cases in clinical trials doesn’t confirm a direct link between SLIT-tablets and EoE. See abstract 382 on page 57.
• Percentage of peripheral blood GPR15+ pathogenic effector Th2 cells that are CD38 positive may identify active eosinophilic esophagitis. Recent research in eosinophilic esophagitis (EoE) has shown that certain types of immune cells called GPR15+ pathogenic effector Th2 cells (GPR15+peTh2s) are specific to food triggers and tend to accumulate in the esophagus. CD38 is a marker of activation in these cells after exposure to allergens.
• In this study, blood cells and esophageal tissue samples from 48 subjects with active EoE, EoE in remission, or without EoE were analyzed. The percentage of GPR15+peTh2s expressing CD38 was higher in active EoE compared to remission or no EoE. The optimal cut-off points for distinguishing EoE status were identified. GPR15+peTh2s with CD38 expression had higher levels of GPR15. In esophageal biopsies, the percentage of GPR15+CD38+ peTh2s was higher in active EoE. In conclusion, the presence of CD38 in GPR15+peTh2s appears to be a useful marker for detecting EoE and its status during dietary elimination. These findings suggest that GPR15 and CD38 could help identify and track disease-causing cells in EoE for further research. Activation of GPR15+peTh2s by allergens may contribute to their migration to the esophagus. See abstract 454 on page 79.
• Dupilumab Is Efficacious Up To 52 Weeks In Patients With Eosinophilic Esophagitis Irrespective Of Prior Food Elimination Diet Or History Of Food Allergy. Eosinophilic esophagitis (EoE) is a chronic inflammatory condition often linked with food allergies. While elimination diets can help manage symptoms, they can be difficult to stick to. Dupilumab, approved for EoE treatment in the US, showed positive results in patients with and without food allergies in a 24-week study. This follow-up analysis looked at the effectiveness of dupilumab over 52 weeks. Patients who completed the initial study received 28 weeks of dupilumab treatment. The goal was to see how many patients achieved a reduction in eosinophil count and improvement in symptoms. Results showed that a high proportion of patients, regardless of previous food elimination or allergies, had improved eosinophil counts and symptom scores. Dupilumab also helped maintain or further improve the condition of the esophagus as seen in endoscopic assessments. In conclusion, dupilumab continued to show positive effects on histological, symptomatic, and endoscopic aspects of EoE for up to 52 weeks, regardless of prior diet restrictions or food allergies. See abstract 457 on page 80.
• Non-esophageal Eosinophilic Gastrointestinal Disorders with Blood Hypereosinophilia: A 10- year Retrospective Review of Clinical Features and Treatment Regimens. Eosinophilic gastrointestinal disorders (EGIDs) can be linked to high levels of eosinophils in the blood, a condition called hypereosinophilia. However, it’s uncertain how this blood condition relates to the symptoms of EGIDs. To understand this connection, researchers looked at medical records from the Mayo Clinic between 2012 and 2022, focusing on patients with EGIDs. Among 142 records reviewed, 55 patients had primary EGID and were included in our study. They found that patients with or without hypereosinophilia had similar rates of allergic diseases, heart problems, lung symptoms, and general symptoms like fatigue. Additionally, there were no significant differences in the use of medications or the need for multiple therapies between the two groups. This study suggests that having hypereosinophilia in the blood does not seem to affect the clinical characteristics of EGIDs. However, further research with larger groups of patients is needed to confirm these findings. See abstract 608 on page 45.
• Evaluation of elevated serum tryptase among individuals with eosinophilic gastrointestinal disorders. The study aimed to understand why some people with eosinophilic gastrointestinal disorders (EGIDs) have high levels of a protein called basal serum tryptase (BST). It’s unclear if this is due to a genetic condition called hereditary alpha-tryptasemia (HaT) or another blood disorder. Participants with EGID or atopic dermatitis (AD) were examined, and BST levels were measured. Genetic testing was done to look for HaT and other genetic mutations associated with blood disorders. Results showed that 16% of EGID participants had elevated BST, compared to less than 1% of those with AD. Among those with elevated BST in EGID, some had HaT or a blood disorder called myeloid neoplasm. For others, the cause of high BST was unclear. In conclusion, high BST levels are more common in EGID compared to AD. It may be due to HaT or a blood disorder in some cases. Further research is needed to understand this better. See abstract 609 on page 45.
• Transcriptomic analysis of gastric tissue in pediatric eosinophilic gastritis. Eosinophilic gastritis (EoG) is a chronic stomach inflammation condition, and patients with the persistent form often don’t experience spontaneous recovery, leading to a decrease in their quality of life. Although previous studies have explored the genetic aspects of EoG, more detailed research is required, particularly to understand its specificity and how it responds to different treatments, including dietary changes. Researchers studied 13 patients with EoG, six without inflammation, and four with Crohn’s disease. They analyzed RNA extracted from stomach tissue and gastric samples after inflammation had resolved with dietary therapy. Their analysis found that EoG patients formed a distinct group compared to the control and Crohn’s disease groups. They identified genes specific to EoG and found that IL13 may play a crucial role in the condition. Additionally, our findings suggest that dietary therapy can help normalize gene activity associated with EoG. See abstract 610 on page 46.
• Comparison of Eosinophilic Esophagitis in Native American vs. Non-Native American Children: A Case-Control Study. In this small cohort, researchers noticed that symptoms, allergies, and family history varied among Native American children with EoE depending on their age and race. However, they didn’t find significant differences in their tissue or endoscopy results. It’s important for future research to investigate if these variations in symptoms are linked to ancestry or other social factors affecting health. See abstract 611 on page 46.
• A Diagnosis of an IgE Mediated Egg Allergy Increases the Relative Risk of Developing Eosinophilic Esophagitis within Three-Years in Pediatric Patients. Researchers conducted a study to see if having an egg allergy diagnosis increases the risk of developing EoE in children. They used data from pediatric patients aged 1-18 years and matched those with egg allergy to those without. Over three years, they found that a significantly higher number of patients with egg allergy developed EoE compared to those without egg allergy. This suggests that having an egg allergy diagnosis is linked to a higher risk of EoE. See abstract 613 on page 47.
• Anxiety, Depression, and Resilience In Adolescents And Primary Caregiver Dyads With Eosinophilic Esophagitis Living In Rural And Urban Areas. Researchers aimed to understand how EoE and living environment (urban or rural) affect mental health and quality of life in teenagers with the condition, along with their parents. They enrolled 15 adolescent-parent pairs, with 9 from urban areas and 6 from rural areas and  found that overall resiliency was low in both groups, and there were no significant differences in anxiety, depression, or quality of life between urban and rural pairs. However, there was a trend suggesting that symptom severity might be worse in urban pairs. Further research is needed to explore the mental health impact of EoE and living environment on teenagers. See abstract 617 on page 48.
• Effects of Proton Pump Inhibitors on Esophageal Remodeling and Fibrosis in Eosinophilic Esophagitis. This study investigated the effects of proton pump inhibitors (PPIs) on eosinophilic esophagitis (EoE), a condition causing inflammation and scarring in the esophagus. They examined biopsies from EoE patients before and after PPI treatment and conducted experiments on esophageal cells. They found that PPIs changed gene expression related to scarring in responders and partly reduced it in non-responders. PPIs also decreased scarring-related gene expression and collagen buildup in esophageal cells. This suggests that PPIs may influence scarring in EoE by altering gene expression and countering scarring processes. See abstract 768 on page 96.

Eosinophilic Asthma

• Clinical Remission Outcome in Patients with Severe Asthma with an Eosinophilic Phenotype (SA-EP) Receiving Mepolizumab: A Post-Hoc Analysis of a Phase 3, Randomized, DoubleBlind, Placebo-Controlled Trial. The goal of achieving clinical remission (CR) is becoming increasingly important in asthma treatment. This study looked at the effectiveness of mepolizumab in achieving CR in patients with severe asthma with elevated eosinophils.
• Patients aged 12 years and older, with high eosinophil levels, and experiencing frequent exacerbations despite standard treatment were included in the study. They were randomly assigned to receive either mepolizumab or placebo for 52 weeks. CR was defined as meeting specific criteria related to corticosteroid use, exacerbations, asthma control questionnaire scores, and lung function improvements.
• Results showed that a significantly higher proportion of patients treated with mepolizumab achieved CR compared to those on placebo. Factors like being female, younger age, lower weight, better lung function, and fewer previous exacerbations were associated with higher chances of achieving CR.
• In conclusion, mepolizumab effectively induced clinical remission in patients with severe asthma and elevated eosinophils, highlighting its potential as a treatment option for this condition. See abstract 299 on page 32.
• Patient and Physician Perspectives on Mepolizumab Treatment in Severe Asthma: Data From the REALITI-A Study. Mepolizumab is known to reduce asthma exacerbations and oral corticosteroid use, with a good safety record in severe asthma patients with high eosinophil levels. However, there’s not much information about how satisfied patients and doctors are with mepolizumab treatment.
• The REALITI-A study, lasting for 2 years, enrolled adults with asthma newly prescribed mepolizumab. Patient and physician satisfaction with mepolizumab treatment was assessed over 24 months using questionnaires. The study looked at whether there was a reduction in exacerbations (by more than 50% or less) and oral corticosteroid dose (by more than 50% or less).
• After 24 months, 93% of patients reported their asthma had improved compared to before starting mepolizumab. This improvement was more common in patients with a larger reduction in exacerbations or corticosteroid dose. Similarly, a high proportion of physicians (93%) also observed improvement in patients’ asthma status. Physicians noticed more improvement in patients with a greater reduction in exacerbations or corticosteroid dose.
• In conclusion, real-world data shows that mepolizumab treatment improves asthma status, according to both patients and physicians. This indicates that mepolizumab is beneficial and satisfactory for patients with severe asthma in real-world clinical settings. See abstract 309 on page 35.

Other Abstracts of Interest

• Briquilimab, An Anti-CD117 Antibody, Prevents Cockroach Allergen Induced Allergic Asthma In Mice Expressing Chimeric Human And Mouse CD117. Stem cell factor (SCF) signaling through c-Kit (CD117) is crucial for mast cell (MC) development and survival, making it a target for treating MC-related diseases like allergic asthma. Briquilimab is a humanized monoclonal antibody that blocks CD117, reducing MC numbers. In this study, transgenic mice with human CD117 were used to mimic allergic asthma. After exposure to cockroach allergen, these mice developed airway inflammation and hyperresponsiveness similar to wild-type mice. A single dose of briquilimab significantly reduced lung MCs and eosinophils, similar to MC-deficient mice. Briquilimab also reduced airway inflammation and hyperresponsiveness, suggesting it prevents allergic asthma by depleting MCs. In conclusion, this study suggests briquilimab could be a promising treatment for allergic asthma and eosinophilic disorders by targeting MCs. See abstract 441 on page 75.
• Raman spectroscopy identifies the disease related eosinophils at a single cell level. Raman spectroscopy of eosinophils in the blood has shown promise in distinguishing between patients with eosinophilic diseases and those who are healthy. Our findings indicate that Raman spectroscopy could be valuable in diagnosing eosinophilic diseases in clinical settings. See abstract 668 on page 64.