Published Research

Below is a list of some of the research published this year that focus on eosinophil associated diseases. This is not an exhaustive list by any means, however, many of the key journals are included.

Eosinophilic Asthma

Predictive value of blood eosinophils and exhaled nitric oxide in adults with mild asthma: a prespecified subgroup analysis of an open-label, parallel-group, randomised controlled trial
Pavord ID, Holliday M, Reddel HK, et al; on behalf of the Novel START Study Team. [published online March 11, 2020]. Lancet Respir Med. doi:10.1016/S2213-2600(20)30053-9

The investigators of this study concluded that the results are in line with consistent evidence demonstrating that in patients with more severe asthma, blood eosinophil counts are an independent prognostic marker of risk for disease exacerbations and a predictive biomarker of a patient’s response to inhaled corticosteroids.

In patients with severe asthma with eosinophilia in reslizumab clinical trials, high peripheral blood eosinophil levels are associated with low FEV1 reversibility.
Virchow, J.C., Hickey, L., Du, E. et al. Allergy Asthma Clin Immunol 16, 26 (2020). https://doi.org/10.1186/s13223-020-00424-2

Eosinophilic Granulomatosis with Polyangiitis

Oral corticosteroid-sparing effects of reslizumab in the treatment of eosinophilic granulomatosis with polyangiitis
Brian D. Kent, Grainne d’Ancona, Mariana Fernandes, Linda Green, Cris Roxas, Louise Thomson, Alexandra M. Nanzer, Joanne Kavanagh, Sangita Agarwal, David J. Jackson ERJ Open Research 2020 6: 00311-2019; DOI: 10.1183/23120541.00311-2019.

A study published in European Respiratory Society Open Research reports the oral corticosteroid-sparing results of patients with Eosinophilic Granulomatosis with Polyangiitis (EGPA, aka Churg-Strauss Syndrome) who were treated with intravenous reslizumab, which is a humanized monoclonal antibody against human interleukin-5 (IL-5).

Pharmacogenetic investigation of efficacy response to mepolizumab in eosinophilic granulomatosis with polyangiitis
Condreay LD, Parham LR, Qu XA, Steinfeld J, Wechsler ME, Raby BA, Yancey SW, Ghosh S. Rheumatol Int. 2020 Feb 3. doi: 10.1007/s00296-020-04523-6.

This publication describes the treatment of patients with eosinophilic granulomatosis with polyangiitis (EGPA) with a targeted therapy called mepolizumab, a monoclonal antibody to interleukin-5 (IL-5). They found that in the patients dosed with mepolizumab, as an add-on therapy to treatment with glucocorticoids, had reduced eosinophil counts in the blood, longer remission periods and reduced relapse rates, and reduced steroid usage.

Eosinophilic granulomatosis with polyangiitis: the multifaceted spectrum of clinical manifestations at different stages of the disease.
Berti A, Boukhlal S, Groh M, Cornec D. 2020 Jan;16(1):51-61. doi: 10.1080/1744666X.2019.1697678. Epub 2020 Jan 17.

The authors of this paper reviewed the clinical presentation of EGPA, focusing on specific stages of the disease, such as before overt vasculitis develops, when vasculitis is diagnosed, and during long-term follow up.

“Asthma, chronic rhinosinusitis and blood eosinophilia could anticipate the overt vasculitis for years,” the authors noted in the abstract. “An atopic background may be present in a subset of patients (25-30%), while ANCA presence varies between 10 and 40%. Systemic vasculitis rapidly occurs and clinical features demonstrating vasculitis processes.(neuropathy, purpura, scleritis, alveolar hemorrhage and glomerulonephritis) develop along with systemic symptoms (50%).”

The authors also indicated that for up to 50% of patients, asthma remains severe after vasculitis resolves and there is a high incidence of isolated-asthma and rhinosinus exacerbations. “Interleukin-5 blockers seem to be promising to control the disease and to spare corticosteroids,” they further noted.


Eosinophilic Esophagitis

 

Exposure to Household Detergent May Be Linked to EoE

A study recently published in Allergy indicated that “detergents may be a key environmental trigger in EoE pathogenesis.” Researchers concluded that exposure to sodium dodecyl sulfate, a common household detergent, “decreases esophageal barrier integrity, stimulates IL-33 production, and promotes epithelial hyperplasia and tissue eosinophilia.” APFED funded this groundbreaking study thanks to donations to our organization.

Clinical Severity Index Helps Guide EoE Management

Researchers from CEGIR (the Consortium of Eosinophilic Gastrointestinal Disease Researchers) have created an international consensus severity scoring index for EoE. This new simplified scoring system, called the Index of Severity for Eosinophilic Esophagitis (I-SEE), can be completed at routine clinic visits. The system can help guide practitioners in EoE management by standardizing features of disease severity beyond eosinophil counts.

Esophageal Distensibility Defines Fibrostenotic Severity in Pediatric Eosinophilic Esophagitis
Natalie V. Hoffmann, MD, Kaitlin Keeley, BS, Joshua B. Wechsler, MD, MS. Clinical Gastroenterology and Hepatology, Sept. 16, 2022

Researchers aimed to assess whether esophageal distensibility plays a role in fibrosis severity in a cohort of pediatric EoE patients who have esophageal dysfunction. Esophageal distensibility (determined by EndoFLIP) is a measure of fibrostenotic severity that can be used to clinically phenotype pediatric EoE.

Eosinophilic Oesophagitis in Denmark: Population-based Incidence and Prevalence in a Nationwide Study from 2008 to 2018
Allin, KH, Poulsen, G, Melgaard, D, Frandsen, LT, Jess, T, Krarup, AL. Eosinophilic oesophagitis in Denmark: population-based incidence and prevalence in a nationwide study from 2008 to 2018. United European Gastroenterol J. 2022; 10( 7): 642– 52. https://doi.org/10.1002/ueg2.12273

This Danish nationwide population-based study shows a three-fold increase in EoE incidence and prevalence from 2011 to 2018.

Food Antigen Consumption and Disease Activity Affect Food-specific IgG4 Levels in Patients with Eosinophilic Esophagitis (EoE)

McGowan, ECMedernach, JKeshavarz, B, et al. Food antigen consumption and disease activity affect food-specific IgG4 levels in patients with eosinophilic esophagitis (EoE)Clin Exp Allergy2022001– 9. doi: 10.1111/cea.14215

In this study, researchers found that serum sIgG4 levels to food and aeroallergen proteins were higher in patients with EoE than non-EoE controls. They also found that higher levels of milk sIgG4 were independently associated with milk consumption and the presence of sIgE to milk proteins. Additional research is needed to determine if sIgG4 plays a pathogenic role in EoE or could be used as a biomarker for EoE.

Endoscopic approach to eosinophilic esophagitis: American Society for Gastrointestinal Endoscopy Consensus ConferenceGuidelines for EoE Endoscopy 
Gastrointestinal Endoscopy. August 11, 2022

A group of 20 expert clinicians and investigators recently published consensus guidance for the use of endoscopy in EoE. These guidelines provide comprehensive advice on standards for tissue sampling, assessment of disease activity, dilation, and monitoring. The full article was published in August 2022 by Gastrointestinal Endoscopy can be accessed freely  online.

More Reading

Links to the journals are below. Summaries of the following studies appear in issues of EOSolutions. For subscription information, see APFED membership details.

EOSolutions Summer 2022

Eosinophilic Colitis, Eosinophilic Gastritis, Eosinophilic Gastroenteritis

Clinical Features of Pediatric Eosinophilic Gastroenteritis

Kobayashi, S., Tsunoda, T., Umetsu, S., Inui, A., Fujisawa, T. and Sogo, T. (2022), Clinical Features of Pediatric Eosinophilic Gastroenteritis. Pediatrics International. Accepted Author Manuscript e15322. https://doi.org/10.1111/ped.15322

A Japanese study of eosinophilic gastroenteritis (EGE) in children sought to identify its clinical features. The study indicated that “cracked mucosa may be a specific endoscopic finding for pediatric EGE” and “elimination diet and/or anti-allergic drugs were effective in most patients with pediatric EGE.”

 

Molecular, endoscopic, histologic, and circulating biomarker-based diagnosis of eosinophilic gastritis: Multi-site study
J Allergy Clin Immunol. Jan. 2020 Volume 145, Issue 1, Pages 255–269

This paper describes new testing platforms for blood and tissue that may help guide clinicians to a diagnosis of eosinophilic gastritis (EG) in the future. Currently, there are no consensus guidelines to standardize diagnostic criteria for EG. This is in large part due to EG being a rare condition, which makes it challenging to study, and also because it is common for people who have EG to also have another subset of eosinophilic gastrointestinal disease. The samples analyzed by the CEGIR investigators enabled them to develop a molecular profile that correlated with findings from endoscopy and histology. Levels of eotaxin-3 in the blood were strongly associated with expression of gastric cytokine CCL26. Additional studies are needed to validate these findings before these new testing platforms could be considered for clinical use.

This paper reflects the work of the Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR). APFED works in concert with CEGIR to ensure the patient perspective is included in all aspects of its work. Donations to APFED enable us to provide supplemental funding to CEGIR to ensure the success of the consortium.

Eosinophilic gastrointestinal disease below the belt
J Allergy Clin Immunol. January 2020 Volume 145, Issue 1, Pages 87–89

This article from the Journal of Allergy and Clinical Immunology reviews the current state of eosinophilic gastrointestinal diseases (EGIDs) with a focus on “unmet needs, barriers, and future directions in patients with nonesophageal EGIDs.” While eosinophilic esophagitis (EoE) has been the subject of much focus and advancement, EGIDs that affect other parts of the gastrointestinal tract, including eosinophilic gastritis (EG), eosinophilic gastroenteritis (EGE), and eosinophilic colitis (EC), are poorly understood by comparison and there are no well-established guidelines for diagnosis or management.

The article concludes that: 1. Clear diagnostic criteria for EG, EGE, and EC must be established; 2. outcome measures, such as patient-reported outcomes and endoscopic and histologic assessments, need to be developed; 3. More work is required to understand pathogenesis; and 4. Longitudinal trials are needed to better understand disease mechanisms and long-term outcomes.

This paper reflects the work of the Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR). APFED works in concert with CEGIR to ensure the patient perspective is included in all aspects of its work. Donations to APFED enable us to provide supplemental funding to CEGIR to ensure the success of the consortium.


Hypereosinophilic Syndromes

Single-organ and Multisystem hypereosinophilic syndrome patients with gastrointestinal manifestations share common characteristics

Kuang, FL; Curtin, BF; Alao H; Klion AD; Kumar S; Khoury P; et al.
Journal of Allergy and Clinical Immunology: In Practice; April 25, 2020DOI:https://doi.org/10.1016/j.jaip.2020.04.025

Researchers set out to describe the gastrointestinal disease of patients who were categorized as having hypereosinophilic syndrome (HES) and eosinophilic gastrointestinal disease (EGID) overlap. Their research found that patients with Multisystem HES may experience isolated gastrointestinal symptoms before developing symptoms in other organs. “There are striking clinical similarities between Multisystem HES and HES/EGID overlap patients, despite differing treatment approaches,” the authors concluded.
“Moreover, Multisystem HES can present with isolated GI involvement. Larger prospective studies are needed to confirm these findings.”

The Diagnostic Work-Up of Hypereosinophilia
Wang S.A.
Pathobiology 2019;86:39–52 https://doi.org/10.1159/000489341

Excerpt from abstract: “Hypereosinophilia (HE) is defined as a persistent elevated eosinophil count of ≥1.5 × 109/L. HE can be one of the dominant manifestations of a hematopoietic myeloid neoplasm or secondary/reactive to an underlying medical condition. If a cause of HE and its associated tissue/organ damage is not determined, the condition is considered to be idiopathic hypereosinophilic syndrome (HES). The work-up of HE can be challenging due to a broad range of causes of HE that can be either reactive or neoplastic.”

Long-Term Clinical Outcomes of High-Dose Mepolizumab Treatment for Hypereosinophilic Syndrome
Fei Li Kuang, et. al.
J Allergy Clin Immunol Pract. Sep-Oct 2018;6(5):1518-1527.e5.

Excerpt from Conclusion: “This study confirms that mepolizumab is an effective and well-tolerated therapy for HES, but suggests that response is more likely in GC-responsive subjects with idiopathic or overlap forms of HES. A primary benefit of treatment is the reduction of comorbidity due to discontinuation or the reduction of conventional HES therapies. Although subjects who completely discontinued GC had the most benefit, high-dose mepolizumab was a safe and effective salvage therapy for severe, treatment-refractory HES.”

Other Publications of Interest

Advancing patient care through the Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR)
J Allergy Clin Immunol. Jan. 2020 Volume 145, Issue 1, Pages 28-37.

In this rostum, investigators from CEGIR outline the progress and direction of the consortium and the multidisciplinary relationships and engagement with patient advocacy groups like APFED, the National Institutes of Health and partners from industry and academia. The article outlines CEGIRs work with eosinophilic gastrointestinal diseases, including natural history studies to promote clinical trial readiness tools, clinical trials, investigator training program, and innovative pilot studies.

This paper reflects the work of the Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR). APFED works in concert with CEGIR to ensure the patient perspective is included in all aspects of its work. Donations to APFED enable us to provide supplemental funding to CEGIR to ensure the success of the consortium.