Prospective Registry of Eosinophilia With Respiratory Manifestations With Translational Research Identifying and Characterizing Eosinophils (PROMETHEos)

Introduction: The etiology and therapy of eosinophilic lung diseases are still poorly understood. For individual forms of disease, such as eosinophilic asthma or eosinophilic granulomatosis with polyangiitis (EGPA), new therapeutic approaches exist that block the interleukin IL-5 or the IL-5 receptor. Eosinophilic manifestations of the respiratory tract can exclusively affect the lungs or occur as part of a systemic disease. The manifestations partially overlap and are clinically difficult to differentiate (e.g. eosinophilic asthma, Samter Triad, EGPA or hypereosinophilic syndrome (HES)). It is now known that blood eosinophil counts correlate with the level of eosinophils recruited to the airways. However, it is still unclear whether there is a blood eosinophilia without clinical relevance or whether there is a risk of organ damage (e.g. in HES). Hence, different subtypes of eosinophils with different polarization are discussed.

Aim of the study: A registry of patients with eosinophilia and respiratory manifestation will be established at the University Hospital of Innsbruck. The course of disease will be evaluated prospectively in a non-interventional study. This study stands on three main clinical pillars with focus on further characterization of eosinophilic cells:

1. Patients will be included who switch from a previous application of the anti-IL5 antibody mepolizumab (production and administration of the injection from lyophysate through the doctor) to the pre-mixed pen (self-injection at home).
2. Furthermore, special focus is set on patients suffering from the so-called Samter Triad. In these patients, the control of asthma, nasal polyps and NSAID intolerance will be examined in an interdisciplinary fashion during the course of treatment.
3. Previous clinical studies at our Department indicate that some patients with severe eosinophilic asthma or Samter Triad could represent a mono-organic or limited manifestation of lymphoid HES. This hypothesis is tested by measuring additional chemokines, somatic mutations and FACS parameters in this subgroup to verify a clonal disease.

In addition, translational research will differentiate resident and inflammatory eosinophilic granulocytes by FACS analysis and further characterize them by fluorescence microscopy, electron microscopy, gene chip analysis and lipidomics, in the above-mentioned diseases and in healthy controls, respectively.

Patients and methods: All patients suffering from eosinophilia with pulmonary involvement who are diagnosed with eosinophilic asthma, EGPA, Samter Triad, HES, and eosinophilic pneumonia with signed consent are included in the prospective registry. Provided, that they are registered at the outpatient department of pneumology, ENT, haematology or allergology at the University Hospital Innsbruck. The investigators will collect laboratory analyses, lung function, imaging, bone marrow biopsies, ENT findings and allergological findings over the course of the study. Furthermore, additional blood tubes are collected during routine blood tests, which are used to identify and characterize subtypes of eosinophilic granulocytes.

Risks for patients: No additional examinations, blood sampling or invasive measures are required for the patient. Thus, there is no additional risk for study participants.

Risks for control subjects: In order to be able to compare our results with the healthy population, volunteer subjects are recruited. After consent has been given, a blood sample is taken. Despite the low risk, it is theoretically possible that blood sampling may be accompanied by non-severe complications (such as hematoma, infection).

Benefits: The investigators expect new insights into phenotype and therapy of patients with eosinophilic manifestations of the respiratory tract.

Study Overview

• Status: Recruiting
• Conditions: Eosinophilic Asthma; Eosinophilic Pneumonia; EGPA - Eosinophilic Granulomatosis With Polyangiitis; Samter Triad; HES - Hypereosinophilic Syndrome
• Intervention / Treatment: Other: no intervention

• Study Type: Observational
• Enrollment (Anticipated): 300

Contacts and Locations

• Study Contact: Name: Ivan Tancevski, MD; Phone Number: +43 50504 81602; Email: ivan.tancevski@i-med.ac.at
• Study Contact Backup: Name: Judith Löffler-Ragg; Phone Number: +43 50504 81413; Email: judith.loeffler@i-med.ac.at

Study Locations

• Austria
  • Innsbruck, Austria, 6020
    • Recruiting
    • University Clinic for Internal Medicine II
    • Contact: Ivan Tancevski, MD; Phone Number: +43 50504 81602; Email: ivan.tancevski@i-med.ac.at

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Adult patients suffering from severe, late-onset non-atopic eosinophilic asthma bronchiale on mepolizumab therapy or with planned mepolizumab therapy, recruited at our Dept. of Internal Medicine 2, Pneumology, Innsbruck Medical University.

Description

Inclusion Criteria:

• age ≥ 18 years
• documented blood eosinophilia ≥ 300 cells/µl
• present tissue damage of the respiratory tract caused by eosinophils

Exclusion Criteria:

• age < 18 years
• pregnancy
• dementia
• incapacitated patients

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Healthy subjects	Other: no intervention; no intervention
Subjects with eosinophilia and respiratory manifestation	Other: no intervention; no intervention

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Establishment of a registry and descriptive characterization of the collective (frequencies of the individual types of disease, frequencies of the forms of therapy, documentation of the clinical course).	10 years
Identification of inflammatory and regulatory eosinophils in peripheral blood by FACS analysis in all subtypes of eosinophilic manifestations of the respiratory tract	1 year

Collaborators and Investigators

• Sponsor: Medical University Innsbruck

Study record dates

Study Major Dates

• Study Start (Actual): February 26, 2020
• Primary Completion (Anticipated): February 26, 2021
• Study Completion (Anticipated): February 26, 2030

Study Registration Dates

• First Submitted: August 25, 2020
• First Submitted That Met QC Criteria: September 2, 2020
• First Posted (Actual): September 4, 2020

Study Record Updates

• Last Update Posted (Actual): September 4, 2020
• Last Update Submitted That Met QC Criteria: September 2, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Immune System Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Autoimmune Diseases; Lung Diseases; Hematologic Diseases; Vasculitis; Leukocyte Disorders; Lung Diseases, Interstitial; Systemic Vasculitis; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Granuloma; Eosinophilia; Hypereosinophilic Syndrome; Pulmonary Eosinophilia; Granulomatosis with Polyangiitis; Churg-Strauss Syndrome
• Other Study ID Numbers: 20200303-2218

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No