Characteristics of Type 2- High Inflammatory Endotype of Asthma Using New Biomarkers From Peripheral Blood and Exhaled Air and Its Effect on the Outcome of Therapy

The goal of this study is to identify reliable, valid, easily measurable, interpretable, and useful biomarkers in peripheral blood and exhaled air by people with severe asthma for a more accurate description of the pathogenetic processes of asthma-related to the inflammatory endotype and the choice of biologic therapy.

Study Overview

• Status: Completed
• Conditions: Asthma, Bronchial; Bronchial Asthma; Asthma Chronic; Asthma; Eosinophilic

Detailed Description

According to WHO, asthma bronchiale (AB) is the most frequent non-infectious disease in adults. There are 340 million patients with AB in the world. Approximately 500 000 patients in the Czech Republic are suffering from AB and 2,1 % have severe AB with the indication for conventional anti-inflammatory treatment. This subgroup of patients represents significantly high costs for the healthcare system.

There are many clinical phenotypes and molecular endotypes of AB and each of these groups has a different response to treatment. In the Czech republic is recommended classification into two main groups: eosinophil AB (type 2- high) and non-eosinophil AB (type 2- low). Eosinophil AB is furthered classified into two groups: eosinophil allergic (Th2-high) and eosinophil non-allergic (ILC2-high).

New biologicals, indicated for patients with the most severe form of AB, have entered the market during the last 15 years. These biologicals have confirmed their potential in randomized controlled studies. It can be assumed that there are 4 000 - 5000 patients suffering from this type of AB who could be indicated to this treatment in the Czech republic but, unfortunately, only 10 % of them have the access to such therapies in real practice.

Recommended markers of type 2- high AB don´t have strictly set critical values that are often unspecific, unstable in time, and often affected by other diseases or treatments. Some of the widely accepted predictors of response to biological treatment are eosinophilia, allergic reactivity, level of total and allergic-specific IgE, NO production in inhaled air (FeNO), gender, number of previous exacerbations, and duration of disease. Some of these predictors are used as decision criteria also in Global Initiative for Asthma (GINA) guidelines.

With respect to these facts, enormous efforts are being made worldwide to search for new biomarkers, which would be reliable, valid, easily measurable, interpretable, and useful for a more accurate description of the pathogenetic processes of asthma

• Study Type: Observational
• Enrollment (Actual): 89

Contacts and Locations

• Study Contact: Name: Jan Tužil; Phone Number: +420 727824059; Email: jan.tuzil@valueoutcomes.cz

Study Locations

• Czechia
  • Královehradecký Kraj
    • Hradec Králové, Královehradecký Kraj, Czechia, 50005
      • Fakultni nemocnice Hradec Kralove

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

The patients with severe AB type 2 - high (eosinophilic) and type 2- low (non-eosinophilic)

Description

> Group 1 <

Inclusion Criteria:

• severe persistent eosinophilic AB (type 2- high)
• initiated biological treatment against IL-5 or IL-5R (mepolizumab, benralizumab) on this study visit
• judged by the treating physician, the patient cannot be indicated to treatment against anti IgE or anti IL-4R (omalizumab, dupilumab)
• signed informed consent
• signed consent to the processing of personal data
• willingness and ability to undergo examination

Exclusion Criteria:

• active smoker
• BMI higher than 40kg/m2
• ongoing oncological disease or oncological disease during the last 12 months
• severe cardiovascular disease
• uncontrolled diabetes mellitus

• contraindication of choosen biological treatment per SPC

  • Group 2 <

Inclusion Criteria:

• severe persistent eosinophil AB (type 2- high)
• initiated biological treatment against IgE or IL-4R (omalizumab, dupilumab) at this study visit
• judged by the treating physician, a patient cannot be indicated to treatment against anti IL-5 or anti IL-5R (mepolizumab, benralizumab)
• signed informed consent
• signed consent to the processing of personal data
• willingness and ability to undergo examination

Exclusion Criteria:

• active smoker
• BMI higher than 40kg/m2
• ongoing oncological disease or oncological disease during the last 12 months
• severe cardiovascular disease
• uncontrolled diabetes mellitus

• contraindication of choosen biological treatment per SPC

  • Group 3 <

Inclusion Criteria:

• severe persistent eosinophil AB (type 2- high)
• initiated biological treatment against IgE or IL-4R (omalizumab, dupilumab) or against IL-5 or IL-5R (mepolizumab, benralizumab) at this study visit was
• judged by the treating physician, the patient could be potentially indicated to treatment with all 4 alternatives
• signed informed consent
• signed consent to the processing of personal data
• willingness and ability to undergo examination

Exclusion Criteria:

• active smoker
• BMI higher than 40kg/m2
• ongoing oncological disease or oncological disease during the last 12 months
• severe cardiovascular disease
• uncontrolled diabetes mellitus

• contraindication of choosen biological treatment per SPC

  • Group 4 <

Inclusion Criteria:

• severe persistent non-eosinophil AB (type 2- low)
• judged by the treating physician, the patient cannot be indicated for biological treatment
• signed informed consent
• signed consent to the processing of personal data
• willingness and ability to undergo examination

Exclusion Criteria:

• active smoker
• BMI higher than 40kg/m2
• ongoing oncological disease or oncological disease during the last 12 months
• severe cardiovascular disease
• uncontrolled diabetes mellitus

Study Plan

How is the study designed?

Design Details

• Observational Models: Other
• Time Perspectives: Prospective

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort
1. Eosinophilic AB - initiated biological treatment against IL-5 or IL-5R; initiated biological treatment - mepolizumab or benralizumab; judged by the treating physician, the patient cannot indicated treatment of type anti IgE or anti IL-4R
2. Eosinophilic AB - initiated biological treatment against IgE or IL-4R; initiated biological treatment - omalizumab or dupilumab; judged by the treating physician, patient cannot indicated treatment type anti IL-5 or anti IL-5R
3. Eosinophilic AB - initiated biological treatment against IgE or IL-4R, or against IL-5 or IL-5R; initiated biological treatment - omalizumab or dupilumab, or mepolizumab or benralizumab; judged by the treating physician, the patient could be potentially indicated to treatment with all 4 alternatives
4. Non-eosinophilic AB - without indication for biological treatment; no biological treatment initiated; judged by the treating physician, the patient cannot be indicated to biological treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Laboratory parameters (peripheral blood) - blood count		Baseline
Laboratory parameters (peripheral blood) - atopy		Baseline
Laboratory parameters (peripheral blood) - rheumatology	ANF, ENA, RF, ANCA (if not in the last 12 months)	Baseline
Laboratory parameters (peripheral blood) - immunology	IgE, ECP, IgG, IgA, IgM, classes IgG	Baseline
Laboratory parameters (peripheral blood) - flow cytometry (FACS)	The evaluation of eosinophil surface charakteristics per MFI	Baseline
Clinical parameters (exhaled air) - FeNO		Baseline
Clinical parameters (exhaled air) - alveolar NO		Baseline
Clinical parameters (exhaled air) - eNOSE	The examination with "the electronical nose"	Baseline

Collaborators and Investigators

• Sponsor: Value Outcomes Ltd.
• Collaborators: AstraZeneca
• Investigators: Principal Investigator: Jakub Novosad, MUDr.,Ph.D., Fakultni nemocnice Hradec Kralove

Study record dates

Study Major Dates

• Study Start (Actual): August 16, 2022
• Primary Completion (Actual): March 31, 2023
• Study Completion (Actual): March 31, 2023

Study Registration Dates

• First Submitted: February 23, 2022
• First Submitted That Met QC Criteria: March 7, 2022
• First Posted (Actual): March 8, 2022

Study Record Updates

• Last Update Posted (Actual): February 23, 2024
• Last Update Submitted That Met QC Criteria: February 22, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: biomarkers; mepolizumab; dupilumab; omalizumab; airway disease; airway inflammation; airway obstruction; pulmonary; conservative treatment; benralizumab; biological therapy; cross-sectional study; serious asthma; Exhaled Nitric Oxide Levels (FeNO); alveolar NO; exploratory analysis
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Hematologic Diseases; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Leukocyte Disorders; Eosinophilia; Hypereosinophilic Syndrome; Asthma; Pulmonary Eosinophilia
• Other Study ID Numbers: eNOSE; D3250L00044 (Other Identifier: AstraZeneca plc)

Drug and device information, study documents

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