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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

Completed
Conditions
Asthma, Bronchial
Bronchial Asthma
Asthma; Eosinophilic
Asthma Chronic
Registration Number
NCT05270278
Lead Sponsor
Value Outcomes Ltd.
Brief Summary

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.

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

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
89
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 & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Laboratory parameters (peripheral blood) - immunologyBaseline

IgE, ECP, IgG, IgA, IgM, classes IgG

Clinical parameters (exhaled air) - alveolar NOBaseline
Clinical parameters (exhaled air) - eNOSEBaseline

The examination with "the electronical nose"

Laboratory parameters (peripheral blood) - blood countBaseline
Laboratory parameters (peripheral blood) - atopyBaseline
Laboratory parameters (peripheral blood) - rheumatologyBaseline

ANF, ENA, RF, ANCA (if not in the last 12 months)

Laboratory parameters (peripheral blood) - flow cytometry (FACS)Baseline

The evaluation of eosinophil surface charakteristics per MFI

Clinical parameters (exhaled air) - FeNOBaseline
Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (1)

Fakultní nemocnice Hradec Králové

🇨🇿

Hradec Králové, Královehradecký Kraj, Czechia

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