Environmental Mycobiota: In-depth Characterisation and Determinants Involved in Asthma Emission (MyCADO)

The analysis of the exposome of severe asthmatic patients and its correlation with the response profile to biotherapies used in the treatment of severe asthma and/or the frequency of exacerbations, could make it possible to identify individual and environmental components influencing the evolution of the asthmatic pathology and/or response to treatment. An interventional approach could thus be developed, taking into account in particular the determinants of indoor air quality as well as the obstacles to the implementation of current recommendations for the prevention of exacerbations.

The patient will thus be returned to the center and considered as a main actor in his clinical history by offering him the most suitable intervention possible, according to the evaluation of his exposome, in order to ultimately reduce the morbidity and mortality linked to exacerbations.

This interventional approach could then be validated on a larger scale in a national multicenter study involving a larger number of patients.

Study Overview

• Status: Recruiting
• Conditions: Asthma
• Intervention / Treatment: Procedure: Assessment of the microbial exposome

Detailed Description

Nowadays, 5 to 10% of the population of developed countries suffer from asthma, whose morbidity and mortality represent approximately 1% in years of life lost. Within this asthmatic population, there is a subgroup of patients with severe asthma (10% of total asthmatics). These severe asthma patients have a high risk of complications and exacerbations, poor quality of life, and increased mortality and morbidity. Moreover, these severe asthmatics represent 50% of the total health care costs associated with asthma. Among the formidable complications of severe asthma, exacerbations are still responsible for 900 deaths per year in France, while most of them are considered avoidable.

Severe asthma is currently described as a heterogeneous disease composed of multiple phenotypes, themselves linked to different pathophysiological mechanisms that define theendotypes. Phenotypic and endotypic characterization is important for the management of severe asthma, as recent therapeutic developments now make it possible to specifically target certain endotypes.In effect,in recent years, the development of new treatments using monoclonal antibodies (biotherapies) has improved the management of severe asthmatic patients with the "T2-High" phenotype, with a reduction in the frequency of exacerbations. However, the response to these new biotherapies is heterogeneous with super-responder patients (absence of exacerbations), partial responder patients (decrease but persistence of exacerbations) and non-responder patients (no effect on exacerbations).

Severe asthma, the diversity of phenotypes/endotypes observed, the frequency of exacerbations and the response to treatment, result from a combination of genetic and environmental factors. The exposome, which designates all of the exposures to external and environmental factors that a human undergoes from his development in utero until death, could therefore play a key role in the evolution of severe asthmatic pathology. Among these components of the exposome, the team find in particular microbial exposure (or environmental micro-mycobiota), including the omnipresent fungal spores in the air everybody breathe. Thus, in line with the hygienist hypothesis, recent studies have shown that environmental microbial exposures during early childhood, significantly reduced the incidence of respiratory disease in children with genetic susceptibility at chromosome 17q21. Additionally, chronic exposure to a microbial environment, particularly the fungal indoor environment, is associated with a wide range of adverse health effects, including asthma, and may influence its severity. More recently, severe asthma has also been associated with pulmonary microbial dysbiosis that would activate the inflammasome and other mediated pathways. However, the exposome is one of the factors that can influence this pulmonary microbial dysbiosis. particularly the fungal indoor environment, is associated with a wide range of adverse health effects, including asthma, and may influence its severity. More recently, severe asthma has also been associated with pulmonary microbial dysbiosis that would activate the inflammasome and other mediated pathways. However, the exposome is one of the factors that can influence this pulmonary microbial dysbiosis. particularly the fungal indoor environment, is associated with a wide range of adverse health effects, including asthma, and may influence its severity. More recently, severe asthma has also been associated with pulmonary microbial dysbiosis that would activate the inflammasome and other mediated pathways. However, the exposome is one of the factors that can influence this pulmonary microbial dysbiosis.

• Study Type: Observational
• Enrollment (Estimated): 80

Contacts and Locations

• Study Contact: Name: Sébastien IMBERT; Phone Number: +335 57 82 09 82; Email: sebastien.imbert@chu-bordeaux.fr

Study Locations

• France
  • Bourdeaux, France, 33000
    • Recruiting
    • University Hospital, Bordeaux
    • Contact: Sebatien IMBERT, PharmD; Email: sebastien.imbert@chu-bordeaux.fr
    • Principal Investigator: Patrick BERGER, MD PhD
    • Sub-Investigator: Pierre-Olivier GIRODET, MD PhD
  • Toulouse, France, 31000
    • Recruiting
    • University Hospital, Toulouse
    • Contact: Laurent GUILLEMINAULT, PhD; Email: guilleminault.l@chu-toulouse.fr
    • Principal Investigator: Laurent GUILLEMINAULT, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

The inclusion of patients will be done prospectively among patients > 18 years old, severe "T2-High" asthmatics treated with biotherapy for more than a year and regularly monitored at the University Hospitals of Bordeaux and Toulouse.The monitoring of the asthmatic pathology must also have been well carried out the year preceding inclusion in MyCADO, with in particular the evaluation of the initial response to biotherapy and the number of exacerbations that occurred during this year.

Description

Inclusion Criteria:

• Patients > 18 years old,
• Patient with severe "T2-High" asthmatics,
• Treated with biotherapy for more than a year
• Regularly monitored at the University Hospitals of Bordeaux and Toulouse.

Exclusion Criteria:

• Severe asthmatic patients who have been treated with biotherapy for less than a year
• Severe asthmatic patients who have not been treated,
• Not Severe asthmatic patients
• Patient who are not regularly monitored at the Bordeaux and/or Toulouse University Hospitals
• Patients under the protection of justice, under guardianship, under curatorship.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patient who received antibiotic prophylaxis; Severe "T2-High" asthmatics treated with biotherapy	Procedure: Assessment of the microbial exposome; The assessment of the microbial exposome will be carried out by the deployment of 4 dust collectors (1 per season) at the patient's home. The evaluation of the endogenous myco-microbiome will be carried out by analyzing patient sputum obtained during follow-up visits or during routine care in the event of an exacerbation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
identify differences in bacterial and fungal of the microbial exposome	demonstration of an association between the components of the microbial exposome over an entire year and the response profile to biotherapies used in severe asthma (super-responder vs partial responders), evaluated according to Upham's criteria.	Month 3
identify differences in bacterial and fungal of the microbial exposome	demonstration of an association between the components of the microbial exposome over an entire year and the response profile to biotherapies used in severe asthma (super-responder vs partial responders), evaluated according to Upham's criteria.	Month 6
identify differences in bacterial and fungal of the microbial exposome	demonstration of an association between the components of the microbial exposome over an entire year and the response profile to biotherapies used in severe asthma (super-responder vs partial responders), evaluated according to Upham's criteria.	Month 9
identify differences in bacterial and fungal of the microbial exposome	demonstration of an association between the components of the microbial exposome over an entire year and the response profile to biotherapies used in severe asthma (super-responder vs partial responders), evaluated according to Upham's criteria.	Month 12

Collaborators and Investigators

• Sponsor: University Hospital, Bordeaux
• Collaborators: University of Bordeaux
• Investigators: Principal Investigator: Sébastien IMBERT, University Hospital, Bordeaux

Study record dates

Study Major Dates

• Study Start (Actual): January 17, 2023
• Primary Completion (Estimated): April 17, 2025
• Study Completion (Estimated): April 17, 2025

Study Registration Dates

• First Submitted: March 16, 2023
• First Submitted That Met QC Criteria: March 16, 2023
• First Posted (Actual): March 29, 2023

Study Record Updates

• Last Update Posted (Actual): July 14, 2023
• Last Update Submitted That Met QC Criteria: July 13, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: Asthma; Environment; mycobiota
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma
• Other Study ID Numbers: CHUBX 2021/30

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