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

Recruiting

• Conditions: Asthma
• Interventions: Procedure: Assessment of the microbial exposome

• Registration Number: NCT05789927
• Lead Sponsor: University Hospital, Bordeaux

Brief Summary

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.

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 Timeline

• Study Start: 2023-01-17
• Study First Submitted: 2023-03-16
• Study First Submitted QC: 2023-03-16
• Study First Posted: 2023-03-29
• Status Verified: 2023-07
• Last Update Submitted: 2023-07-13
• Last Update Posted: 2023-07-14
• Primary Completion: 2025-04-17
• Study Completion: 2025-04-17

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 80

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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Patient who received antibiotic prophylaxis	Assessment of the microbial exposome	Severe "T2-High" asthmatics treated with biotherapy

Primary Outcome Measures

Name	Time	Method
identify differences in bacterial and fungal of the microbial exposome	Month 12	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.

Trial Locations

Locations (2)

University Hospital, Toulouse; 🇫🇷 Toulouse, France

University Hospital, Bordeaux; 🇫🇷 Bourdeaux, France