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

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.