Markers of Pulmonary Dysbiosis Associated With Exacerbation in Patients Followed for Cystic Fibrosis

Markers of Pulmonary Dysbiosis Associated With Exacerbation in Patients Followed for Cystic Fibrosis

The aim objective is to identify markers of bacterial, viral and fungal pulmonary dysbiosis, associated with the occurrence of exacerbation in patients followed for cystic fibrosis.

The primary endpoint is the association between a modification of at least 10% of the relative abundance of a bacterial phylum (Proteobacteria, Firmicutes, Actinobacteria, Bacteroidetes, Fusobacteria) or fungal (ascomycetes / hemiascomycetes, basidiomycetes, zygomycetes), or viral, and the occurrence of exacerbations over a period of 12 months.

Therapeutic advances and the organization of care within the "CRCM" have led to an overall improvement in the management of cystic fibrosis. The protein therapies that have marked this progression only target certain genes and concern a small number of patients. The morbidity, mortality and social cost of cystic fibrosis are still considerable. Exacerbations modulate the prognosis of the disease.

We are interested in dysbiosis, which is the association of an imbalance in the composition and functions of commensal complex microbial communities and an alteration of the immune response of the host. It is involved in the development of chronic pulmonary pathologies such as cystic fibrosis Pulmonary microbiota and host responses mutually influence each other, and evidence suggests that changes in microbiota-host interactions play a major role in the evolution of chronic respiratory diseases. The response of the host may be partially measured by protein markers of inflammation or metabolites regulating inflammation (tryptophan metabolites).

Most microbiome studies focus on the bacterial microbiota, while other microorganisms such as fungi and viruses represent an important cofactor in the degradation of respiratory function. Viral dysbiosis probably plays a role in the appearance of exacerbation.

Among the few studies incorporating fungal risk, very few have considered the role of Pneumocystis jirovecii (PCJ). This non-culturable species was found in 12.5% of patients with cystic fibrosis and possibly associated with exacerbations. We will prospectively follow a cohort of cystic fibrosis patients by collecting clinical and microbiological data on various samples (exhaled air condensate (EAC), sputum and serum) on a quarterly basis and during episodes of exacerbations.

Our project will verify the hypothesis of a correlation between the microbiota, inflammation, and the production of metabolites regulating inflammation (dysbiosis), but also to determine what is the initial biological process leading to the exacerbation: dysbiosis induced by variation of the microbiota or dysbiosis induced by modification of host defense systems. In addition, unlike studies in this area, we will be interested in the bacterial, viral and fungal microbiota.

Inclusion Criteria:

• Patients with cystic fibrosis
• Patient agreeing to participate in the study
• Patient with at least 2 exacerbations in the year prior to inclusion (2 antimicrobial treatments at home or in hospital during the last 12 months)
• Patient or legal guardian of the patient able to read and understand the procedure and able to express his / her consent for the study protocol
• Stable patients, away from exacerbation (at 4 weeks from the beginning of exacerbation, found to be resolved by the investigator)
• Patient affiliated to the social security scheme

Exclusion Criteria:

• Patients who can not read
• Patients opposing the use of their medical data
• Unstable patients, less than one month from the beginning of the exacerbation
• Pregnant or lactating women
• Adult patient under curatorship or tutorship, person deprived of liberty
• Patient awaiting transplant or non-invasive ventilation in chronic
• Patient can not be contacted in case of emergency