Cystic Fibrosis Pulmonary Exacerbation
Conditions
Keywords
Cystic fibrosis, Pulmonary Dysbiosis, pulmonary exacerbation, Fungal bacterial pulmonary dysbiosis, Viral bacterial pulmonary dysbiosis, Microbiota
Brief summary
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.
Detailed description
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.
Interventions
None listed
Sponsors
University Hospital, Grenoble
Study design
Observational model
OTHER
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Identification of markers of bacterial fungal and viral dysbiosis associated with the occurrence of exacerbation in patients followed for cystic fibrosis. | One year | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Evaluation of the influence of the global biodiversity of the bacterial and fungal pulmonary microbiome on the occurrence of exacerbations. | One year | Association between a modification of two indices (Faith's Phylogenetic Diversity and Shannon's B H index) and the occurrence of exacerbations over a 12-month period |
| Association between markers of respiratory function and the relative abundance of different bacterial, viral and fungal phyla and taxa | One year | Correlation between FEV1 on the one hand, and changes in the relative abundance of bacterial, viral and fungal phyla and taxa on the other hand |
| Evaluation of the link between an increase in inflammatory markers and the occurrence of exacerbations | One year | Association between serum concentrations of serum inflammatory cytokines and the occurrence of exacerbations over a period of 12 months |
| Evaluation of the influence of the modification of the relative abundance of different bacterial, viral and fungal taxa, on the occurrence of exacerbations | One year | Association between a change of at least 10% in the relative abundance of a bacterial or fungal taxum, and the occurrence of exacerbations over a 12-month period |
| Comparison of two types of sputum samples versus expired air condensate to evaluate the pulmonary microbiome in patients with cystic fibrosis | One year | Comparison of relative abundance of phyla of interest in sputum vs exhaled air condensate |
| Evaluation of the interactions between the different taxa of the pulmonary microbiome of patients with cystic fibrosis | One year | Network co-occurrence (network interference) of the relative abundance of different bacterial and fungal taxa |
| Evaluation of the impact of treatments administered during exacerbations on the pulmonary microbiome, in particular on changes in the relative abundance and diversity of different bacterial, viral and fungal taxa | One year | Comparison of the relative abundance of the phyla of interest and the diversity of the microbiome (Faith's Phylogenetic Diversity and Shannon B H index) in the presence or absence of antimicrobial and anti-inflammatory steroid treatments |
| Association between markers of respiratory function and serum inflammatory markers | One year | Correlation between FEV 1 and CV on the one hand, and different serum inflammatory serum cytokines |
Countries
France
Contacts
Primary ContactBoubou CAMARA, Dr
Outcome results
None listed