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

NCT ID: NCT03569904

Last Updated: 2020-03-18

Basic Information

• Recruitment Status: UNKNOWN
• Total Enrollment: 30 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2018-10-02
• Study Completion Date: 2021-12-31

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.

Conditions

Cystic Fibrosis Pulmonary Exacerbation

Study Design

• Observational Model Type: OTHER
• Study Time Perspective: PROSPECTIVE

Eligibility Criteria

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

• Minimum Eligible Age: 12 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Grenoble

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

University Hospital Grenoble

Grenoble, , France

Site Status: RECRUITING

Countries

France

Central Contacts

Boubou CAMARA, Dr

Role: CONTACT

BCamara@chu-grenoble.fr

+33(0)4 76 76 58 46

Facility Contacts

Boubou Camara

Role: primary

References

Beaumier L, Chanoine S, Camara B, Pison C, Bedouch P. Alemtuzumab and de novo pulmonary arterial hypertension: A potential association? J Heart Lung Transplant. 2017 Mar;36(3):370-371. doi: 10.1016/j.healun.2016.10.013. Epub 2016 Oct 29. No abstract available.

Reference Type: BACKGROUND

PMID: 27889369 (View on PubMed)

Wintenberger C, Maubon D, Charpentier E, Rendu J, Pavese P, Augier C, Malvezzi P, Camara B, Mallaret MR, Bouillet L, Epaulard O. Grouped Cases of Pulmonary Pneumocystosis After Solid Organ Transplantation: Advantages of Coordination by an Infectious Diseases Unit for Overall Management and Epidemiological Monitoring. Infect Control Hosp Epidemiol. 2017 Feb;38(2):179-185. doi: 10.1017/ice.2016.274. Epub 2016 Nov 28.

Reference Type: BACKGROUND

PMID: 27890037 (View on PubMed)

Zhao Y, Garnaud C, Brenier-Pinchart MP, Thiebaut-Bertrand A, Saint-Raymond C, Camara B, Hamidfar R, Cognet O, Maubon D, Cornet M, Perlin DS. Direct Molecular Diagnosis of Aspergillosis and CYP51A Profiling from Respiratory Samples of French Patients. Front Microbiol. 2016 Jul 29;7:1164. doi: 10.3389/fmicb.2016.01164. eCollection 2016.

Reference Type: BACKGROUND

PMID: 27524978 (View on PubMed)

Decorte N, Gruet M, Camara B, Quetant S, Mely L, Vallier JM, Verges S, Wuyam B. Absence of calf muscle metabolism alterations in active cystic fibrosis adults with mild to moderate lung disease. J Cyst Fibros. 2017 Jan;16(1):98-106. doi: 10.1016/j.jcf.2016.05.010. Epub 2016 Jun 15.

Reference Type: BACKGROUND

PMID: 27316662 (View on PubMed)

Claustre J, Brion JP, Quetant S, Bedouch P, Pison C, Camara B. Favorable Evolution of Cryptococcal Meningitis in the Context of Flucytosine Resistance. Exp Clin Transplant. 2018 Feb;16(1):110-113. doi: 10.6002/ect.2015.0217. Epub 2016 Apr 26.

Reference Type: BACKGROUND

PMID: 27143150 (View on PubMed)

Roca A, Oluwalana C, Bojang A, Camara B, Kampmann B, Bailey R, Demba A, Bottomley C, D'Alessandro U. Oral azithromycin given during labour decreases bacterial carriage in the mothers and their offspring: a double-blind randomized trial. Clin Microbiol Infect. 2016 Jun;22(6):565.e1-9. doi: 10.1016/j.cmi.2016.03.005. Epub 2016 Mar 26.

Reference Type: BACKGROUND

PMID: 27026482 (View on PubMed)

Godet C, Laurent F, Bergeron A, Ingrand P, Beigelman-Aubry C, Camara B, Cottin V, Germaud P, Philippe B, Pison C, Toper C, Carette MF, Frat JP, Beraud G, Roblot F, Cadranel J; ACHROSCAN Study Group. CT Imaging Assessment of Response to Treatment in Chronic Pulmonary Aspergillosis. Chest. 2016 Jul;150(1):139-47. doi: 10.1016/j.chest.2016.02.640. Epub 2016 Feb 19.

Reference Type: BACKGROUND

PMID: 26905365 (View on PubMed)

Dumollard C, Bailly S, Perriot S, Brenier-Pinchart MP, Saint-Raymond C, Camara B, Gangneux JP, Persat F, Valot S, Grenouillet F, Pelloux H, Pinel C, Cornet M. Prospective Evaluation of a New Aspergillus IgG Enzyme Immunoassay Kit for Diagnosis of Chronic and Allergic Pulmonary Aspergillosis. J Clin Microbiol. 2016 May;54(5):1236-42. doi: 10.1128/JCM.03261-15. Epub 2016 Feb 17.

Reference Type: BACKGROUND

PMID: 26888904 (View on PubMed)

Godet C, Laurent F, Beraud G, Toper C, Camara B, Philippe B, Germaud P, Cottin V, Beigelman-Aubry C, Khalil A, Blouin P, Pouriel M, Roblot F, Bergeron A, Cadranel J; ACHROSCAN study group. Phenotyping chronic pulmonary aspergillosis by cluster analysis. Eur Respir J. 2015 Nov;46(5):1509-12. doi: 10.1183/13993003.00869-2015. Epub 2015 Sep 17. No abstract available.

Reference Type: BACKGROUND

PMID: 26381520 (View on PubMed)

Gruet M, Decorte N, Mely L, Vallier JM, Camara B, Quetant S, Wuyam B, Verges S. Skeletal muscle contractility and fatigability in adults with cystic fibrosis. J Cyst Fibros. 2016 Jan;15(1):e1-8. doi: 10.1016/j.jcf.2015.05.004. Epub 2015 May 29.

Reference Type: BACKGROUND

PMID: 26033387 (View on PubMed)

Bouvaist H, Thony F, Jondot M, Camara B, Jais X, Pison C. Balloon pulmonary angioplasty in a patient with chronic thromboembolic pulmonary hypertension. Eur Respir Rev. 2014 Sep;23(133):393-5. doi: 10.1183/09059180.00000514. No abstract available.

Reference Type: BACKGROUND

PMID: 25176976 (View on PubMed)

Claustre J, Quetant S, Camara B, France M, Schummer G, Bedouch P, Pavese P, Saint Raymond C, Bardy B, Masson D, Roth H, Pison C; Grenoble Lung Transplantation group. Nonspecific immunoglobulin replacement in lung transplantation recipients with hypogammaglobulinemia: a cohort study taking into account propensity score and immortal time bias. Transplantation. 2015 Feb;99(2):444-50. doi: 10.1097/TP.0000000000000339.

Reference Type: BACKGROUND

PMID: 25099705 (View on PubMed)

Bosc C, Clement M, Deroux A, Mammar A, Pison C, Camara B. [Severe pneumonia due to cytomegalovirus in chronic obstructive pulmonary disease]. Rev Mal Respir. 2014 May;31(5):435-8. doi: 10.1016/j.rmr.2013.09.013. Epub 2013 Dec 2. French.

Reference Type: BACKGROUND

PMID: 24878160 (View on PubMed)

Camara B, Reymond E, Saint-Raymond C, Roth H, Brenier-Pinchart MP, Pinel C, Cadranel J, Ferretti G, Pelloux H, Pison C; Grenoble Aspergillus Committee. Characteristics and outcomes of chronic pulmonary aspergillosis: a retrospective analysis of a tertiary hospital registry. Clin Respir J. 2015 Jan;9(1):65-73. doi: 10.1111/crj.12105. Epub 2014 Feb 17.

Reference Type: BACKGROUND

PMID: 24406138 (View on PubMed)

Other Identifiers

38RC17.317

Identifier Type: -

Identifier Source: org_study_id