Cystic Fibrosis Blood Neutrophils

Study Overview
=================
Brief Summary
-----------------
The purpose of this prospective study is to analyze function and phenotype of blood neutrophils in cystic fibrosis patients and the impact of Pseudomonas aeruginosa chronic infection, treatment with CFTR modulators and acute exacerbation on blood neutrophils phenotype and function.

Official Title
-----------------
Functional and Phenotypic Characteristics of Blood Neutrophils in Cystic Fibrosis

Conditions
-----------------
Cystic Fibrosis

Intervention / Treatment
-----------------
* Other: 1 blood sample
* Other: 2 blood samples


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patient over the age of 18 who is not under legal protection Patients with CF according to the diagnostic criteria of the Cystic Fibrosis Foundation including: 15 patients with severe mutation but not chronically infected with PA and not treated with lumacaftor / ivacaftor 15 patients homozygous phe508del, chronically infected with PA and not treated with lumacaftor / ivacaftor 15 patients homozygous phe508del, chronically infected with PA and treated with lumacaftor / ivacaftor 15 hospitalized patients for respiratory exacerbation 40 patients initiating Ivacaftor-Tezacaftor-Elexacaftor treatment. No change in baseline treatment for 15 days (including antibiotic treatment). Patient affiliated to a social security system Free, informed and written consent, dated and signed by the patient and the investigator, at the latest on the day of inclusion and before any action required by the study. Exclusion Criteria: Informed consent impossible to obtain Involvement in an interventional research protocol in the previous 3 months if exclusion directive was given in this protocol.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Stable state<br>45 adult cystic fibrosis patients followed in the respiratory medicine department of Cochin hospital, paris, France: With severe cftr mutations With or without PA chronic infection Treated or not with Ivacaftor-Lumacaftor | Other: 1 blood sample<br>* 4 tubes of 7 ml per sample (a single sample)<br>|
| Experimental: Starting Ivacaftor-Tezacaftor-Elexacaftor<br>40 adult cystic fibrosis patients followed in the respiratory medicine department of Cochin hospital, paris, France: With at least one severe cftr mutation With or without PA chronic infection Initiating Ivacaftor-Tezacaftor-Elexacaftor | Other: 2 blood samples<br>* 4 tubes of 7 ml per sample / 2 samples : before / after antibiotic treatment<br>|
| Experimental: Exacerbation<br>15 adult cystic fibrosis patients followed in the respiratory medicine department of Cochin hospital, paris, France and hospitalized for respiratory exacerbation | Other: 2 blood samples<br>* 4 tubes of 7 ml per sample / 2 samples : before / after antibiotic treatment<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quantification of blood low density neutrophils in cystic fibrosis (CF) | Quantitative flow cytometric evaluation of neutrophil membrane markers that differ according to whether they are : mature neutrophils : CD16high, CD15high, CD33high, CD10high or Low density neutrophils (LDG) : CD16low, CD15neg, CD33 neg, CD10 neg. Comparison of neutrophil membrane markers profile in CF patients versus control blood-donors. | Through study completion, an average of 1 year | 
| Transcriptomic analysis of blood neutrophils in cystic fibrosis (CF) | Transcriptomic analysis of blood neutrophil proinflammatory or immunomodulatory potential. Comparison of transcriptomic blood neutrophil profile in CF patients versus control blood-donors. | Through study completion, an average of 1 year | 
| Effector function analysis of blood neutrophils in CF. | Comparison of effector function analysis of blood neutrophils of CF patients versus control blood-donors. | Through study completion, an average of 1 year | 
| Phagocytosis potential of blood neutrophils in CF. | Comparison of phagocytosis potential of blood neutrophils of CF patients versus control blood-donors. | Through study completion, an average of 1 year | 
| Survival/apoptosis balance analysis in CF | Survival / apoptosis balance analysis : (PCNA localization) in CF patients blood neutrophils versus control blood-donors. | Through study completion, an average of 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quantification of blood low density neutrophils in CF vs other chronic inflammatory disorders. | Quantitative flow cytometric evaluation of neutrophil membrane markers that differ according to whether they are: mature neutrophils : CD16high, CD15high, CD33high, CD10high Low density neutrophils (LDG) : CD16low, CD15neg, CD33 neg, CD10 neg. Comparison of neutrophil membrane markers profile in CF patients versus patients with other chronic inflammatory disease (eg. Rheumatoid arthritis, inflammatory bowel disease). | Through study completion, an average of 1 year | 
| Quantification of blood low density neutrophils in CF according to different clinical situations. | Quantitative flow cytometric evaluation of neutrophil membrane markers. At stable state: presence or absence of airway chronic infection with PA whether or not patients are treated Ivacaftor-Lumacaftor At beginning of exacerbation or after antibiotic treatment. Before or after Ivacaftor-Tezacaftor-Elexacaftor treatment | Through study completion, an average of 1 year | 
| Transcriptomic analysis of blood neutrophils in CF according to different clinical situations. | Transcriptomic analysis of blood neutrophil proinflammatory or immunomodulatory potential. At stable state: presence or absence of airway chronic infection with PA whether or not patients are treated Ivacaftor-Lumacaftor At beginning of exacerbation or after antibiotic treatment. Before or after Ivacaftor-Tezacaftor-Elexacaftor treatment | Through study completion, an average of 1 year | 
| Effector function analysis of blood neutrophils in CF according to different clinical situations. | Effector function analysis of blood neutrophils: At stable state: presence or absence of airway chronic infection with PA whether or not patients are treated Ivacaftor-Lumacaftor At beginning of exacerbation or after antibiotic treatment. Before or after Ivacaftor-Tezacaftor-Elexacaftor treatment | Through study completion, an average of 1 year | 
| Phagocytosis potential of blood neutrophils in CF according to different clinical situations. | Phagocytosis potential analysis of blood neutrophils in CF: At stable state: presence or absence of airway chronic infection with PA whether or not patients are treated Ivacaftor-Lumacaftor At beginning of exacerbation or after antibiotic treatment. Before or after Ivacaftor-Tezacaftor-Elexacaftor treatment | Through study completion, an average of 1 year | 
| Survival/apoptosis balance analysis in CF according to different clinical situations. | Survival / apoptosis balance analysis (PCNA localization): At stable state: presence or absence of airway chronic infection with PA whether or not patients are treated Ivacaftor-Lumacaftor At beginning of exacerbation or after antibiotic treatment. Before or after Ivacaftor-Tezacaftor-Elexacaftor treatment. | Through study completion, an average of 1 year | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Blood neutrophils, Pseudomonas aeruginosa, Cystic fibrosis, CFTR modulators, respiratory exacerbation, airway chronic infection