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An Atlas of Airways at a Single Cell Level in Chronic Obstructive Pulmonary Disease, Idiopathic Pulmonary Fibrosis and Controls

Study Purpose

The increasing incidence of chronic respiratory disease is a public health problem that affects hundreds of thousands of people worldwide at all ages. Directly exposed to atmospheric airborne contaminants (pollution, allergens), the respiratory tract represents a complex ecosystem involving different cells (multiciliated, basal, mucosecretory, neuroendocrine, etc.) that develop complex interactions with the surrounding connective tissue but also with their rich immune environment and the local microbiota. Although a pathophysiological continuum is postulated between the nasal and bronchial airways in certain diseases, such as allergic diseases, investigators have demonstrated large gene expression gradients between samples taken from the nasal and bronchial airways in different studies. Specifying the cellular variability throughout the respiratory tree in a normal physiological situation is one of the major objectives defined in the establishment of an atlas of all airway cells, as defined in the objectives of the international consortium Human Cell Atlas. The sequencing of the RNAs present specifically in each individual cell ("single-cell RNAseq"), and its comparison with neighbouring cells allows to document the precise cellular contributions, as well as the signalling pathways involved. The development of tissue sampling, stabilization, transport and single cell analysis procedures can be performed on primary respiratory epithelium cultures and can also be extended to respiratory samples from healthy volunteers. This project will analyze gene expression profiles at the single cell level (single cell RNAseq) in volunteers with chronic obstructive pulmonary disease, interstitial pulmonary fibrosis and compared to healthy subjects of the same age. The technical modalities of the samples will be brushing and staged airway biopsies for direct analysis of the samples. This approach will be complemented by an air-liquid interface culture to allow secondary analysis in single cell RNAseq and three-dimensional mapping of the distribution of these cells with single cell in situ analysis. Thanks to sampling at several levels of the respiratory tree (nose, bronchioles, bronchioles), cellular and gene expression variations along the tracheobronchial axis will be exhaustively documented in subjects of different ages, healthy or suffering from pathologies such as chronic obstructive pulmonary disease and interstitial pulmonary fibrosis. These data will serve as worldwide references for comparisons in different physiological and pathological contexts.

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	Yes
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Interventional
Eligible Ages	18 Years and Over
Gender	All

More Inclusion & Exclusion Criteria

Inclusion Criteria:

- Absence of acute pathology.

- Absence of symptom evoking an evolutionary pathology.

For healthy volunteers :

- Non-smoker (active or passive) or ex-smoker of less than 5 packet-years and quit for more than 10 years.

- Absence of known significant chronic pathology.

- Normal Respiratory Function Test (RFT) - Woman of childbearing age using an effective method of contraception.

For COPD patients :

- Diagnosis of COPD based on dyspnea, chronic cough or sputum production, a history of recurrent lower respiratory tract infections and/or a history of exposure to risk factors for the disease associated with spirometry that demonstrates a post-bronchodilator FEV1/FVC ratio < 0.70 and lack of reversibility.

- Stage GOLD 1 (post-bronchodilator FEV1 ≥ 80% theoretical) or 2 (post-bronchodilator FEV1 between 50 and less than 80% theoretical) or 3 (post-bronchodilator FEV1 between 30 and less than 50% theoretical) For IPF patients.

- Diagnosis of idiopathic pulmonary fibrosis made less than 5 years ago on the basis of scannographic and/or histological criteria and validated at a consultation meeting on interstitial pathology according to the ATS/ERS/JRS/ALAT 2018 recommendations.

Exclusion Criteria:

- Recent rhino-bronchial infection (< 6 weeks) - Subjects on antiplatelet or other anticoagulant medication at risk of bleeding during sampling.

- Subjects with a history of clinically significant vaginal discomfort (i.e., recurrent or unconsciousness, etc.) - History of allergy or intolerance to xylocaine and/or propofol.

- History of significant epistaxis (i.e. recurrent epistaxis of any quantity or at least one severe epistaxis) - Subject at risk of difficult intubation according to the criteria of the 2006 FSSR expert conference*.

- Pregnant (a urine test will be performed for all women of childbearing age) or breastfeeding woman.

For patients :

- Long-term systemic corticosteroid therapy regardless of the reason for the prescription.

- Systemic corticosteroid therapy within the previous 3 months.

- Patient on long-term oxygen therapy.

- Chronic cardiovascular, neuro-psychic, metabolic pathology in progress, clinically significant or uncontrolled in the last 6 months.

- Other associated chronic respiratory pathology (COPD, asbestosis, bronchiectasis .

..)

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT04529993
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.	N/A
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	Centre Hospitalier Universitaire de Nice
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	Sylvie LEROY, Dr
Principal Investigator Affiliation	Centre Hospitalier Universitaire de Nice
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Other
Overall Status	Recruiting
Countries	France
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Pulmonary Disease, Chronic Obstructive, Interstitial Pulmonary Fibrosis

Arms & Interventions

Arms

Experimental: Interstitial pulmonary fibrosis

Experimental: Chronic obstructive pulmonary disease

Experimental: Healthy volunteers

Interventions

Procedure: - Bronchoscopy

Multiple level sampling of the respiratory mucosa (cytology brush and biopsies forceps)

Contact a Trial Team

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