Defining the Severe Paediatric Asthma Endotype

NCT04680117 | Completed

• 2 other identifiers: APHP2001352020-A00248-31
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objective of this project is to extensively characterize the endotypes of pre-schoolers (0 to 6 years) and school-age children (6 to 12 years) with SA using an integrated approach, combining a description of their phenotype (asthma symptoms, atopy, and lung function) associated with histological (airway inflammation and remodelling), immune (innate and adaptive immunity), metabolomics, and microbiota analyses. This goal shall be achieved by an unsupervised in-depth analysis of patients requiring bronchial endoscopy, with bronchial alveolar lavage (BAL) and bronchial biopsy, as part of their clinical assessment.

Conditions

Severe Asthma

Keywords

Asthma; Severe; Immunologic; Metabolomic; Microbiologic profil

Outcome Measures

Primary Outcomes (14)

• Description of the environment and smoke exposure

  Environment Living in a urban or non-urban area : n (%) Visible mold/dampness at home: n (%) Pet ownership: : n (%) Smoke exposure : n (%) Presence of pets at home : n (%)

  1 day

• Description of family atopy status

  Atopy in 1 or 2 parents or siblings: n (%) Parental asthma : n (%) Parental atopic dermatitis: n (%) Parental immediate food allergy: n (%) Parental allergic rhinitis: n (%) Asthma in siblings: n (%) Atopic dermatitis in siblings: n (%) Immediate food allergy in siblings: n (%) Allergic rhinitis in siblings: n (%)

  1 day

• Description of Demographics

  Sex male or female: n (%) Age at inclusion: y Weight (kg) Height (m) Body mass index : calculated from weight and height Atopy : n (%) Total IgE : n (%) * 1 positive allergy tests (SPT or sp IgE) to airborne allergens : n (%) * 1 positive SPT or sp IgE to food allergen: n (%) History of food allergy: n (%) History of allergic rhinitis: n (%) History of atopic dermatitis: n (%) Symptomatic gastro-oesophageal reflux: n (%)

  1 day

• Description of Asthma history in the past year

  No of severe exacerbations : n ≥ 2 or 3 severe exacerbations: n (%) No. of cumulated days of oral steroids: n No. of emergency visits for acute asthma : n Asthma control ACT score : n

  1 day

• Description of Lung function

  Lung function FEV1 pre-BD (% predicted) FEV1 post-BD (% predicted) FEV1 pre-BD (Zscore) FEV1 post-BD (Zscore) FEV1/FVC pre-BD (%) FEV1/FVC post-BD (%) FEV1/FVC pre-BD (Zscore) FEV1/FVC post-BD (Zscore) Post BD FEV1 reversibility (%) No of patients with reversibility : n (%) FeNO (ppb) Asthma therapy ICS : (%) ICS doses : µg/day. eq Budesonide ICS + LABA : n (%) Leukotriene modifier : n (%) Maintenance oral corticosteroids: n (%) Immunotherapy: n (%) Omalizumab or biologics: n (%)

  1 day

• Description of Asthma therapy

  ICS : (%) ICS doses : µg/day. eq Budesonide ICS + LABA : n (%) Leukotriene modifier : n (%) Maintenance oral corticosteroids: n (%) Immunotherapy: n (%) Omalizumab or biologics: n (%)

  1 day

• Description of Airway remodeling

  reticular basement membrane thickness expressed in µm; airway smooth muscle area ; epithelial integrity; vessel number; mucus gland area

  1 day

• Description of inflammatory and histological features in bronchoalveolar lavages (BAL)

  Number of eosinophils, neutrophils, macrophages, basophils, lymphocytes expressed as percentage of total cells in BAL

  1 day

• Description of inflammatory and histological features in bronchial mucosa

  Number of eosinophils, neutrophils, macrophages, basophils, lymphocytes expressed per square millimeters of submucosal area

  1 day

• Bronchial mucosa analysis

  The number of IgE stained with anti-IgE Ab in the submucosa and the epithelium will be assessed and expressed per square millimeters of submucosal area The expression of cytokines in the mucosa will be assessed by multiplex and expressed in pg/ml or ng/ml. Quantify by quantitative PCR mRNA encoding cytokines, chemokines and others immune activation markers as relative mRNA levels.

  1 day

• BAL analysis

  The number of mast cells, lymphocytes, innate lymphoid cells, mucosalassosiated invariant T (MAIT) cells, gammadelta T cells expressed as percentage of total cells in BAL, concentrations of Immunoglobulins G, E, M will be assessed and express in Ku/L The expression of cytokines will be assessed by multiplex and expressed in pg/ml or ng/ml.

  1 day

• Blood analysis

  Number of eosinophils, neutrophils, macrophages, basophils, lymphocytes, innate lymphoid cells expressed as percentage of total cells in blood; number of mucosal associated invariant T (MAIT) cells will be assessed and expressed as percentage of total cells and T cells in blood The number of invariant natural killer T cells will be assessed and expressed as percentage of total cells and T cells in blood The number of gammadelta T cells will be assessed and expressed as percentage of total cells and T cells in blood The concentrations of Immunoglobulins G, E, M will be assessed and express in Ku/L The expression of cytokines will be assessed by multiplex and expressed in pg/ml or ng/ml.

  1 day

• Metabolomic signature

  The global concentration of metabolites is first expressed as the signal intensity compared to internal controls. When metabolites are identified, they are quantified and their concentration expressed as pg/ml.

  1 day

• Microbiota analysis

  Quantify by quantitative PCR mRNA and DNA encoding as relative mRNA and DNA levels

  1 day

Secondary Outcomes (9)

• Cluster analysis

  1 year

• Number of severe exacerbations in the 12 months following the inclusion

  1 year

• Asthma Control Test (ACT) score 12 months after inclusion

  1 year

• Asthma control 12 months after inclusion

  1 year

• Description of lung function 12 months after the inclusion

  1 year

Study Arms (2)

Cases with SA, classified by age group

OTHER

Patient hospitalized for assessment of severe asthma

Other: Blood collection; Other: Saliva sample; Other: Nasal

Controls among children w/ SA: frequent&infrequent exacerbators

OTHER

Frequent exacerbators have 2 or more asthma severe exacerbations in the past years

Other: Blood collection; Other: Saliva sample; Other: Nasal

Interventions

Blood collection OTHER

Blood collection with samples of 15ml max by subject (case or control) at J0, M6 and M12: * subject less than 5 kg : 1.8 to 4.5 ml max * subject 5 kg to 10 kg : 4.5 to 9 ml max * subject 10 kg to 15 kg : 9 to 13.5 ml * subject 15 kg to 20 kg : 13.5 to 15 ml max

Cases with SA, classified by age group; Controls among children w/ SA: frequent&infrequent exacerbators

Saliva sample OTHER

Saliva sample by subject at J0

Cases with SA, classified by age group; Controls among children w/ SA: frequent&infrequent exacerbators

Nasal OTHER

Nasal brushing by subject at J0

Cases with SA, classified by age group; Controls among children w/ SA: frequent&infrequent exacerbators

Eligibility Criteria

• Age: Up to 12 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Minors aged 0 to 6 years or 6 to 12 years, hospitalized for assessment of Severe Asthma
• Minors need with his follow-up an bronchial endoscopy with realization of LBA and biopsies of bronchial mucosa
• Social insurance affiliation, except AME
• Parents or legal guardians signed the Informed consent form
• Minors aged 0 to 6 years or 6 to 12 years, hospitalized for assessment of severe respiratory syndrome except severe asthma
• Minors need with his follow-up an bronchial endoscopy with realization of LBA and biopsies of bronchial mucosa
• Social insurance affiliation, except AME
• Parents or legal guardians signed the Informed consent form

You may not qualify if:

• Prematurity (\<37 weeks gestation)
• Broncho-pulmonary dysplasia, immune deficits, non-Severe Asthma bronchopathies, cystic fibrosis, heart disease, ongoing biotherapy

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead
• URC-CIC Paris Descartes Necker Cochin: collaborator

Study Sites (1)

Name: Hôpital Necker-Enfants Malades

Paris, 75015, France

Location

MeSH Terms

Conditions

Asthma; Lymphoma, Follicular

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Guillaume Lezmi, Doctor (PHU)

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 14, 2020
• First Posted: December 22, 2020
• Study Start: June 15, 2021
• Primary Completion: April 24, 2025
• Study Completion: April 24, 2025
• Last Updated: May 6, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)