Defining the Severe Paediatric Asthma Endotype

NCT ID: NCT04680117

Last Updated: 2022-10-31

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 150 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-06-15
• Study Completion Date: 2025-01-31

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.

Detailed Description

Asthma is a chronic disease affecting approximately 235 million people worldwide, and the number is rising. Asthma is not just a public health problem for developed countries; its incidence is also elevated in developing countries. Asthma concerns all age groups, but often starts in childhood. SA in children is infrequent, affecting 2-5% of the asthmatic paediatric population. Children with SA experience frequent SA attacks and have a reduced quality of life . They account for approximately half of the asthma healthcare costs. Asthma has long been thought to be a single disease but is now considered to encompass various conditions characterized by the same symptoms (wheeze, cough, shortness of breath, chest tightness), variable degrees of airflow limitation, and different pattern of inflammation. Recent studies highlighted the heterogeneity of asthma, and the potential influence of various pathogenic mechanisms, including airway inflammation, remodelling, and immune and metabolic pathways in a specific microbial environment. However, there is very little data concerning the pathological process, especially in children. Most of the data describing different asthma endotypes in children are derived from large observational prospective cohorts. Although very informative, these studies were designed to analyse a small number of easily measured parameters, mainly lung function and atopy. The complexity of asthma pathogenesis was therefore underestimated and the individuals' specificities only partially considered. In clinical practice, children with SA require an endoscopy, with broncho-alveolar lavage fluids (BALF) collection and bronchial biopsies to exclude a differential diagnosis and assess airway inflammation and remodelling. This approach also underestimates other components of the endotypes and results in "one size fits all" management based on high doses of inhaled steroids and the use of expensive biotherapy, such as anti-IgE therapy. Thus, although hospital admission and mortality ratesfor asthma decreased until the early 2000's, they have remained stable over the past 10 years. It is therefore imperative to develop new approaches that incorporate relevant parameters analysed in the airways. This project proposes an in-depth analysis, not only of clinical and functional parameters, but also of immune cells, metabolomic compounds, and microbiota present in the airways of asthmatic children.

The primary objective of the 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. The main hypothesis is that the complementarity of those approaches will allow investigators to delineate the immune and metabolic pathways and microbiota involved in children with SA. The secondary objectives are to: (1) cluster all data obtained to define new patient groups and develop biomarkers that summarise the different clusters; (2) determine the immune, metabolomic, and microbiota profile of these children to aid future fundamental research that will focus on dissecting new mechanisms involved in paediatric asthma; (3) determine whether pre-schoolers and school-age children with SA share common endotypic features; and (4) establish the basis for the prospective follow-up of patients to identify endotypes that predict asthma persistence throughout childhood, severity, and response to treatment.

Conditions

Severe Asthma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

Cases with SA, classified by age group

Patient hospitalized for assessment of severe asthma

Group Type: OTHER

Blood collection

Intervention Type: 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

Saliva sample

Intervention Type: OTHER

Saliva sample by subject at J0

Nasal

Intervention Type: OTHER

Nasal brushing by subject at J0

Controls among children w/ SA: frequent&infrequent exacerbators

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

Group Type: OTHER

Blood collection

Intervention Type: 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

Saliva sample

Intervention Type: OTHER

Saliva sample by subject at J0

Nasal

Intervention Type: OTHER

Nasal brushing by subject at J0

Interventions

Blood collection

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

Intervention Type: OTHER

Saliva sample

Saliva sample by subject at J0

Intervention Type: OTHER

Nasal

Nasal brushing by subject at J0

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

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

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

Sponsors

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Guillaume Lezmi, Doctor (PHU)

Role: PRINCIPAL_INVESTIGATOR

Assistance Publique - Hôpitaux de Paris

Locations

Name: Hôpital Necker-Enfants Malades

Paris, , France

Site Status: RECRUITING

Countries

France

Central Contacts

Guillaume Lezmi, Doctor (PHU)

Role: CONTACT

guillaume.lezmi@aphp.fr

+33 1 44 49 48 38

Sandra Colas

Role: CONTACT

sandra.colas@aphp.fr

+33 1 71 19 64 32

Facility Contacts

Guillaume Lezmi, Doctor (PHU)

Role: primary

guillaume.lezmi@aphp.fr

+33 1 44 49 48 38

Other Identifiers

2020-A00248-31

Identifier Type: OTHER

Identifier Source: secondary_id

APHP200135

Identifier Type: -

Identifier Source: org_study_id