Clinical trial NCT03784781: Type 2 Innate Lymphoid Cells in Severe Pediatric Asthma
Official title: Type 2 Innate Lymphoid Cells in Severe Pediatric Asthma
Study type: OBSERVATIONAL
Overall status: WITHDRAWN
Conditions: Severe Asthma
Keywords: Severe asthma in children
Type 2 innate lymphoid cells (ILC2)
bronchial mucosa
bronchoalveolar lavages
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2018-12-24
Enrollment: 0
Sex: ALL
Minimum age (years): 6
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Minors hospitalized in the department of pediatric pulmonology and allergy of Necker Hospital

Brief summary: The main objectives of this study are to show that the number of type 2 innate lymphoid cells (ILC2) of the bronchial mucosa and in bronchoalveolar lavages (BAL) are higher in asthmatic children than in non-asthmatics, that the number of ILC2 of the bronchial mucosa and in BAL correlate with the number of bronchial and BAL eosinophils, and to determine whether there is a correlation between plasma and bronchial and BAL ILC2.

Detailed description: Severe asthma of the child is characterized by chronic eosinophilic infiltration of the bronchial mucosa associated with bronchial remodeling.

The mechanisms responsible for these phenomena are still misunderstood. Animal models suggest that type 2 innate lymphoid cells (ILC2) may be responsible for inflammation and bronchial remodeling in asthma. In mice, ILC2 stimulated by the pulmonary epithelium by viral aggression or allergenic exposure release cytokines of the TH2 type such as IL-5 and IL-13 and amphiregulin, involved in the recruitment and differentiation of eosinophils, bronchoconstriction, mucus secretion and the restoration of epithelial integrity.

In humans, ILC2 would be more abundant in the bronchoalveolar lavage (BAL) and peripheral blood of asthmatic patients compared to control subjects. However, the presence of ILC2 in the bronchial mucosa of asthmatic patients has never been identified.

The hypothesis tested is that ILC2 are more abundant in bronchial mucosa, BAL, and blood in children with severe asthma than in non-asthmatics. The results of this study would improve the knowledge of the mechanisms responsible for bronchial inflammation in asthma, consider therapies to prevent its development and modify the natural history of the disease.

The main objectives of this study are to show that the number of ILC2 in bronchial mucosa and BAL is higher in asthmatic children than in non-asthmatics, that the number of ILC2 in the bronchial mucosa and BAL is correlated with the number of eosinophils in bronchial mucosa and BAL, to determine whether the number of ILC2 in lungs correlate with asthma symptoms, and to determine whether there is a correlation between plasma and bronchial ILC2.

Bronchoscopy with BAL and bronchial mucosal biopsies will be performed in 20 children with severe asthma and 20 control subjects in the department of pediatric pulmonology and allergy of Necker Hospital.

ILC2 will be identified in the BAL, in the bronchial mucosa and peripheral blood by flow cytometry. The median values of the number of ILC2 will be compared between asthmatic and non-asthmatic patients by the Mann-Whitney non-parametric test. The correlations will be established by the Spearman rank test. A value of p \< 0.05 will be considered significant.

Eligibility criteria: Inclusion Criteria:

Controls :

* Minors aged 6 to 18 matched in age with severe asthmatic children
* Non-asthmatic children hospitalized in the department of pediatric pulmonology and allergy in Necker Hospital
* To undergo bronchial endoscopy with bronchoalveolar lavage, biopsy and blood collection

Severe asthmatic children :

* Minors aged 6 to 18
* Children hospitalized in the department of pediatric pulmonology and allergy in Necker Hospital
* To undergo bronchial endoscopy with bronchoalveolar lavage, biopsy and blood collection
* Severe uncontrolled asthma is defined by the need to maintain a treatment with high doses of inhaled corticosteroids and a long-acting bronchodilator (B2LDA) and/or an anti-leukotriene

Exclusion Criteria:

* Children with an immune deficiency, will be excluded

Primary outcomes:
measure: Number of type 2 innate lymphoid cells
timeFrame: Day 0
Secondary outcomes:
measure: Number of Eosinophils
timeFrame: Day 0
measure: Airway remodeling: reticular basement membrane thickness
timeFrame: Day 0
measure: Airway remodeling: airway smooth muscle area
timeFrame: Day 0
measure: Airway remodeling: epithelial integrity
timeFrame: Day 0
measure: Airway remodeling: vessel number
timeFrame: Day 0
measure: Airway remodeling: mucus gland area
timeFrame: Day 0
measure: Airway inflammation: bronchoalveolar lavage (BAL)
timeFrame: Day 0
measure: Airway inflammation: bronchial mucosa
timeFrame: Day 0
measure: Inflammation in blood
timeFrame: Day 0
measure: Metabolomic signature
timeFrame: Day 0
measure: Microbiota analysis
timeFrame: Day 0
Other outcomes:
Locations:
city: Paris
country: France
facility: Hôpital Necker Enfants malades
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Guillaume Lezmi, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: