Type 2 Innate Lymphoid Cells in Severe Pediatric Asthma

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.

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