Type 2 Innate Lymphoid Cells in Severe Pediatric Asthma

Assistance Publique - Hôpitaux de Paris

Overview

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.

Study Type

OBSERVATIONAL

Conditions

Severe Asthma

Interventions

BiopsyBIOLOGICAL

Mucosal biopsies under general anesthesia of the segmental bronchi of the right or left lower lobe

Blood collectionBIOLOGICAL

Blood collection (+15mL/ current care)

Bronchoalveolar lavageBIOLOGICAL

Bronchoalveolar lavage fluid (3mL/Kg)

Eligibility

Sex: ALLMin age: 6 YearsMax age: 18 Years

Medical Language ↔ Plain English

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

Locations (1)

Hôpital Necker Enfants malades

Paris, France

Outcomes

Primary Outcomes

Number of type 2 innate lymphoid cells

Type 2 innate lymphoid cells

Time frame: Day 0

Secondary Outcomes

Number of Eosinophils

Eosinophils

Time frame: Day 0

Airway remodeling: reticular basement membrane thickness

Reticular basement membrane thickness will be expressed in µm.

Time frame: Day 0

Airway remodeling: airway smooth muscle area

The percentage of the submucosa occupied by airway smooth muscle will be determined on hematoxylin-eosin-stained and anti-airway smooth muscle antibody treated sections, respectively. The bundles of airway smooth muscle will be enclosed by a line and the area they occupied will be calculated by image analysis. The airway smooth muscle area will be expressed as the percentage of surface of the submucosa occupied by airway smooth muscle.

Time frame: Day 0

Airway remodeling: epithelial integrity

Epithelial integrity will be defined as the percentage of the total length of epithelium that will be intact.

Time frame: Day 0

Airway remodeling: vessel number

The number of vessels stained with anti-CD31 mAb will be determined from at least one grid (0.1 mm2) per biopsy, and reported as the median number of positive sections per 0.1 mm2.

Time frame: Day 0

Airway remodeling: mucus gland area

The percentage of the submucosa occupied by mucus gland will be determined on hematoxylin-eosin-stained and anti-airway smooth muscle antibody treated sections, respectively. The mucus glands will be enclosed by a line and the area occupied will be calculated by image analysis. The mucus gland area will be expressed as the percentage of surface of the submucosa occupied by mucus gland.

Data from ClinicalTrials.gov

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