Inflammatory and Immune Profiles During a Severe Exacerbation in Preschool Asthmatic Children (<5 Years)

Inflammatory and Immune Profiles at the Time of a Severe Exacerbation in Preschool Asthmatic Children (<5 Years), According to the Phenotype

Asthma/wheeze begins in the first years of life and is the most common chronic disease in preschool children (< 5 years).

Different phenotypes have been suggested: Episodic-Viral Wheeze (EVW), absence of symptoms between exacerbations, among which Severe Intermittent Wheeze (SIW); and Multiple-trigger wheeze (MTW). The determinants of these different clinical phenotypes and their evolution have been poorly studied.

The purpose of this study is to assess preschool wheezers at the time of a severe exacerbation: clinical features and biological determinants (virus/bacteria, molecules and cells involved in the inflammation) and at steady state (8 weeks later) and to follow them up until the age of 7. The investigators hypothesize that the nature of the inflammation at the time of the exacerbation is different between these clinical phenotypes and may be associated with different clinical and functional trajectories

Asthma/wheeze begins in the first years of life and is the most common chronic disease in preschool children (< 5 years).

Different phenotypes have been suggested: Episodic-Viral Wheeze (EVW): wheezing during discrete time periods (exacerbations), absence of symptoms between exacerbations; among which Severe Intermittent Wheeze (SIW): EVW with ≥ 2 exacerbations over the last 6 months; and Multiple-trigger wheeze (MTW): wheezing during exacerbations but also symptoms (cough, exercise-induced symptoms,…) between episodes. The determinants of these different clinical phenotypes and their evolution have been poorly studied.

The purpose of this study is to assess preschool asthmatic children at the time of a severe exacerbation: clinical features and biological determinants (virus/bacteria, molecules and cells involved in the inflammation) and at steady state (8 weeks later) and to follow them up until the age of 7. The investigators hypothesize that the nature of the inflammation at the time of the exacerbation is different between these clinical phenotypes and may be associated with different clinical and functional trajectories.

The primary objective is to compare levels of IFNg, IL-5, IL-13, IL-33, TSLP in blood and induced sputum between the 2 main phenotypes: EVW and MTW.

Preschool asthmatic children hospitalized for a severe exacerbation (requiring a course of systemic steroids) are included in a pediatric ward of one of the hospitals involved in the study, in the Hauts-de-France Region, France.

Clinical phenotype: temporal pattern of wheeze (EVW, SIW, MTW), history and clinical data, allergy diagnosis work-up Microbiological phenotype: viral status (PCR in nasal swab sample), bacteriological status (culture of induced sputum) Inflammatory phenotype: profile of cytokines, phenotype of immune cells in the blood and the sputum, cytokine response to TLR ligands by peripheral blood mononuclear cells will be assessed at the time of inclusion and at steady state 8 weeks later.

Children will be follow-up until the age of 7 (clinical data, control of asthma, lung function).

Inclusion Criteria:

• Preschool children aged 1 to < 5 years
• Asthmatic / recurrent wheezers (≥ 3 discrete exacerbations since birth and/or symptoms between exacerbations, according to the definition from the French HAS and GINA guidelines)
• Hospitalized (less than 3 days ago) for a severe exacerbation (requiring a course of oral steroids)
• In a pediatric ward participating in the study (Hospital centers of Lille, Arras, Bethune, Douai, Lens, Roubaix, Tourcoing, Armentieres, Seclin)
• Parental consent

Exclusion Criteria:

• History of chronic disease (other than asthma)
• History of preterm birth (inf 36 weeks of amenorrhea)
• Lack of understanding from the parents