Clinical trial NCT03960359: Inflammatory and Immune Profiles During a Severe Exacerbation in Preschool Asthmatic Children (<5 Years)
Official title: Inflammatory and Immune Profiles at the Time of a Severe Exacerbation in Preschool Asthmatic Children (<5 Years), According to the Phenotype
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Asthma
Keywords: Asthma
wheeze
preschool
phenotype
Lead sponsor: University Hospital, Lille
Sponsor class: OTHER
Collaborators: name: Région Nord-Pas de Calais, France
name: Stallergenes Greer
First posted: 2019-05-23
Enrollment: 150
Sex: ALL
Minimum age (years): 1
Maximum age (years): 5
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Preschool asthmatic children hospitalized for a severe exacerbation (requiring a course of systemic steroids), in a pediatric ward of one of the hospitals involved in the study, in the Hauts-de-France Region, France.

Brief summary: 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

Detailed description: 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).

Eligibility criteria: 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

Primary outcomes:
measure: Inflammatory profile at exacerbation
timeFrame: At the time of the inclusion
Secondary outcomes:
measure: Inflammatory profile at steady state
timeFrame: at baseline: consult at least 8 weeks after exacerbation
measure: Change of inflammatory profile between exacerbation and steady state
timeFrame: At the time of the inclusion and at baseline (consult at least 8 weeks after exacerbation)
measure: Levels of cytokines in blood
timeFrame: At the time of the inclusion and at baseline (consult at least 8 weeks after exacerbation)
measure: Levels of cytokines in induced sputum
timeFrame: At the time of the inclusion and at baseline (consult at least 8 weeks after exacerbation)
measure: Levels of interferons in blood
timeFrame: At the time of the inclusion and at baseline (consult at least 8 weeks after exacerbation)
measure: Levels of interferons in induced sputum
timeFrame: At the time of the inclusion and at baseline (consult at least 8 weeks after exacerbation)
measure: Levels of chemokines in blood
timeFrame: At the time of the inclusion and at baseline (consult at least 8 weeks after exacerbation)
measure: Levels of chemokines in induced sputum
timeFrame: At the time of the inclusion and at baseline (consult at least 8 weeks after exacerbation)
measure: Expression patterns of mononuclear cells
timeFrame: At the time of the inclusion and at baseline (consult at least 8 weeks after exacerbation)
measure: Percentage of patients with tobacco exposure
timeFrame: At the time of the inclusion
measure: Percentage of patients with mould/moisture exposure
timeFrame: At the time of the inclusion
measure: Percentage of patients with pet ownership
timeFrame: At the time of the inclusion
measure: Percentage of patients living in urban area
timeFrame: At the time of the inclusion
measure: number of asthma exacerbations in the previous year
timeFrame: At the time of the inclusion
measure: Percentage of patients with associated atopic diseases
timeFrame: At the time of the inclusion
measure: Control of asthma
timeFrame: At the time of the inclusion and at baseline (consult at least 8 weeks after exacerbation)
measure: Features of the exacerbation: severity
timeFrame: At the time of the inclusion
measure: Features of the exacerbation: length
timeFrame: At the time of the inclusion
measure: Atopy
timeFrame: At the time of the inclusion and at the age of 7
measure: Blood leukocyte count
timeFrame: At the time of the inclusion and at the age of 7
measure: ImmunoCAP ISAC (Thermo Fisher Scientific)
timeFrame: At the time of the inclusion and at the age of 7
measure: Microbiological phenotype: viral status
timeFrame: At the time of the inclusion and at baseline (consult at least 8 weeks after exacerbation)
measure: Microbiological phenotype: bacteriological status
timeFrame: At the time of the inclusion and at baseline (consult at least 8 weeks after exacerbation)
measure: History at the age of 7
timeFrame: At the age of 7
measure: Control of asthma at the age of 7
timeFrame: At the age of 7
measure: Atopy at the age of 7
timeFrame: At the age of 7
measure: Lung function at the age of 7: forced expiratory volume in one second
timeFrame: At the age of 7
measure: Lung function at the age of 7 : forced vital capacity
timeFrame: At the age of 7
Other outcomes:
Locations:
Study officials:
affiliation: University Hospital, Lille
name: Antoine Deschildre, MD
role: PRINCIPAL_INVESTIGATOR
References: