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).
Study Type
OBSERVATIONAL
Enrollment
150
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.
Inflammatory profile at exacerbation
concentration levels of IFNg, IL-5, IL-13, IL-33, TSLP in blood and induced sputum (all concentrations expressed in pg/ml, obtained with multiplex assays) between wheeze patterns: EVW (among which SIW) vs MTW
Time frame: At the time of the inclusion
Inflammatory profile at steady state
concentration levels of IFNg, IL-5, IL-13, IL-33, TSLP in blood and induced sputum (all concentrations expressed in pg/ml, obtained with multiplex assays) between wheeze patterns: EVW (among which SIW) vs MTW
Time frame: at baseline: consult at least 8 weeks after exacerbation
Change of inflammatory profile between exacerbation and steady state
concentration levels of IFNg, IL-5, IL-13, IL-33, TSLP in blood and induced sputum (all concentrations expressed in pg/ml, obtained with multiplex assays) between wheeze patterns: EVW (among which SIW) vs MTW
Time frame: At the time of the inclusion and at baseline (consult at least 8 weeks after exacerbation)
Levels of cytokines in blood
Concentration levels of cytokines (IL-4, IL-17A, IL-22, TNF-alpha, IL-1beta, IL-6, IL-10) in blood (all concentrations expressed in pg/ml, obtained with multiplex assays) between wheeze patterns: EVW (among which SIW) vs MTW
Time frame: At the time of the inclusion and at baseline (consult at least 8 weeks after exacerbation)
Levels of cytokines in induced sputum
Concentration levels of cytokines (IL-4, IL-17A, IL-22, TNF-alpha, IL-1beta, IL-6, IL-10) in induced sputum (all concentrations expressed in pg/ml, obtained with multiplex assays) between wheeze patterns: EVW (among which SIW) vs MTW
Time frame: At the time of the inclusion and at baseline (consult at least 8 weeks after exacerbation)
Levels of interferons in blood
Concentrations levels of interferons (IFN-beta, IL-29) in blood (all concentrations expressed in pg/ml, obtained with multiplex assays) between wheeze patterns: EVW (among which SIW) vs MTW
Time frame: At the time of the inclusion and at baseline (consult at least 8 weeks after exacerbation)
Levels of interferons in induced sputum
Concentration levels of interferons (IFN-beta, IL-29) in induced sputum (all concentrations expressed in pg/ml, obtained with multiplex assays) between wheeze patterns: EVW (among which SIW) vs MTW
Time frame: At the time of the inclusion and at baseline (consult at least 8 weeks after exacerbation)
Levels of chemokines in blood
Concentration levels of chemokines (CXCL8, CXCL10, CCL5, CCL20) in blood (all concentrations expressed in pg/ml, obtained with multiplex assays) between wheeze patterns: EVW (among which SIW) vs MTW
Time frame: At the time of the inclusion and at baseline (consult at least 8 weeks after exacerbation)
Levels of chemokines in induced sputum
Concentration levels of chemokines (CXCL8, CXCL10, CCL5, CCL20) in induced sputum (all concentrations expressed in pg/ml, obtained with multiplex assays) between wheeze patterns: EVW (among which SIW) vs MTW
Time frame: At the time of the inclusion and at baseline (consult at least 8 weeks after exacerbation)
Expression patterns of mononuclear cells
Percentage of mononuclear cells in peripheral blood and sputum (sorted by flow cytometry): lymphocytes, dendritic cells, innate lymphoid cells
Time frame: At the time of the inclusion and at baseline (consult at least 8 weeks after exacerbation)
Percentage of patients with tobacco exposure
Percentage of tobacco exposure (qualitative data)
Time frame: At the time of the inclusion
Percentage of patients with mould/moisture exposure
Percentage of visible mould/moisture exposure (qualitative data, based on declaration by the parents)
Time frame: At the time of the inclusion
Percentage of patients with pet ownership
Percentage of pet ownership (qualitative data)
Time frame: At the time of the inclusion
Percentage of patients living in urban area
Percentage of urban living (qualitative data)
Time frame: At the time of the inclusion
number of asthma exacerbations in the previous year
number of asthma exacerbations in the previous year (quantitative data)
Time frame: At the time of the inclusion
Percentage of patients with associated atopic diseases
Percentage of associated atopic disorders: atopic dermatitis, atopic rhinitis, food allergy (qualitative data)
Time frame: At the time of the inclusion
Control of asthma
Control of asthma based on symptoms (breath, cough, breathlessness, impact on activity and social behavior) and previous exacerbations in the past year, and classified according to GINA criteria: well-controlled, partly controlled, uncontrolled (semi-quantitative)
Time frame: At the time of the inclusion and at baseline (consult at least 8 weeks after exacerbation)
Features of the exacerbation: severity
Severity assessed during the first hour in the emergency department (before treatment), using PRAM severity score: mild asthma (0-3), moderate asthma (4-7), severe asthma (8-12) (quantitative data)
Time frame: At the time of the inclusion
Features of the exacerbation: length
Length of stay and length of oxygen need (in days)
Time frame: At the time of the inclusion
Atopy
Atopy: positivity of skin prick tests (≥ 3 mm diameter) and/or specific IgE (≥ 0,35 ku/l), mono or polysensitized status (qualitative data)
Time frame: At the time of the inclusion and at the age of 7
Blood leukocyte count
Count of neutrophils and eosinophils (number/mm3)
Time frame: At the time of the inclusion and at the age of 7
ImmunoCAP ISAC (Thermo Fisher Scientific)
Levels of component specific IgE antibodies will be expressed in ISAC standardized units (ISU). We will categorized the raw data into 4 sIgE semiquantitative discrete groups, according to the manufacturer's guidelines: no (\<0.3 ISU), low (0.3-1 ISU), medium (1-15 ISU), and high (\>15 ISU) sensitization
Time frame: At the time of the inclusion and at the age of 7
Microbiological phenotype: viral status
Virus identification by PCR in nasal swab sample (qualitative data)
Time frame: At the time of the inclusion and at baseline (consult at least 8 weeks after exacerbation)
Microbiological phenotype: bacteriological status
Positive identification of bacteria (positive if titer \>= 10.4/ml) by culture of induced sputum (qualitative data)
Time frame: At the time of the inclusion and at baseline (consult at least 8 weeks after exacerbation)
History at the age of 7
History of asthma exacerbations in the previous year, presence of other atopic diseases: atopic dermatitis, atopic rhinitis, food allergy (qualitative data)
Time frame: At the age of 7
Control of asthma at the age of 7
Control of asthma based on symptoms (breath, cough, breathlessness, impact on activity and social behavior) and previous exacerbations in the past year, and classified according to GINA criteria: well-controlled, partly controlled, uncontrolled (semi-quantitative)
Time frame: At the age of 7
Atopy at the age of 7
Atopy: positivity of skin prick tests (≥ 3 mm diameter) and/or specific IgE (≥ 0,35 ku/l), mono or polysensitized status (qualitative data)
Time frame: At the age of 7
Lung function at the age of 7: forced expiratory volume in one second
Forced expiratory volume in one second (FEV1) after administration of short acting beta agonists, obtain with spirometry test (expressed in Z-score)
Time frame: At the age of 7
Lung function at the age of 7 : forced vital capacity
Forced vital capacity (FVC) after administration of short acting beta agonists, obtain with spirometry test (expressed in Z-score)
Time frame: At the age of 7
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