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

Asthma Clinical Trial

— VIRASTHMA2  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03960359
• Other study ID #: 2014_20
• Secondary ID: 2014-A01687-40
• Status: Active, not recruiting
• Start date: February 24, 2015
• Est. completion date: February 2025

Study information

• Verified date: September 2020
• Source: University Hospital, Lille
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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

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).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 150
• Est. completion date: February 2025
• Est. primary completion date: February 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year to 5 Years

Eligibility

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

Related Conditions & MeSH terms

• Asthma

Intervention

Other:
• Clinical, microbiological and inflammatory phenotype
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.

Locations

Country	Name	City	State
n/a

Sponsors (3)

Lead Sponsor	Collaborator
University Hospital, Lille	Région Nord-Pas de Calais, France, Stallergenes Greer

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	At the time of the inclusion
Secondary	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	at baseline: consult at least 8 weeks after exacerbation
Secondary	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	At the time of the inclusion and at baseline (consult at least 8 weeks after exacerbation)
Secondary	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	At the time of the inclusion and at baseline (consult at least 8 weeks after exacerbation)
Secondary	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	At the time of the inclusion and at baseline (consult at least 8 weeks after exacerbation)
Secondary	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	At the time of the inclusion and at baseline (consult at least 8 weeks after exacerbation)
Secondary	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	At the time of the inclusion and at baseline (consult at least 8 weeks after exacerbation)
Secondary	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	At the time of the inclusion and at baseline (consult at least 8 weeks after exacerbation)
Secondary	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	At the time of the inclusion and at baseline (consult at least 8 weeks after exacerbation)
Secondary	Expression patterns of mononuclear cells	Percentage of mononuclear cells in peripheral blood and sputum (sorted by flow cytometry): lymphocytes, dendritic cells, innate lymphoid cells	At the time of the inclusion and at baseline (consult at least 8 weeks after exacerbation)
Secondary	Percentage of patients with tobacco exposure	Percentage of tobacco exposure (qualitative data)	At the time of the inclusion
Secondary	Percentage of patients with mould/moisture exposure	Percentage of visible mould/moisture exposure (qualitative data, based on declaration by the parents)	At the time of the inclusion
Secondary	Percentage of patients with pet ownership	Percentage of pet ownership (qualitative data)	At the time of the inclusion
Secondary	Percentage of patients living in urban area	Percentage of urban living (qualitative data)	At the time of the inclusion
Secondary	number of asthma exacerbations in the previous year	number of asthma exacerbations in the previous year (quantitative data)	At the time of the inclusion
Secondary	Percentage of patients with associated atopic diseases	Percentage of associated atopic disorders: atopic dermatitis, atopic rhinitis, food allergy (qualitative data)	At the time of the inclusion
Secondary	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)	At the time of the inclusion and at baseline (consult at least 8 weeks after exacerbation)
Secondary	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)	At the time of the inclusion
Secondary	Features of the exacerbation: length	Length of stay and length of oxygen need (in days)	At the time of the inclusion
Secondary	Atopy	Atopy: positivity of skin prick tests (= 3 mm diameter) and/or specific IgE (= 0,35 ku/l), mono or polysensitized status (qualitative data)	At the time of the inclusion and at the age of 7
Secondary	Blood leukocyte count	Count of neutrophils and eosinophils (number/mm3)	At the time of the inclusion and at the age of 7
Secondary	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	At the time of the inclusion and at the age of 7
Secondary	Microbiological phenotype: viral status	Virus identification by PCR in nasal swab sample (qualitative data)	At the time of the inclusion and at baseline (consult at least 8 weeks after exacerbation)
Secondary	Microbiological phenotype: bacteriological status	Positive identification of bacteria (positive if titer >= 10.4/ml) by culture of induced sputum (qualitative data)	At the time of the inclusion and at baseline (consult at least 8 weeks after exacerbation)
Secondary	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)	At the age of 7
Secondary	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)	At the age of 7
Secondary	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)	At the age of 7
Secondary	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)	At the age of 7
Secondary	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)	At the age of 7