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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

Status
Active, not recruiting
Phases
Unknown
Study type
Observational
Source
ClinicalTrials.gov
Registry ID
NCT03960359
Acronym
VIRASTHMA2
Enrollment
150
Registered
2019-05-23
Start date
2015-02-24
Completion date
2033-02-28
Last updated
2025-12-16

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Asthma

Keywords

Asthma, wheeze, preschool, phenotype

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).

Interventions

OTHERClinical, 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.

Sponsors

Région Nord-Pas de Calais, France
CollaboratorOTHER
Stallergenes Greer
CollaboratorINDUSTRY
University Hospital, Lille
Lead SponsorOTHER

Study design

Observational model
COHORT
Time perspective
PROSPECTIVE

Eligibility

Sex/Gender
ALL
Age
1 Years to 5 Years
Healthy volunteers
No

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

Design outcomes

Primary

MeasureTime frameDescription
Inflammatory profile at exacerbationAt the time of the inclusionconcentration 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

Secondary

MeasureTime frameDescription
Change of inflammatory profile between exacerbation and steady stateAt the time of the inclusion and at baseline (consult at least 8 weeks after 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
Levels of cytokines in bloodAt the time of the inclusion and at baseline (consult at least 8 weeks after exacerbation)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
Levels of cytokines in induced sputumAt the time of the inclusion and at baseline (consult at least 8 weeks after exacerbation)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
Levels of interferons in bloodAt the time of the inclusion and at baseline (consult at least 8 weeks after exacerbation)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
Levels of interferons in induced sputumAt the time of the inclusion and at baseline (consult at least 8 weeks after exacerbation)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
Levels of chemokines in bloodAt the time of the inclusion and at baseline (consult at least 8 weeks after exacerbation)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
Levels of chemokines in induced sputumAt the time of the inclusion and at baseline (consult at least 8 weeks after exacerbation)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
Expression patterns of mononuclear cellsAt the time of the inclusion and at baseline (consult at least 8 weeks after exacerbation)Percentage of mononuclear cells in peripheral blood and sputum (sorted by flow cytometry): lymphocytes, dendritic cells, innate lymphoid cells
Percentage of patients with tobacco exposureAt the time of the inclusionPercentage of tobacco exposure (qualitative data)
Percentage of patients with mould/moisture exposureAt the time of the inclusionPercentage of visible mould/moisture exposure (qualitative data, based on declaration by the parents)
Percentage of patients with pet ownershipAt the time of the inclusionPercentage of pet ownership (qualitative data)
Percentage of patients living in urban areaAt the time of the inclusionPercentage of urban living (qualitative data)
number of asthma exacerbations in the previous yearAt the time of the inclusionnumber of asthma exacerbations in the previous year (quantitative data)
Inflammatory profile at steady stateat baseline: consult at least 8 weeks after exacerbationconcentration 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
Control of asthmaAt the time of the inclusion and at baseline (consult at least 8 weeks after exacerbation)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)
Features of the exacerbation: severityAt the time of the inclusionSeverity 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)
Features of the exacerbation: lengthAt the time of the inclusionLength of stay and length of oxygen need (in days)
AtopyAt the time of the inclusion and at the age of 7Atopy: positivity of skin prick tests (≥ 3 mm diameter) and/or specific IgE (≥ 0,35 ku/l), mono or polysensitized status (qualitative data)
Blood leukocyte countAt the time of the inclusion and at the age of 7Count of neutrophils and eosinophils (number/mm3)
ImmunoCAP ISAC (Thermo Fisher Scientific)At the time of the inclusion and at the age of 7Levels 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
Microbiological phenotype: viral statusAt the time of the inclusion and at baseline (consult at least 8 weeks after exacerbation)Virus identification by PCR in nasal swab sample (qualitative data)
Microbiological phenotype: bacteriological statusAt the time of the inclusion and at baseline (consult at least 8 weeks after exacerbation)Positive identification of bacteria (positive if titer \>= 10.4/ml) by culture of induced sputum (qualitative data)
History at the age of 7At the age of 7History of asthma exacerbations in the previous year, presence of other atopic diseases: atopic dermatitis, atopic rhinitis, food allergy (qualitative data)
Control of asthma at the age of 7At the age of 7Control 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)
Atopy at the age of 7At the age of 7Atopy: positivity of skin prick tests (≥ 3 mm diameter) and/or specific IgE (≥ 0,35 ku/l), mono or polysensitized status (qualitative data)
Lung function at the age of 7: forced expiratory volume in one secondAt the age of 7Forced expiratory volume in one second (FEV1) after administration of short acting beta agonists, obtain with spirometry test (expressed in Z-score)
Lung function at the age of 7 : forced vital capacityAt the age of 7Forced vital capacity (FVC) after administration of short acting beta agonists, obtain with spirometry test (expressed in Z-score)
Percentage of patients with associated atopic diseasesAt the time of the inclusionPercentage of associated atopic disorders: atopic dermatitis, atopic rhinitis, food allergy (qualitative data)

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026