Respiratory Dysbiosis in Preschool Children With Asthma: Predictive of a Severe Form

Asthma in Children Clinical Trial

— DREAM  

Official title:

Respiratory Dysbiosis in Preschool Children With Asthma: Predictive of a Severe Form

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05192499
• Other study ID #: 29BRC21.0252
• Status: Recruiting
• Phase: N/A
• Start date: February 4, 2022
• Est. completion date: February 4, 2028

Study information

• Verified date: July 2023
• Source: University Hospital, Brest
• Contact: Pierrick CROS
• Phone: 02 98 22 36 59
• Email: pierrick.cros[@]chu-brest.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The prevalence of asthma in preschool children is between 11 and12%. Inhaled corticosteroid therapy is the main therapy used, however this treatment seems insufficiently effective in some children.

Recent research in cystic fibrosis has made it possible to highlight pulmotypes corresponding to the different stages of pulmonary dysbiosis, and a predictive microbiological signature of an increased risk of early primocolonization to P. aeruginosa. These pulmotypes are the result of the so-called "enterotyping" analysis, a biostatistical method that makes it possible to stratify individuals according to the analysis of the microbiota. In the light of these data, it seems interesting to transcribe the concept of using a biomarker of the microbiota in the monitoring of a chronic lung disease such as asthma.

The hypothesis is that there is respiratory dysbiosis causing corticosteroid resistance to treatment in children under 3 years of age with severe asthma.

Description:

The prevalence of asthma in preschool children is estimated to between 11 and 12%.

Inhaled corticosteroid therapy is the main therapy used, however this treatment seems insufficiently effective in some children.

Recent research in cystic fibrosis has made it possible to highlight pulmotypes corresponding to the different stages of pulmonary dysbiosis, and a predictive microbiological signature of an increased risk of early primocolonization to P. aeruginosa. These pulmotypes are the result of the so-called "enterotypeing" analysis, a biostatistical method that makes it possible to stratify individuals according to the analysis of the microbiota. In the light of these data, it seems interesting to transcribe the concept of using a biomarker of the microbiota in the monitoring of a chronic lung disease such as asthma.

The hypothesis is that there is respiratory dysbiosis causing corticosteroid resistance to treatment in children under 3 years of age with severe asthma.

The goal of this study is to research a difference between respiratory dysbiosis and severe asthma (i.e. resistant to doses of inhaled corticosteroids less than or equal to 200μg of fluticasone equivalent).

DREAM is a exploratory multicentric prospective case-control study.

The primary objective is to research a difference between respiratory dysbiosis and severe asthma (i.e. resistant to doses of inhaled corticosteroids less than or equal to 200μg of fluticasone equivalent) in children less than 36 months of age.

The secondary objectives are :

1. To compare the bacterial pulmotypes of children under 36 months of age with severe asthma with children with mild or moderate asthma.

2. To look for microbial biomarkers associated with corticosteroid resistance

3. To assess the association between digestive dysbiosis and severe asthma (i.e. resistant to inhaled corticosteroid doses less than or equal to 200μg fluticasone equivalent)

4. To look for an association between digestive dysbiosis and respiratory dysbiosis

5. To constitute a biocollection (sputum, stool, blood) of children with asthma for future analysis

30 patients are expected to be included in two arms : 15 uncontrolled asthmatic patients at moderate doses of inhaled corticosteroids and 15 asthmatic patients controlled at mild to moderate doses of inhaled corticosteroids.

Inclusion period : 12 months. Duration of patient's participation: 6 years Total study duration: 7 years

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: February 4, 2028
• Est. primary completion date: February 4, 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year to 3 Years

Eligibility

Inclusion Criteria:

• Age greater than 1 year and less than 3 years

• Diagnosis of asthma by a pediatrician

• Parental consent

• Affiliation to the social security system

Exclusion Criteria:

• Chronic pathologies: congenital heart disease, immune deficiency, cystic fibrosis, bronchopulmonary dysplasia, encephalopathy, primary ciliary dyskinesia, laryngomalacia, digestive pathology requiring digestive surgery

• Premature < 34 SA

• Recent antibiotic therapy (< 7 days)

• Treatment with oral corticosteroid therapy within the previous 10 days.

• Patient whose parent(s) is (are) minor(s)

Related Conditions & MeSH terms

• Asthma
• Asthma in Children
• Dysbiosis

Intervention

Procedure:
• Stool test
At inclusion (day 0), stools will be collected with a kit for to remove to 5 mg for each patient.
• Blood test
Blood sample taken during inclusion (day 0) will be collected. There is between 19 and 26 mL for each patient.
• Induced sputum
At inclusion (day 0), bronchial aspiration after inhalation induction of 4 mL of 6% salt serum administered (after 200 µg of salbutamol via an inhalation chamber during a bronchial drainage session).
• nasale virology
At inclusion (Day 0), patients will be taken nasal swab for virology with swab adapted for nasal swab or with suction trap when blowing the child's nose (depending on center practice)and multiplex PCR.

Locations

Country	Name	City	State
France	CHU de Brest	Brest	Finistère

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Brest

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of species in the microbial Community	The main evaluation is the comparison of respiratory biodiversity assessed using quantitative indices such as alpha diversity. Alpha diversity calculates the richness (number of species or OTU) by samples and how these OTUs are distributed (equitability). Richness will be measured with the Chao1 and equity with the Simpson index. The Shannon index is a composite measurethat allows us to have both information together, richness and equity in the same index.	Day 0
Primary	Index of microbial similarity of samples	The main evaluation is the comparison of respiratory biodiversity assessed using quantitative indices such beta diversity. Beta diversity analysis allows samples to be compared with each other. It calculates a matrix of distances between samples with the Bray Curtis/ Unifrac methods, weighted or not/ Jaccard by presence/absence. Next, the Principal Coordinate Analysis (PCoA ) will be used, multidimensional scaling to reduce this matrix to 2/3 dimensions. The samples from similar groups look alike with this analysis will be used.	Day 0
Secondary	Enterotyping analysis	Characterization of bacterial pulmotypes by so-called "enterotyping" analysis in asthmatic children under 36 months of age. The enterotyping technique is a multifactorial technique that aims to group species / OTUs regularly found together. Enterotypes can characterize states of health or dysbiosis in the lung or intestines. OTU groups are used to classify individuals according to their lung / intestinal bacteria. The enterotypes / pulmotypes are considered already present in the literature and use PCA-type analyses to identify these groups of OTUs.	Day 0
Secondary	Relative abundance	Relative abundance (expressed as a percentage) of each of the identified bacteriological taxa	Day 0
Secondary	Indices of diversity	Types of indices of diversity of bacterial taxa identified in the digestive microbiota	Day 0