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

NCT05192499 | Recruiting

• 1 other identifier: 29BRC21.0252
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Asthma in Children; Dysbiosis

Keywords

Paediatric Pulmonology; asthma; respiratory microbiome

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (3)

• Enterotyping analysis

  Day 0

• Relative abundance

  Day 0

• Indices of diversity

  Day 0

Study Arms (2)

Case

OTHER

Patients aged to 1 to 3 years with severe asthma (i.e. resistant to inhaled corticosteroid doses less than or equal to 200μg fluticasone equivalent). "Severe" asthma patients (cases) are defined by poor asthma control under doses of inhaled corticosteroids ≤200μg fluticasone equivalent.

Procedure: Stool test; Procedure: Blood test; Procedure: Induced sputum; Procedure: nasale virology

Control

OTHER

Patients aged to 1 to 3 years with low or moderate asthma (controlled with mild to moderate doses of inhaled corticosteroids less than or equal to 200μg of fluticasone equivalent). "Mild to moderate" asthma patients (controls) are defined by disease control by first-line treatment in asthma, i.e. corticosteroids inhaled at mild to moderate doses of ≤200 micrograms/day of fluticasone equivalent.

Procedure: Stool test; Procedure: Blood test; Procedure: Induced sputum; Procedure: nasale virology

Interventions

Stool test PROCEDURE

At inclusion (day 0), stools will be collected with a kit for to remove to 5 mg for each patient.

Case; Control

Blood test PROCEDURE

Blood sample taken during inclusion (day 0) will be collected. There is between 19 and 26 mL for each patient.

Case; Control

Induced sputum PROCEDURE

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).

Case; Control

nasale virology PROCEDURE

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.

Case; Control

Eligibility Criteria

• Age: 1 Year - 3 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Age greater than 1 year and less than 3 years
• Diagnosis of asthma by a pediatrician
• Parental consent
• Affiliation to the social security system

You may not qualify if:

• 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)

Sponsors & Collaborators

• University Hospital, Brest: lead

Study Sites (1)

CHU de Brest

Brest, Finistère, 29609, France

RECRUITING

MeSH Terms

Conditions

Dysbiosis; Asthma

Interventions

Occult Blood; Hematologic Tests

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques

Central Study Contacts

Pierrick CROS

CONTACT

02 98 22 36 59; pierrick.cros@chu-brest.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: DREAM is a case-controlled study in open label
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Exploratory multicentric prospective case-controlled study

Study Record Dates

• First Submitted: November 16, 2021
• First Posted: January 14, 2022
• Study Start: February 4, 2022
• Primary Completion (Estimated): February 4, 2028
• Study Completion (Estimated): February 4, 2028
• Last Updated: September 23, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Data will be available after the publication of result and ending fifteen years following the last visit of the last patient
• Access Criteria: Data access requests will be reviewed by the internal committee of Brest University Hospital. Requestors will be required to sign and complete a data access agreement.

Locations

FR (1)