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

Overview

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.

Detailed 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

Interventions

• Procedure Stool test
  At inclusion (day 0), stools will be collected with a kit for to remove to 5 mg for each patient.
• Procedure Blood test
  Blood sample taken during inclusion (day 0) will be collected. There is between 19 and 26 mL for each patient.
• Procedure 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).
• Procedure 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.

Primary outcome measures

• Number of species in the microbial Community [Time frame: Day 0]
• Index of microbial similarity of samples [Time frame: Day 0]

Secondary outcome measures (3)

• Enterotyping analysis [Time frame: Day 0]
• Relative abundance [Time frame: Day 0]
• Indices of diversity [Time frame: Day 0]

Eligibility criteria

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)

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Prevention

Study locations

France · 1 center

• CHU de Brest — Brest

Identifiers

NCT: NCT05192499 · 29BRC21.0252

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗