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NCT Number: NCT05192499

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

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.

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Key information

Age range

1 year–3 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

About this study

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 :

  • To compare the bacterial pulmotypes of children under 36 months of age with severe asthma with children with mild or moderate asthma.
  • To look for microbial biomarkers associated with corticosteroid resistance
  • 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)
  • To look for an association between digestive dysbiosis and respiratory dysbiosis
  • 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

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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)

Treatment and study plan

Stool test

Procedure

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

Blood test

Procedure

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

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).

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.

Primary outcomes

  1. Number of species in the microbial Community

    Time frame: Day 0

    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.

  2. Index of microbial similarity of samples

    Time frame: Day 0

    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.

Secondary outcomes

  1. Enterotyping analysis

    Time frame: Day 0

    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.

  2. Relative abundance

    Time frame: Day 0

    Relative abundance (expressed as a percentage) of each of the identified bacteriological taxa

  3. Indices of diversity

    Time frame: Day 0

    Types of indices of diversity of bacterial taxa identified in the digestive microbiota

Study contacts

Contact information is provided by the study sponsor or research team.

Pierrick CROS

CONTACT

[email protected]

02 98 22 36 59

Sponsors and collaborators

Lead sponsor

University Hospital, Brest

Other

Registry information

Acronym: DREAM

Important dates

Study start
2022
Primary completion
2028
Study completion
2028
First posted
Jan 14, 2022
Registry last updated
Sep 23, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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