Preschool Bronchial Remodeling and Risk of Exacerbation (RESPIRE)

Bronchial REmodeling in Severe Preschool Wheezing chIldren and Risk of Exacerbation

Bronchial remodeling is an abnormal tissue repair process of the bronchial wall components that characterizes severe asthma which can include epithelial abrasion, thickening of the reticular basement membrane (RBM), an increase in bronchial fibrosis, blood vessel count, mucosal gland mass and/or bronchial smooth muscle (BSM) mass. We identified using latent class analysis two classes of patients. Compared to the second class, the first class was characterized by an increase in RBM thickness, blood vessel count, BSM mass and a decrease in RBM-BSM distance, mucus gland mass and bronchial fibrosis. We then hypothesized that this first latent class identified children at risk of asthma exacerbations.

Study Overview

• Status: Completed
• Conditions: Preschool Severe Asthma
• Intervention / Treatment: Other: asthma exacerbations

Detailed Description

Asthma is the most frequent chronic disease in children. Severe asthma is characterized by airway hyperresponsiveness, bronchial inflammation and bronchial remodeling 1. Bronchial remodeling is an abnormal tissue repair process of the bronchial wall components which can include epithelial abrasion, thickening of the reticular basement membrane (RBM), an increase in bronchial fibrosis, blood vessel count, mucosal gland mass and/or bronchial smooth muscle (BSM) mass. At preschool age (before 6 years old), asthmatic children constitute a heterogeneous population and several classifications have been proposed to identify distinct phenotypes according to the chronology of asthma 2, the triggers of asthma 3, the trajectory of lung function as measured by forced expiratory volume in 1 second (FEV1) 4 or according to a combination of clinical and inflammatory variables 5. More recently, we demonstrated for the first time using latent class analysis (LCA) that subgroups of severe asthmatic children could also be identified according to bronchial remodeling parameters (unpublished data). Indeed, we identified two latent classes of patients. Compared to the second class, the first latent class was characterized by an increase in RBM thickness, blood vessel count, BSM mass and a decrease in RBM-BSM distance, seromucosal gland mass and bronchial fibrosis (unpublished data). Since, previous studies showed that bronchial remodeling could have negative impact on the patients' outcomes, we therefore hypothesized that the latent classes identified from the bronchial remodeling data in severe preschool asthmatic children included in the "P'tit Asthme" study (NCT02806466) could identify children at risk of asthma exacerbations requiring systemic corticosteroids therapy.

• Study Type: Observational
• Enrollment (Actual): 56

Contacts and Locations

Study Locations

• France
  • Aquitaine
    • Bordeaux, Aquitaine, France, 33000
      • CHU de Bordeaux
  • Languedoc-Roussillon-Midi-Pyrénées
    • Toulouse, Languedoc-Roussillon-Midi-Pyrénées, France, 31026
      • CHU de TOULOUSE

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 5 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Severe preschool wheezers (1-5 years old) according to ERS and ATS modified criteria and requiring flexible bronchoscopy according to ERS guidelines.

Description

Inclusion Criteria:

• To have been previously included in the "P'tit Asthme" study (NCT02806466)
• To have performed bronchoscopy with analyzable biopsies
• To have been asthmatic at the inclusion in the P'tit Asthme study (NCT02806466)

Exclusion Criteria:

• To refuse the use of children data as expressed by representatives of parental authority

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Retrospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of asthma exacerbations	Number of asthma exacerbations requiring systemic corticosteroid therapy within the year following the bronchoscopy performed in the "P'tit Asthme" study.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Presence of the exacerbation prone asthma	Presence of the exacerbation prone asthma defined by the occurrence of 3 or more asthma exacerbations requiring systemic corticosteroid therapy within one year	1 year
Number of asthma exacerbations requiring systemic corticosteroid therapy	Number of asthma exacerbations requiring systemic corticosteroid therapy each month within the year following the bronchoscopy performed in the P'tit Asthme study.	1 year

Collaborators and Investigators

• Sponsor: University Hospital, Bordeaux

Publications and helpful links

General Publications

• Fayon M, Beaufils F, Esteves P, Campagnac M, Maurat E, Michelet M, Siao-Him-Fa V, Lavrand F, Simon G, Begueret H, Berger P. Bronchial Remodeling-based Latent Class Analysis Predicts Exacerbations in Severe Preschool Wheezers. Am J Respir Crit Care Med. 2022 Sep 15. doi: 10.1164/rccm.202205-0913OC. Online ahead of print.

Study record dates

Study Major Dates

• Study Start (Actual): September 16, 2020
• Primary Completion (Actual): September 24, 2020
• Study Completion (Actual): September 24, 2020

Study Registration Dates

• First Submitted: September 16, 2020
• First Submitted That Met QC Criteria: September 16, 2020
• First Posted (Actual): September 22, 2020

Study Record Updates

• Last Update Posted (Actual): September 29, 2020
• Last Update Submitted That Met QC Criteria: September 28, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Keywords: exacerbation; children; asthma; bronchial remodeling; wheezing
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma
• Other Study ID Numbers: CHUBX 2020/32

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No