Clinical trial NCT04558671: Preschool Bronchial Remodeling and Risk of Exacerbation
Official title: Bronchial REmodeling in Severe Preschool Wheezing chIldren and Risk of Exacerbation
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Preschool Severe Asthma
Keywords: exacerbation
children
asthma
bronchial remodeling
wheezing
Lead sponsor: University Hospital, Bordeaux
Sponsor class: OTHER
First posted: 2020-09-22
Enrollment: 56
Sex: ALL
Minimum age (years): 1
Maximum age (years): 5
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
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.

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of asthma exacerbations
timeFrame: 1 year
Secondary outcomes:
measure: Presence of the exacerbation prone asthma
timeFrame: 1 year
measure: Number of asthma exacerbations requiring systemic corticosteroid therapy
timeFrame: 1 year
Other outcomes:
Locations:
city: Bordeaux
country: France
facility: CHU de Bordeaux
state: Aquitaine
city: Toulouse
country: France
facility: CHU de Toulouse
state: Languedoc-Roussillon-Midi-Pyrénées
Study officials:
References:
citation: Fayon M, Beaufils F, Esteves P, Campagnac M, Maurat E, Michelet M, Siao-Him-Fa V, Lavrand F, Simon G, Begueret H, Berger P; P'tit Asthme Study Group. Bronchial Remodeling-based Latent Class Analysis Predicts Exacerbations in Severe Preschool Wheezers. Am J Respir Crit Care Med. 2023 Feb 15;207(4):416-426. doi: 10.1164/rccm.202205-0913OC.