Preschool Severe Asthma Clinical Trial
Official title:
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.
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that subgroups of severe asthmatic children could also be identified according to bronchial remodeling parameters (unpublished data).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blood vessel count, BSM mass and a decrease in RBM-BSM distance, seromucosal gland mass and bronchial fibrosis (unpublished data).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. ;