Bronchial Remodeling-based Latent Class Analysis Predicts Exacerbations in Severe Preschool Wheezers

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Fayon, Michael | Beaufils, Fabien | Esteves, Pauline | Campagnac, Maryline | Maurat, Elise | Michelet, Marine | Siao-Him-Fa, Valerie | Lavrand, Frederic | Simon, Guillaume | Begueret, Hugues | Berger, Patrick | Auriol, Françoise | Blanchon, Sylvain | Carles, Dominique | Boisserie-Lacroix, Vincent | Brémont, François | Bui, Stéphanie | Choukroun, Marie-Luce | Debelleix, Stéphane | Feghali, Hala | Labouret, Géraldine | Blondel, Audrey Martin | Marais, Sébastien | Mittaine, Marie | Nacka, Fabienne | Ousova, Olga | Rouquette, Isabelle | Semjen, François | Sgoifo, Frédérique | Trian, Thomas

Edité par CCSD ; American Thoracic Society -

International audience. Rationale: Children with preschool wheezing represent a very heterogeneous population with wide variability regarding their clinical, inflammatory, obstructive, and/or remodeling patterns. We hypothesized that assessing bronchial remodeling would help clinicians to better characterize severe preschool wheezers. Objectives: The main objective was to identify bronchial remodeling-based latent classes of severe preschool wheezers. Secondary objectives were to compare cross-sectional and longitudinal clinical and biological data between classes and to assess the safety of bronchoscopy. Methods: This double-center prospective study (NCT02806466) included severe preschool wheezers (1-5 yr old) requiring fiberoptic bronchoscopy. Bronchial remodeling parameters (i.e., epithelial integrity, reticular basement membrane [RBM] thickness, mucus gland, fibrosis and bronchial smooth muscle [BSM] areas, the density of blood vessels, and RBM-BSM distance) were assessed and evaluated by latent class analysis. An independent cohort of severe preschool wheezers (NCT04558671) was used to validate our results. Measurements and Main Results: Fiberoptic bronchoscopy procedures were well tolerated. A two-class model was identified: Class BR1 was characterized by increased RBM thickness, normalized BSM area, the density of blood vessels, decreased mucus gland area, fibrosis, and RBM-BSM distance compared with Class BR2. No significant differences were found between classes in the year before fiberoptic bronchoscopy. By contrast, Class BR1 was associated with a shorter time to first exacerbation and an increased risk of both frequent (3 or more) and severe exacerbations during the year after bronchoscopy in the two cohorts. Conclusions: Assessing bronchial remodeling identified severe preschool wheezers at risk of frequent and severe subsequent exacerbations with a favorable benefit to risk ratio.

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