INTRODUCTION
Wheezing during preschool age is a very common symptom which occurs at least once in about one third of children under 3 years of age and about a half under 6 years of age (1). Among these patients about 25% have recurrent preschool wheezing which increases the risk of asthma persistence at school age and altered lung function throughout life (2–4). Several risk factors for persistent recurrent wheezing have been identified, such as tobacco smoke exposure, the early onset of atopic dermatitis, allergic sensitization and/or the first episode of wheezing. However, the mechanisms are yet not fully understood (5).
Belgrave et al. reported that severe exacerbations within the first three years of life was predictive of persistent low lung function throughout life (3). In addition, Deliu et al . described an early-onset frequent exacerbation trajectory characterized by a persistent wheezing phenotype, an increased prevalence of atopic dermatitis at 1 and 3 years of age, decreased lung function at school age and an increased prevalence of asthma persistence at 16 years of age compared to preschool wheezers without exacerbations or those with infrequent exacerbation trajectories (6).
Exacerbations are frequently related to viral and/or bacterial infections (7), which involve most frequently respiratory syncytial viruses, rhinoviruses, Moraxella catarrhalis , Haemophilus influenzae or Streptococcus pneumoniae (8) in preschool wheezers. Moreover, bronchial dysbiosis which contributes to recurrent wheeze heterogeneity and severity independently of allergic sensitization (9,10), increases the risk of subsequent exacerbations in recurrent wheezing children (11). Indeed, a longitudinal study demonstrated that appropriate antibiotics course administered when bronchoalveolar lavage fluid (BALF) bacterial culture was positive decreased wheeze-related frequency for at least 6 months (11).
Previous studies also demonstrated that the risk of subsequent exacerbations in preschool wheezers was increased in patients previously hospitalized for severe wheezing exacerbation (12,13). Using bronchial remodelling-based latent class analysis, we recently identified two classes of severe preschool wheezers, one being characterized by a decreased reticular basement membrane (RBM) to bronchial smooth muscle (BSM) distance, submucosal fibrosis area, mucus gland area, and an increased BSM area, density of blood vessels, and RBM thickness compared to the other (14). This class was at increased risk of frequent subsequent exacerbations (i.e ., 3 or more in the year following fibreoptic bronchoscopy) despite not being significantly different from the second class in terms of clinical, biological or BALF parameters at baseline (14). However, even if our bronchial remodelling-based latent classes identified patients at increased risk of subsequent exacerbations, it failed to distinguish patients without exacerbations or those with infrequent exacerbations (i.e. , one or two) in the year following fibreoptic bronchoscopy (14).
We thus hypothesized that several additional parameters to those of bronchial remodelling, may be independently associated with short-term exacerbation frequency. The objective was then to identify clinical, biological and bronchial remodelling parameters independently associated with exacerbation frequency group membership in the year following fibreoptic bronchoscopy.