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.