Methods
Study design and
participants
COBRAPed is a prospective, observational, multicenter cohort study that
was initiated in France, and has been described elsewhere (11).
Institutional ethical approval (CPP Ile de France 1) and written
informed consent from parents/caregivers of all participants were
obtained. The study is registered in ClinicalTrial.gov (NCT02114034).
Preschool (3-6 years) and
school-age (7-12 years) children were enrolled and assigned to one of
four groups: (a) non-severe preschool recurrent wheezers (NSRW), (b)
severe preschool recurrent wheezers (SRW), (c) non-severe school-age
asthmatic children (NSA), and (d) severe school-age asthmatic children
(SA).
Preschool
children with SRW and school-age children with SA had persistent
symptoms or a need for short-acting β-agonist (SABA) and/or frequent or
severe exacerbations and/or persistent airflow obstruction for
school-age children, despite being treated with high doses of inhaled
corticosteroids (ICS) and another
controller therapy (12). A full
description of the cohort, inclusion and exclusion criteria, and details
of the clinical assessments has been previously published (11) and is
available in the Online Supporting Information.
Atopy was defined as having at
least one positive skin-prick test (SPT) (wheal diameter ≥3 mm) and/or
specific IgE levels (≥0.35 kuA/l) against common airborne and/or food
allergens. Patients with SRW and SA receiving anti-IgE treatment with
omalizumab were excluded for this analysis.
Detection and
classification of component-specific IgE antibodies
IgE to 112 allergenic components were measured using an ImmunoCAP Immuno
Solid-Phase Allergen Chip (ISAC) (Thermo Fisher/Phadia A, Uppsala,
Sweden). Levels of component-specific IgE (c-sIgE) antibodies were
reported in ISAC Standardized Units (ISU). Sensitization was defined at
the c-sIgE level and biological source level. To determine sensitization
at the c-sIgE level, depending on the nature of the analysis, we
dichotomized c-sIgE using a binary threshold (< or ≥ 0.30 ISU)
or based on the supplier’s four-group categorical classification
(negative: <0.3 ISU, low: 0,3-1 ISU, medium/high: ≥1-15 ISU,
very high: ≥15 ISU), depending on the nature of the analysis (Fig 1)
(10,13,14). Sensitization was also defined at the biological source
level based on the food/airborne biological sources (e.g., egg, cow’s
milk, etc.) or molecular family for cross-reactive components (e.g.,
PR-10: pathogenesis-related protein family 10 (PR-10), etc.).