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.).