Background: It is unclear whether sensitization patterns differentiate children with severe recurrent wheeze (SRW) / severe asthma (SA) from those with non-severe recurrent wheeze (NSRW) / non-severe asthma (NSA). Our objective was to compare the sensitization patterns between children with SRW/SA and NSRW/NSA from the French COBRAPed cohort. Methods: IgE to 112 components (c-sIgE) (ImmunoCAP® ISAC) were analyzed in 125 preschool (3-6 years) and 170 school-age children (7-12 years). Supervised analyses and clustering methods were applied to identify patterns of sensitization among children with positive c-sIgE. Results: We observed c-sIgE sensitization in 51% of preschool and 75% of school-age children. Sensitization to house dust mite (HDM) components was more frequent among NSRW than SRW (53% vs 24%, p<0.01). Sensitization to non-specific lipid transfer protein (nsLTP) components was more frequent among SA than NSA (16% vs 4%, p<0.01) and associated with a FEV1/FVC <-1.64 z-score. Among sensitized children, seven clusters with varying patterns were identified. The two broader clusters identified in each age group were characterized by “few sensitizations, mainly to HDM”. One cluster (n=4) with “multiple sensitizations, mainly to grass pollen, HDM, PR-10, and nsLTP” was associated with SA in school-age children. Conclusions: Although children with wheeze/asthma display frequent occurrences and high levels of sensitization, the sensitization patterns did not clearly discriminate children with severe disease from those with milder disease. These results suggest that the severity of wheeze/asthma may depend on both IgE- and non-IgE-mediated mechanisms.

Background : Several major sensitization profiles have been described in children with asthma, but it remains unclear how these profiles relate to asthma phenotypes. The aim of this study was to determine allergenic sensitization profiles in a megacity cohort (SAMP). Methods : This was a cross-sectional analysis performed from 2011 to 2015 including preschool and school-age children with severe and moderate asthma from the SAMP cohort. We performed ALEX multiplex array and carried out cluster analysis. Results: Data from 367 children were analysed: 224 of preschool age and 143 of school age, respectively 84 (38%) and 114 (80%) presented at least one allergic sensitization. At preschool age, three clusters were identified: Cluster 1, Few sensitizations to inhaled allergen molecular families and non-type 2 (T2) inflammation (n=61); Cluster 2, Predominant sensitization to HDM molecular families. (n=16); Cluster 3, Severe asthma with multiple sensitizations to inhaled and food allergen molecular families (n=7). At school age, five clusters were identified: Cluster 1, Few sensitizations to inhaled allergen molecular families and non-T2 inflammation (n=43); Cluster 2, Predominant sensitization to HDM molecular families (n=31); Cluster 3, Predominant sensitization to PR-10 family (n=25); Cluster 4, Severe asthma with predominant sensitization to tropomyosin family (n=11); Cluster 5, Severe asthma with multiple sensitizations to inhaled and food allergen molecular families (n=4). Conclusion: These results underline the heterogeneity of sensitization profiles in severe allergic childhood asthma. The most severe asthma phenotypes were associated with multiple sensitizations to both inhaled and food allergen molecular families as expected, and to the tropomyosin molecular family, a novel finding.

Background. Whether small airway dysfunction (SAD), which is prevalent in asthma, helps to characterize wheezing phenotypes is undetermined. The objective was to assess whether SAD parameters obtained from impedance measurement and asthma probability are linked. Methods. One hundred and thirty-nine preschool children (mean age 4.7 years, 68% boys) suffering from recurrent wheeze underwent impulse oscillometry that allowed calculating peripheral resistance and compliance of the respiratory system (markers of SAD) using the extended RIC model (central and peripheral Resistance, Inertance and peripheral Compliance of the respiratory system). Children were classified using the probability-based approach of GINA guidelines (few, some, most having asthma). A principal component analysis (PCA) that determined the dimensions of wheezing disease evaluated the links between SAD and asthma probability. Results. Forty-seven children belonged to the few, 28 to the some and 64 to the most having asthma groups. Whereas their anthropometrics and measured parameters were similar, the most having asthma group exhibited the lowest mean value of airway inertance after bronchodilator probably due to airway inhomogeneities. PCA characterized nine independent dimensions including a peripheral resistance (constituted by baseline peripheral resistance, AX, R5-20Hz, X5Hz), a central resistance (baseline central resistance, R20Hz) and an airway size dimension (post-bronchodilator inertance and central resistance). PCA showed that the SAD markers were independent from clinical dimensions (control and asthma probability were two other dimensions) and did not help to define wheezing phenotypes. Conclusions. Lung function parameters obtained from impulse oscillometry and asthma probability were belonging to independent dimensions of the wheezing disease.