Impact of wheat sensitization on wheeze and T2 phenotypes in general population of children.

Background: The association between sensitization to specific aeroallergens and outcomes in patients with asthma is well researched; however, the association between childhood-onset wheeze/asthma and sensitization to various aeroallergens and food allergens in the general pediatric population remains poorly understood. Objective: We sought to investigate the association between sensitization to common aeroallergens and food allergens with wheeze and type 2 (T2) inflammation in the general pediatric population. Methods: Specific IgEs against 9 aeroallergens and 4 food allergens were measured in the prospective Hokkaido birth cohort of 428 school-age children (age ∼10 years). Wheeze and other allergic symptoms were assessed using the International Study of Asthma and Allergies in Childhood questionnaire. Blood eosinophil count and fractional exhaled nitric oxide level were assessed as T2 biomarkers. The Isle of Wight birth cohort in the United Kingdom was used for replication analysis (n = 1032). Results: The prevalence of sensitization to at least 1 aeroallergen and food allergen was 70.5% and 22.3%, respectively. A significant association between wheeze and sensitization to aeroallergens such as ragweed, Japanese cedar, mugwort, and pet dander was found. However, the association between wheeze and wheat sensitization was highly significant (Hokkaido birth cohort: odds ratio, 4.67; 95% CI, 1.98-11.01; Isle of Wight birth cohort, odds ratio, 4.01; 95% CI, 1.78-9.07). Sensitization to most aeroallergens, though not any food allergen, was associated with the T2-high phenotype. Conclusions: Sensitization to wheat may be an important risk factor for wheeze/asthma development, especially the pathogenesis of T2-non/low asthma, independent of aeroallergens, in the general pediatric population.