Reliability of Total Serum IgE Levels to Define Type 2 High and Low Asthma Phenotypes.

Background: High total IgE levels are weak predictors of T2 High and have been reported in nonallergic asthma. Therefore, the role of total serum IgE (IgE) in the T2 High phenotype is still debated. Objective: This study investigated the reliability of stratifying asthmatics into IgE High and IgE Low within the T2 High and T2 Low phenotypes. Methods: This cross-sectional single-center study investigated the association of clinical, functional, and bio-humoral parameters in a large asthmatic population stratified by IgE ≥ 100 kU/L, allergen sensitization, B-EOS ≥ 300/µL, and F E NO ≥ 30 ppb. Results: Combining T2 biomarkers and IgE identifies (1) T2 Low -IgE Low (15.5%); (2) T2 Low -IgE High (5.1%); (3) T2 High -IgE Low (33.6%); and T2 High -IgE High (45.7%). T2 Low -IgE Low patients have more frequent cardiovascular and metabolic comorbidities, a higher prevalence of emphysema, and higher LAMA use than the two T2 High subgroups. Higher exacerbation rates, rhinitis, and anxiety/depression syndrome characterize the T2 Low -IgE High phenotype vs. the T2 Low -IgE Low phenotype. Within the T2 High , low IgE was associated with female sex, obesity, and anxiety/depression. Conclusions: High IgE in T2 Low patients is associated with a peculiar clinical phenotype, similar to T2 High in terms of disease severity and nasal comorbidities, while retaining the T2 Low features. IgE may represent an additional biomarker for clustering asthma in both T2 High and T2 Low phenotypes rather than a predictor of T2 High asthma " per se ".