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_ENO ≥ 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".