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”.