D1.108 - Optimization of phenotyping in severe T2-bronchial asthma

Precise phenotyping of T2 severe asthma (SA) is essential for personalized therapy but remains challenging in clinical practice. 

Objective: To determine key clinical and laboratory parameters for optimizing the phenotyping of T2 SA based on a patient registry data analysis. 

The analysis included 198 patients with SA receiving immunobiological therapy (2016-2023). A detailed cohort description and analysis of comorbidities were performed. To address the phenotyping task, cluster analysis was conducted to identify significant features. For quantitative parameters (age of asthma onset, Phadiatop test level), ROC analysis was performed to calculate threshold values for phenotype determination. 

The studied cohort was predominantly female (79.8%) and had a non-allergic (eosinophilic) phenotype (46.5%). Key features for phenotype differentiation were: age of asthma onset, positive Phadiatop test, presence of allergic rhinitis (AR), proven allergy, chronic rhinosinusitis with nasal polyps (CRSwNP), and hypersensitivity to NSAIDs. Threshold values were established: age of asthma onset < 18 years is characteristic of the allergic phenotype; ≥ 18 and < 32 years – for the mixed phenotype; ≥ 32 years – for the non-allergic (eosinophilic) phenotype. Phadiatop test: a level ≥ 1.53 PAU/L indicates a high probability of an allergic component (sensitivity 75.0%, specificity 93.3%). Based on the analysis, phenotype criteria were formulated: Allergic phenotype: onset < 18 years, proven allergy; additional criteria – AR and/or AD, Phadiatop ≥ 1.53 PAU/L. Non-allergic (eosinophilic) phenotype: onset ≥ 32 years, absence of proven allergy, blood eosinophilia ≥ 150 cells/µL; additional criteria – CRSwNP and NSAID hypersensitivity. Mixed phenotype: onset between 18–32 years, combination of proven allergy with eosinophilia ≥ 300 cells/µL. 

Objective and reproducible criteria (age of onset and Phadiatop level) for differentiating phenotypes of severe T2 asthma have been defined. The obtained threshold values allow for optimization of the phenotyping process, which is important for the personalized selection of targeted biological therapy.