Comprehensive characterisation of difficult-to-treat asthma reveals near absence of T2-low status

BACKGROUND: Asthma is conventionally stratified as type 2-inflammation (T2) high or T2-low disease. Identifying T2-status has therapeutic implications for patient management but real-world understanding of this T2 paradigm in difficult-to-treat/ severe asthma remains limited.

OBJECTIVES: To identify prevalence of T2-high status in difficult-to-treat asthma patients using a multicomponent definition and compare clinical and pathophysiological characteristics between patients classified as T2-high and T2-low.

METHODS: 388 biologic naïve patients from the Wessex Asthma Cohort of difficult asthma (WATCH) study, United Kingdom, were evaluated. T2-high asthma was defined as fractional exhaled nitric oxide (FeNO)≥20ppb and/or peripheral blood eosinophils (PBE) ≥150 cells/ul and/or need for maintenance oral corticosteroids and/or clinically allergy-driven asthma.

RESULTS: This multicomponent assessment identified T2-high asthma in 93% (360/388) of patients. Body Mass Index, inhaled corticosteroid dose, asthma exacerbations and common comorbidities did not differ by T2-status. Significantly worse airflow limitation was found in T2-high compared to T2-low patients (FEV1/FVC 65.9% vs 74.6%). 75% patients defined as T2-low asthma had raised PBE within the preceding 10-years, leaving only 7 patients (1.8%) who never had T2-signals. Incorporation of sputum eosinophilia ≥2% into the multicomponent definition in a subset of 117 patients with induced sputum data similarly found that 96% (112/117) met criteria for T2-high asthma of which 50% (56/112), had sputum eosinophils ≥2%.

CONCLUSION: Almost all patients with difficult-to-treat asthma have T2-high disease with <2% of patients never displaying T2-defining criteria. This highlights a need to comprehensively assess T2 status in clinical practice before labelling a patient with difficult-to-treat asthma as T2-low.