Distribution of type 2 biomarkers and association with severity, clinical characteristics and comorbidities in the BREATHE real-life asthma population

Background Type 2 (T2) high asthma is recognised as a heterogenous entity consisting of several endotypes; however, the prevalence and distribution of the T2 biomarkers in the general asthma population, across asthma severity, and across compartments is largely unknown. The objective of the present study was to describe expression and overlaps of airway and systemic T2 biomarkers in a clinically representative asthma population. Methods Patients with asthma from the real-life BREATHE cohort referred to a specialist centre were included and grouped according to T2 biomarkers: blood and sputum eosinophilia (.0.3x109 cells center dot L-1 and 3% respectively), total IgE (.150 U center dot mL-1), and fractional exhaled nitric oxide (.25 ppb). Results Patients with mild-to-moderate asthma were younger (41 versus 49 years, p < 0.001), had lower body mass index (25.9 versus 28.0 kg center dot m-2, p=0.002) and less atopy (47% versus 58%, p=0.05), higher forced expiratory volume in 1 s (3.2 versus 2.8 L, p < 0.001) and forced vital capacity (4.3 versus 3.9 L, p < 0.001) compared with patients with severe asthma, who had higher blood (0.22x109 versus 0.17x109 cells center dot L-1, p=0.01) and sputum (3.0% versus 1.5%, p=0.01) eosinophils. Co-expression of all T2 biomarkers was a particular characteristic of severe asthma ( p < 0.001). In patients with eosinophilia, sputum eosinophilia without blood eosinophilia was present in 45% of patients with mild-to-moderate asthma and 35% with severe asthma. Conclusion Severe asthma is more commonly associated with activation of several T2 pathways, indicating that treatments targeting severe asthma may need to act more broadly on T2 inflammatory pathways. Implementation of airway inflammometry in clinical care is of paramount importance, as the best treatable trait is otherwise is overlooked in a large proportion of patients irrespective of disease severity.