D1.175 - Clinical Phenotypes of Difficult-to-treat and Mild Asthma Defined by Cluster Analysis

Cluster modelling has demonstrated the heterogeneity of asthma but has previously focused mainly on severe disease with limited assessment of mild disease or treatable traits like comorbidities. We aim to identify and characterise difficult-to-treat and mild asthma clusters in two UK cohorts: Wessex AsThma CoHort of Difficult Asthma (WATCH-DA) and a mild-asthma cohort from the Epigenetics of Severe Asthma study (EOSA-MA).

Separate K-means clustering was applied to WATCH-DA (n=498; 11 variables) and EOSA-MA (n=67; 12 variables). Post-hoc comparisons evaluated demographic, inflammatory, physiological, comorbidity and patient-reported outcome profiles. 

Six difficult-to-treat and two mild asthma clusters were identified respectively, all Type-2 (T2)-predominant. Difficult-to-treat asthma clusters differed by sex, age of asthma-onset, body mass index (BMI) and comorbidities. Two clinically-controlled clusters, cluster-1 (early-onset–clinically-controlled–atopic disease) and cluster-4 (adult-onset–clinically-controlled–least-atopic disease), showed distinct comorbidity patterns despite lower overall morbidity. Three severe, exacerbation-prone, adult-onset, female predominant difficult-to-treat clusters (cluster-2, cluster-5, cluster-6) varied by blood eosinophil counts (BEC), spirometry, BMI, treatment needs, comorbidities, and quality of life. An adolescent-onset–obese–atopic–airflow-obstructive disease (cluster-3) showed fewer exacerbations but high BEC with worst spirometry and poor asthma control. In mild asthma, cluster-1 (early-onset-atopic-mild-asthma) showed worse pathophysiological indices and asthma control than cluster-2 (adolescent-onset-mild-asthma) but similarly high comorbidity prevalence.

Characterisation of difficult-to-treat and mild asthma clusters reveals diverse associated clinical traits and outcomes across the asthma severity spectrum. Recognition of these clusters and their associated comorbidities should prompt early personalised asthma management to address both airway-centric and comorbid disease aspects.