Cucco, A., Simpson, A., Haider, S., Murray, C., Turner, S., Cullinan, P., Filippi, S., Fontanella, S., Custovic, A. and STELAR/UNICORN Investigators (2025) Allergy. https://doi.org/10.1111/all.16617
ABSTRACT
Background
Many studies used information on wheeze presence/absence to determine asthma-related phenotypes. We investigated whether clinically intuitive asthma subtypes can be identified by applying data-driven semi-supervised techniques to information on frequency and triggers of different respiratory symptoms.
Methods
Partitioning Around Medoids clustering was applied to data on multiple symptoms and their triggers in school-age children from three birth cohorts: MAAS (n = 947, age 8 years), SEATON (n = 763, age 10) and ASHFORD (n = 584, age 8). ‘Guided’ clustering, incorporating asthma diagnosis, was used to select the optimal number of clusters.
Results
Five-cluster solution was optimal. Based on their clinical characteristics, including frequency of asthma diagnosis, we interpreted one cluster as ‘Healthy’. Two clusters were characterised by high asthma prevalence (95.89% and 78.13%). We assigned children with asthma in these two clusters as ‘persistent, multiple-trigger, more severe’ (PMTS) and ‘persistent, triggered by infection, milder’ (PIM). Children with asthma in the remaining two clusters were assigned as ‘mild-remitting wheeze’ (MRW) and ‘post-bronchiolitis resolving asthma’ (PBRA). PBRA was associated with RSV bronchiolitis in infancy. In most children with asthma in this cluster wheezing resolved by age 5–6, and predominant symptoms were shortness of breath and chest tightness. Children in PBRA had the highest hospitalisation rates and wheeze exacerbations in infancy. From age 8 years (cluster derivation) to early adulthood (18–20 years), lung function was significantly lower, and FeNO and airway hyperreactivity significantly higher in PMTS compared to all other clusters.
Conclusions
Patterns of coexisting symptoms identified by semi-supervised data-driven methods may reflect pathophysiological mechanisms of distinct subtypes of childhood wheezing disorders.
Graphical Abstract
We performed guided multi-domain clustering of symptoms and triggers in school-age children across three birth cohorts. Using 15 variables, five clusters were identified. Two clusters showed a high prevalence of asthma with persistent symptoms. Questions on shortness of breath and chest tightness upon awakening were key to identifying ‘post-bronchiolitis resolving asthma’. ASHFORD, birth cohort study established in 1991 in Ashford, UK; LRTIs, lower respiratory tract infections; MAAS, Manchester Asthma and Allergy Study; SEATON, The Study of Eczema and Asthma to Observe the influence of Nutrition.