This study explores the application of k-means cluster analysis to identify distinct phenotypic groups in asthma populations. The researchers analyzed three independent asthma populations: a primary care population with predominantly mild to moderate disease, a secondary care population with refractory asthma, and a third population of refractory asthma patients participating in a randomized trial comparing inflammation-guided management with standard care. The primary-care population was divided into two clusters: early-onset atopic and obese, noneosinophilic. The secondary care population showed two additional clusters characterized by discordance between symptom expression and eosinophilic airway inflammation. In the third population, inflammation-guided management was superior for both discordant subgroups, leading to a reduction in exacerbation frequency and a dose reduction of inhaled corticosteroids. The study highlights the utility of cluster analysis in identifying asthma phenotypes with distinct clinical responses to treatment algorithms.This study explores the application of k-means cluster analysis to identify distinct phenotypic groups in asthma populations. The researchers analyzed three independent asthma populations: a primary care population with predominantly mild to moderate disease, a secondary care population with refractory asthma, and a third population of refractory asthma patients participating in a randomized trial comparing inflammation-guided management with standard care. The primary-care population was divided into two clusters: early-onset atopic and obese, noneosinophilic. The secondary care population showed two additional clusters characterized by discordance between symptom expression and eosinophilic airway inflammation. In the third population, inflammation-guided management was superior for both discordant subgroups, leading to a reduction in exacerbation frequency and a dose reduction of inhaled corticosteroids. The study highlights the utility of cluster analysis in identifying asthma phenotypes with distinct clinical responses to treatment algorithms.