Heterogeneity of chronic cough in asthma: a prospective cohort study with hierarchical cluster analysis

Background Although chronic cough in asthma is heterogeneous, yet the clinical variability remains largely unexplored. Methods Participants with stable asthma and chronic cough from the Australasian Severe Asthma Network underwent multidimensional assessment. They were then asked to prospectively participate in a 12-month longitudinal cohort study. We explored potential clusters using a hierarchical cluster analysis and validated the differential future risk of asthma exacerbation in the identified clusters. A decision tree analysis was developed to predict cluster assignments. Results Three clusters were identified in 142 patients with asthma and chronic cough. Cluster 1 (n=37; 26.1%) was characterized by female-dominant nonsmokers with atopy and younger age, Cluster 2 (n=45; 31.7%) by older female-dominant non-atopic late-onset asthma with more severe cough, and Cluster 3 by male smokers with fixed airflow obstruction. Cluster 2 had a greater proportion of participants with moderate-t-severe exacerbations (p=0.001) and severe exacerbations (p=0.020) than Cluster 1. The decision tree assigned 88.0% of participants correctly. Conclusion We identified three clinical clusters of chronic cough in asthma, with different risk profiles and treatment implications. Cluster 2 represents a poorly-controlled subtype with an elevated risk of exacerbations. These findings have clinical implications for the management of cough in asthma.