Heterogeneity of paucigranulocytic asthma: A prospective cohort study with hierarchical cluster analysis

BACKGROUND: Asthma, a heterogeneous disease, can be divided into four inflammatory phenotypes using induced sputum cell counts -eosinophilic asthma (EA), neutrophilic asthma (NA), mixed granulocytic asthma (MGA), and paucigranulocytic asthma (PGA). While research has focused on EA and NA, there is little known on PGA.

OBJECTIVE: To study the heterogeneity of PGA, and identify possible PGA clusters to guide clinical treatment.

METHODS: Patients with PGA were grouped by hierarchical cluster analysis, and enrolled into a prospective cohort study to validate the clusters, relative to future risk of asthma exacerbations in a real-world setting. Clusters were validated by tree analysis in a separate population. Finally, we explored PGA stability.

RESULTS: Cluster analysis of 145 patients with PGA identified three clusters: Cluster 1 (n = 110, 75.9%) was "mild PGA," Cluster 2 (n = 20, 13.8%) was "PGA with psychological dysfunction and rhinoconjunctivitis and other allergic diseases," and Cluster 3 (n = 15, 10.3%) was "smoking-associated PGA." Cluster 3 had significantly increased risk of severe exacerbation (RR = 6.43, P = 0.01), emergency visit (RR = 8.61, P = 0.03), and hospitalization (RR = 12.94, P < 0.01). Results of the cluster analysis were successfully validated in an independent PGA population classified using decision tree analysis. Although PGA can transform into or develop from other phenotypes, 70% were stable over time.

CONCLUSIONS: Among three identified PGA clusters, Cluster 3 had a higher risk of severe exacerbation. PGA heterogeneity indicates the requirement of novel targeted interventions.