Using Cluster Analysis to Identify Phenotypes and Validation of Mortality in Men with COPD

Purpose: Cluster analysis has been proposed to examine phenotypic heterogeneity in chronic obstructive pulmonary disease (COPD). The aim of this study was to use cluster analysis to define COPD phenotypes and validate them by assessing their relationship with mortality.

Methods: Male subjects with COPD were recruited to identify and validate COPD phenotypes. Seven variables were assessed for their relevance to COPD, age, FEV₁ % predicted, BMI, history of severe exacerbations, mMRC, SpO₂, and Charlson index. COPD groups were identified by cluster analysis and validated prospectively against mortality during a 4-year follow-up.

Results: Analysis of 332 COPD subjects identified five clusters from cluster A to cluster E. Assessment of the predictive validity of these clusters of COPD showed that cluster E patients had higher all cause mortality (HR 18.3, p < 0.0001), and respiratory cause mortality (HR 21.5, p < 0.0001) than those in the other four groups. Cluster E patients also had higher all cause mortality (HR 14.3, p = 0.0002) and respiratory cause mortality (HR 10.1, p = 0.0013) than patients in cluster D alone.

Conclusion: COPD patient with severe airflow limitation, many symptoms, and a history of frequent severe exacerbations was a novel and distinct clinical phenotype predicting mortality in men with COPD.