Biomarker-based clustering of patients with chronic obstructive pulmonary disease

Rationale COPD has been repeatedly associated with single biomarkers of systemic inflammation, ignoring the complexity of inflammatory pathways.

Objectives This study aimed to cluster patients with COPD based on systemic markers of inflammatory processes and to evaluate differences in their clinical characterization and examine how these differences may relate to altered biological pathways.

Methods Two hundred thirteen patients with moderate to severe COPD in a clinically stable state were recruited and clinically characterized, which included a venous blood sample for analysis of serum biomarkers. Patients were clustered based on the overall similarity in systemic levels of 57 different biomarkers. To determine interactions among the regulated biomarkers, protein networks and biological pathways were examined for each patient cluster.

Results Four clusters were identified: two clusters with lower biomarker levels (I and II) and two clusters with higher biomarker levels (III and IV) with only a small number of biomarkers with similar trends in expression. Pathway analysis indicated that 3 of the 4 clusters were enriched in RAGE and Oncostatin M pathway components. Although the degree of airflow limitation was similar, the clinical characterization of clusters ranged from (I) better functional capacity, health status and fewer comorbidities, (II) more underweight, osteoporosis and more static hyperinflation, (III) more metabolically deranged and (IV) older subjects with worse functional capacity and higher comorbidity load.

Conclusions These new insights may help to understand the functionally relevant inflammatory interactions in the pathophysiology of COPD as a heterogeneous disease.