Specific networks of plasma acute phase reactants are associated with the severity of chronic obstructive pulmonary disease: a case-control study

Objectives. A detailed understanding of the intricate relationships between different acute phase reactants (APRs) in chronic obstructive pulmonary disease (COPD) can shed new light on its clinical course. In this case-control study, we sought to identify the interaction networks of a number of plasma APRs in COPD, with a special focus on their association with disease severity. Methods. COPD cases and healthy smoking controls (3:1 ratio) were recruited in our outpatient pulmonary clinic. Cardiopulmonary exercise testing was used to rule out the presence of ischemic heart disease. All subjects were males as per protocol. Multiple plasma APRs - including alpha-2-macroglobulin, C-reactive protein (CRP), ferritin, fibrinogen, haptoglobin, procalcitonin (PCT), serum amyloid A (SAA), serum amyloid P, and tissue plasminogen activator (tPA) - were measured using commercial Acute Phase Bio-Plex Pro Assays and analyzed on the Bio-Plex manager software. Correlations between different APRs were investigated using a heat map. Network visualization and analyses were performed with the Cytoscape software platform. Results. A total of 96 COPD cases and 33 controls were included in the study. Plasma A2M, CRP, and SAP levels were higher in COPD patients than in controls. Circulating concentrations of haptoglobin and tPA were found to increase in parallel with the severity of the disease. Increasing disease severity was associated with distinct intricate networks of APRs, which were especially evident in advanced stages. Conclusions. We identified different networks of APRs in COPD, which were significantly associated with disease severity.