Int J Med Sci 2017; 14(1):67-74. doi:10.7150/ijms.16907 This issue

Research Paper

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

Elena Arellano-Orden1✉, Carmen Calero-Acuña1, 2,3, Juan Antonio Cordero1, María Abad-Arranz2, Verónica Sánchez-López1, Eduardo Márquez-Martín1, 2, Francisco Ortega-Ruiz1,2,3, José Luis López-Campos1,2,3

1. Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/Universidad de Sevilla, Seville, Spain;
2. Unidad Médico-Quirúrgica de Enfermedades Respiratorias, Hospital Virgen del Rocío. Seville, Spain;
3. CIBER de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Madrid, Spain.

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) License. See for full terms and conditions.
Arellano-Orden E, Calero-Acuña C, Cordero JA, Abad-Arranz M, Sánchez-López V, Márquez-Martín E, Ortega-Ruiz F, López-Campos JL. Specific networks of plasma acute phase reactants are associated with the severity of chronic obstructive pulmonary disease: a case-control study. Int J Med Sci 2017; 14(1):67-74. doi:10.7150/ijms.16907. Available from

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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 α-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.

Keywords: acute phase reactants, chronic obstructive pulmonary disease