title: Specific networks of plasma acute phase reactants are associated with the severity of chronic obstructive pulmonary disease: a case-control study.
abstract: 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.
authors.affiliation: Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/Universidad de Sevilla, Seville, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Arellano-Orden
authors.affiliation: Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/Universidad de Sevilla, Seville, Spain;; Unidad Médico-Quirúrgica de Enfermedades Respiratorias, Hospital Virgen del Rocío. Seville, Spain;; CIBER de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Calero-Acuña
authors.affiliation: Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/Universidad de Sevilla, Seville, Spain.
authors.forename: Juan Antonio
authors.initials: JA
authors.lastname: Cordero
authors.affiliation: Unidad Médico-Quirúrgica de Enfermedades Respiratorias, Hospital Virgen del Rocío. Seville, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Abad-Arranz
authors.affiliation: Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/Universidad de Sevilla, Seville, Spain.
authors.forename: Verónica
authors.initials: V
authors.lastname: Sánchez-López
authors.affiliation: Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/Universidad de Sevilla, Seville, Spain;; Unidad Médico-Quirúrgica de Enfermedades Respiratorias, Hospital Virgen del Rocío. Seville, Spain.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Márquez-Martín
authors.affiliation: Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/Universidad de Sevilla, Seville, Spain;; Unidad Médico-Quirúrgica de Enfermedades Respiratorias, Hospital Virgen del Rocío. Seville, Spain;; CIBER de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Ortega-Ruiz
authors.affiliation: Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/Universidad de Sevilla, Seville, Spain;; Unidad Médico-Quirúrgica de Enfermedades Respiratorias, Hospital Virgen del Rocío. Seville, Spain;; CIBER de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: José Luis
authors.initials: JL
authors.lastname: López-Campos
mesh_terms: D000209:Acute-Phase Proteins / Q000378:metabolism*; D000368:Aged; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D006801:Humans; D008297:Male; D053858:Metabolic Networks and Pathways; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000378:metabolism* / Q000503:physiopathology*
chemical_list: D000209:Acute-Phase Proteins; D015415:Biomarkers
keywords: acute phase reactants; chronic obstructive pulmonary disease