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.

Comprehensive Analysis of miRNA-mRNA-lncRNA Networks in Non-Smoking and Smoking Patients with Chronic Obstructive Pulmonary Disease

“…A2M, alpha 2-Macroglobulin is a major human plasma protease inhibitor that was speculated to play a role in the regulation of protease activity in the lung [24]. Dysregulation of A2M was found in smoking and nonsmoking patients with COPD compared with normal controls in both previous study [25] and this present study which suggested that A2M was a potential biomarker of COPD.…”

Fibrinogen is a promising biomarker for chronic obstructive pulmonary disease: evidence from a meta-analysis

“…Fibrinogen is a major acute-phase reactant, and its synthesis is up-regulated in response to inflammation [61], a major clinical feature of COPD. There is evidence that fibrinogen is implicated in clot formation and is associated with advanced COPD [11]. In addition, elevated fibrinogen in circulation was found to be associated with an increased risk of acute exacerbations in COPD [62].…”

“…On the basis of titles and abstracts, 187 articles were excluded with obvious reasons, leaving 111 articles for further evaluation in full texts. Finally, there were 45 articles in this meta-analysis [8][9][10][11][12][13], involving 5586 COPD patients and 18604 controls, and all articles were published from the year 1997 to 2019. Because two articles respectively provided data in COPD patients as a whole [46] and by COPD severity (stable and acute exacerbations) [9] based on the same study participants, we combined results from the two articles as a single study.…”

“…The association between circulating fibrinogen and COPD risk has been investigated by a large number of studies, with inconsistent and inconclusive findings. For example, some researchers have reported a significantly higher concentration of circulating fibrinogen in COPD patients than healthy controls [ 8–10 ], whereas others found that circulating fibrinogen concentration was comparable between the two groups [ 11 ], and even a significantly higher concentration in controls [ 12 , 13 ]. In a recent umbrella review of meta-analyses, Bellou and colleagues synthesized observational data on environmental factors and biomarkers in possible association with COPD, and found that circulating fibrinogen was a promising clinical marker of COPD, yet with very large heterogeneity [ 14 ].…”

Correlation in gene expression between the aggravation of chronic obstructive pulmonary disease and the occurrence of complications

“…COPD is a disease rising from inflammation and involving many cytokines and mediums. It can cause systematic inflammatory reactions, including the activation of C-reactive protein (CRP), IL-6, fibrinogen, leukocyte, and tumor necrosis factor (TNF)-α3, thereby markedly increasing the HP of the lung tissues and peripheral blood of COPD patients [11][12][13]. HP is an acute phase protein, and consequently, it would rise more significantly in COPD aggravation.…”