Cardenas Eduardo I, Andelid Kristina, Pournaras Nikolaos, Jansson Ann Ekberg-, Orsini Nicola, Stratelis Georgios, Jernberg Tomas, Lindén Anders
Division of Lung and Airway Research, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
COPD Center, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Clin Sci (Lond). 2025 May 9;139(9):449-462. doi: 10.1042/CS20255852.
During exacerbations, patients with chronic obstructive pulmonary disease (COPD) are at risk for severe cardiovascular disease (CVD). Despite this, the available literature on systemic biomarkers of CVD during exacerbations is limited. In the present study, a proteomic approach was used to assess alterations in the concentrations of 177 biomarkers of CVD and inflammation in serum samples from 26 long-term smokers (LTS) with mild-to-severe COPD (GOLD stage 1-3) and chronic bronchitis (COPD-CB) but no allergy. These patients were followed for 60 weeks, and they all provided paired samples during stable disease and exacerbations. Serum samples from ten healthy non-smokers (HNS) and ten LTS without COPD or CB constituted controls. Of all the proteins analyzed, only chymotrypsin C (CTRC), oncostatin M (OSM), and matrix metalloproteinase 10 (MMP-10) displayed significantly altered concentrations during exacerbations in the COPD-CB group. Here, the concentrations of CTRC and OSM correlated with exacerbation severity, CRP, blood leukocytes, and other cardiovascular biomarkers. In contrast, the concentration of MMP-10 during stable disease correlated with blood eosinophil counts and exacerbation numbers. Finally, the concentrations of OSM and MMP-10 during stable disease correlated with blood leukocytes and tobacco load, respectively. Our study suggests that CTRC, OSM, and MMP-10 bear potential as cardiorespiratory biomarkers in patients with COPD and CB. Collectively, these biomarkers display substantial alterations during exacerbations and correlate with the severity and number of exacerbations. These results motivate prospective studies to determine the clinical utility of CTRC, OSM, and MMP-10 in assessing cardiorespiratory risk in patients with COPD.
在慢性阻塞性肺疾病（COPD）急性加重期，患者有发生严重心血管疾病（CVD）的风险。尽管如此，关于急性加重期CVD系统性生物标志物的现有文献有限。在本研究中，采用蛋白质组学方法评估了26名患有轻至重度COPD（GOLD 1-3期）和慢性支气管炎（COPD-CB）但无过敏的长期吸烟者（LTS）血清样本中177种CVD和炎症生物标志物浓度的变化。这些患者随访60周，并且在疾病稳定期和急性加重期均提供了配对样本。来自10名健康非吸烟者（HNS）和10名无COPD或CB的LTS的血清样本作为对照。在所有分析的蛋白质中，只有胰凝乳蛋白酶C（CTRC）、抑瘤素M（OSM）和基质金属蛋白酶10（MMP-10）在COPD-CB组急性加重期显示出浓度有显著变化。在此，CTRC和OSM的浓度与急性加重严重程度、CRP、血液白细胞及其他心血管生物标志物相关。相比之下，稳定期MMP-10的浓度与血液嗜酸性粒细胞计数和急性加重次数相关。最后，稳定期OSM和MMP-10的浓度分别与血液白细胞和吸烟量相关。我们的研究表明，CTRC、OSM和MMP-10有潜力作为COPD和CB患者的心肺生物标志物。总体而言，这些生物标志物在急性加重期有显著变化，并与急性加重的严重程度和次数相关。这些结果促使进行前瞻性研究，以确定CTRC、OSM和MMP-10在评估COPD患者心肺风险中的临床效用。
