Escamilla-Gil Jose Miguel, Torres-Duque Carlos A, Llinás-Caballero Kevin, Proaños-Jurado Nadia Juliana, De Vivero María M, Ramirez Jonathan Camilo, Regino Ronald, Florez de Arco Lucila Teresa, Dennis Rodolfo, González-García Mauricio, Caraballo Luis, Acevedo Nathalie
Institute for Immunological Research, University of Cartagena, Cartagena, Colombia.
CINEUMO, Research Center, Fundación Neumológica Colombiana, Bogotá, Colombia.
Int J Chron Obstruct Pulmon Dis. 2025 Apr 22;20:1161-1174. doi: 10.2147/COPD.S506517. eCollection 2025.
Asthma and chronic obstructive pulmonary disease overlap patients (ACO) have more exacerbations and a worse prognosis than pure asthma or COPD, and it is of great interest to identify differential biomarkers of ACO. We compared blood eosinophil counts, plasma IgE and protein levels among patients with asthma, ACO, COPD, and healthy subjects to identify those associated with ACO.
397 adults (age 40-90 years) were recruited from two Colombian cities: asthma (n=123), COPD (n=100), ACO (n=74) and healthy control (HC, n=100). Plasma protein levels were measured using the Proximity Extension Assay (Olink Proteomics).
There were no differences in blood eosinophil counts between the patient groups. Total and specified IgE levels were higher in patients with ACO than in those with COPD. Ten plasma proteins showed significant differences between the patients with ACO and HC. In patients above 60 years old, CXCL9 discriminates ACO from asthma patients with AUC 0.73 (0.63-0.82, DeLong test p=0.007), and in patients below 60 years old, MCP-3 discriminates ACO from COPD patients with AUC 0.84 (0.62-1.0, DeLong test p=0.006). CUB domain-containing protein 1 (CDCP1) levels (OR, 0.47; p=0.008) and age > 60 years (OR, 0.25; p=0.001) were negatively associated with ACO.
CXCL9 levels could be used to discriminate ACO from asthma patients and MCP-3 to discriminate ACO from COPD. Protein inflammatory signatures in plasma of ACO patients were similar to the COPD group. This study revealed novel biomarkers that may help characterize patients with ACO.
哮喘与慢性阻塞性肺疾病重叠患者（ACO）比单纯哮喘或慢性阻塞性肺疾病患者有更多的急性加重发作且预后更差，因此识别ACO的差异生物标志物具有重要意义。我们比较了哮喘、ACO、慢性阻塞性肺疾病患者及健康受试者的血液嗜酸性粒细胞计数、血浆免疫球蛋白E（IgE）和蛋白质水平，以确定与ACO相关的指标。
从哥伦比亚的两个城市招募了397名成年人（年龄40 - 90岁）：哮喘患者（n = 123）、慢性阻塞性肺疾病患者（n = 100）、ACO患者（n = 74）和健康对照者（HC，n = 100）。使用邻位延伸分析（Olink蛋白质组学）测量血浆蛋白水平。
各患者组之间血液嗜酸性粒细胞计数无差异。ACO患者的总IgE水平和特定IgE水平高于慢性阻塞性肺疾病患者。10种血浆蛋白在ACO患者和健康对照者之间存在显著差异。在60岁以上的患者中，CXC趋化因子配体9（CXCL9）区分ACO与哮喘患者的曲线下面积（AUC）为0.73（0.63 - 0.82，德龙检验p = 0.007）；在60岁以下的患者中，单核细胞趋化蛋白3（MCP - 3）区分ACO与慢性阻塞性肺疾病患者的AUC为0.84（0.62 - 1.0，德龙检验p = 0.006）。含CUB结构域蛋白1（CDCP1）水平（比值比，0.47；p = 0.008）和年龄>60岁（比值比，0.25；p = 0.001）与ACO呈负相关。
CXCL9水平可用于区分ACO与哮喘患者，MCP - 3可用于区分ACO与慢性阻塞性肺疾病患者。ACO患者血浆中的蛋白质炎症特征与慢性阻塞性肺疾病组相似。本研究揭示了可能有助于ACO患者特征化的新型生物标志物。
