Molin Magnus, Incamps Anne, Lemasson Manon, Andersson Mats, Pertsinidou Eleftheria, Högman Marieann, Lisspers Karin, Ställberg Björn, Sjölander Anders, Malinovschi Andrei, Janson Christer
Thermo Fisher Scientific, Uppsala, Sweden.
Thermo Fisher Scientific, Nimes, France.
ERJ Open Res. 2024 Feb 12;10(1). doi: 10.1183/23120541.00751-2023. eCollection 2024 Jan.
COPD affects 300 million people worldwide and is the third leading cause of death according to World Health Organization global health estimates. Early symptoms are subtle, and so COPD is often diagnosed at an advanced stage. Thus, there is an unmet need for biomarkers that can identify individuals at early stages of the disease before clinical symptoms have manifested. To date, few biomarkers are available for clinical diagnostic use in COPD.
We evaluated a panel of serum biomarkers related to inflammation and infection for their ability to discriminate between 77 subjects with chronic airflow limitation (CAL) and 142 subjects with COPD, 150 healthy subjects (divided into two control groups that were matched with regards to age, gender and smoking to CAL and COPD). Healthy subjects and CAL were from Burden of Obstructive Lung Disease (BOLD), a population-based study. CAL was defined by post-bronchodilatory forced expiratory volume in 1 s/forced vital capacity ratio <0.7 in the BOLD population. COPD subjects were from Tools for Identifying Exacerbations (TIE), a COPD patient cohort. Quantification of 100 biomarker candidates was done by liquid chromatography-tandem mass spectrometry.
Several protein-derived peptides were upregulated in CAL, compared to controls; most notably peptides representing histidine-rich glycoprotein (HRG), α-acid glycoprotein (AGP1), α-antitrypsin (α1AT) and fibronectin. Out of these, HRG-, AGP1- and α1AT-specific peptides were also elevated in the COPD cohort.
HRG, AGP1 and α1AT biomarkers distinguish subjects with CAL and COPD from healthy controls. HRG and AGP1 represent novel findings.
根据世界卫生组织的全球健康评估，慢性阻塞性肺疾病（COPD）影响着全球3亿人，是第三大死亡原因。其早期症状不明显，因此COPD常常在晚期才被诊断出来。所以，对于能够在临床症状出现之前识别疾病早期个体的生物标志物存在未满足的需求。迄今为止，几乎没有生物标志物可用于COPD的临床诊断。
我们评估了一组与炎症和感染相关的血清生物标志物区分77例慢性气流受限（CAL）患者、142例COPD患者以及150例健康受试者（分为两个对照组，在年龄、性别和吸烟方面与CAL组和COPD组相匹配）的能力。健康受试者和CAL组来自慢性阻塞性肺疾病负担（BOLD）这一基于人群的研究。在BOLD人群中，CAL由支气管扩张后1秒用力呼气容积/用力肺活量比值<0.7定义。COPD患者来自识别急性加重的工具（TIE）这一COPD患者队列。通过液相色谱 - 串联质谱法对100种生物标志物候选物进行定量分析。
与对照组相比，CAL组中几种蛋白质衍生肽上调；最显著的是代表富含组氨酸糖蛋白（HRG）、α-酸性糖蛋白（AGP1）、α-抗胰蛋白酶（α1AT）和纤连蛋白的肽。其中，HRG、AGP1和α1AT特异性肽在COPD队列中也升高。
HRG、AGP1和α1AT生物标志物可将CAL和COPD患者与健康对照区分开来。HRG和AGP1代表了新的发现。
