Winter Natasha A, Gibson Peter G, Fricker Michael, Simpson Jodie L, Wark Peter A, McDonald Vanessa M
National Health and Medical Research Council Centre for Research Excellence in Severe Asthma and The Priority Research Centre for Health Lungs, The University of Newcastle, Newcastle, NSW, Australia.
School of Medicine and Public Health, The University of Newcastle, Newcastle, NSW, Australia.
Allergy Asthma Immunol Res. 2021 May;13(3):450-467. doi: 10.4168/aair.2021.13.3.450.
Systemic inflammatory biomarkers can improve diagnosis and assessment of chronic obstructive pulmonary disease (COPD) and asthma. We aimed to validate an airway disease biomarker panel of 4 systemic inflammatory biomarkers, α2-macroglobulin, ceruloplasmin, haptoglobin and hemopexin, to establish their relationship to airway disease diagnosis and inflammatory phenotypes and to identify an optimized biomarker panel for disease differentiation.
Participants with COPD or asthma were classified by inflammatory phenotypes. Immunoassay methods were used to measure levels of validation biomarkers in the sera of participants with disease and non-respiratory disease controls. Markers were analyzed individually and in combination for disease differentiation and compared to established biomarkers (C-reactive protein, interleukin-6, and white blood cell/blood eosinophil count).
The study population comprised of 141 COPD, 127 severe asthma, 54 mild-moderate asthma and 71 control participants. Significant differences in ceruloplasmin, haptoglobin and hemopexin levels between disease groups and between systemic inflammatory phenotypes were observed. However, no differences were found between airway inflammatory phenotypes. Hemopexin was the best performing individual biomarker and could diagnose COPD versus control participants (area under the curve [AUC], 98.3%; 95% confidence interval [CI], 96.7%-99.9%) and differentiate COPD from asthmatic participants (AUC, 97.0%; 95% CI, 95.4%-98.6%), outperforming established biomarkers. A biomarker panel, including hemopexin, haptoglobin and other established biomarkers, could diagnose asthma versus control participants (AUC, 87.5%; 95% CI, 82.8%-92.2%).
Hemopexin can be a novel biomarker with superior diagnostic ability in differentiating COPD and asthma. We propose an anti-inflammatory axis between the airways and systemic circulation, in which hemopexin is a protective component in airway disease.
全身性炎症生物标志物可改善慢性阻塞性肺疾病(COPD)和哮喘的诊断与评估。我们旨在验证由4种全身性炎症生物标志物(α2-巨球蛋白、铜蓝蛋白、触珠蛋白和血红素结合蛋白)组成的气道疾病生物标志物组,以确定它们与气道疾病诊断及炎症表型的关系,并确定用于疾病鉴别的优化生物标志物组。
将患有COPD或哮喘的参与者按炎症表型进行分类。采用免疫测定法测量患有疾病的参与者和非呼吸道疾病对照者血清中验证生物标志物的水平。对标志物进行单独和联合分析以进行疾病鉴别,并与既定生物标志物(C反应蛋白、白细胞介素-6以及白细胞/血液嗜酸性粒细胞计数)进行比较。
研究人群包括141名COPD患者、127名重度哮喘患者、54名轻中度哮喘患者和71名对照参与者。观察到疾病组之间以及全身性炎症表型之间铜蓝蛋白、触珠蛋白和血红素结合蛋白水平存在显著差异。然而,气道炎症表型之间未发现差异。血红素结合蛋白是表现最佳的单个生物标志物,可诊断COPD与对照参与者(曲线下面积[AUC],98.3%;95%置信区间[CI],96.7%-99.9%),并区分COPD与哮喘患者(AUC,97.0%;95%CI,95.4%-98.6%),优于既定生物标志物。一个包括血红素结合蛋白、触珠蛋白和其他既定生物标志物的生物标志物组可诊断哮喘与对照参与者(AUC,87.5%;95%CI,82.8%-92.2%)。
血红素结合蛋白可能是一种在鉴别COPD和哮喘方面具有卓越诊断能力的新型生物标志物。我们提出气道与体循环之间存在抗炎轴,其中血红素结合蛋白是气道疾病中的一种保护成分。