School of Pharmacy and Biomedical Sciences, Institute of Biomedical and Biomolecular Sciences, University of Portsmouth, Portsmouth, UK -
Minerva Med. 2022 Feb;113(1):63-78. doi: 10.23736/S0026-4806.21.07381-X. Epub 2021 Jul 8.
Biomarkers may be diagnostic of asthma, they may predict or reflect response to therapy or they may identify patients at risk of asthma exacerbation. A biomarker is most often measured in biologic fluids that are sampled using relatively non-invasive sampling techniques such as blood, sputum, urine or exhaled breath. Biomarkers should be stable, readily quantifiable and their measurement should be reproducible and not confounded by other host factors, or the presence of comorbidities. However, asthma comprises multiple molecular endotypes and single, sensitive, specific, biomarkers reflecting these endotypes may not exist. Combining biomarkers may improve their predictive capability in asthma. The most well-established endotypes are those described as type 2 and non-type 2 asthma. Clinical trials established the fraction of exhaled nitric oxide (FeNO) and blood eosinophil counts as key biomarkers of response to corticosteroid or targeted anti-inflammatory therapy in type 2 asthma. However, these biomarkers may have limited value in the management of asthma in real-life settings or routine clinical practice. Biomarkers for type 2 asthma are not well described or validated and more research is needed. Breathomics has provided evidence to propose a number of exhaled volatile organic compounds (VOCs) as surrogate biomarkers for airway inflammatory phenotypes, disease activity and adherence to therapy. Analysis of urinary eicosanoids has identified eicosanoids related to type 2 and non-type 2 inflammation. Future clinical trials will be important in determining how exhaled VOCs or urinary eicosanoid profiles can be used to direct precision treatments. Their future clinical use will also depend on developing simplified instrumentation for biomarker analysis at the point-of-care.
生物标志物可用于诊断哮喘,预测或反映治疗反应,或识别哮喘恶化风险患者。生物标志物通常在使用相对非侵入性采样技术(如血液、痰液、尿液或呼气)采集的生物液体中进行测量。生物标志物应稳定、易于定量,其测量应具有可重复性,不受其他宿主因素或合并症的影响。然而,哮喘包含多种分子表型,反映这些表型的单一、敏感、特异的生物标志物可能并不存在。组合生物标志物可能会提高其在哮喘中的预测能力。最成熟的表型是 2 型和非 2 型哮喘。临床试验确立了呼出气一氧化氮(FeNO)和血嗜酸性粒细胞计数作为 2 型哮喘对皮质类固醇或靶向抗炎治疗反应的关键生物标志物。然而,这些生物标志物在真实环境或常规临床实践中的哮喘管理中的价值可能有限。2 型哮喘的生物标志物描述或验证不足,需要更多的研究。呼吸组学提供了证据,提出了一些呼气挥发性有机化合物(VOC)作为气道炎症表型、疾病活动和治疗依从性的替代生物标志物。对尿类二十烷酸的分析确定了与 2 型和非 2 型炎症相关的类二十烷酸。未来的临床试验将重要,以确定呼气 VOC 或尿类二十烷酸谱如何用于指导精准治疗。它们未来的临床应用还取决于开发用于在床边进行生物标志物分析的简化仪器。