CNC-Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal; CIBB-Center for Innovation in Biomedicine and Biotechnology, University of Coimbra, Coimbra, Portugal; PDBEB-Doctoral Programme in Experimental Biology and Biomedicine, Institute for Interdisciplinary Research (IIIUC), University of Coimbra, Coimbra, Portugal; IIIUC-Institute of Interdisciplinary Research, University of Coimbra, Coimbra, Portugal.
CNC-Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal; CIBB-Center for Innovation in Biomedicine and Biotechnology, University of Coimbra, Coimbra, Portugal; IIIUC-Institute of Interdisciplinary Research, University of Coimbra, Coimbra, Portugal.
Sleep Med Rev. 2022 Aug;64:101659. doi: 10.1016/j.smrv.2022.101659. Epub 2022 Jun 7.
Obstructive Sleep Apnea (OSA) has been recognized as a major health concern worldwide, given its increasing prevalence, difficulties in diagnosis and treatment, and impact on health, economy, and society. Clinical guidelines highlight the need of biomarkers to guide OSA clinical decision-making, but so far, without success. In this systematic review and meta-analysis, registered on the International Prospective Register of Systematic Reviews database (ID CRD42020132556), we proposed to gather and further explore candidates identified in the literature as potential OSA biomarkers.
Search strategies for eight different databases (PubMed/Medline, Cochrane Library, Biblioteca Virtual da Saúde, Web of Science, EMBASE, World Intellectual Property Organization database, and bioRxiV and medRxiV Preprint Servers) were developed. We identified studies exploring potential biomarkers of OSA, in peripheral samples of adults, with and without OSA, with no comorbidities defined in study inclusion criteria, published after the last systematic review and meta-analysis conducted on OSA biomarkers, until May 31st, 2020. Risk of bias was assessed through the 14-item Quality Assessment Tool for Diagnostic Accuracy Studies. Demographic, clinical, and candidate biomarkers' data were collected and analyzed via random effects meta-analyses.
Among the 1512 unique studies screened, 120 met the inclusion criteria and 16 studies with low risk of bias were selected for meta-analyses. The selected 16 studies enrolled a total of 2156 participants, from which 1369 were diagnosed with OSA and 787 were disease-free controls. The assessed variables showed high heterogeneity. From the 38 biomarker candidates evaluated, only two were evaluated in more than one study. Most studies pinpointed candidates with more potential for OSA prognosis. ADAM29, FLRT2 and SLC18A3 mRNA levels in PBMCs, Endocan and YKL-40 levels in serum, and IL-6 and Vimentin levels in plasma revealed the most promising candidates for OSA diagnosis.
Although the current systematic review and meta-analysis allowed us to identify candidates to further explore as potential biomarkers in future studies, it is evident that OSA biomarkers research is still at an early stage. Most findings derive from small-size single-center study cohorts and single-candidate studies. We point several gaps in current OSA biomarker research that may guide into new directions and approaches towards the identification of OSA biomarkers.
阻塞性睡眠呼吸暂停（OSA）已被认为是全球主要的健康问题，因为它的患病率不断增加，诊断和治疗困难，以及对健康、经济和社会的影响。临床指南强调需要生物标志物来指导 OSA 的临床决策，但迄今为止，这一目标尚未实现。在这项已在国际前瞻性系统评价登记处（ID CRD42020132556）注册的系统评价和荟萃分析中，我们提出收集并进一步探索文献中确定的候选生物标志物，这些标志物被认为是潜在的 OSA 生物标志物。
为八个不同的数据库（PubMed/Medline、Cochrane 图书馆、Virtual da Saúde 图书馆、Web of Science、EMBASE、世界知识产权组织数据库、bioRxiV 和 medRxiV 预印本服务器）开发了搜索策略。我们确定了研究成人外周样本中潜在 OSA 生物标志物的研究，这些样本既有 OSA 也无 OSA，纳入标准中没有定义合并症，发表于最后一次 OSA 生物标志物系统评价和荟萃分析之后，直到 2020 年 5 月 31 日。通过 14 项诊断准确性研究质量评估工具评估偏倚风险。通过随机效应荟萃分析收集和分析人口统计学、临床和候选生物标志物数据。
在筛选出的 1512 篇独特研究中，有 120 篇符合纳入标准，有 16 篇研究被选为偏倚风险低的荟萃分析。入选的 16 项研究共纳入 2156 名参与者，其中 1369 名被诊断为 OSA，787 名无疾病对照组。评估的变量显示出高度异质性。在评估的 38 个候选生物标志物中，只有两个在超过一项研究中进行了评估。大多数研究指出了对 OSA 预后更有潜力的候选生物标志物。外周血单个核细胞（PBMCs）中 ADAM29、FLRT2 和 SLC18A3 mRNA 水平、血清中 Endocan 和 YKL-40 水平、血浆中 IL-6 和 Vimentin 水平被认为是 OSA 诊断最有前途的候选生物标志物。
尽管目前的系统评价和荟萃分析使我们能够确定候选生物标志物，以进一步探索未来的研究，但显然 OSA 生物标志物研究仍处于早期阶段。大多数发现来自于小样本单中心研究队列和单一候选生物标志物研究。我们指出了当前 OSA 生物标志物研究中的几个空白，这可能为确定 OSA 生物标志物的新方向和方法提供指导。
