Ahasic Amy M, Christiani David C
Section of Pulmonary, Critical Care, and Sleep Medicine, Yale University School of Medicine, New Haven, Connecticut.
Department of Environmental Genetics, Harvard School of Public Health, Harvard Medical School and Massachusetts General Hospital, Harvard, Massachusetts.
Semin Respir Crit Care Med. 2015 Dec;36(6):809-22. doi: 10.1055/s-0035-1564852. Epub 2015 Nov 23.
Personalized medicine has typically referred to the use of genomics in clinical care. However, the concept more broadly refers to recognizing the heterogeneity of each individual patient, particularly their unique risk factors for developing disease or having poor outcomes, and using this to inform treatment decisions. Pharmacogenomics was perhaps the first major clinical application that came out of the Human Genome Project, but its translation to the critical care arena has been limited by numerous factors. Biomarkers have been widely studied in critical illnesses such as sepsis and acute respiratory distress syndrome in an attempt to aid in accurate diagnostic classification, to predict outcomes, and to assess response to therapy. Clinical use of such biomarkers has remained limited, but multi-biomarker panels have attempted to better reflect the complex physiology of critical illness, and to assist in design and recruitment for clinical trials. Genetic association and gene expression studies have been aimed at classifying risk for and severity in disease, as well as in predicting outcomes. While our understanding of the pathogenesis of critical illness has progressed significantly, the clinical utility of genetic markers remains limited. Novel methods are reaching closer to clinically applicable platforms, both for use in clinical trials and in direct patient care. Although we are not yet living in an era of personalized and precise medical care in the intensive care unit, the future is promising.
个性化医疗通常是指在临床护理中使用基因组学。然而,这一概念更广泛地是指认识到每个患者的异质性,特别是他们患疾病或预后不良的独特风险因素,并利用这些信息来指导治疗决策。药物基因组学可能是人类基因组计划产生的首个主要临床应用,但它在重症监护领域的转化受到诸多因素的限制。生物标志物已在脓毒症和急性呼吸窘迫综合征等危重病中得到广泛研究,旨在帮助进行准确的诊断分类、预测预后以及评估对治疗的反应。此类生物标志物的临床应用仍然有限,但多生物标志物组合已试图更好地反映危重病的复杂生理学,并协助临床试验的设计和受试者招募。基因关联研究和基因表达研究旨在对疾病的风险和严重程度进行分类,以及预测预后。虽然我们对危重病发病机制的理解有了显著进展,但遗传标志物的临床效用仍然有限。新方法正越来越接近可用于临床试验和直接患者护理的临床应用平台。尽管我们尚未生活在重症监护病房的个性化精准医疗时代,但未来充满希望。