Schuetz Philipp, Marlowe Robert J, Mueller Beat
Clin Chem Lab Med. 2015 Mar;53(4):521-39. doi: 10.1515/cclm-2014-0748.
Plasma proadrenomedullin (ProADM) is a blood biomarker that may aid in multidimensional risk assessment of patients with chronic obstructive pulmonary disease (COPD). Co-secreted 1:1 with adrenomedullin (ADM), ProADM is a less biologically active, more chemically stable surrogate for this pluripotent regulatory peptide, which due to biological and ex vivo physical characteristics is difficult to reliably directly quantify. Upregulated by hypoxia, inflammatory cytokines, bacterial products, and shear stress and expressed widely in pulmonary cells and ubiquitously throughout the body, ADM exerts or mediates vasodilatory, natriuretic, diuretic, antioxidative, anti-inflammatory, antimicrobial, and metabolic effects. Observational data from four separate studies totaling 1366 patients suggest that as a single factor, ProADM is a significant independent, and accurate, long-term all-cause mortality predictor in COPD. This body of work also suggests that combined with different groups of demographic/clinical variables, ProADM provides significant incremental long-term mortality prediction power relative to the groups of variables alone. Additionally, the literature contains indications that ProADM may be a global cardiopulmonary stress marker, potentially supplying prognostic information when cardiopulmonary exercise testing results such as 6-min walk distance are unavailable due to time or other resource constraints or to a patient's advanced disease. Prospective, randomized, controlled interventional studies are needed to demonstrate whether ProADM use in risk-based guidance of site-of-care, monitoring, and treatment decisions improves clinical, quality-of-life, or pharmacoeconomic outcomes in patients with COPD.
血浆前肾上腺髓质素(ProADM)是一种血液生物标志物,可能有助于对慢性阻塞性肺疾病(COPD)患者进行多维度风险评估。ProADM与肾上腺髓质素(ADM)以1:1的比例共同分泌,它是这种多能调节肽的生物活性较低、化学稳定性更高的替代物,由于其生物学和体外物理特性,难以可靠地直接定量。ADM受缺氧、炎性细胞因子、细菌产物和剪切应力上调,在肺细胞中广泛表达且在全身普遍存在,发挥或介导血管舒张、利钠、利尿、抗氧化、抗炎、抗菌和代谢作用。来自四项总计1366例患者的独立研究的观察数据表明,作为单一因素,ProADM是COPD中一个显著的独立且准确的长期全因死亡率预测指标。这项工作还表明,与不同组的人口统计学/临床变量相结合,ProADM相对于单独的变量组提供了显著的额外长期死亡率预测能力。此外,文献表明ProADM可能是一种全身性心肺应激标志物,当由于时间或其他资源限制或患者病情晚期而无法获得心肺运动测试结果(如6分钟步行距离)时,可能提供预后信息。需要进行前瞻性、随机、对照干预研究,以证明在基于风险的医疗护理地点、监测和治疗决策指导中使用ProADM是否能改善COPD患者的临床、生活质量或药物经济学结局。