The prognostic blood biomarker proadrenomedullin for outcome prediction in patients with chronic obstructive pulmonary disease (COPD): a qualitative clinical review

Abstract

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 allcause 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, qualityof-life, or pharmacoeconomic outcomes in patients with COPD.

The TRIAGE-ProADM Score for an Early Risk Stratification of Medical Patients in the Emergency Department - Development Based on a Multi-National, Prospective, Observational Study

“…Even though triage scores are developed to predict high initial treatment priority, daily decisions have to take into account harmful adverse events to further improve early risk stratification. As biomarker, ProADM was shown to provide relevant prognostic information in regard to the risk for adverse events within several prior studies focusing on selected patient subgroups with CAP [32–34], chronic obstructive pulmonary disease (COPD) [15, 35], or cardiovascular diseases [36, 37]. Our study now expands these findings and shows the prognostic value of ProADM for the first time in an unselected patient population.…”

“…The recent TRIAGE trial found a high prognostic ability of the inflammatory marker pro-adrenomedullin (ProADM) for the prediction of 30-day mortality, intensive care unit (ICU) admission, and high initial treatment priority [13, 14]. ProADM was also found to be of a high prognostic utility in several other studies in patients with respiratory tract infections and sepsis [15–21]. Physiologically, ProADM reveals natriuretic and vasodilatatory effects, and is expressed in different tissues, where it acts both as an autocrine and paracrine mediator [22, 23].…”

Mid-regional pro-adrenomedullin and copeptin to predict short-term prognosis of COPD exacerbations: a multicenter prospective blinded study

“…Along the same line, in our study but not in that of Stolz et al,11 investigators were informed to exclude patients with suspected heart failure or pneumonia. This may be of importance to explain the lower short-term prognostic value in our study compared to that of Stolz et al,11 since MR-proADM has been associated with cardiovascular stress and infection 28…”

Diagnosing sepsis – The role of laboratory medicine

“…It is upregulated in inflammatory and infectious conditions, and expressed in many clinical conditions including sepsis, respiratory infections and pneumonia, as well as also heart failure and myocardial infarction (37, 38). ProADM has been used as a prognostic marker, either alone or in risk stratification with other hormonal propeptides in patients with sepsis and severe pneumonia (39).…”