From the Department of Preventive Medicine, Northwestern University Feinberg School of Medicine.
CORRESPONDENCE TO: Rhami Khorfan, BA, Northwestern University Feinberg School of Medicine, Department of Preventive Medicine, 680 N Lake Shore Dr, Ste 1400, Chicago, IL 60611; e-mail: firstname.lastname@example.org
FINANCIAL/NONFINANCIAL DISCLOSURES: The author has reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.
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In a recent article in CHEST (March 2014) by Zuur-Telgen et al1 about the usefulness of midrange-proadrenomedullin (MR-proADM) in predicting mortality in patients with COPD, the authors confirm previous findings by Stolz et al2 that higher MR-proADM levels during hospitalization for an acute exacerbation of COPD are associated with increased mortality. In addition, Zuur-Telgen et al1 demonstrate the association between high levels of MR-proADM in the stable state and increased mortality, even after adjustment for comorbidities. These results provide hopeful evidence for the use of MR-proADM measurement in the prognosis of COPD. However, several steps must be taken before this biomarker can be accepted as a strong predictor of mortality in COPD.
The authors discuss an existing measure of prognosis used in COPD, an index of BMI, airflow obstruction, dyspnea, and exercise capacity (BODE) and compare the C statistic for each test. However, they do not provide a test of the incremental usefulness of MR-proADM. Therefore, it is not clear whether the MR-proADM is measuring the same risk as the BODE index or if it is predicting risk that is not measured by the BODE index. The construction of a composite receiver operating characteristic curve that includes both the BODE index and MR-proADM level and calculation of that C statistic is an important step. This would provide insight into how much information the use of MR-proADM is adding to prognosis, in terms of the improvement in net benefit. This information could help guide the decision about whether to use MR-proADM as an adjunct or potential replacement to the BODE index.
Another important step in evaluating the usefulness of a new biomarker as a prediction tool is replication. The Prognosis Research Strategy (PROGRESS) group set forth recommendations for the conduct and reporting of prognostic factor research, a major component of which is replication.3 Much like Zuur-Telgen et al1 confirmed the results of Stolz et al,2 it is necessary to validate the results of the study in a different cohort of patients, in the initial study when possible. This is especially important because of the limitations inherent in the study, especially selection bias. As noted by the authors, patients included in the study were hospitalized for acute exacerbations of COPD, meaning they may have only included patients with a higher severity of disease necessitating hospitalization. This could have an effect on both the levels of MR-proADM and the mortality rate.
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