Predicting Mortality in COPD with Validated and Sensitive Biomarkers; Fibrinogen and Mid-Range-Proadrenomedullin (MR-proADM).

Although fibrinogen is a FDA qualified prognostic biomarker in COPD, it still lacks sufficient resolution to be clinically useful. Next to replication of findings in different cohorts also the combination with other validated biomarkers should be investigated. Therefore, the aim of this study was to confirm in a large well-defined population of COPD patients whether fibrinogen can predict mortality and whether a combination with the biomarker MR-proADM can increase prognostic accuracy. From the COMIC cohort study we included COPD patients with a blood sample obtained in stable state (n = 640) and/or at hospitalization for an acute exacerbation of COPD (n = 262). Risk of death during 3 years of follow up for the separate and combined biomarker models was analyzed with Cox regression. Furthermore, logistic regression models for death after one year were constructed. When both fibrinogen and MR-proADM were included in the survival model, a doubling in fibrinogen and MR-proADM levels gave a 2.2 (95% CI 1.3-3.7) and 2.1 (95% CI 1.5-3.0) fold increased risk of dying, respectively. The prediction model for death after 1 year improved significantly when MR-proADM was added to the model with fibrinogen (AUC increased from 0.78 to 0.83; p = 0.02). However, the combined model was not significantly more adequate than the model with solely MR-proADM (AUC 0.83 vs 0.82; p = 0.34). The study suggests that MR-proADM is more promising than fibrinogen in prediciting mortality. Adding fibrinogen to a model containing MR-proADM does not significantly increase the predictive capacity of the model.

Stable-State Midrange-Proadrenomedullin Level Is a Strong Predictor of Mortality in Patients With COPD.

BACKGROUND: Midrange-proadrenomedullin (MR-proADM) has been shown to be elevated in patients hospitalized for an acute exacerbation of COPD (AECOPD) and in patients with community-acquired pneumonia. When measured during AECOPDs, MR-proADM has also been shown to be a predictor of mortality. We hypothesized that MR-proADM levels measured in a stable state could also predict mortality. METHODS: We included 181 patients in whom we had paired plasma samples for MR-proADM determinations during a stable state and at hospitalization for an AECOPD when they also produced sputum. Time to death or censoring was compared between patients with MR-proADM above or below the median of 0.71 nmol/L. The predictive value of MR-proADM for survival was determined by calculating the C statistic. RESULTS: Patients with COPD and MR-proADM levels > 0.71 nmol/L in the stable state had a threefold-higher risk of dying than did patients with MR-proADM levels < 0.71 nmol/L (hazard ratio, 2.98 [95% CI, 1.51-5.90]; C statistic, 0.76). The corrected OR for 1-year mortality was 8.90 (95% CI, 1.94-44.6) in patients with high MR-proADM levels measured in the stable state, compared with patients with low levels measured in the stable state. CONCLUSIONS: MR-proADM measured in the stable state appeared to be a strong predictor of mortality in patients with COPD. MR-proADM is far easier to measure than other predictors of mortality in COPD, such as BMI, airflow obstruction, dyspnea, and exercise capacity score.