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 Proadrenomedullin Level in COPD Patients: A Validation Study

In patients with stable COPD, proadrenomedullin (MR-proADM) has been shown to be a good predictor for mortality. This study aims to provide an external validation of earlier observed cut-off values used by Zuur-Telgen et al. and Stolz.et al. in COPD patients in stable state and at hospitalization for an acute exacerbation of COPD (AECOPD). From the COMIC cohort study we included 545 COPD patients with a blood sample obtained in stable state (n = 490) and/or at hospitalization for an AECOPD (n = 101). Time to death was compared between patients with MR-proADM cut-off scores 0.71 and 0.75 nmol/L for stable state or 0.79 and 0.84 nmol/l for AECOPD. The predictive value of MR-proADM for survival was represented by the C statistic. Risk ratios were corrected for sex, age, BMI, presence of heart failure, and GOLD stage. Patients above the cutoff of 0.75 nmol/l had a 2-fold higher risk of dying than patient below this cut-off (95% CI: 1.20-3.41). The cutoff of 0.71 nmol/l showed only a borderline significantly higher risk of 1.67 (95% CI: 0.98-2.85). The corrected odds ratios for one-year mortality were 3.15 (95% CI 1.15-8.64) and 3.70 (95% CI 1.18-11.6) in patients with MR-proADM levels above versus below the cut-off of respectively 0.75 and 0.71 nmol/l measured in stable state. MR-proADM levels in samples at hospitalization for an AECOPD were not predictive for mortality in this validation cohort. MR-proADM in stable state is a powerful predictor for mortality

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

Stable-State Midrange Proadrenomedullin Is Associated With Severe Exacerbations in COPD

Background: Elevated levels of midrange proadrenomedullin (MR-proADM) are associated with worse outcome in different diseases, including COPD. The association of stable-state MR-proADM with severe acute exacerbations of COPD (AECOPDs) requiring hospitalization, or with community-acquired pneumonia (CAP) in patients with COPD, has not been studied yet. The aim of this study was to evaluate the association of stable-state MR-proADM with severe AECOPD and CAP in patients with COPD. Methods: This study pooled data of 1,285 patients from the Cohort of Mortality and Inflammation in COPD (COMIC) and PRedicting Outcome using systemic Markers In Severe Exacerbations of Chronic Obstructive Pulmonary Disease (PROMISE-COPD) cohort studies. Time until first severe AECOPD was compared between patients with high (≥ 0.87 nmol/L) or low (< 0.87 nmol/L) levels of plasma MR-proADM in stable state as previously defined. For time until first CAP, only COMIC data (n = 795) were available. Results: Patients with COPD with high-level stable-state MR-proADM have a significantly higher risk for severe AECOPD compared with those with low-level MR-proADM with a corrected hazard ratio (HR) of 1.30 (95% CI, 1.01-1.68). Patients with high-level stable-state MR-proADM had a significantly higher risk for CAP compared with patients with COPD with low-level MR-proADM in univariate analysis (HR, 1.93; 95% CI, 1.24-3.01), but after correction for age, lung function, and previous AECOPD, the association was no longer significant (corrected HR, 1.10; 95% CI, 0.68-1.80). Conclusions: Stable-state high-level MR-proADM in patients with COPD is associated with severe AECOPD but not with CAP

Adrenomedullin optimises mortality prediction in COPD patients

Background: Current multicomponent scores that predict mortality in COPD patients might underestimate the systemic component of COPD. Therefore, we evaluated the accuracy of circulating levels of proadrenomedullin (MR-proADM) alone or combined with the ADO (Age, Dyspnoea, airflow Obstruction), updated ADO or BOD (Body mass index, airflow Obstruction, Dyspnoea) index to predict all-cause mortality in stable COPD patients. Methods: This study pooled data of 1285 patients from the COMIC and PROMISE-COPD study. Results: Patients with high MR-proADM levels (>= 0.87 nmol/l) had a 2.1 fold higher risk of dying than those with lower levels (p < 0.001). Based on the C-statistic, the ADOA index (ADO plus MR-proADM) (C = 0.72) was the most accurate predictor followed by the BODA (BOD plus MR-proADM) (C = 0.71) and the updated ADOA index (updated ADO plus MR-proADM) (C = 0.70). Adding MR-proADM to ADO and BOD was superior in forecasting 1- and 2-year mortality. The net percentages of persons with events correctly reclassified (NRI+) within respectively 1-year and 2-year was 31% and 20% for ADO, 31% and 20% for updated ADO and 25% and 19% for BOD. The net percentages of persons without events correctly reclassified (NRI-) within respectively 1-year and 2-year was 26% and 27% for ADO, 27% and 28% for updated ADO and 34% and 34% for BOD. Conclusions: Adding MR-proADM increased the predictive power of BOD, ADO and updated ADO index. (C) 2015 Elsevier Ltd. All rights reserved

Adrenomedullin optimises mortality prediction in COPD patients

Background: Current multicomponent scores that predict mortality in COPD patients might underestimate the systemic component of COPD. Therefore, we evaluated the accuracy of circulating levels of proadrenomedullin (MR-proADM) alone or combined with the ADO (Age, Dyspnoea, airflow Obstruction), updated ADO or BOD (Body mass index, airflow Obstruction, Dyspnoea) index to predict all-cause mortality in stable COPD patients.Methods: This study pooled data of 1285 patients from the COMIC and PROMISE-COPD study.Results: Patients with high MR-proADM levels (&gt;= 0.87 nmol/l) had a 2.1 fold higher risk of dying than those with lower levels (p &lt;0.001). Based on the C-statistic, the ADOA index (ADO plus MR-proADM) (C = 0.72) was the most accurate predictor followed by the BODA (BOD plus MR-proADM) (C = 0.71) and the updated ADOA index (updated ADO plus MR-proADM) (C = 0.70). Adding MR-proADM to ADO and BOD was superior in forecasting 1- and 2-year mortality. The net percentages of persons with events correctly reclassified (NRI+) within respectively 1-year and 2-year was 31% and 20% for ADO, 31% and 20% for updated ADO and 25% and 19% for BOD. The net percentages of persons without events correctly reclassified (NRI-) within respectively 1-year and 2-year was 26% and 27% for ADO, 27% and 28% for updated ADO and 34% and 34% for BOD.Conclusions: Adding MR-proADM increased the predictive power of BOD, ADO and updated ADO index. (C) 2015 Elsevier Ltd. All rights reserved.</p