Stable State Proadrenomedullin Level in COPD Patients: A Validation Study

Abstract

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 cut-off 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 cut-off 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 Is Associated With Severe Exacerbations in COPD

“…To establish whether the value of 0.87 nmol/l is the ideal cut-off level for morbidity as well we performed additional analyses with different validated cut-off levels of MR-proADM used in a recent validation study. (28) The different cut-off levels did not result in a stronger association (data not shown), thus the cut-off value of 0.87 nmol/l seems to be reasonable for morbidity as well.…”

Role of Atypical Chemokines and Chemokine Receptors Pathways in the Pathogenesis of COPD

“…Although increased serum MR-proAM levels in stable COPD patients (n=490, mean age 67 years) were correlated with an increased risk of mortality, there was no correlation between serum MR-proAM levels and mortality in COPD patients during exacerbation (n=101, mean age 71 years) [435].…”

“…1 2 (EDN) Serum + [350] 3 (ECP) Serum + [371][372] Induced sputum + [367-368, 370,372] BAL + [367] Serum + [350] 4 5 (angiogenin) Serum + [426] AM Serum + [433][434][435]437] Serum + [436] -MSH…”

“…Literature data seems to indicate that MR-proAM may have a key role in the pathogenesis of COPD and their acute exacerbations correlated to release of several pro-inflammatory and pro-angiogenic mediators such as CXCL1 and CXCL5 MR-proAM mediated. In addition, MR-proAM can be represent as useful potential biomarker of disease severity [433][434][435][436][437].…”

Admission of patients with chest pain and/or breathlessness from the emergency department in relation to risk assessment and copeptin levels – an observational study

“…P-values < 0.05 were considered statistically significant. The biomarkers MR-proANP, MR-proADM, and copeptin were dichotomized by cut-off values used in previous studies (23,27,28). Data were analyzed with binary logistic regression to estimate adjusted odds ratio (ORs) for the single outcome variable identified above.…”