Midrange-proadrenomedullin as a marker for mortality and morbidity in COPD

Chronic Obstructive Pulmonary Disease (COPD) is a heterogeneric and complex disease. The prediction of mortality is relevant to identify patients in whom adjustment of care may be appropriate. There is growing interest in biomarkers to assess disease heterogeneity and predict progression. One possible biomarker is midrange-proadrenomedullin (MR-proADM) The main objective of this thesis was to see if MR-proADM is associated with morbidity and mortality in COPD patients. In our cohort 23% of patients did not survive 2 years in the follow-up period. We showed that high levels of MR-proADM in stable state are associated with a 3-fold increased risk of mortality when corrected for potential confounding variables.
This finding was confirmed in a validation study in a different set of COPD patients. Another biomarker associated with mortality in COPD is fibrinogen. We found that adding MR-proADM to fibrinogen increases the accuracy of the short term mortality prediction model (one year follow-up) both relevantly and significantly. However, the combined model was not superior in predicting short term mortality compared to a model with solely MR-proADM. Furthermore, we added MR-proADM to several multicomponent indices to increase predicating capacity. We combined MR-proADM with the ADO (Age, Dyspnea and airflow Obstruction) the updated ADO and the BOD (BMI, airflow Obstruction and Dyspnea). Adding MR-proADM to the indices ADO, updated ADO and BOD improved mortality prediction of all three indices. Finally, we looked at the risk of acute exacerbations of COPD (AECOPDs). We showed that MR-proADM, measured in stable state, was a good predictor for the occurrence of a future severe AECOPD. We conclude that MR-proADM is a useful biomarker in predicting mortality and morbidity in COPD. Future studies are needed to determine if it can be used to adjustments of care.