Mortality risk prediction in COPD by a prognostic biomarker panel

Abstract

Chronic obstructive pulmonary disease (COPD) is a complex disease with various phenotypes. The simultaneous determination of multiple biomarkers reflecting different pathobiological pathways could be useful in identifying individuals with an increased risk of death.We derived and validated a combination of three biomarkers (adrenomedullin, arginine vasopressin and atrial natriuretic peptide), assessed in plasma samples of 385 patients, to estimate mortality risk in stable COPD. Biomarkers were analysed in combination and defined as high or low.In the derivation cohort (n5142), there were 73 deaths during the 5-year follow-up. Crude hazard ratios for mortality were 3.0 (95% CI 1.8-5.1) for one high biomarker, 4.8 (95% CI 2.4-9.5) for two biomarkers and 9.6 (95% CI 3.3-28.3) for three high biomarkers compared with no elevated biomarkers. In the validation cohort (n5243), 87 individuals died. Corresponding hazard ratios were 1.9 (95% CI 1.1-3.3), 3.1 (95% CI 1.8-5.4) and 5.4 (95% CI 2.5-11.4). Multivariable adjustment for clinical variables as well as the BODE (body mass index, airflow obstruction, dyspnoea, exercise capacity) index and stratification by the Global Initiative for Chronic Obstructive Lung Disease stages provided consistent results. The addition of the panel of three biomarkers to the BODE index generated a net reclassification improvement of 57.9% (95% CI 21.7-92.4%) and 45.9% (95% CI 13.9-75.7%) at 3 and 5 years, respectively.Simultaneously elevated levels of adrenomedullin, arginine vasopressin and atrial natriuretic peptide are associated with increased risk of death in patients with stable COPD. @ERSpublications Simultaneously elevated levels of ADM, AVP and ANP are associated with increased risk of death in COPD

Patient Heterogeneity in Health Economic Decision Models for Chronic Obstructive Pulmonary Disease: Are Current Models Suitable to Evaluate Personalized Medicine?

“…All models included a strong association between age and mortality, which was in line with studies found in the literature [32,33,[35][36][37][38]. Validation against trial results also showed a difference in 12 mortality between young and old patients for the trial as well as most models.…”

“…The difference in mortality is less clear from the literature. Some studies reported lower mortality rates for females [32][33][34], while others found no difference [35][36][37][38]. Only two models specified quality of life by gender, while several studies found a lower quality of life for female patients [39][40][41].…”

“…Exacerbations for example are highly associated with the number of previous exacerbations [29 -31, 52]. Mortality in COPD is associated with age and FEV1, but also with co-morbidities, BMI, dyspnea and several other clinical parameters [32,34,36,38,53]. BMI also seems to be associated with quality of life in COPD [39,54] and co-morbidities may affect COPD-related costs [44,45,55,56].…”

Adding biological markers to COPD categorisation schemes: a way towards more personalised care?

“…acute coronary syndrome [45]. Altogether, several studies found some prognostic value of cardiac biomarkers in stable or exacerbated COPD, individually or as part of a panel [46]. In a previous study, STOLZ et al [47] found that adrenomedullin increases the predictive ability of the BODE index, while combining this biomarker to the BOD (body mass index, FEV1 and dyspnoea) components of the BODE index provided better discrimination than the BODE index itself, therefore alleviating the need for a 6-min walk test.…”

A sum greater than its parts

“…While the mechanisms explaining these unique phenotypes or the relationship between COPD and extrapulmonary comorbidities remain a mystery, clearly the notion of a single laboratory test capturing this diversity is hard to endorse. In this issue, STOLZ et al [10] have successfully rectified some of the past shortcomings of biomarker research by broadening the approach to biomarkers, which may have previously been too confined to allow for success. The authors have studied a panel of three biomarkers (adrenomedullin, arginine-vasopressin and atrial natriuretic peptide) in patients with stable COPD, revealing that elevations in all three biomarkers are associated with a five-fold increased risk of death.…”