Mid-regional pro-adrenomedullin and copeptin to predict short-term prognosis of COPD exacerbations: a multicenter prospective blinded study

Abstract

BackgroundExacerbations of COPD (ECOPD) are a frequent cause of emergency room (ER) visits. Predictors of early outcome could help clinicians in orientation decisions. In the current study, we investigated whether mid-regional pro-adrenomedullin (MR-proADM) and copeptin, in addition to clinical evaluation, could predict short-term outcomes.Patients and methodsThis prospective blinded observational study was conducted in 20 French centers. Patients admitted to the ER for an ECOPD were considered for inclusion. A clinical risk score was calculated, and MR-proADM and copeptin levels were determined from a venous blood sample. The composite primary end point comprised 30-day death or transfer to the intensive care unit or a new ER visit.ResultsA total of 379 patients were enrolled in the study, of whom 277 were eventually investigated for the primary end point that occurred in 66 (24%) patients. In those patients, the median (interquartile range [IQR]) MR-proADM level was 1.02 nmol/L (0.77–1.48) versus 0.83 nmol/L (0.63–1.07) in patients who did not meet the primary end point (P=0.0009). In contrast, copeptin levels were similar in patients who met or did not meet the primary end point (P=0.23). MR-proADM levels increased with increasing clinical risk score category: 0.74 nmol/L (0.57–0.89), 0.83 nmol/L (0.62–1.12) and 0.95 nmol/L (0.75–1.29) for the low-, intermediate- and high-risk categories, respectively (P<0.001). MR-proADM was independently associated with the primary end point (odds ratio, 1.65; 95% confidence interval [CI], 1.10–2.48; P=0.015). MR-proADM predicted the occurrence of primary end point with a sensitivity of 46% (95% CI, 33%–58%) and a specificity of 79% (95% CI, 74–84).ConclusionMR-proADM but not copeptin was significantly associated with outcomes at 30 days, even after adjustment for clinical risk category. Overall, MR-proADM, alone or combined with the clinical risk score, was a moderate strong predictor of short-term outcomes.

Time to move from prognostication to diagnosis and treatment of heart disease in acute exacerbation of COPD

“…Biomarkers are invariably associated with adverse outcomes, the strength of association influenced by population, comorbidities, inclusion/exclusion criteria, follow-up period, outcome studied, and adjustment methods. In the current and most previous studies, the lack of blinded endpoint adjudication using standardised criteria represents a major limitation in correlating biomarkers with cardiac specific outcomes and mortality [19,22,23]. In the present study, all biomarkers displayed similar AUCs for predicting 30-day mortality to the CURB-65 score.…”

“…Further, recently, a multicentre study has developed a novel, simplified, prognostic tool for COPD, independent of lung function, and copeptin was included among the independent predictors of long-term mortality [23]. Interestingly, a French study including 277 patients hospitalised for acute exacerbation of COPD reported opposite results, as copeptin levels were not independently related to 30-day outcomes, including death; however, in the same cohort, copeptin was independently associated with 7-day death/need for ICU [22]. Thus, the debate on the utility of copeptin in acute exacerbation of COPD is actual and ongoing.…”

Prognostic and diagnostic significance of copeptin in acute exacerbation of chronic obstructive pulmonary disease and acute heart failure: data from the ACE 2 study

“…Finally, a newly published multicenter study of AECOPD patients did not find any association between copeptin and a short-term (30 days) composite outcome that included mortality, transfer to the intensive care unit, or a new visit to the emergency room. Notably, patients who required immediate intensive care unit monitoring and/or assisted ventilation (invasive or non-invasive) were excluded from the study and only 14 of 277 included patients died [ 30 ]. To clarify the prognostic properties of copeptin with respect to mortality in COPD in the acute setting we categorized unselected patients with acute dyspnea by established guidelines under the scrutiny of two experts working independently and analyzed the prognostic properties of copeptin in AECOPD and acute HF separately.…”

Copeptin in hyponatremia: is there a role for this biomarker in the diagnostic workup?

“…In spite of the promising results of recent studies focused on the diagnostic and prognostic role of copeptin in the setting of acute dyspnea-related both to heart failure [ 10 – 12 ] and acute exacerbations of chronic obstructive pulmonary disease [ 10 , 11 , 13 ]; the findings in the field of hyponatremia are more controversial.…”