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

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          Abstract

          Background

          Exacerbations 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 methods

          This 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.

          Results

          A 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).

          Conclusion

          MR-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.

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          Most cited references 22

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          Measurement of midregional proadrenomedullin in plasma with an immunoluminometric assay.

          Adrenomedullin (ADM) is a potent vasodilatory peptide, and circulating concentrations have been described for several disease states, including dysfunction of the cardiovascular system and sepsis. Reliable quantification has been hampered by the short half-life, the existence of a binding protein, and physical properties. Here we report the technical evaluation of an assay for midregional pro-ADM (MR-proADM) that does not have these problems. MR-proADM was measured in a sandwich immunoluminometric assay using 2 polyclonal antibodies to amino acids 45-92 of proADM. The reference interval was defined in EDTA plasma of 264 healthy individuals (117 male, 147 female), and increased MR-proADM concentrations were found in 95 patients with sepsis and 54 patients with cardiovascular disease. The assay has an analytical detection limit of 0.08 nmol/L, and the interassay CV was 0.12 nmol/L. The assay was linear on dilution with undisturbed recovery of the analyte. EDTA-, heparin-, and citrate-plasma samples were stable (<20% loss of analyte) for at least 3 days at room temperature, 14 days at 4 degrees C, and 1 year at -20 degrees C. MR-proADM values followed a gaussian distribution in healthy individuals with a mean (SD) of 0.33 (0.07) nmol/L (range, 0.10-0.64 nmol/L), without significant difference between males or females. The correlation coefficient for MR-proADM vs age was 0.50 (P < 0.001). MR-proADM was significantly (P < 0.001) increased in patients with cardiovascular disease [median (range), 0.56 (0.08-3.9) nmol/L] and patients with sepsis [3.7 (0.72-25.4) nmol/L]. MR-proADM is stable in plasma of healthy individuals and patients. MR-proADM measurements may be useful for evaluating patients with sepsis, systemic inflammation, or heart failure.
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            Copeptin, C-reactive protein, and procalcitonin as prognostic biomarkers in acute exacerbation of COPD.

            A novel approach to estimate the severity of COPD exacerbation and predict its outcome is the use of biomarkers. We assessed circulating levels of copeptin, the precursor of vasopressin, C-reactive protein (CRP), and procalcitonin as potential prognostic parameters for in-hospital and long-term outcomes in patients with acute exacerbation of COPD (AECOPD) requiring hospitalization. Data of 167 patients (mean age, 70 years; mean FEV(1), 39.9 +/- 16.9 of predicted [+/- SD]) presenting to the emergency department due to AECOPD were analyzed. Patients were evaluated based on clinical, laboratory, and lung function parameters on hospital admission, at 14 days, and at 6 months. Plasma levels of all three biomarkers were elevated during the acute exacerbation (p /= 40 pmol/L and a history of hospitalization (p < 0.0001). We suggest copeptin as a prognostic marker for short-term and long-term prognoses in patients with AECOPD requiring hospitalization.
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              In-hospital mortality following acute exacerbations of chronic obstructive pulmonary disease.

              Acute exacerbations of chronic obstructive pulmonary disease (COPD) are a frequent cause of hospitalization in the United States. Previous studies of selected populations of patients with COPD have estimated in-hospital mortality to range from 4% to 30%. Our objective was to obtain a generalizable estimate of in-hospital mortality from acute exacerbation of COPD in the United States and to identify predictors of in-hospital mortality using administrative data. We performed a cross-sectional study utilizing the 1996 Nationwide Inpatient Sample, a data set of all hospitalizations from a 20% sample of nonfederal US hospitals. The study population included 71 130 patients aged 40 years or older with an acute exacerbation of COPD at hospital discharge. The primary outcome assessed was in-hospital mortality. In-hospital mortality for patients with an acute exacerbation of COPD was 2.5%. Multivariable analyses identified older age, male sex, higher income, nonroutine admission sources, and more comorbid conditions as independent risk factors for in-hospital mortality. Mortality during hospitalization in this nationwide sample of patients with acute exacerbations of COPD was lower than that of previous studies of select populations. This estimate should provide optimism to both clinicians and patients regarding prognoses from COPD exacerbations requiring hospitalization. Our results indicate that the use of administrative data can help to identify subsets of patients with acute exacerbations of COPD that are at higher risk of in-hospital mortality.
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                Author and article information

                Journal
                Int J Chron Obstruct Pulmon Dis
                Int J Chron Obstruct Pulmon Dis
                International Journal of COPD
                International Journal of Chronic Obstructive Pulmonary Disease
                Dove Medical Press
                1176-9106
                1178-2005
                2017
                31 March 2017
                : 12
                : 1047-1056
                Affiliations
                [1 ]Pulmonary and Critical Care Department, Pitié-Salpêtrière Hospital, AP-HP
                [2 ]UMRS1158: Clinical and Experimental Respiratory Neurophysiology, Paris 6 University
                [3 ]Emergency Department, Hôpital Pitié-Salpêtrière, AP-HP
                [4 ]Sorbonne Universités UPMC Univ-Paris06, GRC-14 BIOSFAST
                [5 ]Clinical Research Department, Necker Cochin Hospital, AP-HP
                [6 ]EA 7323, Sorbonne Paris-Cité
                [7 ]Biochemistry Department, Pitié-Salpêtrière Hospital, AP-HP, Paris
                [8 ]Emergency Department, Charles Nicolle Hospital, Rouen
                [9 ]Department of Emergency Medicine, Lapeyronie Hospital, Montpellier
                [10 ]Emergency Department, Pellegrin Hospital, Bordeaux
                [11 ]Emergency Department, Gabriel Montpied Hospital, Clermont-Ferrand
                [12 ]Emergency Department, Grenoble University Hospital, Grenoble
                [13 ]Clinical Research Department, Paris Descartes University, Hôpital Cochin, AP-HP
                [14 ]Pulmonary Department, Cochin Hospital, AP-HP
                [15 ]Paris Descartes University, Paris, France
                Author notes
                Correspondence: Nicolas Roche, Department of Respiratory Diseases, Cochin Hospital, AP-HP and University Paris Descartes, Sorbonne Paris Cité, Paris 27 rue du Faubourg Saint-Jacques, 75014 Paris, France, Email nicolas.roche@ 123456aphp.fr
                Article
                copd-12-1047
                10.2147/COPD.S126400
                5383071
                © 2017 Dres et al. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                Categories
                Original Research

                Respiratory medicine

                emergency department, copd, mid-regional pro-adrenomedullin, copeptin, biomarker

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