Plasma pro-adrenomedullin but not plasma pro-endothelin predicts survival in exacerbations of COPD.
BACKGROUND
Plasma endothelin and adrenomedullin are increased in patients with pulmonary arterial hypertension, hypoxia, and pulmonary infections, conditions that predict survival in patients with COPD. We investigated whether plasma pro-endothelin-1 (proET-1) and/or pro-adrenomedullin (proADM) on admission to the hospital for acute exacerbation predict survival in patients with COPD.


METHODS
We examined 167 patients who had been admitted to the hospital for acute exacerbation, and we followed them up for 2 years. We measured plasma C-terminal (CT) proET-1 and mid-regional (MR) proADM on hospital admission, after 14 to 18 days, and after 6 months. In addition to plasma CT proET-1 and MR proADM, we assessed with Cox regression univariate and multivariate analyses the predictive value of clinical, functional, and laboratory parameters on 2-year survival. We analyzed the time to death by Kaplan-Meier curves.


RESULTS
Compared to recovery and stable state, CT-proET-1 and MR-proADM were significantly increased on hospital admission (p < 0.001 and p = 0.002, respectively). MR-proADM, but not CT-proET-1, was associated with increased in-hospital mortality (p = 0.049) and independently predicted 2-year survival (p = 0.017). ProADM plasma levels > 0.84 nmol/L on hospital admission increased the mortality risk within 2 years from 13 to 32% (p = 0.004). By contrast, age (p = 0.779), Charlson comorbidity score (p = 0.971), body mass index (p = 0.802), FEV(1) percent predicted (p = 0.741), PAo(2) (p = 0.744), PAco(2) (p = 0.284), leukocyte counts (p = 0.333), C-reactive protein (p = 0.772), procalcitonin (p = 0.069), pulmonary arterial hypertension (p = 0.971), and CT-proET-1 (p = 0.223) were not independently associated with 2-year survival.


CONCLUSIONS
This study shows that plasma proADM but not plasma proET-1 on admission to the hospital for acute exacerbation independently predicts survival, thus suggesting that this biomarker could be used to predict prognosis in patients with COPD.
Stolz
Daiana
D
Clinic of Pneumology and Pulmonary Cell Research, University Hospital Basel, Basel, Switzerland. Electronic address: stolzd@uhbs.ch.
Christ-Crain
Mirjam
M
Clinic of Endocrinology, Diabetes, and Clinical Nutrition, University Hospital Basel, Basel, Switzerland.
Morgenthaler
Nils G
NG
Research Department, BRAHMS AG, Biotechnology Centre, Hennigsdorf, Germany.
Miedinger
David
D
Clinic of Pneumology and Pulmonary Cell Research, University Hospital Basel, Basel, Switzerland.
Leuppi
Jörg
J
Clinic of Pneumology and Pulmonary Cell Research, University Hospital Basel, Basel, Switzerland.
Müller
Christian
C
Department of Internal Medicine, University Hospital Basel, Basel, Switzerland.
Bingisser
Roland
R
Department of Internal Medicine, University Hospital Basel, Basel, Switzerland.
Struck
Joachim
J
Research Department, BRAHMS AG, Biotechnology Centre, Hennigsdorf, Germany.
Müller
Beat
B
Clinic of Endocrinology, Diabetes, and Clinical Nutrition, University Hospital Basel, Basel, Switzerland.
Tamm
Michael
M
Clinic of Pneumology and Pulmonary Cell Research, University Hospital Basel, Basel, Switzerland.
D053607:Adrenomedullin / Q000097:blood*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019332:Endothelin-1 / Q000097:blood*; D005260:Female; D005500:Follow-Up Studies; D017052:Hospital Mortality; D006801:Humans; D053208:Kaplan-Meier Estimate; D007902:Length of Stay; D008297:Male; D008875:Middle Aged; D010343:Patient Admission; D011237:Predictive Value of Tests; D011498:Protein Precursors / Q000097:blood*; D029424:Pulmonary Disease, Chronic Obstructive / Q000097:blood* / Q000150:complications / Q000401:mortality*
D019332:Endothelin-1; D011498:Protein Precursors; C088633:proadrenomedullin; C093240:proendothelin 1; D053607:Adrenomedullin