Chest
Volume 134, Issue 2, August 2008, Pages 263-272
Journal home page for Chest

Original Research
COPD
Plasma Pro-Adrenomedullin But Not Plasma Pro-Endothelin Predicts Survival in Exacerbations of COPD

https://doi.org/10.1378/chest.08-0047Get rights and content

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), FEV1 percent predicted (p = 0.741), PAo2 (p = 0.744), PAco2 (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.

Section snippets

Setting and Study Population

This prospective cohort study took advantage of baseline data from 167 patients with acute exacerbations of COPD, who were admitted to the emergency department of the University Hospital Basel and were included in a prospective, randomized trial.8 A predefined secondary end point was the assessment of further biomarkers in COPD patients.38, 39

The diagnosis of COPD was based on clinical history, physical examination findings, and spirometric criteria according to the Global Initiative for

Results

The detailed baseline characteristics of the 167 patients are presented in Table 1. Overall, 116 patients (69.5%) had relevant comorbidities. Sputum cultures grew bacterial pathogens in 65 cases (38.9%). Echocardiography results were available for 123 patients (73.7%). A total of 38 patients (22.8.%) demonstrated clinically relevant pulmonary arterial hypertension.45 In 12 cases (7.2%), echocardiography showed decreased left ventricular ejection fraction (ejection fraction, ≤ 40%).

The median

Discussion

In this investigation, we have examined the predictive value of plasma proET-1 and proADM levels on survival in patients with acute exacerbations of COPD requiring hospitalization. We have reported three major findings. First, proET-1 and proADM levels were markedly increased at exacerbation and decreased significantly in the recovery and stable phases of the disease. Second, neither proET-1 nor proADM levels correlated consistently with the clinical presentation on hospital admission. Finally,

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    Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal.org/misc/reprints.shtml).

    1

    Dr. Stolz was partially supported by grants from the Swiss National Foundation and the Margarete and Walter Lichtenstein Foundation.

    2

    Dr. Stolz has received speakers' honoraria from BRAHMS AG (the manufacturer of proADM, pro-endothelin, and procalcitonin assays).

    3

    Drs. Müller, Müller, and Christ-Crain served as consultants and were sponsored by BRAHMS AG for attending advisory board meetings, speaking engagements, and research.

    4

    Drs. Morgenthaler and Struck are employees of BRAHMS AG.

    5

    Drs. Christ-Cain, Miedinger, Leuppi, Bingisser, and Tamm have reported to the ACCP that no significant conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

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