Abstract
Background:
The release of hormones from the adrenal gland is vital in acute and chronic illnesses such as chronic obstructive pulmonary disease (COPD) involving recurrent exacerbations. Using a metabolomic approach, we aim to investigate associations of different adrenal hormone metabolites with short- and long-term mortality in COPD patients.
Methods:
We prospectively followed 172 COPD patients (median age 75 years, 62% male) from a previous Swiss multicenter trial. At baseline, we measured levels of a comprehensive spectrum of adrenal hormone metabolites, including glucocorticoid, mineralocorticoid and androgen hormones by liquid chromatography coupled with tandem mass spectrometry (MS). We calculated Cox regression models adjusted for gender, age, comorbidities and previous corticosteroid therapy.
Results:
Mortality was 6.4% after 30 days and increased to 61.6% after 6 years. Higher initial androgen hormones predicted lower long-term mortality with significant results for dehydroepiandrosterone (DHEA) [adjusted hazard ratio (HR), 0.82; 95% confidence interval (CI), 0.70–0.98; p=0.026] and dehydroepiandrosterone sulfate (DHEA-S) (adjusted HR, 0.68; 95% CI, 0.50–0.91; p=0.009). An activation of stress hormones (particularly cortisol and cortisone) showed a time-dependent effect with higher levels pointing towards higher mortality at short term, but lower mortality at long term. Activation of the mineralocorticoid axis tended to be associated with increased short-term mortality (adjusted HR of aldosterone, 2.76; 95% CI, 0.79–9.65; p=0.111).
Conclusions:
Independent of age, gender, corticosteroid exposure and exacerbation type, adrenal hormones are associated with mortality at short and long term in patients with COPD exacerbation with different time-dependent effects of glucocorticoids, androgens and mineralocorticoids. A better physiopathological understanding of the causality of these effects may have therapeutic implications.
Acknowledgments
We are grateful to the emergency department, medical clinic and central laboratory staff of the University Hospital Basel and the Cantonal Hospitals Aarau, Liestal, Lucerne, Muensterlingen and the ‘Buergerspital’ Solothurn for their assistance and technical support. In particular, we thank all patients, their relatives and all local general practitioners who participated in this study. Finally, we acknowledge the ProHOSP Study Group for their important support.
The ProHOSP Study Group included the following persons: Ursula Schild, RN; Katharina Regez, RN; Rita Bossart, RN; Robert Thomann, MD; Claudine Falconnier, MD; Marcel Wolbers, PHD; Stefanie Neidert, MD; Thomas Fricker, MD; Claudine Blum, MD; Thomas Bregenzer, MD; Claus Hoess, MD; Heiner C. Bucher, MD; Fabian Mueller; Jeannine Haeuptle; Roya Zarbosky; Rico Fiumefreddo, MD; Melanie Wieland, RN; Charly Nusbaumer, MD; Andres Christ, MD; Roland Bingisser, MD; Kristian Schneider, RN; Brigitte Walz, PhD; Verena Briner, MD; Dieter Conen, MD; Andreas Huber, MD; Jody Staehelin, MD; Chantal Bruehlhardt, RN; Ruth Luginbuehl, RN; Agnes Muehlemann, PhD; Ineke Lambinon; Werner Zimmerli, MD; and Max Zueger, MD.
Author contributions: MCC, BM and PS created concept and design, wrote the protocol and initiated the initial ProHOSP study. SZ and PS drafted the present manuscript and performed statistical analyses. CS and AH performed laboratory measurements of glucocorticoids. All authors contributed to the data acquisition, interpretation and drafting of the analyses, as well as to critical review for important intellectual content, and final approval of the manuscript. PS had full access to all data in the present study and takes responsibility for the integrity of the work and the accuracy of the data analyses.
Availability of data and material: The data sets used and analyzed during the present study are available from the corresponding author on reasonable request.
Research funding: This study was supported in part by the Swiss National Science Foundation (SNSF Professorship, Funder ID: 10.13039/501100001711, PP00P3_150531/1) and the Research Council of the Kantonsspital Aarau (1410.000.044). The initial trial was funded by the Swiss National Science Foundation (Funder ID: 10.13039/501100001711, grant SNF 3200BO-116177/1), Santé Suisse, the Gottfried and Julia Bangerter-Rhyner Foundation.
Employment or leadership: None declared.
Honorarium: None declared.
Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.
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The online version of this article offers supplementary material (https://doi.org/10.1515/cclm-2017-0873).
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