Seline Zurfluh1, Manuela Nickler1, Manuel Ottiger1, Christian Steuer2, Alexander Kutz1, Mirjam Christ-Crain3, Werner Zimmerli4, Robert Thomann5, Claus Hoess6, Christoph Henzen7, Luca Bernasconi2, Andreas Huber2, Beat Mueller1, Philipp Schuetz1. 1. Division of General Internal and Emergency Medicine, Medical University Department, Kantonsspital Aarau, Aarau, Switzerland. 2. Department of Laboratory Medicine, Kantonsspital Aarau, Aarau, Switzerland. 3. Division of Endocrinology, Diabetes and Clinical Nutrition, Department of Internal Medicine, University Hospital Basel, Basel, Switzerland. 4. Basel University Medical Clinic Liestal, Liestal, Switzerland. 5. Department of Internal Medicine, Bürgerspital Solothurn, Solothurn, Switzerland. 6. Department of Internal Medicine, Kantonsspital Münsterlingen, Münsterlingen, Switzerland. 7. Department of Internal Medicine, Kantonsspital Lucerne, Lucerne, Switzerland.
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.
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 COPDpatients. METHODS: We prospectively followed 172 COPDpatients (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.
Authors: Giancarlo Pesce; Kai Triebner; Diana A van der Plaat; Dominique Courbon; Steinar Hustad; Torben Sigsgaard; Dennis Nowak; Joachim Heinrich; Josep M Anto; Sandra Dorado-Arenas; Jesús Martinez-Moratalla; Jose A Gullon-Blanco; José L Sanchez-Ramos; Chantal Raherison; Isabelle Pin; Pascal Demoly; Thorarinn Gislason; Kjell Torén; Bertil Forsberg; Eva Lindberg; Elisabeth Zemp; Rain Jogi; Nicole Probst-Hensch; Shyamali C Dharmage; Debbie Jarvis; Judith Garcia-Aymerich; Alessandro Marcon; Francisco Gómez-Real; Bénédicte Leynaert Journal: EClinicalMedicine Date: 2020-06-06
Authors: Victor Pinto-Plata; Ciro Casanova; Miguel Divo; Yohannes Tesfaigzi; Vince Calhoun; Jing Sui; Francesca Polverino; Carmen Priolo; Hans Petersen; Juan Pablo de Torres; Jose Maria Marin; Caroline A Owen; Rebeca Baz; Elizabeth Cordova; Bartolome Celli Journal: Respir Res Date: 2019-10-15
Authors: Tomasz Karauda; Kamil Kornicki; Amer Jarri; Adam Antczak; Joanna Miłkowska-Dymanowska; Wojciech J Piotrowski; Sebastian Majewski; Paweł Górski; Adam Jerzy Białas Journal: Sci Rep Date: 2021-02-26 Impact factor: 4.379