Division of General Internal and Emergency Medicine, Medical University Department, Kantonsspital Aarau, Aarau, Switzerland.
Department of Laboratory Medicine, Kantonsspital Aarau, Aarau, Switzerland.
Clin Chem Lab Med. 2018 Mar 28;56(4):669-680. doi: 10.1515/cclm-2017-0873.
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.
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.
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).
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.
肾上腺激素的释放对于急性和慢性疾病（如慢性阻塞性肺疾病（COPD））至关重要，这些疾病涉及反复发作的恶化。我们采用代谢组学方法，旨在研究不同肾上腺激素代谢物与 COPD 患者短期和长期死亡率的相关性。
我们前瞻性地随访了来自先前瑞士多中心试验的 172 名 COPD 患者（中位年龄 75 岁，62%为男性）。在基线时，我们通过液相色谱-串联质谱法（MS）测量了广泛的肾上腺激素代谢物水平，包括糖皮质激素、盐皮质激素和雄激素。我们计算了 Cox 回归模型，模型中调整了性别、年龄、合并症和既往皮质类固醇治疗。
30 天后死亡率为 6.4%，6 年后增加到 61.6%。较高的初始雄激素激素预示着较低的长期死亡率，其中脱氢表雄酮（DHEA）[调整后的危险比（HR），0.82；95%置信区间（CI），0.70-0.98；p=0.026]和硫酸脱氢表雄酮（DHEA-S）（调整后的 HR，0.68；95%CI，0.50-0.91；p=0.009）具有显著结果。应激激素（特别是皮质醇和可的松）的激活呈现出时间依赖性效应，即较高的水平预示着短期死亡率较高，但长期死亡率较低。盐皮质激素轴的激活倾向于与短期死亡率增加相关（醛固酮的调整后 HR，2.76；95%CI，0.79-9.65；p=0.111）。
在 COPD 恶化患者中，独立于年龄、性别、皮质类固醇暴露和恶化类型，肾上腺激素与短期和长期死亡率相关，具有不同的糖皮质激素、雄激素和盐皮质激素的时间依赖性效应。对这些效应因果关系的更好生理病理理解可能具有治疗意义。
