Dihydrotestosterone is a predictor for mortality in males with community-acquired pneumonia: results of a 6-year follow-up study.

BACKGROUND: Adrenal hormone metabolite levels are altered in acute illnesses such as community-acquired pneumonia (CAP). Our aim was to investigate associations of sex and mineralocorticoid hormone metabolites with short- and long-term mortality and severity of CAP in male and female patients. METHODS: We prospectively followed 285 patients (60.4% male, mean age 71 years) with CAP from a previous multicenter trial. At baseline, levels of different metabolites of sex hormones and mineralocorticoids were measured by liquid chromatography coupled to tandem mass spectrometry. We calculated Cox regression models adjusted for age and comorbidities. RESULTS: All-cause mortality was 5.3% after 30 days and increased to 47.4% after 6 years. In males, high levels of dihydrotestosterone were associated with higher 6-year mortality (adjusted HR 2.84, 95%CI 1.15-6.99, p = 0.023), whereas high levels of 17-OH-progesterone were associated with lower 6-year mortality (adjusted HR 0.72, 95%CI 0.54-0.97, p = 0.029). Testosterone levels in males correlated inversely with inflammatory markers (CRP rho = - 0.39, p < 0.001; PCT rho = - 0.34, p < 0.001) and disease severity as assessed by the Pneumonia severity index (PSI) (rho = - 0.23, p = 0.003). No similar association was found for female patients. CONCLUSION: Whereas in males with CAP, sex and mineralocorticoid hormone metabolite levels correlated with inflammation, disease severity and long-term survival, no similar association was found for females. Further study of sex and mineralocorticoid hormones in acute illness could generate predictive signatures with implementation in clinical practice.

Association of adrenal hormone metabolites and mortality over a 6-year follow-up in COPD patients with acute exacerbation.

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.

Relationship of Nutritional Status, Inflammation, and Serum Albumin Levels During Acute Illness: A Prospective Study.

BACKGROUND: Low serum albumin levels resulting from inflammation-induced capillary leakage or disease-related anorexia during acute illness are associated with poor outcomes. We investigated the relationship of nutritional status and inflammation with low serum albumin levels and 30-day mortality in a large cohort. METHODS: We prospectively enrolled adult patients in the medical emergency department of a Swiss tertiary care center and investigated associations of C-reactive protein (CRP) and Nutritional Risk Screening 2002 as markers of inflammation and poor nutritional status, respectively, with low serum albumin levels and mortality using multivariate regression analyses. RESULTS: Among the 2465 patients, 1019 (41%) had low serum albumin levels (<34 g/L), 619 (25.1%) had increased nutritional risk (Nutritional Risk Screening 2002 ≥3), and 1086 (44.1%) had CRP values >20 mg/L. Multivariate analyses adjusted for age, gender, diagnosis, and comorbidities revealed elevated CRP values (adjusted odds ratio [OR] 10.51, 95% confidence interval, 7.51-14.72, P <.001) and increased malnutrition risk (adjusted OR 2.87, 95% confidence interval, 1.98-4.15, P <.001) to be associated with low serum albumin levels, even adjusting for both parameters. Low serum albumin levels, elevated CRP values, and increased nutritional risk independently predicted 30-day mortality, with areas under the curve of 0.77, 0.70, and 0.75, respectively. Combination of these 3 parameters showed an area under the curve of 0.82 to predict mortality. CONCLUSIONS: Elevated parameters of inflammation and high nutritional risk were independently associated with hypoalbuminemia. All 3 parameters independently predicted mortality. Combining them during initial evaluation of patients in emergency departments facilitates mortality risk stratification.

The role of metabolomic markers for patients with infectious diseases: implications for risk stratification and therapeutic modulation.

INTRODUCTION: Metabolomics is a rapidly growing area of research. Metabolomic markers can provide information about the interaction of different organ systems, and thereby improve the understanding of physio-pathological processes, disease risk, prognosis and therapy responsiveness in a variety of diseases. Areas covered: In this narrative review of recent clinical studies investigating metabolomic markers in adult patients presenting with acute infectious disease, we mainly focused on patients with sepsis and lower respiratory tract infections. Currently, there is a growing body of literature showing that single metabolites from distinct metabolic pathways, as well as more complex metabolomic signatures are associated with disease severity and outcome in patients with systemic infections. These pathways include, among others, metabolomic markers of oxidative stress, steroid hormone and amino acid pathways, and nutritional markers. Expert commentary: Metabolic profiling has great potential to optimize patient management, to provide new targets for individual therapy and thereby improve survival of patients. At this stage, research mainly focused on the identification of new predictive signatures and less on metabolic determinants to predict treatment response. The transition from observational studies to implementation of novel markers into clinical practice is the next crucial step to prove the usefulness of metabolomic markers in patient care.