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

Zurfluh, Seline; Nickler, Manuela; Ottiger, Manuel; Kutz, Alexander; Zimmerli, Werner; Thomann, Robert V.; Hoess, Claus; Henzen, Christoph; Bernasconi, Luca; Huber, Andreas; Müeller, Beat; Schuetz, Philipp

doi:10.1515/cclm-2017-0873

Cited by 11 publications

(8 citation statements)

References 36 publications

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“…DHEA has benefited patients with COPD [28,33] and pulmonary hypertension [28,34] in small trials, as well as animal models [35,36]. Therefore, we hypothesize that DHEA treatment may also improve asthma outcomes.…”

Section: Background and Significance Regarding Androgens For Patientsmentioning

confidence: 95%

Dehydroepiandrosterone Supplementation May Benefit Women with Asthma Who Have Low Androgen Levels: A Pilot Study

et al. 2019

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Introduction: Among individuals with severe asthma, FEV 1 is low in individuals with low dehydroepiandrosterone (DHEA) sulfate (DHEAS) levels. In the Severe Asthma Research Program (SARP), no women with DHEAS [ 200 lg/dL had an FEV 1 \ 60% predicted. DHEA has benefited patients with COPD and pulmonary hypertension in small trials. Therefore, we hypothesized that DHEA supplementation may improve FEV 1 in asthmatic women with low DHEAS. Methods: Premenopausal, nonsmoking, otherwise healthy women, 18-50 years old, with mild or moderate asthma and baseline FEV 1 [ 60% predicted received 100 mg DHEA orally every 12 h for 2 weeks. Spirometry and DHEAS were measured at the initial visit and 2 weeks later, after completion of DHEA treatment. Based on our previous work, the primary outcome variable for this pilot study was post-albuterol spirometry in the low-DHEAS group. Subjects also continued their other routine asthma management. Results: Serum DHEAS increased with DHEA treatment in women with starting DHEAS \ 200 lg/dL: this increase was from 71 ± 23 to 725 ± 295 lg/dL (n = 10; p = 0.0001). The increase in the high-DHEAS group was smaller. Post-albuterol FEV 1 increased by 51 mL, from 3.026 ± 0.5 to 3.077 ± 0.49 L (n = 10; p = 0.034 by paired t test, significant after Bonferroni), in women with low DHEAS. In the high-DHEAS group (baseline DHEAS C 200 lg/dl), post-albuterol FEV 1 did not change significantly (n = 3, p = NS). Three subjects were excluded: one had comorbid COPD, one could not perform spirometry, and one did not take the DHEA. There were no adverse effects of DHEA treatment in this trial. Conclusions: Endocrine treatments (corticosteroids) are a mainstay of anti-inflammatory management for moderate and severe asthma. Their use has improved asthma outcomes. Androgens also reduce airway inflammation and promote airway smooth muscle relaxation, but are rarely used clinically for asthma treatment. Our results suggest that the over-thecounter steroid DHEA may improve lung function in asthma outcomes among women with DHEAS \ 200 ug/dL. Enhanced Digital Features To view enhanced digital features for this article go to https://doi.org/10.6084/ m9.figshare.9939215. Key Summary PointsEndocrine treatments (corticosteroids) are a mainstay of anti-inflammatory management for moderate and severe asthma.Their use has improved asthma outcomes.Androgens also reduce airway inflammation and promote airway smooth muscle relaxation, but are rarely used clinically.Our results suggest that the over-thecounter steroid DHEA may also improve lung function in asthma outcomes among women with DHEAS \ 200 ug/dL.

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Section: Background and Significance Regarding Androgens For Patientsmentioning

confidence: 95%

Dehydroepiandrosterone Supplementation May Benefit Women with Asthma Who Have Low Androgen Levels: A Pilot Study

et al. 2019

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“…DHEA and DHEA-S are also lower in patients with COPD than in healthy controls, and COPD leads to pulmonary hypertension (PH). DHEA supplementation improved the 6-min walk test, pulmonary hemodynamics, and the diffusing capacity of the lungs for carbon monoxide of patients with PH-COPD (311,312). The therapeutic potential of DHEA is currently being investigated in 24 patients with PH in the EDIPHY (Effects of DHEA in Pulmonary Hypertension) trial.…”

Section: Testosterone and Dhea Administration In Asthma And Copdmentioning

confidence: 99%

Androgen and Androgen Receptors as Regulators of Monocyte and Macrophage Biology in the Healthy and Diseased Lung

2020

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Androgens, the predominant male sex hormones, drive the development and maintenance of male characteristics by binding to androgen receptor (AR). As androgens are systemically distributed throughout the whole organism, they affect many tissues and cell types in addition to those in male sexual organs. It is now clear that the immune system is a target of androgen action. In the lungs, many immune cells express ARs and are responsive to androgens. In this review, we describe the effects of androgens and ARs on lung myeloid immune cells-monocytes and macrophages-as they relate to health and disease. In particular, we highlight the effect of androgens on lung diseases, such as asthma, chronic obstructive pulmonary disease and lung fibrosis. We also discuss the therapeutic use of androgens and how circulating androgens correlate with lung disease. In addition to human studies, we also discuss how mouse models have helped to uncover the effect of androgens on monocytes and macrophages in lung disease. Although the role of estrogen and other female hormones has been broadly analyzed in the literature, we focus on the new perspectives of androgens as modulators of the immune system that target myeloid cells during lung inflammation.

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“…Metabolites of glycolysis are fed into PPP to generate nicotinamide adenine dinucleotide phosphate, which is employed for fatty acid biosynthesis and antioxidant protection [89]. Metabolomic analysis found that PPP was activated in COPD patients with CS exposure [90], which might be a protective mechanism to alleviate oxidative stress. In addition, the abnormal citrate level in COPD reflects the disturbance of TCA cycle, which might be associated with the decreased activities of enzymes involved in oxidative energy metabolism and mitochondrial dysfunction [91].…”

Section: The Role Of Metabolism Dysfunction In Copd Pathogenesismentioning

confidence: 99%

An Updated Overview of Metabolomic Profile Changes in Chronic Obstructive Pulmonary Disease

Ran

Pang

et al. 2019

Metabolites

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Chronic obstructive pulmonary disease (COPD), a common and heterogeneous respiratory disease, is characterized by persistent and incompletely reversible airflow limitation. Metabolomics is applied to analyze the difference of metabolic profile based on the low-molecular-weight metabolites (<1 kDa). Emerging metabolomic analysis may provide insights into the pathogenesis and diagnosis of COPD. This review aims to summarize the alteration of metabolites in blood/serum/plasma, urine, exhaled breath condensate, lung tissue samples, etc. from COPD individuals, thereby uncovering the potential pathogenesis of COPD according to the perturbed metabolic pathways. Metabolomic researches have indicated that the dysfunctions of amino acid metabolism, lipid metabolism, energy production pathways, and the imbalance of oxidations and antioxidations might lead to local and systematic inflammation by activating the Nuclear factor kappa-light-chain-enhancer of activated B cells signaling pathway and releasing inflammatory cytokines, like interleutin-6 (IL-6), tumor necrosis factor-α, and IL-8. In addition, they might cause protein malnutrition and oxidative stress and contribute to the development and exacerbation of COPD.

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

Cited by 11 publications

References 36 publications

Dehydroepiandrosterone Supplementation May Benefit Women with Asthma Who Have Low Androgen Levels: A Pilot Study

Dehydroepiandrosterone Supplementation May Benefit Women with Asthma Who Have Low Androgen Levels: A Pilot Study

Androgen and Androgen Receptors as Regulators of Monocyte and Macrophage Biology in the Healthy and Diseased Lung

An Updated Overview of Metabolomic Profile Changes in Chronic Obstructive Pulmonary Disease

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