Systemic steroids in severe forms of COPD exacerbations: a question of balance?

Similowski, Thomas; Suissa, Samy

doi:10.1183/09031936.00000214

Cited by 6 publications

(5 citation statements)

References 23 publications

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“…Endogenous circulating GCs are significantly upregulated through the hypothalamic-pituitary-adrenal (HPA) axis, in response to various acute inflammatory stressors, including sepsis and the acute exacerbation of COPD ( 47 , 48 ). Although elevated levels of endogenous circulating GCs support the suppression of systemic inflammation and improve survival outcomes ( 49 ), the increased activation of GC signaling in skeletal muscle drives proteolysis and reduced anabolic signaling.…”

Section: Discussionmentioning

confidence: 99%

11β-HSD1 determines the extent of muscle atrophy in a model of acute exacerbation of COPD

Webster

Waaijenberg

Worp

et al. 2023

American Journal of Physiology-Lung Cellular and Molecular Phys

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Muscle atrophy is an extra-pulmonary complication of acute exacerbations (AE) in chronic obstructive pulmonary disease (COPD). The endogenous production and therapeutic application of glucocorticoids (GCs) have been implicated as drivers of muscle loss in AE-COPD. The enzyme 11 beta-hydroxysteroid dehydrogenase 1 (11β-HSD1) activates GCs and contributes towards GC-induced muscle wasting. To explore the potential of 11βHSD1 inhibition to prevent muscle wasting here, the objective of this study was to ascertain the contribution of endogenous GC activation and amplification by 11βHSD1 in skeletal muscle wasting during AE-COPD. Emphysema was induced by intra-tracheal (IT) instillation of elastase to model COPD in WT and 11βHSD1/KO mice, followed by vehicle or IT-LPS administration to mimic AE. µCT scans were obtained prior and at study endpoint 48h following IT-LPS, to assess emphysema development and muscle mass changes, respectively. Plasma cytokine and GC profiles were determined by ELISA. In vitro myonuclear accretion and cellular response to plasma and GCs were determined in C2C12 and human primary myotubes. Muscle wasting was exacerbated in LPS-11βHSD1/KO animals compared to WT controls. RT-qPCR and western blot analysis showed elevated catabolic and suppressed anabolic pathways in muscle of LPS-11βHSD1/KO animals relative to WTs. Plasma corticosterone levels were higher in LPS-11βHSD1/KO animals, whilst C2C12 myotubes treated with LPS-11βHSD1/KO plasma or exogenous GCs displayed reduced myonuclear accretion relative to WT counterparts. This study reveals that 11β-HSD1 inhibition aggravates muscle wasting in a model of AE-COPD, suggesting that therapeutic inhibition of 11β-HSD1 may not be appropriate to prevent muscle wasting in this setting.

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Section: Discussionmentioning

confidence: 99%

11β-HSD1 determines the extent of muscle atrophy in a model of acute exacerbation of COPD

Webster

Waaijenberg

Worp

et al. 2023

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…Therefore, the scientific issues discussed in this study have important academic significance and clinical application value; the basis for the project is sufficient, and the research plan is reasonable. It can screen out AECOPD that can benefit from systemic glucocorticoid therapy, and increase the number of patients the understanding of systemic metabolic control pathways in the acute exacerbation of pulmonary obstruction provides a theoretical basis for the establishment of precise treatment strategies for AECOPD [3,5,9,12].…”

Section: Discussionmentioning

confidence: 99%

“…On the contrary, it also increases the risk of diabetes [11], which may be caused by glucocorticoids. The catabolism of skeletal muscle is strong, which in turn leads to a decrease in respiratory muscle volume and weakened respiratory muscle strength [12].…”

mentioning

confidence: 99%

Rationale and design of REGULATE: an observational study protocol for relationship between plasma metabolome and the efficacy of systemic glucocorticoid in acute exacerbation of chronic obstructive pulmonary disease

Pan

et al. 2021

BMC Pulm Med

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Background Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) significantly increases the mortality of patients with COPD. Guidelines have recommended systemic glucocorticoid as a regular treatment. Recently, evidence has shown that systemic glucocorticoid cannot be a benefit to all of the patients with AECOPD. Thus, the problem that how the clinicians can screen the patients who can benefit from systemic glucocorticoid needs to be solved urgently. This study is aimed to detect the metabolic biomarkers and metabolic pathways that are related to the efficacy of systemic glucocorticoid and contribute to the precise treatment of COPD. Methods and design In this study, we will utilize ultraperformance liquid chromatography/mass spectrometry (LC–MS) and gas chromatography/mass spectrometry (GC–MS) methods for the analysis of the metabolites in AECOPD patients and compare the metabolites profiles between patients with systemic glucocorticoid treatment success group and treatment failure group. We aim to detect the metabolic biomarkers and metabolic pathways that are related to the efficacy of systemic glucocorticoid and contribute to the precise treatment of COPD. Discussion Previous studies have found that plasma metabolome changed significantly after dexamethasone treatment in healthy participants. Furthermore, inter-person variability was high and remained uninfluenced by treatment, suggesting the potential of metabolomics for predicting the efficacy and side effects of systemic glucocorticoid. Therefore, we hypothesized that metabolome changes in patients with AECOPD may be associated with the efficacy of systemic glucocorticoid. Trial registration Clinicaltrials.gov registration number NCT04710849. Registered 15 January 2021, https://clinicaltrials.gov/ct2/show/NCT04710849.

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“…Osteoporosis is one of the main complications of COPD patients, and the progressive aggravation of COPD will lead to vitamin D deficiency, hypogonadism, and chronic hypoxemia. Moreover, the use of steroid drugs will also cause an occurrence of COPD and aggravate osteoporosis (3)(4)(5)(6)(7).…”

Section: Introductionmentioning

confidence: 99%

Ultrasonic examination of differences in bone density of chronic obstructive pulmonary disease (COPD) rats constructed by different methods

Wang

et al. 2020

Ann Palliat Med

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Background: Osteoporosis is one of the main complications of chronic obstructive pulmonary disease (COPD) patients. We investigated the bone density in rat model of COPD induced by different method.Methods: We developed seven distinct groups to evaluate the differences in bone density. Based on these seven different ways, rats were categorized into distinct groups in which simple cigarette inhalation, sulfur dioxide inhalation, lipopolysaccharide intubation, protease induction, bacterial nasal injection, smoking combined with endotoxin, smoking combined bacterial infection, and smoking combined with protease were tested. The results from the male Sprague-Dawley (SD) rats were used to construct the COPD model, and then the bone density of the rats' right femurs was examined by the ultrasonic bone density testing. Results:The compound factor-induced COPD rat model provides a better simulation of the clinical characteristics and pathophysiological processes of COPD. Smoking combined with bacterial infection method has the most apparent effect on reducing bone density, with statistical differences (P<0.05). Conclusions:The COPD rat model constructed by the combination of smoking and bacterial infection method has a much lower bone density.

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Systemic steroids in severe forms of COPD exacerbations: a question of balance?

Cited by 6 publications

References 23 publications

11β-HSD1 determines the extent of muscle atrophy in a model of acute exacerbation of COPD

11β-HSD1 determines the extent of muscle atrophy in a model of acute exacerbation of COPD

Rationale and design of REGULATE: an observational study protocol for relationship between plasma metabolome and the efficacy of systemic glucocorticoid in acute exacerbation of chronic obstructive pulmonary disease

Ultrasonic examination of differences in bone density of chronic obstructive pulmonary disease (COPD) rats constructed by different methods

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