Endocrine regulation of airway contractility is overlooked

Bossé, Ynuk

doi:10.1530/joe-14-0220

Cited by 23 publications

(13 citation statements)

References 117 publications

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“…The potential protective effects of DHEAS likely involve effects both on airway smooth muscle and on airway inflammation. Indeed, there is evidence to support cross-talk between DHEAS anti-inflammatory effects and airway smooth muscle relaxation [38,40]. DHEAS inhibits human airway smooth muscle and fibroblast proliferation [39,41], may benefit airway epithelial-to-mesenchymal transition [42], and is itself a bronchodilator [43].…”

Section: Potential Mechanisms By Which Androgens May Benefit Patientsmentioning

confidence: 99%

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: Potential Mechanisms By Which Androgens May Benefit Patientsmentioning

confidence: 99%

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

et al. 2019

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“…We believe that better understanding of these pathways will be paradigm changing by potentially extending the use of metformin, routinely prescribed for insulin resistance, into management of obesity-related asthma. 132 …”

Section: Association With Insulin Resistancementioning

confidence: 99%

Pediatric Obesity-Related Asthma: The Role of Metabolic Dysregulation

2016

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The burden of obesity-related asthma among children, particularly among ethnic minorities, necessitates an improved understanding of the underlying disease mechanisms. Although obesity is an independent risk factor for asthma, not all obese children develop asthma. Several recent studies have elucidated mechanisms, including the role of diet, sedentary lifestyle, mechanical fat load, and adiposity-mediated inflammation that may underlie the obese asthma pathophysiology. Here, we review these recent studies and emerging scientific evidence that suggest metabolic dysregulation may play a role in pediatric obesity-related asthma. We also review the genetic and epigenetic factors that may underlie susceptibility to metabolic dysregulation and associated pulmonary morbidity among children. Lastly, we identify knowledge gaps that need further exploration to better define pathways that will allow development of primary preventive strategies for obesity-related asthma in children.

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“…Oestrogens can regulate the synthesis of nitric oxide, a potent bronchodilator, within human bronchial epithelium,1 32 as well as regulate airway bronchoconstriction in response to acetylcholine or histamine 33 34. There is also evidence that progesterone may affect airway smooth muscle constriction, although these reports are limited to animal studies 35. In addition to regulating bronchodilation and bronchoconstriction, in vitro studies report that oestrogen can also modulate the proliferation of airway smooth muscle cells,36 37 which is a key feature of COPD 38.…”

Section: Discussionmentioning

confidence: 99%

Female reproductive history in relation to chronic obstructive pulmonary disease and lung function in UK biobank: a prospective population-based cohort study

2019

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ObjectivesSex differences in respiratory physiology and predilection for developing chronic obstructive pulmonary disease (COPD) have been documented, suggesting that female sex hormones may influence pathogenesis. We investigated whether aspects of female reproductive health might play a role in risk of COPD among women.DesignPopulation-based prospective cohort study.SettingUK Biobank recruited across 22 centres in the UK between 2006 to 2010.Primary and secondary outcomes measuresWe examined a range of female reproductive health indicators in relation to risk of COPD-related hospitalisation/death (n=271 271) using Cox proportional hazards regression; and lung function (n=273 441) using linear regression.ResultsParity >3 was associated with greater risk of COPD-related hospitalisation/death (adjusted HR 1.45; 95% CI: 1.16 to 1.82) and lower forced expiratory volume at 1 second/forced vital capacity ratio (FEV1/FVC) (adjusted mean difference −0.06; 95% CI: -0.07 to 0.04). Any oral contraception use was associated with lower risk of COPD-related hospitalisation/death (adjusted HR 0.85; 95% CI: 0.74 to 0.97) and greater FEV1/FVC (adjusted mean difference 0.01; 95% CI: 0.003 to 0.03). Late menarche (age >15) and early menopause (age <47) were also associated with greater risk of COPD-related hospitalisation/death (but not lung function), while endometriosis was associated with greater FEV1/FVC (not COPD-related hospitalisation/death). Early menarche (age <12 years) was associated with lower FEV1/FVC (but not COPD hospitalisation/death). Associations with polycystic ovary syndrome (PCOS) or ovarian cysts, any hormone replacement therapy (HRT) use, hysterectomy-alone and both hysterectomy and bilateral oophorectomy were in opposing directions for COPD-related hospitalisation/death (greater risk) and FEV1/FVC (positive association).ConclusionsMultiple female reproductive health indicators across the life course are associated with COPD-related hospitalisation/death and lung function. Further studies are necessary to understand the opposing associations of PCOS/ovarian cysts, HRT and hysterectomy with COPD and objective measures of airway obstruction.

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Endocrine regulation of airway contractility is overlooked

Cited by 23 publications

References 117 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

Pediatric Obesity-Related Asthma: The Role of Metabolic Dysregulation

Female reproductive history in relation to chronic obstructive pulmonary disease and lung function in UK biobank: a prospective population-based cohort study

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