Effects of endogenous sex hormones on lung function and symptom control in adolescents with asthma

DeBoer, Mark D.; Phillips, Brenda R.; Mauger, David T.; Zein, Joe; Erzurum, Serpil C.; Fitzpatrick, Anne M.; Gaston, Benjamin; Myers, Ross; Ross, Kristie; Chmiel, James F.; Lee, Min Jie; Fahy, John V.; Peters, Michael C.; Ly, Ngoc P.; Wenzel, Sally E.; Fajt, Merritt L.; Holguin, Fernando; Moore, Wendy C.; Peters, Stephen P.; Meyers, Deborah A.; Bleecker, Eugene R.; Castro, Mario; Coverstone, Andrea M.; Bacharier, Leonard B.; Jarjour, Nizar N.; Sorkness, Ronald L.; Ramratnam, Sima; Irani, Anne Marie; Israel, Elliot; Levy, Bruce D.; Phipatanakul, Wanda; Gaffin, Jonathan M.; Teague, W. Gerald

doi:10.1186/s12890-018-0612-x

Cited by 84 publications

(81 citation statements)

References 35 publications

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“…We found that post-albuterol FEV 1 was strongly associated with low DHEA levels [15] and that DHEAS levels were twice as high in non-severe as in severe asthma. We also found that women with severe asthma had low levels of DHEAS compared with women with nonsevere asthma (58.1 vs 131.5 lg/dL, p \ 0.001).…”

Section: Background and Significance Regarding Androgens For Patientsmentioning

confidence: 64%

“…These data also suggest a protective effect of androgens on lung function. Further, DHEAS levels were strongly associated with lung function in male children [15]. For the majority of women and younger boys, adrenalderived DHEAS is the predominant androgen: the effect of testosterone is smaller.…”

Section: Background and Significance Regarding Androgens For Patientsmentioning

confidence: 91%

“…Before puberty, the majority of patients with asthma are boys, while the majority of late adolescents and adults with asthma are women [12][13][14]. We measured circulating sex steroid levels and sex hormonebinding globulin (SHBG) in SARP subjects; specific hormones measured were estradiol, testosterone, progesterone, and dehydroepiandrosterone sulfate (DHEAS) [15]. Note that DHEAS is endogenously sulfated DHEA, and accounts for the majority of circulating DHEA.…”

Section: Background and Significance Regarding Androgens For Patientsmentioning

confidence: 99%

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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: 64%

Section: Background and Significance Regarding Androgens For Patientsmentioning

confidence: 91%

Section: Background and Significance Regarding Androgens For Patientsmentioning

confidence: 99%

See 1 more Smart Citation

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

et al. 2019

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“…Epidemiological studies in women have shown variations in lung function and asthma exacerbations throughout the menstrual cycle. Some women report worsening of symptoms in the periovulatory period, and with most complications occurring in the preor peri-menstrual period (Zein and Erzurum 2015;DeBoer et al 2018). Therefore, it is likely that asthmatic women exposed to high ozone levels during the follicular phase experience a worsening of symptoms versus asthmatic women exposed in the luteal phase.…”

Section: Discussionmentioning

confidence: 99%

Modulation of the lung inflammatory response to ozone by the estrous cycle

et al. 2019

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Emerging evidence suggests that sex differences exist in the control of lung innate immunity; however, the specific roles of sex hormones in the inflammatory response, and the mechanisms involved are unclear. Here, we investigated whether fluctuations in circulating hormone levels occurring in the mouse estrous cycle could affect the inflammatory response to air pollution exposure. For this, we exposed female mice (C57 BL /6J, 8 weeks old) at different phases of the estrous cycle to 2 ppm of ozone or filtered air ( FA ) for 3 h. Following exposure, we collected lung tissue and bronchoalveolar lavage fluid ( BAL ), and performed lung function measurements to evaluate inflammatory responses and respiratory mechanics. We found a differential inflammatory response to ozone in females exposed in the luteal phase (metestrus, diestrus) versus the follicular phase (proestrus, estrus). Females exposed to ozone in the follicular phase had significantly higher expression of inflammatory genes, including Ccl2, Cxcl2, Ccl20, and Il6, compared to females exposed in the luteal phase ( P < 0.05), and displayed differential activation of regulatory pathways. Exposure to ozone in the follicular phase also resulted in higher BAL neutrophilia, lipocalin levels, and airway resistance than exposure in the luteal phase ( P < 0.05). Together, these results show that the effects of ozone exposure in the female lung are affected by the estrous cycle phase, and potentially hormonal status. Future studies investigating air pollution effects and inflammation in women should consider the menstrual cycle phase and/or circulating hormone levels.

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“…However, despite the overwhelming evidence showing the influence of sex or obesity in the development of respiratory diseases in humans, the mechanisms by which these two factors interact to influence asthma is not well understood. To date, the vast majority of publications in this field are longitudinal or cross‐sectional studies of human populations . Some reports have shown that nearly 75 percent of emergency room visits for asthma have been among obese individuals, and several cross‐sectional studies have found an increase in the prevalence of asthma among obese patients .…”

Section: Introductionmentioning

confidence: 99%

Sex differences in the influence of obesity on a murine model of allergic lung inflammation

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et al. 2019

Clin Experimental Allergy

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Background: Despite the overwhelming evidence showing the influence of sex or obesity in the development of respiratory diseases in humans and animals, the mechanisms by which these combined two factors influence allergic asthma are not well understood. Objective:We have investigated the interaction between sex and weight gain in an experimental model of lung allergic inflammation induced by chicken egg ovalbumin (OVA) in mice. Methods:Animals were fed a high-fat diet for 8 weeks and then sensitized and challenged with OVA. Results:Our results demonstrate that in comparison with males, high-fat diet (HFD) allergic female mice exhibit a reduction in the number of leucocytes in the lung lumen when challenged with OVA and, in contrast, an accumulation of these cells in the lung tissue. In addition, we also observed that allergic HFD female mice presented a robust lung remodelling in comparison with HFD males, evidenced by higher deposition of collagen in the airways and TGF-β in lung fluid. Measuring epithelial adhesion molecule expression, we observed that female mice presented a significantly lower expression of CD103 than males in BAL cells, regardless of the diet. Similarly, HFD female mice express lower levels of EpCAM in lung tissue in comparison with males and lean females. Levels of A20/TNFAIP3 expression in lung tissue demonstrated that HFD female mice express lower levels of these regulatory factors than all the other groups. However, this reduction was not accompanied by an increase in activated NF-κB. Conclusions:Our results present evidence that the interaction between sex and weight gain alters the progression of allergic asthma in mice with females developing airway remodelling at a much earlier stage than males.Clinical Relevance: These data may contribute to a better understanding of the clinical differences in the development and severity of allergic asthma observed between men and women of reproductive age.

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Effects of endogenous sex hormones on lung function and symptom control in adolescents with asthma

Cited by 84 publications

References 35 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

Modulation of the lung inflammatory response to ozone by the estrous cycle

Sex differences in the influence of obesity on a murine model of allergic lung inflammation

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