Marozkina Nadzeya, Zein Joe, DeBoer Mark D, Logan Laurie, Veri Laura, Ross Kristie, Gaston Benjamin
Case Western Reserve University, Cleveland, OH, USA.
University of Virginia, Charlottesville, VA, USA.
Pulm Ther. 2019 Dec;5(2):213-220. doi: 10.1007/s41030-019-00101-9. Epub 2019 Oct 21.
Among individuals with severe asthma, FEV is low in individuals with low dehydroepiandrosterone (DHEA) sulfate (DHEAS) levels. In the Severe Asthma Research Program (SARP), no women with DHEAS > 200 μg/dL had an FEV < 60% predicted. DHEA has benefited patients with COPD and pulmonary hypertension in small trials. Therefore, we hypothesized that DHEA supplementation may improve FEV in asthmatic women with low DHEAS.
Premenopausal, nonsmoking, otherwise healthy women, 18-50 years old, with mild or moderate asthma and baseline FEV > 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.
Serum DHEAS increased with DHEA treatment in women with starting DHEAS < 200 µg/dL: this increase was from 71 ± 23 to 725 ± 295 µg/dL (n = 10; p = 0.0001). The increase in the high-DHEAS group was smaller. Post-albuterol FEV 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 ≥ 200 µg/dl), post-albuterol FEV 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.
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-the-counter steroid DHEA may improve lung function in asthma outcomes among women with DHEAS < 200 ug/dL.
在重度哮喘患者中，硫酸脱氢表雄酮（DHEAS）水平低的个体第一秒用力呼气量（FEV）较低。在重度哮喘研究项目（SARP）中，DHEAS>200μg/dL的女性中没有FEV<预测值60%的情况。在小型试验中，脱氢表雄酮（DHEA）已使慢性阻塞性肺疾病（COPD）和肺动脉高压患者受益。因此，我们假设补充DHEA可能会改善DHEAS水平低的哮喘女性的FEV。
18至50岁、绝经前、不吸烟、其他方面健康、患有轻度或中度哮喘且基线FEV>预测值60%的女性，每12小时口服100mg DHEA，持续2周。在初次就诊时以及DHEA治疗结束2周后测量肺功能和DHEAS。根据我们之前的研究，该初步研究的主要结局变量是低DHEAS组使用沙丁胺醇后的肺功能测定结果。受试者也继续他们的其他常规哮喘管理。
起始DHEAS<200µg/dL的女性在接受DHEA治疗后血清DHEAS升高：从71±23µg/dL升至725±295µg/dL（n = 10；p = 0.0001）。高DHEAS组的升高幅度较小。低DHEAS组女性使用沙丁胺醇后的FEV增加了51mL，从3.026±0.5L增至3.077±0.49L（n = 10；配对t检验p = 0.034，经Bonferroni校正后具有显著性）。在高DHEAS组（基线DHEAS≥200µg/dl）中，使用沙丁胺醇后的FEV没有显著变化（n = 3，p = 无显著性差异）。三名受试者被排除：一名患有合并症COPD，一名无法进行肺功能测定，一名未服用DHEA。在该试验中，DHEA治疗没有不良反应。
内分泌治疗（皮质类固醇）是中度和重度哮喘抗炎治疗的主要手段。它们的使用改善了哮喘的治疗效果。雄激素也可减轻气道炎症并促进气道平滑肌松弛，但在临床上很少用于哮喘治疗。我们的结果表明，非处方类固醇DHEA可能会改善DHEAS<200μg/dL的女性哮喘患者的肺功能。
