Lerner Research Institute and.
Respiratory Institute, Cleveland Clinic, Cleveland, Ohio.
Am J Respir Crit Care Med. 2021 Aug 1;204(3):285-293. doi: 10.1164/rccm.202009-3720OC.
Androgens are potentially beneficial in asthma, but (androgen receptor) has not been studied in human airways. To measure whether and its ligands are associated with human asthma outcomes. We compared the effects of expression on lung function, symptom scores, and fractional exhaled nitric oxide (Fe) in adults enrolled in SARP (Severe Asthma Research Program). The impact of sex and of androgens on asthma outcomes was also evaluated in the SARP with validation studies in the Cleveland Clinic Health System and the NHANES (U.S. National Health and Nutrition Examination Survey). In SARP ( = 128), gene expression from bronchoscopic epithelial brushings was positively associated with both FEV/FVC ratio ( = 0.135, = 0.0002) and the total Asthma Quality of Life Questionnaire score ( = 0.056, = 0.016) and was negatively associated with Fe ( = 0.178, = 9.8 × 10) and (nitric oxide synthase gene) expression ( = 0.281, = 1.2 × 10). In SARP ( = 1,659), the Cleveland Clinic Health System ( = 32,527), and the NHANES ( = 2,629), women had more asthma exacerbations and emergency department visits than men. The levels of the ligand precursor dehydroepiandrosterone sulfate correlated positively with the FEV in both women and men. Higher bronchial expression and higher androgen levels are associated with better lung function, fewer symptoms, and a lower Fe in human asthma. The role of androgens should be considered in asthma management.
雄激素在哮喘中可能有益,但雄激素受体在人类气道中尚未得到研究。为了测量雄激素及其配体是否与人类哮喘结局相关。我们比较了雄激素受体表达对成年人肺功能、症状评分和呼出的一氧化氮分数(Fe)的影响,这些成年人参加了 SARP(严重哮喘研究计划)。还在 SARP 中评估了性别和雄激素对哮喘结局的影响,并在克利夫兰诊所健康系统和 NHANES(美国国家健康和营养检查调查)中进行了验证研究。在 SARP( = 128)中,支气管镜上皮刷取物的基因表达与 FEV/FVC 比值( = 0.135, = 0.0002)和总哮喘生活质量问卷评分( = 0.056, = 0.016)均呈正相关,与 Fe( = 0.178, = 9.8 × 10)和一氧化氮合酶基因( = 0.281, = 1.2 × 10)呈负相关。在 SARP( = 1659)、克利夫兰诊所健康系统( = 32527)和 NHANES( = 2629)中,女性哮喘加重和急诊就诊次数多于男性。女性和男性的雄激素前体脱氢表雄酮硫酸酯水平与 FEV 呈正相关。人类哮喘中较高的支气管雄激素受体表达和较高的雄激素水平与更好的肺功能、更少的症状和较低的 Fe 相关。在哮喘管理中应考虑雄激素的作用。