A Prospective Study of the Effects of Sex Hormones on Lung Function and Inflammation in Women with Cystic Fibrosis
A Prospective Study of the Effects of Sex Hormones on Lung Function and Inflammation in Women with Cystic Fibrosis
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DOI：
10.1513/annalsats.202008-1064oc
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发表时间：
2021-07-01
影响因子：
8.3
通讯作者：
Jain, Raksha
中科院分区：
文献类型：
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作者：
Holtrop, Melanie;Heltshe, Sonya;Jain, Raksha
理由：流行病学研究表明，女性囊性纤维化 (CF) 患者的预后比男性差。女性较早被呼吸道病原体定植，并且在青春期后和临近排卵时肺部病情恶化的发生率增加。这种差异的病因尚不清楚，但性激素可能是导致这些差异的原因。 目的：我们试图探讨自然激素波动和激素避孕是否与肺功能、呼吸道症状或炎症标志物的变化相关。方法：我们前瞻性地跟踪未服用激素避孕药并报告月经周期规律的 CF 女性。我们在与月经、排卵和黄体期相对应的时间点进行了研究访问。随后，一部分受试者服用标准口服雌激素/黄体酮复方避孕药，即炔雌醇/炔诺酮（loestrin），并进行重新评估。测量内容包括肺功能、症状问卷、汗液测试、血液中的激素浓度、痰中的炎症标志物、细菌密度和细胞学。 结果：23 名女性参与了这项研究。激素避孕前后的激素浓度均符合预期。在雌激素高峰（排卵）时，痰促炎细胞因子（无中性粒细胞弹性蛋白酶）显着增加，肺功能相应下降。采用激素避孕后，促炎细胞因子（IL-8、TNF-α 和中性粒细胞游离弹性蛋白酶）得到改善。结论：我们的结果表明，肺部炎症生物标志物存在潜在的重要波动，与 CF 女性肺功能的变化相关。为了更好地了解这些反应的临床影响，有必要进行更大规模的研究来评估性激素对气道炎症和免疫反应的影响。
Rationale: Epidemiologic studies demonstrate worse outcomes in women with cystic fibrosis (CF) than men. Women are colonized earlier with respiratory pathogens and have increased rates of pulmonary exacerbations after puberty and near ovulation. The etiology of this disparity is unclear, but sex hormones may contribute to these differences.Objectives: We sought to explore whether natural hormonal fluctuations and hormonal contraception associate with changes in lung function, respiratory symptoms, or inflammatory markers.Methods: We prospectively followed women with CF who were not on hormonal contraceptives and reported regular menstrual cycles. We captured study visits at points that corresponded with menses, ovulation, and the luteal phase. A subset of subjects were subsequently placed on a standard oral estrogen/progesterone combination contraceptive pill, ethinyl estradiol/norethindrone (loestrin), and reevaluated. Measurements included lung function, symptom questionnaires, sweat tests, blood for hormone concentrations, and sputum for inflammatory markers, bacterial density, and cytology.Results: Twenty-three women participated in this study. Hormone concentrations were as expected on and off hormonal contraception. At times of peak estrogen (ovulation), there was a significant increase in sputum proinflammatory cytokines (neutrophil-free elastase) and a corresponding pattern of decrease in lung function. Proinflammatory cytokines (IL-8, TNF-alpha, and neutrophil-free elastase) improved when placed on hormone contraception.Conclusions: Our results show that there are potentially important fluctuations in inflammatory biomarkers in the lungs that correlate with changes in lung function in women with CF. Larger studies evaluating the impact of sex hormones on airway inflammation and immune response are necessary to better understand the clinical impact of these responses.