Nwaru Bright I, Simpson Colin R, Soyiri Ireneous N, Pillinger Rebecca, Appiagyei Francis, Ryan Dermot, Critchley Hilary, Price David B, Hawrylowicz Catherine M, Sheikh Aziz
Krefting Research Centre, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.
Wallenberg Centre for Molecular and Translational Medicine, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.
BMJ Open. 2018 Jun 27;8(6):e020075. doi: 10.1136/bmjopen-2017-020075.
Female sex steroid hormones have been implicated in sex-related differences in the development and clinical outcomes of asthma. The role of exogenous sex steroids, however, remains unclear. Our recent systematic review highlighted the lack of high-quality population-based studies investigating this subject. We aim to investigate whether the use of hormonal contraception and hormone replacement therapy (HRT), subtypes and route of administration are associated with asthma onset and clinical outcomes in reproductive age and perimenopausal/postmenopausal females.
Using the Optimum Patient Care Research Database (OPCRD), a national primary care database in the UK, we will construct a retrospective longitudinal cohort of reproductive age (16-45 years) and perimenopausal/postmenopausal (46-70 years) females. We will estimate the risk of new-onset asthma using Cox regression and multilevel modelling for repeated asthma outcomes, such as asthma attacks. We will adjust for confounding factors in all analyses. We will evaluate interactions between the use of exogenous sex hormones and body mass index and smoking by calculating the relative excess risk due to interaction and the attributable proportion due to interaction. With 90% power, we need 23 700 reproductive age females to detect a 20% reduction (risk ratio 0.8) in asthma attacks for use of any hormonal contraception and 6000 perimenopausal/postmenopausal females to detect a 40% (risk ratio 1.40) increased risk of asthma attacks for use of any HRT.
We have obtained approval (ADEPT1317) from the Anonymised Data Ethics and Protocol Transparency Committee which grants project-specific ethics approvals for the use of OPCRD data. Optimum Patient Care has an existing NHS Health Research Authority ethics approval for the use of OPCRD data for research (15/EM/150). We will present our findings at national and international scientific meetings and publish the results in international peer-reviewed journals.
EUPAS22967.
女性性甾体激素与哮喘的发生发展及临床结局中的性别差异有关。然而，外源性性甾体激素的作用仍不明确。我们最近的系统评价强调了缺乏高质量的基于人群的研究来调查这一主题。我们旨在研究激素避孕和激素替代疗法（HRT）的使用、亚型及给药途径是否与育龄期及围绝经期/绝经后女性的哮喘发病及临床结局相关。
利用英国的一个全国初级保健数据库——最佳患者护理研究数据库（OPCRD），我们将构建一个育龄期（16 - 45岁）和围绝经期/绝经后（46 - 70岁）女性的回顾性纵向队列。我们将使用Cox回归和重复哮喘结局（如哮喘发作）的多水平模型来估计新发哮喘的风险。我们将在所有分析中对混杂因素进行校正。我们将通过计算交互作用导致的相对超额危险度和交互作用归因比例来评估外源性性激素的使用与体重指数及吸烟之间的相互作用。在检验效能为90%的情况下，我们需要23700名育龄期女性来检测使用任何激素避孕措施使哮喘发作减少20%（风险比0.8），以及6000名围绝经期/绝经后女性来检测使用任何HRT使哮喘发作风险增加40%（风险比1.40）。
我们已获得匿名数据伦理与方案透明度委员会的批准（ADEPT1317），该委员会为使用OPCRD数据授予特定项目的伦理批准。最佳患者护理已获得英国国家医疗服务体系健康研究管理局对使用OPCRD数据进行研究的现有伦理批准（15/EM/150）。我们将在国内和国际科学会议上展示我们的研究结果，并在国际同行评审期刊上发表研究结果。
EUPAS22967。
