Responsiveness to Ipratropium Bromide in Male and Female Patients with Mild to Moderate Chronic Obstructive Pulmonary Disease
Responsiveness to Ipratropium Bromide in Male and Female Patients with Mild to Moderate Chronic Obstructive Pulmonary Disease
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DOI：
10.1016/j.ebiom.2017.04.020
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发表时间：
2017-05-01
期刊：
影响因子：
11.1
通讯作者：
Sin, Don D.
中科院分区：
文献类型：
--
作者：
Li, Xuan;Obeidat, Ma'en;Sin, Don D.
虽然慢性阻塞性肺疾病（COPD）的患病率在男性和女性之间相似，但目前用于支持支气管扩张剂治疗的证据是在主要招募男性患者的治疗试验中产生的。在这里，我们确定了异丙托溴铵对FEV1的反应是否存在显著的性别相关差异。方法：使用来自肺健康研究（n = 5887, 37%为女性）的数据来确定5年以上轻至中度COPD男性和女性受试者中异丙托品或安慰剂的FEV1变化。使用肺表达定量性状位点（Quantitative Trait Loci, eQTL）数据集确定男性和女性患者肺中毒蕈碱（M2和M3）受体基因表达是否存在性别相关差异。结果：4个月后，异丙托品治疗使女性受试者FEV1较基线值增加6.0%，男性受试者增加2.9% （p = 2.42 × 10(-16)）。体重指数（BMI）改变了这种效果，因此在瘦弱的女性受试者中观察到异丙托品对FEV1的最大改善（BMI *性别相互作用p = 0.044）。异丙托品相关的FEV1性别相关变化持续2年（p = 0.0134）。女性肺中M3受体基因表达高于男性肺中M2受体基因表达（p = 6.86 × 10(-8)）。结论：异丙托品在女性患者中诱导的支气管扩张反应比男性患者更大，在非肥胖女性中效果尤其显著。相对于M2受体，女性肺中M3毒蕈碱受体的基因表达高于男性肺。因此，女性患者比男性COPD患者更有可能从异丙托品中获益。(C) 2017年作者。Elsevier B.V.出版
Introduction: Although the prevalence of chronic obstructive pulmonary disease (COPD) is similar between men and women, current evidence used to support bronchodilator therapy has been generated in therapeutic trials that have predominately enrolled male patients. Here, we determined whether there is any significant sex-related differences in FEV1 responses to ipratropium bromide.Methods: Data from the Lung Health Study (n = 5887; 37% females) were used to determine changes in FEV1 with ipratropium or placebo in male and female subjects with mild to moderate COPD over 5 years. Lung Expression Quantitative Trait Loci (eQTL) dataset was used to determine whether there were any sex-related differences in gene expression for muscarinic (M2 and M3) receptors in lungs of male and female patients.Results: After 4 months, ipratropium therapy increased FEV1 by 6.0% in female and 2.9% in male subjects from baseline values (p = 2.42 x 10(-16)). This effect was modified by body mass index (BMI) such that the biggest improvements in FEV1 with ipratropium were observed in thin female subjects (p for BMI * sex interaction = 0.044). The sex-related changes in FEV1 related to ipratropium persisted for 2 years (p = 0.0134). Female compared with male lungs had greater gene expression for M3 relative to M2 receptors (p = 6.86 x 10(-8)).Conclusion: Ipratropium induces a larger bronchodilator response in female than in male patients and the benefits are particularly notable in non-obese females. Female lungs have greater gene expression for the M3 muscarinic receptor relative to M2 receptors than male lungs. Female patients are thus more likely to benefit from ipratropium than male COPD patients. (C) 2017 The Authors. Published by Elsevier B.V.