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首页> 外文期刊>EBioMedicine >Responsiveness to Ipratropium Bromide in Male and Female Patients with Mild to Moderate Chronic Obstructive Pulmonary Disease
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Responsiveness to Ipratropium Bromide in Male and Female Patients with Mild to Moderate Chronic Obstructive Pulmonary Disease

机译：轻度至中度慢性阻塞性肺疾病男女患者对异丙托溴铵的反应性

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Abstract 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 × 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 × 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.
机译：摘要简介尽管慢性阻塞性肺疾病（COPD）的患病率在男性和女性之间相似，但目前在支持男性支气管扩张性疾病的治疗性试验中已经获得了用于支持支气管扩张剂治疗的最新证据。在这里，我们确定{FEV1}对异丙托溴铵的反应中是否存在明显的性别相关差异。方法使用来自肺健康研究（n = 5887; 37％的女性）的数据来确定在5年中轻度至中度{COPD}的男性和女性受试者中异丙托溴铵或安慰剂引起的{FEV1}变化。肺表达定量性状位点（eQTL）数据集用于确定男性和女性患者肺中毒蕈碱（M2和M3）受体的基因表达是否存在性别相关的差异。结果4个月后，异丙托溴铵治疗使女性受试者的{FEV1}从基线值增加了6.0％，而男性受试者则增加了2.9％（p = 2.42×10？16）。该效应已通过体重指数（BMI）进行了修改，从而在瘦弱的女性受试者中观察到了异丙托溴铵对{FEV1}的最大改善（​​{BMI}的p =性别相互作用= 0.044）。与异丙托溴铵相关的{FEV1}中与性别相关的变化持续了2年（p = 0.0134）。与{M2}受体相比，女性与男性肺相比{M3}的基因表达更高（p = 6.86×10？8）。结论异丙托铵在女性中诱发的支气管扩张剂反应比男性患者大，并且非肥胖女性的获益尤为明显。相对于{M2}受体，女性肺部的{M3}毒蕈碱受体基因表达高于男性肺部。因此，女性患者比男性{COPD}患者更有可能从异丙托品中获益。

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