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Exhaled Volatile Organic Compounds as Markers for Medication Use in Asthma
European Respiratory Journal ( IF 16.6 ) Pub Date : 2019-09-12 , DOI: 10.1183/13993003.00544-2019
Paul Brinkman , Waqar M. Ahmed , Cristina Gómez , Hugo H. Knobel , Hans Weda , Teunis J. Vink , Tamara M. Nijsen , Craig E. Wheelock , Sven-Erik Dahlen , Paolo Montuschi , Richard G. Knowles , Susanne J. Vijverberg , Anke H. Maitland-van der Zee , Peter J. Sterk , Stephen J. Fowler

Introduction Asthma is a heterogeneous condition, characterised by chronic inflammation of the airways, typically managed with inhaled bronchodilators and corticosteroids. In the case of uncontrolled asthma, oral corticosteroids (OCSs) are often prescribed. Good adherence and inhalation technique are associated with improved outcomes; however, it is difficult to monitor appropriate drug intake and effectiveness in individual patients. Exhaled breath contains thousands of volatile organic compounds (VOCs) that reflect changes in the body's chemistry and may be useful for monitoring drug pharmacokinetics/pharmacodynamics. We aimed to investigate the association of exhaled VOCs in severe asthma patients from the U-BIOPRED cohort (by gas chromatography coupled with time-of-flight mass spectrometry) with urinary levels of salbutamol and OCSs (by liquid chromatography coupled with high-resolution mass spectrometry). Methods Samples were collected at baseline and after 12–18 months of follow-up. Statistical analysis was based on univariate and multivariate modelling, followed by area under the receiver operating characteristic curve (AUC) calculation. Results were verified through longitudinal replication and independent validation. Results Data were available for 78 patients (baseline n=48, replication n=30 and validation n=30). Baseline AUC values were 82.1% (95% CI 70.4–93.9%) for salbutamol and 78.8% (95% CI 65.8–91.8%) for OCS. These outcomes could be adequately replicated and validated. Additional regression analysis between qualified exhaled VOCs and urinary concentrations of salbutamol and prednisone showed statistically significant correlations (p<0.01). Conclusion We have linked exhaled VOCs to urinary detection of salbutamol and OCSs. This merits further development of breathomics into a point-of-care tool for therapeutic drug monitoring. Exhaled volatile organic compounds can be linked to urinary traces of salbutamol and oral corticosteroids. This suggests that breathomics qualifies for development into a point-of-care tool for monitoring asthma drug level changes. http://bit.ly/2Hu4TOf

中文翻译:

呼出的挥发性有机化合物作为哮喘药物使用的标志物

介绍 哮喘是一种异质性疾病,以气道慢性炎症为特征,通常通过吸入支气管扩张剂和皮质类固醇进行治疗。在未控制的哮喘的情况下,经常开具口服皮质类固醇 (OCS)。良好的依从性和吸入技术与改善的结果相关;然而,很难监测个体患者的适当药物摄入量和有效性。呼出气中含有数以千计的挥发性有机化合物 (VOC),它们反映身体化学的变化,可用于监测药物的药代动力学/药效学。我们旨在研究来自 U-BIOPRED 队列的重度哮喘患者呼出的 VOC(通过气相色谱结合飞行时间质谱)与尿中沙丁胺醇和 OCS 水平(通过液相色谱结合高分辨率质谱)的关联。光谱)。方法 在基线和 12-18 个月的随访后收集样本。统计分析基于单变量和多变量建模,然后是接受者操作特征曲线下面积 (AUC) 计算。结果通过纵向复制和独立验证进行验证。结果 78 名患者的数据可用(基线 n=48,重复 n=30,验证 n=30)。沙丁胺醇的基线 AUC 值为 82.1%(95% CI 70.4-93.9%),OCS 为 78.8%(95% CI 65.8-91.8%)。这些结果可以被充分复制和验证。合格呼出 VOC 与尿中沙丁胺醇和泼尼松浓度之间的附加回归分析显示出统计学上显着的相关性 (p<0.01)。结论 我们已将呼出的 VOC 与尿液中沙丁胺醇和 OCS 的检测联系起来。这值得将呼吸组学进一步发展为用于治疗药物监测的即时护理工具。呼出的挥发性有机化合物可能与尿液中的沙丁胺醇和口服皮质类固醇的痕迹有关。这表明呼吸组学有资格发展成为监测哮喘药物水平变化的即时工具。http://bit.ly/2Hu4TOf 合格呼出 VOC 与尿中沙丁胺醇和泼尼松浓度之间的附加回归分析显示出统计学上显着的相关性 (p<0.01)。结论 我们已将呼出的 VOC 与沙丁胺醇和 OCS 的尿液检测联系起来。这值得将呼吸组学进一步发展为用于治疗药物监测的即时护理工具。呼出的挥发性有机化合物可能与尿液中的沙丁胺醇和口服皮质类固醇的痕迹有关。这表明呼吸组学有资格发展成为监测哮喘药物水平变化的即时工具。http://bit.ly/2Hu4TOf 合格呼出 VOC 与尿中沙丁胺醇和泼尼松浓度之间的附加回归分析显示出统计学上显着的相关性 (p<0.01)。结论 我们已将呼出的 VOC 与尿液中沙丁胺醇和 OCS 的检测联系起来。这值得将呼吸组学进一步发展为用于治疗药物监测的即时护理工具。呼出的挥发性有机化合物可能与尿液中的沙丁胺醇和口服皮质类固醇的痕迹有关。这表明呼吸组学有资格发展成为监测哮喘药物水平变化的即时工具。http://bit.ly/2Hu4TOf 呼出的挥发性有机化合物可能与尿液中的沙丁胺醇和口服皮质类固醇的痕迹有关。这表明呼吸组学有资格发展成为监测哮喘药物水平变化的即时工具。http://bit.ly/2Hu4TOf 呼出的挥发性有机化合物可能与尿液中的沙丁胺醇和口服皮质类固醇的痕迹有关。这表明呼吸组学有资格发展成为监测哮喘药物水平变化的即时工具。http://bit.ly/2Hu4TOf
更新日期:2019-09-12
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