泼尼松龙/皮质醇测定在重症哮喘患者中维持口服泼尼松龙依从性的研究及临床应用
2020/05/14
摘要
背景：口服泼尼松龙的不依从性是重症哮喘控制不佳的重要原因，有必要对其进行检测以指导治疗。
目的：探讨液相色谱-串联质谱（LC-MS/MS）联用技术在测定重症哮喘患者口服泼尼松龙依从性中的应用。
方法：在口服泼尼松龙维持治疗的患者中观察到泼尼松龙的摄入量后，使用经过验证的LC-MS / MS测定法测定泼尼松龙、皮质醇和代谢产物的时间线血清水平。从峰值血药浓度分析确定依从性和不依从性的模式。在第二组接受泼尼松龙维持治疗的患者和对照组中，对依从性（可检测到泼尼松龙和抑制皮质醇）进行现场测试。
结果：泼尼松龙吸收试验包括27例患者[平均年龄38.6岁（17-63），24女性（83％）]。我们发现依从性13例（48％），不依从性13例（48％）和1例（3.7％）吸收不良。与不依从组相比，依从组的血清中位数（IQR）峰值血清测定（nmol / L）为：皮质醇36（39.5）比295（153），泼尼松龙1810（590）比1730（727）。现场测试队列包括111名患者（67例泼尼松龙维持治疗和44例对照，平均年龄42.4岁，女性占79％）。不依从性患者占到40.3％，依从组与不依从组的比较显示：皮质醇27（48）比211（130）和泼尼松龙259（622）比<20。依从性患者的平均BMI较高（38.4±8.7 vs 32±7.5kg / m2，p = 0.03），血液嗜酸性粒细胞中位数较低（90（310）vs 510（530）细胞/μl，p <0.001），并且与不依从性患者相比，年平均严重急性发作率有降低的趋势（3.0±2.6 vs 4.3±2.4，p = 0.3）。
结论：在重症哮喘中，口服泼尼松龙不依从性的情况很常见，临床上可以用LC-MS / MS测定法检测到。
Development and Clinical Application of a Prednisolone/Cortisol Assay to Determine Adherence to Maintenance Oral Prednisolone in Severe Asthma.
Adel H Mansur, Maged Hassan, Joanne Duffy, Craig Webster.
Abstract
BACKGROUND:Non-adherence to oral prednisolone is an important driver of poor control in severe asthma, and its detection is warranted to guide management.
OBJECTIVE:to study the utility of liquid chromatography and tandem mass spectrometry (LC-MS/MS) in determining the adherence status to oral prednisolone in severe asthma.
METHODS:timeline serum levels of prednisolone, cortisol and metabolites were measured using a validated LC-MS/MS assay following observed intake of prednisolone in patients on maintenance oral prednisolone. Patterns of adherence and non-adherence were determined from analysis of peak blood levels. The performance of a spot test for adherence (detectable prednisolone and suppressed cortisol) was assessed in a second cohort of patients on maintenance prednisolone and a control group.
RESULTS:In the prednisolone absorption test 27 patients [mean age 38.6 years (17-63), 24 (83%) females] were included. We identified adherence in 13 (48%), non-adherence in 13 (48%), and malabsorption in 1(3.7%). The median (IQR) peak serum assays (nmol/L) of the adherent compared to the non-adherent groups were; cortisol 36(39.5) vs 295(153), prednisolone 1810 (590) vs 1730(727). The spot test cohort included 111 patients [67 on maintenance prednisolone and 44 control, the mean age was 42.4 years and 79% were females. Non-adherence was detected in 40.3% of patients and comparison of the adherent versus non-adherent groups showed; cortisol 27(48) vs 211(130) and prednisolone 259 (622) vs <20 respectively. The adherent patients had higher mean BMI (38.4±8.7 vs 32±7.5kg/m2, p= 0.03), lower median blood eosinophils (90 (310) vs 510 (530) cells/μl, p< 0.001) and a trend towards reduced mean annual severe exacerbations (3.0±2.6 vs 4.3±2.4, p=0.3) than the non-adherent patients.
CONCLUSIONS:non-adherence to oral prednisolone is common in severe asthma and can be reliably detected in the clinic using the LC-MS/MS assay.
背景：口服泼尼松龙的不依从性是重症哮喘控制不佳的重要原因，有必要对其进行检测以指导治疗。
目的：探讨液相色谱-串联质谱（LC-MS/MS）联用技术在测定重症哮喘患者口服泼尼松龙依从性中的应用。
方法：在口服泼尼松龙维持治疗的患者中观察到泼尼松龙的摄入量后，使用经过验证的LC-MS / MS测定法测定泼尼松龙、皮质醇和代谢产物的时间线血清水平。从峰值血药浓度分析确定依从性和不依从性的模式。在第二组接受泼尼松龙维持治疗的患者和对照组中，对依从性（可检测到泼尼松龙和抑制皮质醇）进行现场测试。
结果：泼尼松龙吸收试验包括27例患者[平均年龄38.6岁（17-63），24女性（83％）]。我们发现依从性13例（48％），不依从性13例（48％）和1例（3.7％）吸收不良。与不依从组相比，依从组的血清中位数（IQR）峰值血清测定（nmol / L）为：皮质醇36（39.5）比295（153），泼尼松龙1810（590）比1730（727）。现场测试队列包括111名患者（67例泼尼松龙维持治疗和44例对照，平均年龄42.4岁，女性占79％）。不依从性患者占到40.3％，依从组与不依从组的比较显示：皮质醇27（48）比211（130）和泼尼松龙259（622）比<20。依从性患者的平均BMI较高（38.4±8.7 vs 32±7.5kg / m2，p = 0.03），血液嗜酸性粒细胞中位数较低（90（310）vs 510（530）细胞/μl，p <0.001），并且与不依从性患者相比，年平均严重急性发作率有降低的趋势（3.0±2.6 vs 4.3±2.4，p = 0.3）。
结论：在重症哮喘中，口服泼尼松龙不依从性的情况很常见，临床上可以用LC-MS / MS测定法检测到。
(中日友好医院呼吸与危重症医学科 王瑞茵 摘译 林江涛 审校)
(Chest. 2020 Apr 13; S0012-3692(20)30682-6.)
(Chest. 2020 Apr 13; S0012-3692(20)30682-6.)
Development and Clinical Application of a Prednisolone/Cortisol Assay to Determine Adherence to Maintenance Oral Prednisolone in Severe Asthma.
Adel H Mansur, Maged Hassan, Joanne Duffy, Craig Webster.
Abstract
BACKGROUND:Non-adherence to oral prednisolone is an important driver of poor control in severe asthma, and its detection is warranted to guide management.
OBJECTIVE:to study the utility of liquid chromatography and tandem mass spectrometry (LC-MS/MS) in determining the adherence status to oral prednisolone in severe asthma.
METHODS:timeline serum levels of prednisolone, cortisol and metabolites were measured using a validated LC-MS/MS assay following observed intake of prednisolone in patients on maintenance oral prednisolone. Patterns of adherence and non-adherence were determined from analysis of peak blood levels. The performance of a spot test for adherence (detectable prednisolone and suppressed cortisol) was assessed in a second cohort of patients on maintenance prednisolone and a control group.
RESULTS:In the prednisolone absorption test 27 patients [mean age 38.6 years (17-63), 24 (83%) females] were included. We identified adherence in 13 (48%), non-adherence in 13 (48%), and malabsorption in 1(3.7%). The median (IQR) peak serum assays (nmol/L) of the adherent compared to the non-adherent groups were; cortisol 36(39.5) vs 295(153), prednisolone 1810 (590) vs 1730(727). The spot test cohort included 111 patients [67 on maintenance prednisolone and 44 control, the mean age was 42.4 years and 79% were females. Non-adherence was detected in 40.3% of patients and comparison of the adherent versus non-adherent groups showed; cortisol 27(48) vs 211(130) and prednisolone 259 (622) vs <20 respectively. The adherent patients had higher mean BMI (38.4±8.7 vs 32±7.5kg/m2, p= 0.03), lower median blood eosinophils (90 (310) vs 510 (530) cells/μl, p< 0.001) and a trend towards reduced mean annual severe exacerbations (3.0±2.6 vs 4.3±2.4, p=0.3) than the non-adherent patients.
CONCLUSIONS:non-adherence to oral prednisolone is common in severe asthma and can be reliably detected in the clinic using the LC-MS/MS assay.
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