Development and Clinical Application of a Prednisolone/Cortisol Assay to Determine Adherence to Maintenance Oral Prednisolone in Severe Asthma
Development and Clinical Application of a Prednisolone/Cortisol Assay to Determine Adherence to Maintenance Oral Prednisolone in Severe Asthma
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DOI：
10.1016/j.chest.2020.03.056
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发表时间：
2020-09-01
期刊：
影响因子：
9.6
通讯作者：
Webster, Craig
中科院分区：
文献类型：
--
作者：
Mansur, Adel H.;Hassan, Maged;Webster, Craig
背景技术背景：不遵守口服泼尼松龙是一个重要的驱动程序，控制不良的严重哮喘，其检测是必要的，以指导management.RESEARCH问题：本研究的目的是评估实用程序的液相色谱和串联质谱（LC-MS/MS）在确定严重哮喘患者口服泼尼松龙的遵守状态。研究设计和方法：在观察到接受维持口服泼尼松龙的患者摄入泼尼松龙后，使用经验证的LC-MS/MS测定法测量泼尼松龙、皮质醇和代谢物的时间轴血清水平。通过分析血药浓度峰值确定依从性和非依从性模式。在第二个队列的患者接受维持泼尼松龙和对照组的现场试验的坚持（可检测的泼尼松龙和抑制皮质醇）的性能进行了评估。结果：在泼尼松龙吸收试验，27例（平均年龄，38.6岁;年龄范围，17-63岁; 83%的女性）被列入。我们确定了13例（48%）依从性，13例（48%）不依从性，1例（3.7%）吸收不良。与非粘附组相比，粘附组的中位[四分位距]峰值血清测定为：皮质醇，36 [39.5] vs 295 [153] nmol/L;泼尼松龙，1，810 [590] vs 1，730 [727] nmol/L。斑点试验队列包括111名患者（67名接受泼尼松龙维持治疗，44名对照受试者）;平均年龄为42.4岁，79%为女性。在40.3%的患者中检测到不依从;依从组与不依从组的比较显示皮质醇的中位数[四分位数间距]分别为27 [48] nmol/L vs 211 [130] nmol/L，泼尼松龙的中位数[四分位数间距]分别为259 [622] nmol/L vs < 20 nmol/L。坚持治疗的患者平均BMI较高（38.4 +/- 8.7 vs 32 +/- 7.5 kg/m2; P = .03），血嗜酸性粒细胞中位数较低（0.09 [0.31] vs 0.51 [0.53] x 109/L; P <0.001），以及平均每年重度急性加重减少的趋势（3.0 +/- 2.6 vs 4.3 +/- 2.4; P = 0.3）。解释：口服泼尼松龙的不依从性在严重哮喘中很常见，并且可以通过使用LC-MS/MS分析在临床上可靠地检测到。
BACKGROUND: Nonadherence to oral prednisolone is an important driver of poor control in severe asthma, and its detection is warranted to guide management.RESEARCH QUESTION: The goal of this study was to evaluate the utility of liquid chromatography and tandem mass spectrometry (LC-MS/MS) in determining the adherence status to oral prednisolone in severe asthma. STUDY DESIGN AND METHODS: Timeline serum levels of prednisolone, cortisol, and metabolites were measured by using a validated LC-MS/MS assay following observed intake of prednisolone in patients receiving maintenance oral prednisolone. Patterns of adherence and nonadherence 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 receiving maintenance prednisolone and a control group.RESULTS: In the prednisolone absorption test, 27 patients (mean age, 38.6 years; age range, 17-63 years; 83% female) were included. We identified adherence in 13 (48%), nonadherence in 13 (48%), and malabsorption in one (3.7%). The median [interquartile range] peak serum assays of the adherent group compared with the nonadherent group were: cortisol, 36 [39.5] vs 295 [153] nmol/L; and prednisolone, 1,810 [590] vs 1,730 [727] nmol/L. The spot test cohort included 111 patients (67 on maintenance prednisolone and 44 control subjects); the mean age was 42.4 years, and 79% were female. Nonadherence was detected in 40.3% of patients; comparison of the adherent vs nonadherent groups revealed median [interquartile range] levels for cortisol of 27 [48] nmol/L vs 211 [130] nmol/L and for prednisolone of 259 [622] nmol/L vs < 20 nmol/L, respectively. Adherent patients had higher mean BMI (38.4 +/- 8.7 vs 32 +/- 7.5 kg/m2; P = .03), lower median blood eosinophils (0.09 [0.31] vs 0.51 [0.53] x 109/L; P < .001), and a trend toward reduced mean annual severe exacerbations (3.0 +/- 2.6 vs 4.3 +/- 2.4; P = .3) than nonadherent patients.INTERPRETATION: Nonadherence to oral prednisolone is common in severe asthma and can be reliably detected in the clinic by using the LC-MS/MS assay.