中文译文：用于确定严重哮喘患者维持口服泼尼松龙治疗依从性的泼尼松龙/皮质醇检测的开发和临床应用。
Development and Clinical Application of a Prednisolone/Cortisol Assay to Determine Adherence to Maintenance Oral Prednisolone in Severe Asthma.
机构信息
Birmingham Regional Severe Asthma Service, Heartlands Hospital, University Hospitals Birmingham, Birmingham, England; Institute of inflammation and Ageing, University of Birmingham, Birmingham, England.
Birmingham Regional Severe Asthma Service, Heartlands Hospital, University Hospitals Birmingham, Birmingham, England.
出版信息
Chest. 2020 Sep;158(3):901-912. doi: 10.1016/j.chest.2020.03.056. Epub 2020 Apr 13.
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/m; P = .03), lower median blood eosinophils (0.09 [0.31] vs 0.51 [0.53] × 10/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.
背景
在严重哮喘中，不遵医嘱口服泼尼松龙是导致控制不佳的重要因素，因此有必要对其进行检测，以指导治疗。
研究问题
本研究的目的是评估液相色谱-串联质谱（LC-MS/MS）在确定严重哮喘患者口服泼尼松龙的依从性方面的应用价值。
研究设计和方法
在接受维持剂量口服泼尼松龙的患者中，通过观察泼尼松龙的摄入量，采用经验证的 LC-MS/MS 测定方法，检测患者血清中泼尼松龙、皮质醇及其代谢物的时间依赖性水平。通过分析血药峰浓度来确定患者的依从性或不依从性模式。在接受维持剂量泼尼松龙治疗的第二组患者和对照组中，评估了一种用于检测依从性的点测试（可检测到泼尼松龙和抑制皮质醇）的性能。
结果
在泼尼松龙吸收试验中，纳入了 27 名（平均年龄 38.6 岁；年龄范围 17-63 岁；83%为女性）患者。我们发现 13 名（48%）患者为依从性，13 名（48%）患者为不依从性，1 名（3.7%）患者为吸收不良。与不依从组相比，依从组患者的中位（四分位距）血清检测结果为：皮质醇，36 [39.5] vs 295 [153] nmol/L；泼尼松龙，1810 [590] vs 1730 [727] nmol/L。点测试队列包括 111 名患者（67 名接受维持剂量泼尼松龙治疗，44 名对照组）；平均年龄为 42.4 岁，79%为女性。检测到 40.3%的患者存在不依从性；与依从组相比，不依从组患者的皮质醇中位数（四分位距）水平为 27 [48] nmol/L，泼尼松龙中位数（四分位距）水平为 259 [622] nmol/L vs < 20 nmol/L。依从组患者的平均 BMI（38.4 ± 8.7 vs 32 ± 7.5 kg/m；P =.03）更高，中位血嗜酸粒细胞计数（0.09 [0.31] vs 0.51 [0.53] × 10/L；P <.001）更低，且年严重加重次数（3.0 ± 2.6 vs 4.3 ± 2.4；P =.3）呈下降趋势。
结论
严重哮喘患者中口服泼尼松龙不依从的情况很常见，可通过 LC-MS/MS 检测在临床中可靠地检测到。
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