• Adel H Mansur, Maged Hassan, Joanne Duffy, and Craig Webster.
• Birmingham Regional Severe Asthma Service, Heartlands Hospital, University Hospitals Birmingham, Birmingham, England; Institute of inflammation and Ageing, University of Birmingham, Birmingham, England. Electronic address: adel.mansur@heartofengland.nhs.uk.
• Chest. 2020 Sep 1; 158 (3): 901-912.

BackgroundNonadherence to oral prednisolone is an important driver of poor control in severe asthma, and its detection is warranted to guide management.Research QuestionThe 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 MethodsTimeline 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.ResultsIn 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] × 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.InterpretationNonadherence to oral prednisolone is common in severe asthma and can be reliably detected in the clinic by using the LC-MS/MS assay.Copyright © 2020 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

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