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Serum Inhaled Corticosteroid Detection for Monitoring Adherence in Severe Asthma
Fahad H Alahmadi1, Brian Keevil2, Lynn Elsey2
1School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, United Kingdom; NIHR Manchester Biomedical Research Centre, Manchester University Hospitals NHS Foundation Trust, Manchester, United Kingdom; Respiratory Therapy Department, College of Medical Rehabilitation Sciences, Taibah University, Madinah, Saudi Arabia.
Background:
Daily inhaled corticosteroids (ICSs) are fundamental to asthma management, but adherence is low.
Objectives:
To investigate (1) whether LC-MS/MS could be used to detect ICSs in serum and (2) whether serum levels related to markers of disease severity.
Methods:
We collected blood samples over an 8-hour period from patients with severe asthma prescribed at least 1000 μg daily of beclomethasone dipropionate equivalent. Following baseline sampling, patients were observed taking their usual morning dose. Subsequent blood samples were obtained 1, 2, 4, and 8 hours postinhalation and analyzed by LC-MS/MS. Correlations between serum ICS levels and severity markers were investigated.
Results:
A total of 60 patients were recruited (41 females; 39 prescribed maintenance prednisolone; mean age, 49 ± 12 years; FEV1, 63 ± 20 %predicted). Eight hours postinhalation, all patients using budesonide (n = 10) and beclomethasone dipropionate (15), and all but 1 using fluticasone propionate (28), had detectable serum drug levels. Fluticasone furorate was detected in 2 patients (of 4), ciclesonide in none (of 7). Low adherence by repeat prescription records (<80%) was identified in 43%. Blood ICS levels correlated negatively with exacerbation rate, and (for fluticasone propionate only) positively with FEV1 %predicted.
Conclusions:
Commonly used ICSs can be reliably detected in the blood at least 8 hours after dosing, and could therefore be used as a measure of adherence in severe asthma. Higher exacerbation rates and poorer lung function (for fluticasone propionate) were associated with lower blood levels.
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