Abstract
BackgroundDaily Inhaled corticosteroids (ICS) are fundamental to asthma management, but adherence to them is low in around two-thirds of patients and associated with increased risk of exacerbations and poor symptom control. Currently there is no direct way of assessing adherence to ICS. The primary aim of this project was to determine whether liquid chromatography tandem mass spectrometry (LC-MS/MS) could be used to detect ICS in serum within a time frame that may enable monitoring in clinic; a secondary aim was to investigate whether serum levels related to markers of disease severity.MethodsWe collected five blood samples over an 8 hr period from patients with severe asthma prescribed at least 1000 mcg daily of beclomethasone dipropionate (BDP) equivalent. Following baseline sampling, patients were observed taking their usual morning dose. Subsequent blood samples were obtained 1, 2, 4 and 8 hrs post-inhalation and analysed by LC-MS/MS. Limit of quantification (LOQ) for all ICS inhalers was 10 ng/L except for Ciclesonide (CIC) which was 50 ng/l. Correlations between serum ICS levels and clinical data (including exacerbation rate, and spirometry) were investigated.Results60 patients were recruited, 41 female, 39 prescribed maintenance prednisolone, mean (SD) age 49 (12) yrs, FEV1 63 (20)%predicted. 8 hrs post-inhalation, all patients using budesonide (BUD, n=10) and BDP (15), and all but one using fluticasone propionate (FP, 28) had detectable serum drug levels. Fluticasone Furorate (FF) was detected in two patients (of 4 using FF), while CIC was not detected in any (of 7). Low adherence by prescription refill was identified in 43%. Log blood ICS levels negatively correlated with exacerbation rate, daily ICS dose and log daily prednisolone dose, and (for FP only) positively correlated with FEV1%predicted.ConclusionCommonly used ICS (FP, BUD, BDP) can be reliably detected in the blood at least 8 hrs after dosing, and could therefore have a potential future application as a direct measure of adherence. Higher exacerbation rates and prescribed doses of ICS and prednisolone were associated with lower blood levels. Potential reasons include poor adherence (with inappropriate increase in prescribed dose) and/or poor absorption in those with severe airflow obstruction.