Article Text
Abstract
Background Inhaled anti-inflammatory therapy is fundamental to asthma management, but adherence is very poor. This increases the risk of exacerbations and poor symptom control. Currently there is no direct way of assessing adherence to inhaled steroids accurately. The primary aim of this project was to determine whether liquid chromatography tandem mass spectrometry could be used to detect fluticasone propionate (FP) in human serum as a potential aid to therapeutic monitoring. The secondary aim was to relate serum levels of FP to markers of asthma severity.
Methods We collected blood samples over an 8 hr period from inpatients with severe asthma on a stable dose of inhaled FP. Following baseline (trough) sampling, patients were observed using their inhaler, with inhaler technique documented. Subsequent samples were obtained 1, 2s, 4 and 8 hrs post inhalation. Demographic details and spirometry were also recorded.
Results Thirteen patients were recruited: 8 males, 5 females; age range 22–64 yrs; FEV1 range 53–101% predicted; 10 patients on 1000 mcg/day, and three on 2000 mcg/day FP. The mean concentration of FP at 1 hr post inhaler (peak in 7/13 patients) was 95.5 (SD 89.1) ng/L. The mean pre-dose trough concentration was 32.9 (SD 41.5) ng/L. Two patients were noted to have poor inhaler technique; these patients had some of the lowest serum FP levels recorded. The FEV1% predicted was found to be strongly correlated with the peak serum FP concentration (Pearson’s r = 0.8, p = 0.001).
Conclusion We have demonstrated that FP can be detected in the blood of patients with severe asthma following directly observed therapy; this could have a potential future application as a direct measure of adherence and perhaps inhaler technique. We also demonstrated a profound effect of reduced lung function predicting low serum FP levels. Future work will explore whether poor absorption reflects relatively poor efficacy in the most severe patients.