Effects of oral and inhaled corticosteroid on lymphocyte β2-adrenoceptor function in asthmatic patients

Aims We have previously demonstrated that a single dose of oral prednisolone but not single doses of inhaled fluticasone had facilitatory effects on lymphocyte β₂-adrenoceptor (AR) function. To address possible differences in steady-state time-course, the aim of this study was to determine if repeated dosing with inhaled fluticasone would have facilitatory effects on lymphocyte β₂-AR. Plasma cortisol was also evaluated as a measure of systemic bioactivity.Methods Ten asthmatic subjects, mean (s.e.mean) age 29 (3) years, FEV₁ 89 (5) % predicted, were randomised in a double-blind crossover study to receive inhaled placebo (PL), inhaled fluticasone 1000 μg day⁻¹ (F1000) and inhaled fluticasone 2000 μg day⁻¹, each for 4 days and also a single dose of oral prednisolone 50 mg (PRED). Prednisolone was given as open medication. The last dose of study drug was taken at 22.00 h and subjects attended the laboratory at 08.00 h the following day.Results β₂-AR density (B_max; fmol/10⁶ cells) was significantly increased after PRED compared with PL and inhaled fluticasone. B_max (geometric mean) after each treatment were: PL 1.51, F1000 1.20, F2000 1.20 and PRED 2.14 (a 1.4 fold difference PRED vs PL; 95% CI 1.05 to 1.95; P<0.001). There was significant (P<0.001) suppression of plasma cortisol (nmol l⁻¹ ) following F2000 and PRED compared with PL: 393.8, F1000 302.1, F2000 205.0 (95% CI F2000 vs PL 58.1 to 319.4) and PRED 87.0 (95% CI PRED vs PL 176.2 to 437.5). The estimated milligram equivalence ratio for adrenal suppression was calculated at 1:11 for fluticasone vs prednisolone.Conclusions Repeated dosing with high-dose inhaled fluticasone did not up-regulate lymphocyte β₂-AR as compared with a single dose of oral prednisolone, despite having significantly suppressed early morning plasma cortisol. This study confirms our previous finding of a dissociation in sensitivity between effects of inhaled corticosteroid on adrenal suppression and lymphocyte β₂-AR regulation, at least for doses up to 2 mg day⁻¹ of fluticasone.