Comparison of the systemic effects of fluticasone propionate and budesonide given by dry powder inhaler in healthy and asthmatic subjects

Background-The potential for long term adverse effects from inhaled cortico steroids relates to their systemic absorption, usually assessed from proxy markers in short term studies. When fluticasone propionate and budesonide h ave been compared in this way the results have been inconsistent. To determ ine whether this is because of the subjects studied or the sensitivity of t he systemic marker used, we have compared the effects of fluticasone propio nate and budesonide in healthy and asthmatic subjects and investigated the effect of treatment on three systemic markers. Methods-Forty six healthy subjects were randomised to receive inhaled fluti casone propionate 1500 mug/day (via an Accuhaler), budesonide 1600 mug/day (via a Turbuhaler), or placebo; 31 subjects with moderately severe asthma w ere randomised to receive the same doses of fluticasone propionate or budes onide but not placebo. Systemic effects in healthy and asthmatic subjects w ere compared after 7 days. Treatment was continued for another 21 days in t he subjects with asthma when systemic effects and asthma control were asses sed. Results-At baseline healthy subjects had higher urinary levels of total cor tisol metabolites (TCM) than subjects with asthma. After 7 days of treatmen t with fluticasone propionate urinary TCM levels in the healthy subjects we re significantly lower than in the subjects with asthma (mean difference be tween groups 1663 mug/day, 95% CI 328 to 2938). This was not the case with budesonide, however, where urinary TCM levels in the healthy subjects remai ned above those in the asthmatic subjects (mean difference between groups 1 210 mug/day, 95% CI -484 to 2904). Urinary TCM levels were considerably mor e sensitive to the effects of inhaled corticosteroids than morning serum co rtisol or osteocalcin concentrations. Only budesonide reduced the serum lev el of osteocalcin. Conclusions-When given by dry powder inhaler for 7 days, fluticasone propio nate 1500 mug/day has a greater effect on the hypothalamic-pituitary-adrena l axis in healthy subjects than in subjects with asthma, but this is not th e case for budesonide 1600 mug/day. These findings, together with the diffe rences in sensitivity between systemic markers, explain many of the discrep ancies in the literature.