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a Division of
Respiratory Medicine, Nottingham City Hospital, Nottingham NG5
1PB, UK, b Department of Chemical Pathology,
University College London Hospitals, London W1N 8AA, UK
Correspondence to: Dr T Harrison tim.harrison{at}nottingham.ac.uk
Received 23 May 2000; Returned to authors 20 July 2000; Revised version received 25 August 2000; Accepted for publication 18 September 2000
BACKGROUND
The
potential for long term adverse effects from inhaled corticosteroids
relates to their systemic absorption, usually assessed from proxy
markers in short term studies. When fluticasone propionate and
budesonide have been compared in this way the results have been
inconsistent. To determine whether this is because of the subjects
studied or the sensitivity of the systemic marker used, we have
compared the effects of fluticasone propionate and budesonide in
healthy and asthmatic subjects and investigated the effect of treatment
on three systemic markers.
METHODSForty six
healthy subjects were randomised to receive inhaled fluticasone
propionate 1500 µg/day (via an Accuhaler), budesonide 1600 µg/day
(via a Turbuhaler), or placebo; 31 subjects with moderately severe
asthma were randomised to receive the same doses of fluticasone propionate or budesonide but not placebo. Systemic effects in healthy
and asthmatic subjects were compared after 7 days. Treatment was
continued for another 21 days in the subjects with asthma when systemic
effects and asthma control were assessed.
RESULTSAt baseline
healthy subjects had higher urinary levels of total cortisol
metabolites (TCM) than subjects with asthma. After 7 days of treatment
with fluticasone propionate urinary TCM levels in the healthy
subjects were significantly lower than in the subjects with asthma
(mean difference between groups 1663 µg/day, 95% CI 328 to 2938).
This was not the case with budesonide, however, where urinary TCM
levels in the healthy subjects remained above those in the asthmatic
subjects (mean difference between groups 1210 µg/day, 95% CI -484
to 2904). Urinary TCM levels were considerably more sensitive to the
effects of inhaled corticosteroids than morning serum cortisol or
osteocalcin concentrations. Only budesonide reduced the serum level of osteocalcin.
CONCLUSIONSWhen given
by dry powder inhaler for 7 days, fluticasone propionate 1500 µg/day
has a greater effect on the hypothalamic-pituitary-adrenal axis in
healthy subjects than in subjects with asthma, but this is not the case
for budesonide 1600 µg/day. These findings, together with the
differences in sensitivity between systemic markers, explain many of
the discrepancies in the literature.
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