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Department of
Clinical Pharmacology and Therapeutics and Department of Respiratory
Medicine, Ninewells Hospital and Medical School, University of Dundee,
Dundee DD1 9SY, UK
Correspondence to: Professor B J Lipworth.
Received 5 June 1998; Returned to authors 17 August 1998; Revised version received 1 September 1998; Accepted for publication 16 September 1998
BACKGROUND
As both
rhinitis and asthma are allergic conditions, they frequently occur
together. The objective of this study was to assess the diurnal
adrenocortical activity in asthmatics receiving inhaled (inh) and
intranasal (n) formulations of two different corticosteroids, fluticasone propionate (FP) and triamcinolone acetonide (TAA), both
given at clinically recommended doses.
METHODSTwelve stable
moderately severe asthmatic subjects of mean age 23.9 years and mean
forced expiratory volume in one second (FEV1) 84%
predicted were recruited into a randomised placebo (PL) controlled
two-way crossover study comparing nPL + inhPL, nPL + inhFP (880 µg
bid), and nFP (200 µg once daily) + inhFP (880 µg bid) with nPL + inhPL, nPL + inhTAA (800 µg bid) and nTAA (220 µg once daily) + inhTAA (800 µg bid), each given for five days with a 10 day washout
period. Twenty four hour integrated and fractionated (overnight, 08.00 hours, daytime) serum cortisol levels and urinary cortisol/creatinine
excretion were measured.
RESULTSFor 24 hour
and fractionated serum cortisol levels and corrected urinary
cortisol/creatinine excretion there were significant (p<0.05)
differences between all active treatments and placebo. For 24 hour
integrated serum cortisol levels the ratio between inhaled TAA and FP
was 2.3 fold (95% CI 1.2 to 4.3), and for 24 hour urinary
cortisol/creatinine excretion the ratio was two-fold (95% CI 1.2 to
3.4). For 24 hour urinary cortisol excretion, with all active
treatments, individual abnormal low values of <40 nmol (<14.4 µg)
occurred in 17/24 with FP compared with 4/24 with TAA (p<0.0005). The
24 hour serum cortisol profile was flattened by FP but not with TAA.
The addition of nasal corticosteroid did not produce further
significant suppression of mean cortisol values, although with
intranasal FP there were three more abnormal values for 24 hour urinary
cortisol excretion than with inhaled FP alone.
CONCLUSIONSBoth
inhaled FP and TAA caused significant suppression of adrenocortical
activity which was twice as great with FP, the latter being associated
with significantly more individual abnormal values and loss of the
normal diurnal circadian rhythm. Fractionated serum cortisol levels and
urinary cortisol/creatinine excretion were as sensitive as the
respective integrated 24 hour measurements. Although the addition of
intranasal formulations did not produce further significant suppression
of mean values, there were more individual abnormal cortisol values
associated with the addition of intranasal FP.
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