SYSTEMIC EFFECTS OF HIGH-DOSE INHALED STEROIDS - COMPARISON OF BECLOMETHASONE DIPROPIONATE AND BUDESONIDE IN HEALTHY-SUBJECTS

Background-Systemic absorption of inhaled corticosteroids may adversel y influence the function of the hypothalamo-pituitary-adrenal axis, bo ne metabolism, and circulating leucocytes. These changes can be used t o assess the safety of different types and modes of administration of these drugs. Methods-The study was a randomised, double dummy, crossov er design with nine healthy adults. It compared the effects of beclome thasone dipropionate and budesonide (given by metered dose aerosols wi th and without their respective large volume spacers (Volumatic and Ne buhaler) attached) on serum cortisol, 24 hour urinary free cortisol, a nd plasma osteocalcin concentrations, and circulating neutrophils and lymphocytes. Subjects inhaled the drug (1 mg) and matching placebo at 0900 and 2200 hours on each of six study days. Blood samples were take n hourly for six hours after the morning dose and at the end of the st udy period. Results-All results were within the reference ranges. Both drugs caused similar reductions in serum cortisol four to six hours a fter inhalation. These changes were not affected by the use of a large spacer and did not persist at 24 hours. Use of spacers tended to incr ease the haematological effects of the steroids. Beclomethasone diprop ionate inhaled through a Volumatic provoked a rise in circulating neut rophils compared with placebo although lymphocyte numbers were unaffec ted. Budesonide did not influence neutrophil numbers but did reduce ci rculating lymphocytes, numbers of which were further reduced when the Nebuhaler was used. There were no significant changes in plasma osteoc alcin concentration or 24 hour urinary free cortisol excretion with bu desonide, with or without a spacer. Beclomethasone dipropionate inhale d without a spacer reduced urinary cortisol and plasma osteocalcin at 24 hours; however, use of the Volumatic protected against these effect s. Conclusions-Attaching a Volumatic reduces the systemic effects of 2 mg aerosol beclomethasone dipropionate on the hypothalamo-pituitary-a drenal axis and circulating osteocalcin concentrations. This study did not establish whether the Nebuhaler reduces the systemic effects of b udesonide. When large spacers are used, 2 mg per day of beclomethasone dipropionate and budesonide seem to be equivalent in terms of unwante d effects.