Although inhaled corticosteroids appear to be safe in children, their safety has not been evaluated adequately in randomized, placebo-controlled trials. Concerns center on the possible suppression of the hypothalamic-pituitary-adrenal (HPA) axis, as measured by changes in serum cortisol levels and 24-hour urinary free cortisol (UFC) excretion. Bacharier and colleagues studied the long-term effects of budesonide in a subset of children enrolled in the Childhood Asthma Management Program.

Participants included 63 children with stable, mild to moderate asthma, as demonstrated during a 28-day screening period. Patients were randomized to budesonide at a dosage of 400 mcg per day, nedocromil at a dosage of 16 mg per day, or placebo. Serum cortisol levels were measured before and after administration of adrenocorticotrophic hormone (ACTH), and urinary cortisol levels were tested at baseline, 12 months, and 36 months. However, only the 36-month urine UFC levels could be used because of laboratory discrepancies in the baseline and 12-month samples.

Abnormal cortisol levels following ACTH stimulation were found in four children, all of whom were in the placebo and nedocromil groups. After adjustment for confounding factors, no significant differences in cortisol levels were found between groups over the course of the study, or at any time after ACTH stimulation. UFC levels also were similar in all groups, although slightly lower in patients who had used inhaled corticosteroids in the previous four months. Correlations between cumulative inhaled corticosteroids use or prednisone exposure and serum cortisol levels at 36 months were low or nonsignificant.

This study shows that long-term exposure to inhaled corticosteroids does not suppress HPA axis response to ACTH, and the addition of supplemental inhaled corticosteroids or prednisone does not alter these findings. Cumulative steroid dosage over the three-year period also appears to have no suppressive effect on the HPA axis. UFC measurement results are similarly reassuring.