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Inhaled Corticosteroids in Asthma« Back to Volume 22, Issue 4, December 2006 - Table of Contents Inhaled corticosteroids may cause long-term systemic effects in children with chronic asthma. As many as 30% of these children may present with decreased adrenal function. Recently, symptomatic adrenal insufficiency with hypoglycemia and convulsions have been observed in patients receiving high doses of inhaled corticosteroids. These reports have shed a new light on the long-term outcome of asthmatic children treated with these drugs. The present study by Raux Demay and colleagues evaluated the effect of currently used inhaled corticosteroids and compared these different preparations. A low dose ACTH stimulation test was used to evaluate residual cortisol secretion and to define a cohort of patients at risk because of chronic adrenal suppression. A strategy was defined to safely reduce the inhaled corticosteroid dosage without asthma exacerbation. The study included 100 outpatient children with persistent asthma. The inhaled corticosteroids were of different types; equipotent doses were calculated comparing efficiency of the drugs and their responsibility for systemic effects. The dose of beclomethasone dipropionate was used as a reference, and conversion factors for budesonide and fluticasone propionate were 1.25 and 2.0, respectively. The mean duration of treatment was 14 months. Pituitary and adrenal function were assessed by the low dose (1 mcg) IV corticotropin stimulation test. The stimulated cortisol levels were considered below normal if they were 2 SD below mean normal level (<422 mmol/L). Following discovery of subnormal response to the test, patients were informed of adrenal crisis risk and a progressive decrease in corticosteroid dosage was performed until a normal response was obtained without reduced control of the persistent asthma. Twenty-eight out of 100 patients had a stimulated cortisol level in the subnormal range. Values did not differ significantly according to treatment types. The mean equipotent doses received by patients with subnormal cortisol levels were higher than those with normal responses. In 27 patients, treatment change was performed with a decrease in dosage until the response to corticotrophin was in the normal range. In 13 patients, normalization was obtained within 5 months. In the group, repeated stimulation tests were normalized over a mean duration of 13 months (range 6–24 months). Only one patient suffered an acute asthmatic episode while decreasing the daily dose. The authors concluded that decreasing daily doses (calculated according to established equipotency of the 4 types of treatment that were evaluated) allowed recovery of a normal hypothalamic-pituitary-adrenal axis without exacerbation of asthma. The authors obtained a progressive decrease to the consensus-recommended doses in a group of patients who had evidence of drug-induced adrenal deficiency. Editor’s CommentThis study confirms previous data and provides a practical tool in current management of asthmatic patients. Interestingly, a quarter of the cohort followed in an asthma clinic was exposed to rather high doses of various corticosteroids. In most of the patients with subnormal cortisol response to corticotrophin, the corticosteroid doses were higher than recommended by a recent consensus meeting,1 and an Asthma Clinical Research Network2 found that moderate doses were sufficient to maximize improvement in respiratory function. Further increase in dosage would not increase efficacy. For instance, inhaled doses of 100 – 200 mcg/day would achieve 90% of the benefit. Raux Demay et al have carefully compared 4 types of corticosteroids, taking into account complex pharmacokinetics to calculate equipotency. The proposed test is of practical value and quite reliable because of the low dose of corticotrophin. It should be useful at least in patients receiving doses in the high range as defined by Consensus Meetings, and would also allow a more appropriate management of chronic asthma. Because of well-known individual variations, each case should be handled with care. The authors have shown that their approach is safe as long as the doses are slowly decreased over several months. Raphaël Rappaport , MD References - (linked to
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Volume 24 Number 1
May 2008
www.GGHjournal.com
ISSN 1932-9032
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