Systemic adverse effects of inhaled corticosteroid therapy - A systematic review and meta-analysis

Objective: To appraise the data on systemic adverse effects of inhaled cort icosteroids. Methods: A computerized database search from January 1, 1966, through July 31, 1998, using MEDLINE, EMBASE, and BIDS and using appropriate indexed ter ms. Reports dealing with the systemic effects of inhaled corticosteroids on adrenal gland, growth, bone, skin, and eye, and reports on pharmacology an d pharmacokinetics were reviewed where appropriate. Studies were included t hat contained evaluable data on systemic effects in healthy volunteers as w ell as in asthmatic children and adults. A statistical meta-analysis using regression was performed for parameters of adrenal suppression in 27 studie s. Results: Marked adrenal suppression occurs with high doses of inhaled corti costeroid above 1.5 mg/d (0.75 mg/d for fluticasone propionate), although t here is a considerable degree of interindividual susceptibility. Metaanalys is showed significantly greater potency for dose-related adrenal suppressio n with fluticasone compared with beclomethasone dipropionate, budesonide, o r triamcinolone acetonide, whereas prednisolone and fluticasone propionate were approximately equivalent on a 10:1-mg basis. Inhaled corticosteroids i n doses above 1.5 mg/d (0.75 mg/d for fluticasone propionate) may be associ ated with a significant reduction in bone density, although the risk for os teoporosis may be obviated by postmenopausal estrogen replacement therapy. Although medium-term growth studies showed suppressive effects with 400-mu g/d beclomethasone dipropionate, there was no evidence to support any signi ficant effects on final adult height. Long-term, high-dose inhaled corticos teroid exposure increases the risk for posterior subcapsular cataracts, and , to a much lesser degree, the risk for ocular hypertension and glaucoma. S kin bruising is most likely to occur with high-dose exposure, which correla tes with the degree of adrenal suppression. Conclusions: All inhaled corticosteroids exhibit dose-related systemic adve rse effects, although these are less than with a comparable dose of oral co rticosteroids. Metaanalysis shows that fluticasone propionate exhibits grea ter dose-related systemic bioactivity compared with other available inhaled corticosteroids, particularly at doses above 0.8 mg/d. The long-term syste mic burden will be minimized by always trying to achieve the lowest possibl e maintenance dose that is associated with optimal asthmatic control and qu ality of life.