Systemic effects of inhaled corticosteroids.

The effectiveness of, and increasing indications for, the use of inhaled corticosteroids in asthma of varying severity prompts important questions to be raised relating to safety and the possibility of adverse systemic steroid effects. This concern is not new and has already resulted in guidelines on the use of spacer devices for high dose inhaled steroids in order to decrease systemic absorption. Important questions remain, however, and this issue of the journal contains two papers addressing various aspects of this problem. The paper by Brown et al ' in this issue of Thorax (pp 967-973) assesses the relative effects of equivalent high doses of beclomethasone dipropionate and budesonide in normal volunteers. Their data show clearly that, with the exception of the use of beclomethasone dipropionate without a spacer, the effects on hypothalamic-pituitaryadrenal (HPA) function are limited to short term minor suppression of serum cortisol levels which is not of sufficient magnitude to reduce 24 hour urinary free cortisol levels. Approaches to the assessment of the HPA axis in previous studies in patients receiving treatment with inhaled steroids have included measurements of morning serum cortisol levels,23 integrated serum cortisol levels,45 urinary free cortisol levels,56 and serum cortisol response to tetracosactrin;5 the interpretation of these studies and their possible relevance to the prediction of adverse systemic steroid effects is discussed further below. Brown et al also document the absence of an effect of inhaled steroids on bone metabolism as indicated by serum levels of osteocalcin, a marker of osteoblastic activity. This aspect of their study is more contentious because, although treatment with inhaled steroids has been shown to reduce serum levels of osteocalcin,7 the relation of this to increased bone loss is speculative. Kiviranta and Turpeinen8 on pp 974-978 of this issue of Thorax provide interesting data indicating a paradoxically beneficial effect of treatment with inhaled steroids on various indices of carbohydrate metabolism, including insulin sensitivity and glucose tolerance, which they attribute to improved control of the condition with consequent reduction in endogenous stress responses. These findings are particularly important because they suggest that any adverse effects of absorbed steroids may be insignificant in comparison with the perturbations of normal physiology occurring with poorly controlled asthma. This may not, however, remain the case once asthma has been brought under control, and it is therefore appropriate to consider the accumulated evidence for potential adverse effects of inhaled steroids on the HPA axis, bone, and carbohydrate metabolism, and also on linear growth in children.