Effects of inhaled steroids on growth, bone metabolism, and adrenal function.

For children who have persistent asthma of any degree, ICS treatment is recommended. Although topical airway corticosteroid therapy has improved the control of asthma markedly while lessening the risk of corticosteroid side effects, the use of ICS continues to be accompanied by a fear of potential adverse systemic effects. Unfortunately, these fears result in some children being deprived of appropriate and effective treatment or even exposed to a greater risk of periodic oral corticosteroid treatment. Nevertheless, because these agents may be used for long periods of time in a large number of children, safety issues are paramount. Important overall conclusions seem well supported by the literature. First, ICS used in small doses present no significant risk for systemic side effects. When ICS are used at higher dosages and continuously for long periods of time, important differences in drug characteristics, in particular the efficiency of inactivation of swallowed drug (which does not exert a therapeutic effect prior to gaining access to the systemic circulation), affect the ratio of therapeutic to systemic effect of individual ICS. From a practical viewpoint, the long-term clinical history of ICS therapy is informative. Clinically significant suppression of the HPA axis resulting from ICS therapy alone is rare. Detectable suppression of childhood growth can occur when ICS with relatively poor first-pass inactivation are administered at doses greater than or equal to 400 microg per day; this effect on 1-year growth is reduced when clinically equivalent doses of ICS with improved first-pass inactivation of swallowed drug are used. Administration of ICS alone, however, is not associated with any detectable effects on final adult height. Harmful effects of ICS on bone metabolism, although not yet studied adequately, are not expected with the use of an ICS dosage that does not suppress basal HPA axis function or childhood growth. An important caveat to these conclusions is that they refer to the use of ICS used alone and in recommended doses, not in combination with intranasal or other topical corticosteroids. Differences in safety profiles among the available ICS exist, but there are few direct comparative studies attempting to establish rank in benefit-to-risk ratios. The safety profile of all ICS preparations, which focus anti-inflammatory effects on the lung, is markedly better than that of oral glucocorticoids. Risk of adverse effects is minimized by using the lowest effective dosage, by limiting systemic availability of the drug through careful selection of the inhalation device and proper technique, by the adjunct use of alternative anti-inflammatory agents, and, when higher doses are required, by choice of ICS medication. Monitoring growth in children is a sensitive method of detecting significant ICS systemic effects and can enhance a family's confidence in the safety of the medication. When long-term, high-dose therapy is required, periodic evaluations of adrenal function and bone density may be advisable. ICS are highly effective and, because their benefits clearly exceed potential risks, can be used safely in children who have persistent asthma.