Inhaled corticosteroids: past lessons and future issues.

Inhaled corticosteroids play a pivotal role in the treatment of asthma. Inhalation permits effective delivery of the corticosteroid in high concentration to target sites within the lung while minimizing systemic exposure. Consequently, the safety profile of inhaled corticosteroids is markedly better than that of oral corticosteroid therapy. However, although it was first thought that direct delivery might eliminate systemic adverse effects, this has not been confirmed by clinical trials and experience. Inhaled corticosteroids are absorbed from the lungs into the systemic circulation, in which they can acutely decrease growth velocity in children, an effect that fortunately appears to be temporary and might have no effect on final adult height. In sufficient dosages, they also produce bone mineral loss leading to osteoporosis and might increase the risk of cataracts, glaucoma, skin atrophy, and vascular changes that increase the risk of ecchymoses. Effective evaluation of the severity and significance of these complications is challenging because highly sensitive tests do not reliably predict clinically significant events, and short-term observations do not predict long-term consequences. Also, compliance wanes with long-term treatment, and susceptibility to a particular adverse event can vary over time, even in the same individual, because of developmental or hormonal changes. This journal supplement will review what has been learned about the safety of inhaled cortico-steroids during the past decade, discussing some of the questions that remain and considering the characteristics of an "ideal" inhaled corticosteroid: one with high local activity in the lung and minimal or no adverse systemic effects.