Inhaled corticosteroids: Clinical relevance of safety measures

Abstract

There seem to be individual, end organ, and tissue variations in responsiveness to glucocorticoids. In some children, 400-800 micrograms/day of inhaled steroid reduces cortisol excretion and short-term growth of the lower leg. These effects only become clinically relevant if the capacity of the adrenal gland to respond to stress is impaired or there is an adverse effect on bone metabolism and height velocity. Low morning plasma cortisol or reduced the cortisol excretion suggests the possibility of adrenal suppression. A stimulation test using adrenocorticotrophic hormone 500 ng is safer and more discriminating than using adrenocorticotrophic hormone 250 micrograms. For research purposes, measurement of urine cortisol metabolites over 24 hours closely approximates adrenal corticosteroid production. The dynamics of bone turnover of children are different to those of adults. Biochemical and physical studies of bone metabolism of children are hampered by a lack of age- and sex-specific normal values. Osteocalcin is probably the marker of choice for bone formation and pyridinium crosslinks for bone resorption. Bone density data in asthmatic children are limited, but so far reassuring. Knemometry is a sensitive technique for comparing the systemic absorption of different inhaled steroids, but does not relate to long-term growth. Growth velocity in asthmatic children is influenced by seasonal variation, delay in puberty, disease severity, and the use of oral steroids. These variables must be taken into account when assessing the effects of inhaled steroids. Height measurements made over a period of less than 1 year are liable to error and misinterpretation. There is no evidence that inhaled steroids, when appropriately prescribed in standard doses, have an adverse effect on long-term growth. However, children taking above-standard doses of inhaled steroids need their growth monitored using stadiometric measurements every 3-4 months by trained personnel using regularly calibrated equipment.