The influence of high dose inhaled corticosteroids on the hypothalamo-pituitary-adrenal axis in asthma
The studies in this thesis investigated the influence of high dose inhaled corticosteroids (HDICS) on the hypothalamo-pituitary-adrenal axis. The function of this axis was assessed by measuring 0900 h serum cortisol, 24 h urinary free cortisol excretion and the short tetracosactrin test and, in some patients, by isulin stress tests. In a survey of 78 chronic asthmatics taking long term HDIC, 20% had subnormal HPA function. Both urinary free cortisol and the response to tetracosactrin correlated well with the response to insulin. Risk factors for HPA suppression were a previous requirement for long term systemic corticosteroids and increasing duration of HDICS treatment. In some patients HPA function improved after they inhaled the same dose of beclomethasone dipropionate (BDP) through a large (750 ml) spacer device. The protective effect of the spacer against unwanted systemic effects of BDP was confirmed in a controlled study. Another study found that serum cortisol levels were appropriately increased in most patients during acute severe asthma despite HDICS and that these levels were related to the degree of hypoxaemia. A long term prospective study of the effects of increasing doses of BDP above currently accepted maximum levels (2 mg/day) showed that whether or not a spacer was used, there was substantial variation between patients in the dose which caused subnormal HPA function and that many patients were able to tolerate these higher doses without HPA suppression.