One year follow-up study of endocrine and lung function of asthmatic children on inhaled budesonide

Abstract

To weigh the benefits and risks of long-term treatment, 12 children with moderately severe asthma were assessed in a follow-up study on budesonide 200 µg b.i.d.After 1 yr, the nocturnal cortisol production was significantly reduced by 19%, but no greater compared to 2 and 4 weeks of treatment. Growth and growth hormone levels were normal. Lung function tests were significantly better, not only versus baseline values but also versus 2 and 4 weeks of treatment.We conclude that systemic effects of inhaled corticosteroids in conventionally low doses do not accumulate with length of treatment, whilst lung function parameters will continue to improve. Therefore, inhaled corticosteroids once started in asthmatic children not controlled on other medications should be continued, but their use should be carefully considered and the minimal dose required to control the asthma employed. Eur Respir J 1997; 10: 2596-2601 Inhaled corticosteroids (ICS) are the principal drugs used in the management of moderate-to-severe childhood as well as adult asthma [1,2]. However, awareness of the possible systemic effects of ICS in children has been a source of concern, particularly when they are used in high doses [3]. Previous studies of the systemic effects of ICS have employed very insensitive techniques, such as the measurement of morning cortisol, and have failed to show any significant effect even at moderately high doses [4]. However, integrated overnight plasma cortisol concentrations or urinary-free cortisol have been suggested as more sensitive tests of reduced hypothalamic pituitary adrenal axis function and as being superior to stimulation tests [5,6].In a cross-sectional study of plasma cortisol measured every 20 min during sleep in 19 asthmatic children, we demonstrated that there was a dose-related effect of inhaled beclomethasone dipropionate (BDP) on overnight cortisol production, despite the fact that there was no difference in the height of the morning peak of cortisol [7]. As this study did not account for the effect of asthma itself, we conducted a subsequent prospective cross-over study of integrated plasma cortisol concentrations and urinary-free cortisol in 12 children commencing ICS for the first time. Both BDP or budesonide (BUD), at a dose of 200 µg b.i.d. for 2 weeks in randomized order, caused identical significant suppressive effects on overnight cortisol production [8]. We found similar suppression in a controlled study administering either a single dose of 400 µg of BUD in the evening to healthy adults, or administering 400 µg twice daily for 2 weeks [9].The above studies were of very short duration and there remained a concern that there might be a cumulative effect of continuing ICS over longer periods. Indeed, nocturnal serum cortisol production was reduced by 27% after 2 weeks and 35% after 4 weeks of treatment in the paediatric study, with similar apparent increases in effects in suppression of urinary-free cortisol (33 and 48%, respectively). We therefore, repeated the studies on the same patients af...

Lung function in school-aged asthmatic children with inhaled cromoglycate, nedocromil and corticosteroid therapy

“…day -1 BDP as dry powder as well as MDI, although the levels stayed within the normal range. Sustained, but not cumulative, effects on the HPA axis by inhaled steroids have also been demonstrated in a study by NIKOLAIZIK et al [24] over a 1-yr period. These results have to be balanced against the conclusions of other studies which did not find significant variation in either urine or plasma cortisol levels at various doses of BDP [25,26].…”

Systemic effects of inhaled corticosteroids on growth and bone turnover in childhood asthma: a comparison of fluticasone with beclomethasone

“…W yatt et al [22] in 1978 and C hang and T am [23] in 1991 have also shown significant changes in urinary cortisol excretion in children on 400 µg·day ‐1 BDP as dry powder as well as MDI, although the levels stayed within the normal range. Sustained, but not cumulative, effects on the HPA axis by inhaled steroids have also been demonstrated in a study by N ikolaizik et al [24] over a 1‐yr period. These results have to be balanced against the conclusions of other studies which did not find significant variation in either urine or plasma cortisol levels at various doses of BDP [25, 26].…”

Monitoring growth in asthmatic children treated with high dose inhaled glucocorticoids does not predict adrenal suppression

“…With regards to the frequency of testing adrenal function the study reported by Nikolaizik et al is reassuring in that although nocturnal cortisol production was significantly reduced by 19% after one year of treatment, this was no greater than that observed after two and four weeks' treatment. 25 However, their patients were taking low to moderate doses of inhaled glucocorticoids (400 mg/day), and they did not look at adrenal reserve and therefore the capacity to respond to stress. An alternative approach would be to assume that all children on high dose inhaled glucocorticoid have adrenal suppression, and to issue them with steroid cards and recommend glucocorticoid supplementation during stressful illness.…”