Nocturnal Adrenal Suppression in Asthmatic Children Taking Inhaled Beclomethasone Dipropionate

Law, Caroline; Honour, JW; Marchant, J L; Preece, M A; Warner, Jill A.

doi:10.1016/s0140-6736(86)91045-7

Cited by 138 publications

(40 citation statements)

References 21 publications

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“…They were considered to be devoid of systemic effects, at least in conventional low doses, until we demonstrated nocturnal cortisol suppression even at a relatively low dose of 400 µg·day -1 BDP or BUD [7,8]. These studies did not take into account the effect of the asthma itself, but a placebo-controlled study in healthy adult volunteers finally confirmed that the suppressive effect was due to the drug and not related to the underlying problem, namely asthma [9].…”

Section: Discussionmentioning

confidence: 88%

“…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.…”

mentioning

confidence: 87%

“…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.…”

mentioning

confidence: 99%

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

Nikolaizik¹,

Preece²,

Warner³

1997

Eur Respir J

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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...

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Section: Discussionmentioning

confidence: 88%

mentioning

confidence: 87%

mentioning

confidence: 99%

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

Nikolaizik¹,

Preece²,

Warner³

1997

Eur Respir J

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“…A recent study of children with asthma found that beclomethasone reduces nocturnal cortisol secretion and early morning cortisol concentrations, these effects being dependent on dose. 30 In older children long term use of regularly inhaled corticosteroids has not produced clinically important systemic effects. "3-`We used a comparatively high dose of budesonide and its potential for systemic corticosteroid effects in preschool children needs to be assessed for longer.…”

Section: Discussionmentioning

confidence: 99%

Controlled trial of budesonide given by the nebuhaler in preschool children with asthma.

Gleeson

Price

1988

BMJ

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“…The evaluation of adrenal function was made by using plasma cortisol levels, a method with a poor sensitivity. With more sensitive tests, however, the suppressive effects of relatively modest doses of inhaled corticosteroid therapy have been detected [4,5].…”

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confidence: 99%

Bone mineral density in asthmatic patients treated with inhaled corticosteroids: a case-control study

Luengo

Río²,

Pons³

et al. 1997

Eur Respir J

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Recent studies suggest that inhaled corticosteroids can adversely affect bone metabolism. The objective of this study was to evaluate the importance of these adverse effects in a case-control study.Bone mineral density (BMD) was measured in 48 asthmatic adults (15 males and 33 females) treated with inhaled steroids (beclomethasone or budesonide) and in 48 gender and age-matched healthy subjects at baseline and at 2 yrs. Vertebral BMD was measured by dual energy X-ray densitometry.Patients had been treated with a dose of 662±278 µg (range 300-1,000 µg) of beclomethasone dipropionate or budesonide for more than 1 yr (mean duration of treatment 10.6 yrs, range 1-16 yrs). Twenty four patients had needed 1-6 short courses of oral steroids and seven had received oral corticosteroids (mean daily dose 6.2 mg prednisone) for 2-15 yrs more than 4 yrs prior to the BMD measurements. During the follow-up, 14 patients required 1-3 short courses of oral steroids. There was no correlation either between inhaled corticosteroid doses or duration of treatment and BMD values. There were no significant differences in BMD baseline values between patients and healthy controls. BMD significantly decreased in both groups at 2 yrs, from 1.08±0.19 to 1.05±0.19 g·cm -2 (p=0.002) in asthmatics versus 1.12±0.17 to 1.09±0.18 g·cm -2 (p=0.008) in controls. There were no significant differences in BMD loss between patients and healthy controls. Furthermore, no differences were found in bone loss when pre-and postmenopausal women were compared with their healthy control counterparts. No differences in baseline BMD were found between patients who had received regular oral corticosteroid therapy or booster courses of oral corticosteroids and those who had not.Inhaled corticosteroid treatment at a mean dose of 662 µg·day -1 and sporadic booster courses of oral corticosteroids do not further increase bone mass loss with respect to that expected from natural bone mass loss.

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Nocturnal Adrenal Suppression in Asthmatic Children Taking Inhaled Beclomethasone Dipropionate

Cited by 138 publications

References 21 publications

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

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

Controlled trial of budesonide given by the nebuhaler in preschool children with asthma.

Bone mineral density in asthmatic patients treated with inhaled corticosteroids: a case-control study

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