Inhaled glucocorticoid therapy in children: How much is safe?

Kamada, Alan K.; Parks, David P.; Szefler, Stanley J.

doi:10.1002/ppul.1950120202

Cited by 28 publications

(11 citation statements)

References 18 publications

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“…The use of these drugs is very widespread in Europe, and has recently been supported at an earlier stage in the treatment of asthma [3][4][5]. Nevertheless, few controlled prospective studies have evaluated whether this form of therapy is associated with long-term side-effects, in particular on bone metabolism of growing children, although research in this direction has been encouraged by many authors [6,7]. Many studies [6,8] have looked for changes in the hypothalamic-pituitary-adrenocortical function in children treated with inhaled corticosteroids, yielding contradictory results.…”

Section: Effect Of Beclomethasone Dipropionate On Bone Mineral Contenmentioning

confidence: 99%

Effect of beclomethasone dipropionate on bone mineral content assessed by X-ray densitometry in asthmatic children: a longitudinal evaluation

Baraldi¹,

Bollini²,

Marchi³

et al. 1994

Eur Respir J

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There is little information on bone turnover in asthmatic children taking long-term treatment with inhaled steroids (ICS). The aim of this longitudinal study was to determine the effects of inhaled beclomethasone dipropionate (BDP) on bone mineral density (BMD), in asthmatic children treated over a period of six months. BMD and growth were studied in two age- and sex-matched groups of asthmatic children. These comprised: 14 asthmatic children (Group 1) who had taken BDP in a dosage of 300-400 micrograms daily through a 145 ml spacer device for at least 6 months (mean age 9.1 yrs); and a control group of 16 age- and sex-matched asthmatic patients (Group 2) not treated with ICS (mean age 9.5 yrs). Mean duration of asthma was 5.7 yrs in Group 1 and 5.5 yrs in Group 2. Vertebral BMD (L2-L4) was measured by dual energy X-ray absorptiometry (DEXA) at the beginning (baseline) of the study and 6 months later. There were no significant differences in the baseline bone mass (mean +/- SEM) between the two groups (0.63 +/- 0.03 and 0.64 +/- 0.02 g.cm-2 in Group 1 and 2, respectively). During the observation period, bone density increased, by 4% (95% confidence interval (95% CI) 2-6) in the control group and by 2.3% (95% CI 0.4-4.2) in the group under BDP treatment, showing no significant influence of the treatment. No difference was found in height velocity evaluated before starting BDP and after 6 months of therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

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Section: Effect Of Beclomethasone Dipropionate On Bone Mineral Contenmentioning

confidence: 99%

Effect of beclomethasone dipropionate on bone mineral content assessed by X-ray densitometry in asthmatic children: a longitudinal evaluation

Baraldi¹,

Bollini²,

Marchi³

et al. 1994

Eur Respir J

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“…In addition, children may receive higher dosages of corticosteroid, on a g/kg basis, than adults [3] .…”

Section: Introductionmentioning

confidence: 99%

Intranasal Corticosteroids and Adrenal Suppression

Bruni¹,

Luca²,

Venturoli³

et al. 2009

Neuroimmunomodulation

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Allergic rhinitis is a common condition that frequently coexists with asthma and atopic dermatitis. It is commonly treated with intranasal corticosteroids which may increase the potential inception of side effects of the same type of drugs used for the treatment of other allergic diseases. A method to assess the systemic effect of corticosteroids is the evaluation of their effect on the hypothalamic-pituitary-adrenal (HPA) axis. However, it is not clear which test is best for detection of clinically relevant HPA axis suppression in children Morning plasma cortisol levels are twice that of late afternoon and evening values and a delay in the time of onset in peak cortisol levels has been observed in children treated with inhaled corticosteroids. Single morning cortisol level has a low sensitivity for detecting adrenal insufficiency in children. 24-Hour plasma cortisol is a good test because it is a non-invasive measure of the biologically active free cortisol levels for the entire day. For research purposes, the 24-hour integrated concentration plasma cortisol test is preferred. Studies that have looked at HPA axis suppression with intranasal corticosteroids indicate that overall, intranasal corticosteroids have a minimal effect on the HPA axis. A review of the literature reveals one study in which there was a decreased output of urinary cortisol during treatment with either budesonide or fluticasone propionate in adults. Other studies with fluticasone propionate or budesonide have shown no effect on the HPA axis in children. Beclomethasone dipropionate was shown to affect urinary cortisol output in one study on healthy volunteers. However, in a long-term study in children, no effect on the HPA axis was found. Mometasone furoate has been extensively studied in more than 20 trials of adults and children. No effects on the HPA axis were detected in either children or adults. Fluticasone furoate nasal spray was not associated with HPA axis suppression. It is unlikely that children are more sensitive to corticosteroids than adults. There is no reason to perform routine monitoring of adrenal function in children who are treated with intranasal corticosteroid unless those drugs are used concomitantly with inhaled corticosteroids and/or steroid ointments for the possible concomitant presence of asthma and/or atopic dermatitis.

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“…This increase may reflect the beginning of a growth spurt, due to the imminent onset of puberty in some patients. Inhaled corticosteroids have greatly improved the management of childhood asthma [3,19]. The present study was not designed to investigate efficacy, which would have required placebo control.…”

Section: Discussionmentioning

confidence: 99%

“…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].…”

mentioning

confidence: 99%

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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Inhaled glucocorticoid therapy in children: How much is safe?

Cited by 28 publications

References 18 publications

Effect of beclomethasone dipropionate on bone mineral content assessed by X-ray densitometry in asthmatic children: a longitudinal evaluation

Effect of beclomethasone dipropionate on bone mineral content assessed by X-ray densitometry in asthmatic children: a longitudinal evaluation

Intranasal Corticosteroids and Adrenal Suppression

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

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