Growth in asthmatic children treated with fluticasone propionate

doi:10.1016/S0022-3476(98)70023-X

The Journal of Pediatrics

Volume 132, Issue 3, March 1998, Pages 472-477

https://doi.org/10.1016/S0022-3476(98)70023-X Get rights and content

Abstract

Objective: To determine whether inhaled fluticasone propionate has long-term effects on growth in children with persistent asthma. Study Design: In a double-blind, randomized, parallel-group, multicenter study, 325 prepubescent children with persistent asthma and normal growth rates were treated with placebo or inhaled fluticasone propionate powder 50 μg or 100 μg administered twice daily by a breath-actuated device for 1 year. Growth was evaluated monthly, whereas other safety variables and pulmonary function were evaluated periodically. Results: The prepubescent patients showed no statistically significant differences in mean height, mean growth velocity, or mean skeletal age between any of the treatment groups at any time. Over a period of 1 year, mean height (± SE) increased 6.15 ± 0.17 cm in the placebo group, 5.94 ± 0.16 cm in the fluticasone propionate 50 μg group, and 5.73 ± 0.13 cm in the fluticasone propionate 100 μg group (p = 0.308, overall). Conclusions: Prepubescent children treated with fluticasone propionate 50 μg and 100 μg administered twice daily for 1 year grew at rates similar to placebo-treated control subjects and at rates equal to expected growth velocity for age. (J Pediatr 1998;132:472-7.)

Section snippets

Patient Selection

Children were eligible for the study if they met the American Thoracic Society criteria²¹ for asthma and had normal growth rates as defined by height measurements (one measurement taken 6 to 18 months before the study and one at screening) between the 5th and 95th centiles and growth velocity between the 10th and 97th centiles (Serono Laboratories, Norwell, Mass.). All height measurements were taken using identical wall-mounted Harpenden stadiometers (manufactured by Holtain, Crymmych, Wales).

Study Population

Three hundred forty-four patients were entered into the single-blind screening period. Nineteen patients were not entered into the double-blind treatment period because of the following factors: abnormal ophthalmic findings (4 patients), unstable asthma (3 patients), use of prohibited concurrent medications (3 patients), failure to meet inclusion or exclusion criteria (2 patients), or miscellaneous reasons (7 patients). Of the remaining 325 patients assigned to use the study drug, 57 showed

Discussion

This is the first prospective, 1-year study evaluating the effects of fluticasone propionate on growth in children. The results of this study demonstrate that long-term administration of inhaled fluticasone propionate 100 μg/day and 200 μg/day is well tolerated in children with persistent asthma. No statistically significant differences were noted between fluticasone propionate and placebo treatment groups with respect to height measurement, growth velocity, or skeletal age. During this study,

Acknowledgements

The Fluticasone Propionate Asthma Study Group was composed of Kimberly Baker, BA, Research Triangle Park, N.C.; R. J. Dockhorn, MD, Lenexa, KS; L. B. Ford, MD, Papillion, NE; S. P. Galant, MD, Orange, CA; Abbas G. Hamedani, Research Triangle Park, NC; Donald J. Kellerman, PharmD, Research Triangle Park; Michael Lawrence, MD, Taunton, MA; R. F. Lemanske, MD, Madison, WI; L. M. Mendelson, MD, West Hartford, CT; N. K. Ostrom, MD, San Diego, CA; D. S. Pearlman, MD, Aurora, CO; R. H. Schwartz, MD,

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This systematic review and meta-analysis was performed to determine the safety of long-term use of ICS in patients with asthma.
A systematic search was made of PubMed, Embase, Web of Science, Cochrane Library, and clinicaltrials.gov, without language restrictions. Randomized controlled trials (RCTs) on treatment of asthma with ICS, compared with non-ICS treatment (placebo or other active drugs), were reviewed.
Eighty-six RCTs (enrolling 51,538 participants) met the inclusion criteria. Oral or oropharyngeal candidiasis (RR 2.58, 95% CI 2.00 to 3.33), and dysphonia/hoarseness (RR 1.56, 95% CI 1.31 to 1.85) were less frequent in the control group. There was no statistically significant difference in the risk of upper respiratory tract infection, lower respiratory tract infection, influenza, decline in bone mineral density, and fractures between the two groups.
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However, the similarity across trials or inadequate reporting prevented such analyses. Three industry-funded trials with high methodological quality (resulting in four dose comparisons) contributed data to the main outcome [3–5]. They pertained to 728 school-aged children measured by stadiometry, who had mild or moderate asthma and were treated with one of three ICS molecules (fluticasone, ciclesonide or mometasone) in whom a dose difference ≤ 150 μg was compared over 52 weeks.
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Finally, the events after drug deposition on the respiratory epithelium, the effect of lung–particle interactions on final dose, and how cell-level mechanisms differ between formulations are under investigation.36 Findings from clinical trials7,28,29 in which several doses of a given inhaled corticosteroid were compared have shown dose-dependent effects on growth, although most trials did not assess more than one dose in children (table) and of the trials that did assess more than one dose, not all doses were shown to significantly affect growth.29 In the CAMP trial18 there were sufficient numbers of patients to analyse dose–response; the results showed a significant daily dose–response association during the first 2 years of treatment, with a 0·1 cm decrement in height for each 1 μg/kg bodyweight increase (p=0·007).
Potent, topically active corticosteroids with minimum systemic activity have fewer adverse effects than do systemic corticosteroids, and can control both asthma and allergic rhinitis when given in recommended doses. However, study findings show that children with asthma receiving budesonide and beclometasone dipropionate have decreased linear growth, and that children who receive long-term inhaled corticosteroid therapy for asthma have height deficits 1–2 years after treatment initiation that persist into adulthood. The effects of inhaled corticosteroids on growth seem to be dependent on both dose and duration; the degree of systemic effects is dependent on pharmacokinetic properties (ie, absorption, distribution, and elimination), whereas the effective dose delivered is dependent on the delivery system and potency of the molecule. The effects of corticosteroids on bone mineral density in children seem to be more amenable to intervention; long-term therapy with inhaled corticosteroid therapy is safer than frequent bursts of oral corticosteroids on bone mineral accretion in this regard. Importantly, adequate nutrition (particularly sufficient intake of calcium and vitamin D) should prevent or blunt the effects of corticosteroids on bone mineral density. The potential adverse effects of inhaled corticosteroids need to be weighed against the large and well established benefit of these drugs to control persistent asthma. To minimise any adverse effects, treatment with inhaled corticosteroids should always aim to reach the lowest effective dose that gives the patient good asthma control.
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^☆: From the University of Wisconsin Children's Hospital, Madison, Wisconsin; AAAA Medical Research Group, Salt Lake City, Utah; Carolina Allergy & Asthma Research Group, Raleigh, North Carolina; University of Colorado Health Sciences Center, Denver, Colorado; Atlanta Allergy & Immunology Research Foundation, Atlanta, Georgia; Clinical Research of the Ozarks, Rolla, Missouri; and the University of Missouri-Columbia School of Medicine, Columbia, Missouri.

^☆☆: Sponsored by a grant from Glaxo Wellcome Inc., Research Triangle Park, North Carolina.

^★: Members of the Fluticasone Propionate Asthma Study Group are listed in the acknowledgments.

^★★: Reprint requests: David B. Allen, MD, University of Wisconsin Children's Hospital, H4/448, Clinical Science Center, 600 Highland Ave., Madison, WI 53792-4108.

^♢: 9/21/85589

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Growth in asthmatic children treated with fluticasone propionate☆,☆☆,★,★★,♢

Abstract

Section snippets

Patient Selection

Study Population

Discussion

Acknowledgements

J Allergy Clin Immunol

Respir Med

Lancet

J Allergy Clin Immunol

J Pediatr

Respir Med

Lancet

A six-part asthma management program

The effect of two months of treatment with inhaled budesonide on bronchial responsiveness to histamine and house-dust mite antigen in asthmatic children

Am Rev Respir Dis

Effects of 22 months of treatment with inhaled corticosteroids and/or beta-2-agonists on lung function, airway responsiveness, and symptoms in children with asthma

Am Rev Respir Dis

Effect of long term budesonide treatment on growth, weight and lung function in children with asthma [abstract]

Am Rev Respir Dis

Long-term effect of inhaled cortico steroids on growth rate in adolescents with asthma

Pediatrics