Impact of Inhaled Corticosteroids on Growth in Children with Asthma: Systematic Review and Meta-Analysis

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2015 Jul 21

PMID 26191797

Citations 30

Authors

Yoon Kong Loke

Patricia Blanco

Menaka Thavarajah

Andrew M Wilson

Affiliations

Soon will be listed here.

Abstract

Background: Long-term inhaled corticosteroids (ICS) may reduce growth velocity and final height of children with asthma. We aimed to evaluate the association between ICS use of >12 months and growth.

Methods: We initially searched MEDLINE and EMBASE in July 2013, followed by a PubMed search updated to December 2014. We selected RCTs and controlled observational studies of ICS use in patients with asthma. We conducted random effects meta-analysis of mean differences in growth velocity (cm/year) or final height (cm) between groups. Heterogeneity was assessed using the I2 statistic.

Results: We found 23 relevant studies (twenty RCTs and three observational studies) after screening 1882 hits. Meta-analysis of 16 RCTs showed that ICS use significantly reduced growth velocity at one year follow-up (mean difference -0.48 cm/year (95% CI -0.66 to -0.29)). There was evidence of a dose-response effect in three RCTs. Final adult height showed a mean reduction of -1.20 cm (95% CI -1.90 cm to -0.50 cm) with budesonide versus placebo in a high quality RCT. Meta-analysis of two lower quality observational studies revealed uncertainty in the association between ICS use and final adult height, pooled mean difference -0.85 cm (95% CI -3.35 to 1.65).

Conclusion: Use of ICS for >12 months in children with asthma has a limited impact on annual growth velocity. In ICS users, there is a slight reduction of about a centimeter in final adult height, which when interpreted in the context of average adult height in England (175 cm for men and 161 cm for women), represents a 0.7% reduction compared to non-ICS users.

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References

Bensch G, Greos L, Gawchik S, Kpamegan E, Newman K . Linear growth and bone maturation are unaffected by 1 year of therapy with inhaled flunisolide hydrofluoroalkane in prepubescent children with mild persistent asthma: a randomized, double-blind, placebo-controlled trial. Ann Allergy Asthma Immunol. 2011; 107(4):323-9. DOI: 10.1016/j.anai.2011.07.017. View

Verberne A, Frost C, Roorda R, van der Laag H, Kerrebijn K . One year treatment with salmeterol compared with beclomethasone in children with asthma. The Dutch Paediatric Asthma Study Group. Am J Respir Crit Care Med. 1997; 156(3 Pt 1):688-95. DOI: 10.1164/ajrccm.156.3.9611067. View

Acun C, Tomac N, Ermis B, Onk G . Effects of inhaled corticosteroids on growth in asthmatic children: a comparison of fluticasone propionate with budesonide. Allergy Asthma Proc. 2005; 26(3):204-6. View

Merkus P, van Essen-Zandvliet E, Duiverman E, van Houwelingen H, Kerrebijn K, Quanjer P . Long-term effect of inhaled corticosteroids on growth rate in adolescents with asthma. Pediatrics. 1993; 91(6):1121-6. View

Turpeinen M, Pelkonen A, Nikander K, Sorva R, Selroos O, Juntunen-Backman K . Bone mineral density in children treated with daily or periodical inhaled budesonide: the Helsinki Early Intervention Childhood Asthma study. Pediatr Res. 2010; 68(2):169-73. DOI: 10.1203/PDR.0b013e3181e69e36. View

Zhang L, Prietsch S, Ducharme F . Inhaled corticosteroids in children with persistent asthma: effects on growth. Cochrane Database Syst Rev. 2014; (7):CD009471. PMC: 8407362. DOI: 10.1002/14651858.CD009471.pub2. View

Becker A, Kuznetsova O, Vermeulen J, Soto-Quiros M, Young B, Reiss T . Linear growth in prepubertal asthmatic children treated with montelukast, beclomethasone, or placebo: a 56-week randomized double-blind study. Ann Allergy Asthma Immunol. 2006; 96(6):800-7. DOI: 10.1016/s1081-1206(10)61342-7. View

Ferguson A, Van Bever H, Teper A, Lasytsya O, Goldfrad C, Whitehead P . A comparison of the relative growth velocities with budesonide and fluticasone propionate in children with asthma. Respir Med. 2006; 101(1):118-29. DOI: 10.1016/j.rmed.2006.04.009. View

Pedersen S . Clinical safety of inhaled corticosteroids for asthma in children: an update of long-term trials. Drug Saf. 2006; 29(7):599-612. DOI: 10.2165/00002018-200629070-00005. View

10.

Higgins J, Thompson S, Deeks J, Altman D . Measuring inconsistency in meta-analyses. BMJ. 2003; 327(7414):557-60. PMC: 192859. DOI: 10.1136/bmj.327.7414.557. View

11.

De Benedictis F, Teper A, Green R, Boner A, Williams L, Medley H . Effects of 2 inhaled corticosteroids on growth: results of a randomized controlled trial. Arch Pediatr Adolesc Med. 2001; 155(11):1248-54. DOI: 10.1001/archpedi.155.11.1248. View

12.

Skoner D, Meltzer E, Milgrom H, Stryszak P, Teper A, Staudinger H . Effects of inhaled mometasone furoate on growth velocity and adrenal function: a placebo-controlled trial in children 4-9 years old with mild persistent asthma. J Asthma. 2011; 48(8):848-59. DOI: 10.3109/02770903.2011.604883. View

13.

Garcia Garcia M, Wahn U, Gilles L, Swern A, Tozzi C, Polos P . Montelukast, compared with fluticasone, for control of asthma among 6- to 14-year-old patients with mild asthma: the MOSAIC study. Pediatrics. 2005; 116(2):360-9. DOI: 10.1542/peds.2004-1172. View

14.

Skoner D, Szefler S, Welch M, Cruz-Rivera M, Smith J . Longitudinal growth in infants and young children treated with budesonide inhalation suspension for persistent asthma. J Allergy Clin Immunol. 2000; 105(2 Pt 1):259-68. DOI: 10.1016/s0091-6749(00)90074-5. View

15.

Gradman J, Wolthers O . A randomized trial of lower leg and height growth in children with asthma treated with inhaled budesonide from a new dry powder inhaler. Pediatr Allergy Immunol. 2009; 21(1 Pt 2):e206-12. DOI: 10.1111/j.1399-3038.2009.00875.x. View

16.

Skoner J, Schaffner T, Schad C, Kwon A, Skoner D . Addressing steroid phobia: improving the risk-benefit ratio with new agents. Allergy Asthma Proc. 2008; 29(4):358-64. DOI: 10.2500/aap.2008.29.3132. View

17.

Kelly H, Sternberg A, Lescher R, Fuhlbrigge A, Williams P, Zeiger R . Effect of inhaled glucocorticoids in childhood on adult height. N Engl J Med. 2012; 367(10):904-12. PMC: 3517799. DOI: 10.1056/NEJMoa1203229. View

18.

Agertoft L, Pedersen S . Effect of long-term treatment with inhaled budesonide on adult height in children with asthma. N Engl J Med. 2000; 343(15):1064-9. DOI: 10.1056/NEJM200010123431502. View

19.

Szefler S, Weiss S, Tonascia J, Adkinson N, Bender B, Cherniack R . Long-term effects of budesonide or nedocromil in children with asthma. N Engl J Med. 2000; 343(15):1054-63. DOI: 10.1056/NEJM200010123431501. View

20.

Rossi G, Cerasoli F, Cazzola M . Safety of inhaled corticosteroids: room for improvement. Pulm Pharmacol Ther. 2005; 20(1):23-35. DOI: 10.1016/j.pupt.2005.10.008. View