Skip to main content
Log in

Inhaled Corticosteroids in Children with Asthma

Pharmacologic Determinants of Safety and Efficacy and Other Clinical Considerations

  • Review Article
  • Published:
Pediatric Drugs Aims and scope Submit manuscript

Abstract

The role of inhaled corticosteroids (ICS) in the treatment of childhood asthma has been well established. An ideal corticosteroid should demonstrate high pulmonary deposition and residency time, in addition to a low systemic bioavailability and rapid systemic clearance. The lung depositions of the ICS have been compared, with beclomethasone (beclometasone)-hydrofluoroalkane (HFA) and ciclesonide showing the highest lung deposition. Lung deposition is influenced by not only the inhalation device and type of propellant (HFA or chlorofluorocarbon), but also by whether the aerosol is a solution or suspension, and the particle size of the respirable fraction. Pulmonary residency time increases when budesonide and des-ciclesonide undergo reversible fatty acid esterification. The bioavailability of the drug depends on the oral bioavailable fraction and the amount absorbed directly from the pulmonary vasculature. The clearance rate of des-ciclesonide is very high (228 L/h), increasing its safety profile by utilizing extra-hepatic clearance mechanisms. Both des-ciclesonide and mometasone have a high protein binding fraction (98–99%). The volume of distribution (Vd) is proportional to the lipophilicity of the drug, with the Vd of fluticasone being 332L compared with 183L for budesonide. Increasing the Vd will also increase the elimination half-life of a drug. The pharmacodynamics of ICS depend on both the receptor binding affinity and the dose-response curve. Among the ICS, fluticasone and mometasone have the highest receptor binding affinity (1800 and 2200, respectively), followed by budesonide at 935 (relative to dexamethasone = 100).

Compared with other nonsteroid asthma medications (long-acting β-agonists, theophylline, and montelukast) ICS have proven superiority in improving lung function, symptom-free days, and inflammatory markers. One study suggests that early intervention with ICS reduces the loss in lung function (forced expiratory volume in 1 second) over 3 years. Whether airway remodeling is reduced or prevented in the long term is unknown. Potential adverse drug effects of ICS include adrenal and growth suppression. While in low-to-medium doses ICS have shown little suppression of the adrenal pituitary axis, in high doses the potential for significant adrenal suppression and adrenal crisis exists. Several longitudinal studies evaluating the effect of ICS on growth have shown a small decrement in growth velocity (≈1–2cm) during the first year of treatment. However, when investigators followed children treated with budesonide for up to 10 years, no change in target adult height was noted.

In conclusion, the development of optimal delivery devices for young children, as well as optimizing favorable pharmacokinetic properties of ICS should be priorities for future childhood asthma management.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Table I
Fig. 1

Similar content being viewed by others

References

  1. Masoli M, Fabian D, Holt S, et al. The global burden of asthma: executive summary of the GINA Dissemination Committee report. Allergy 2004; 59: 469–78

    Article  PubMed  Google Scholar 

  2. National Center for Health Statistics. Faststats: asthma [online]. Available from URL: http://www.cdc.gov/nchs/faststats/asthma/htm [Accessed 2007 Feb 9]

  3. National Asthma Education and Prevention Program. Expert panel report: guidelines for the diagnosis and management of asthma update on selected topics: 2002. J Allergy Clin Immunol 2002; 110 (5 Suppl.): S141–219

    Article  Google Scholar 

  4. Davies RJ, Stampone P, O’Connor BJ. Hydrofluoroalkane-134a beclomethasone dipropionate extrafine aerosol provides equivalent asthma control to chlorofluorocarbon beclomethasone dipropionate at approximately half the total daily dose. Respir Med 1998; 92Suppl. A: 23–31

    Article  PubMed  Google Scholar 

  5. Micheletto C, Guerriero M, Tognella S, et al. Effects of HFA- and CFC-beclo-methasone dipropionate on the bronchial response to methacholine (MCh) in mild asthma. Respir Med 2005; 99: 850–5

    Article  PubMed  Google Scholar 

  6. Leach CL, Davidson PJ, Boudreau RJ. Improved airway targeting with the CFC-free HFA-beclomethasone metered-dose inhaler compared with CFC-beclo-methasone. Eur Respir J 1998; 12(6): 1346–53

    Article  PubMed  CAS  Google Scholar 

  7. Thorsson L, Dahlstrom K, Edsbacker S, et al. Pharmacokinetics and systemic effects of inhaled fluticasone propionate in healthy subjects. Br J Clin Pharmacol 1997; 43(2): 155–61

    Article  PubMed  CAS  Google Scholar 

  8. Leach CL, Davidson PJ, Hasselquist BE, et al. Influence of particle size and patient dosing technique on lung deposition of HFA-beclomethasone from a metered dose inhaler. J Aerosol Med 2005; 18(4): 379–85

    Article  PubMed  CAS  Google Scholar 

  9. Whelan GJ, Blumer JL, Martin RJ, et al. Fluticasone propionate plasma concentration and systemic effect: effect of delivery device and duration of administration. J Allergy Clin Immunol 2005; 116(3): 525–30

    Article  PubMed  CAS  Google Scholar 

  10. Daley-Yates PT, Price AC, Sisson JR, et al. Beclomethasone dipropionate: absolute bioavailability, pharmacokinetics and metabolism following intravenous, oral, intranasal and inhaled administration in man. Br J Clin Pharmacol 2001; 51(5): 400–9

    Article  PubMed  CAS  Google Scholar 

  11. Ryrfeldt A, Andersson P, Edsbacker S, et al. Pharmacokinetics and metabolism of budesonide, a selective glucocorticoid. Eur J Respir Dis Suppl 1982; 122: 86–95

    PubMed  CAS  Google Scholar 

  12. Mackie AE, Ventresca GP, Fuller RW, et al. Pharmacokinetics of intravenous fluticasone propionate in healthy subjects. Br J Clin Pharmacol 1996; 41(6): 539–42

    Article  PubMed  CAS  Google Scholar 

  13. Nave R, Bethke TD, van Marle SP, et al. Pharmacokinetics of [14C]ciclesonide after oral and intravenous administration to healthy subjects. Clin Pharmacokinet 2004; 43(7): 479–86

    Article  PubMed  CAS  Google Scholar 

  14. Rohatagi S, Arya V, Zech K, et al. Population pharmacokinetics and pharmacodynamics of ciclesonide. J Clin Pharmacol 2003; 43(4): 365–78

    Article  PubMed  CAS  Google Scholar 

  15. Mitchell JP, Nagel MW, Archer AD. Size analysis of a pressurized metered dose inhaler-delivered suspension formulation by the API Aerosizer time-of-flight aerodynamic particle size analyzer. J Aerosol Med 1999; 12(4): 255–64

    Article  PubMed  CAS  Google Scholar 

  16. Waugh J, Goa KL. Flunisolide HFA. Am J Respir Med 2002; 1(5): 369–72; discussion 373

    Article  PubMed  CAS  Google Scholar 

  17. Kunka R, Andrews S, Pimazzoni M, et al. From hydrofluoroalkane pressurized metered dose inhalers (pMDIs) and comparability with chlorofluorocarbon pMDIs. Respir Med 2000; 94Suppl. B: S10–6

    PubMed  Google Scholar 

  18. Leach CL, Bethke TD, Boudreau RJ, et al. Two-dimensional and three-dimensional imaging show ciclesonide has high lung deposition and peripheral distribution: a nonrandomized study in healthy volunteers. J Aerosol Med 2006; 19(2): 117–26

    Article  PubMed  CAS  Google Scholar 

  19. Thorsson L, Edsbacker S, Conradson TB. Lung deposition of budesonide from Turbuhaler is twice that from a pressurized metered-dose inhaler P-MDI. Eur Respir J 1994; 7(10): 1839–44

    Article  PubMed  CAS  Google Scholar 

  20. Richter K, Kanniess F, Biberger C, et al. Comparison of the oropharyngeal deposition of inhaled ciclesonide and fluticasone propionate in patients with asthma. J Clin Pharmacol 2005; 45(2): 146–52

    Article  PubMed  CAS  Google Scholar 

  21. Leach CL, Davidson PJ, Hasselquist BE, et al. Lung deposition of hydrofluoroalkane-134a beclomethasone is greater than that of chlorofluorocarbon fluticasone and chlorofluorocarbon beclomethasone: a cross-over study in healthy volunteers. Chest 2002; 122(2): 510–6

    Article  PubMed  CAS  Google Scholar 

  22. Boobis AR. Comparative physicochemical and pharmacokinetic profiles of inhaled beclomethasone dipropionate and budesonide. Respir Med 1998; 92Suppl. B: 2–6

    Article  PubMed  Google Scholar 

  23. Affrime MB, Cuss F, Padhi D, et al. Bioavailability and metabolism of mometasone furoate following administration by metered-dose and dry-powder inhalers in healthy human volunteers. J Clin Pharmacol 2000; 40(11): 1227–36

    PubMed  CAS  Google Scholar 

  24. Dickens GR, Wermeling DP, Matheny CJ, et al. Pharmacokinetics of flunisolide administered via metered dose inhaler with and without a spacer device and following oral administration. Ann Allergy Asthma Immunol 2000; 84(5): 528–32

    Article  PubMed  CAS  Google Scholar 

  25. Mollmann H, Wagner M, Krishnaswami S, et al. Single-dose and steady-state pharmacokinetic and pharmacodynamic evaluation of therapeutically clinically equivalent doses of inhaled fluticasone propionate and budesonide, given as Diskus or Turbohaler dry-powder inhalers to healthy subjects. J Clin Pharmacol 2001; 41(12): 1329–38

    Article  PubMed  CAS  Google Scholar 

  26. Pickering H, Pitcairn GR, Hirst PH, et al. Regional lung deposition of a technetium 99m-labeled formulation of mometasone furoate administered by hydrofluoroalkane 227 metered-dose inhaler. Clin Ther 2000; 22: 1483–93

    Article  PubMed  CAS  Google Scholar 

  27. Schering-Plough Ltd. Asmanex twisthaler (mometasone furoate dry powder inhaler). Welwyn Garden City: Schering-Plough Ltd, 2004

    Google Scholar 

  28. Nolting A, Sista S, Abramowitz W. Flunisolide HFA vs flunisolide CFC: pharmacokinetic comparison in healthy volunteers. Biopharm Drug Dispos 2001; 22(9): 373–82

    Article  PubMed  CAS  Google Scholar 

  29. Crim C, Pierre LN, Daley-Yates PT. A review of the pharmacology and pharmacokinetics of inhaled fluticasone propionate and mometasone furoate. Clin Ther 2001; 23(9): 1339–54

    Article  PubMed  CAS  Google Scholar 

  30. Kelly HW. Comparative potency and clinical efficacy of inhaled corticosteroids. Respir Care Clin N Am 1999; 5(4): 537–53

    PubMed  CAS  Google Scholar 

  31. Derendorf H. Pharmacokinetic and pharmacodynamic properties of inhaled corticosteroids in relation to efficacy and safety. Respir Med 1997; 91Suppl. A: 22–8

    Article  PubMed  Google Scholar 

  32. Dietzel K, Engelstätter R, Keller A, et al. Ciclesonide: an on-site activated steroid. In: Hansel TT, Barnes PJ, editors. New drugs for asthma, allergy and COPD. Basel: Karger, 2001: 91–3

    Chapter  Google Scholar 

  33. Corren J, Nelson H, Greos LS, et al. Effective control of asthma with hydrofluoroalkane flunisolide delivered as an extrafine aerosol in asthma patients. Ann Allergy Asthma Immunol 2001; 87(5): 405–11

    Article  PubMed  CAS  Google Scholar 

  34. Marshall BG, Wangoo A, Harrison LI, et al. Tumour necrosis factor-alpha production in human alveolar macrophages: modulation by inhaled corticosteroid. Eur Respir J 2000; 15(4): 764–70

    Article  PubMed  CAS  Google Scholar 

  35. Hauber HP, Gotfried M, Newman K, et al. Effect of HFA-flunisolide on peripheral lung inflammation in asthma. J Allergy Clin Immunol 2003; 112(1): 58–63

    Article  PubMed  CAS  Google Scholar 

  36. Ederle K, Multicentre Study Group. Improved control of asthma symptoms with a reduced dose of HFA-BDP extrafine aerosol: an open-label, randomised study. Eur Rev Med Pharmacol Sci 2003; 7(2): 45–55

    PubMed  CAS  Google Scholar 

  37. Thongngarm T, Silkoff PE, Kossack WS, et al. Hydrofluoroalkane-134A beclomethasone or chlorofluorocarbon fluticasone: effect on small airways in poorly controlled asthma. J Asthma 2005; 42(4): 257–63

    Article  PubMed  CAS  Google Scholar 

  38. Agertoft L, Pedersen S. Effects of long-term treatment with an inhaled corticosteroid on growth and pulmonary function in asthmatic children. Respir Med 1994; 88(5): 373–81

    Article  PubMed  CAS  Google Scholar 

  39. Zeiger RS, Dawson C, Weiss S. Relationships between duration of asthma and asthma severity among children in the Childhood Asthma Management Program (CAMP). J Allergy Clin Immunol 1999; 103 (3 Pt 1): 376–87

    Article  PubMed  CAS  Google Scholar 

  40. Long-term effects of budesonide or nedocromil in children with asthma: the Childhood Asthma Management Program Research Group. N Engl J Med 2000; 343(15): 1054–63

    Google Scholar 

  41. Ulrik CS, Backer V. Markers of impaired growth of pulmonary function in children and adolescents. Am J Respir Crit Care Med 1999; 160(1): 40–4

    PubMed  CAS  Google Scholar 

  42. Brown PH, Blundell G, Greening AP, et al. Screening for hypothalamo-pituitary-adrenal axis suppression in asthmatics taking high dose inhaled corticosteroids. Respir Med 1991; 85(6): 511–6

    Article  PubMed  CAS  Google Scholar 

  43. Lipworth BJ, Seckl JR. Measures for detecting systemic bioactivity with inhaled and intranasal corticosteroids. Thorax 1997; 52(5): 476–82

    Article  PubMed  CAS  Google Scholar 

  44. Brocklebank D, Wright J, Cates C. Systematic review of clinical effectiveness of pressurised metered dose inhalers versus other hand held inhaler devices for delivering corticosteroids in asthma. BMJ 2001; 323(7318): 896–900

    Article  PubMed  CAS  Google Scholar 

  45. Thorsson L, Edsbacker S. Lung deposition of budesonide from a pressurized metered-dose inhaler attached to a spacer. Eur Respir J 1998; 12(6): 1340–5

    Article  PubMed  CAS  Google Scholar 

  46. Howarth PH. Why particle size should affect clinical response to inhaled therapy. J Aerosol Med 2001; 14Suppl. 1: S27–34

    Article  PubMed  CAS  Google Scholar 

  47. Lipworth BJ, Jackson CM. Safety of inhaled and intranasal corticosteroids: lessons for the new millennium. Drug Saf 2000; 23(1): 11–33

    Article  PubMed  CAS  Google Scholar 

  48. Lipworth BJ, Jackson CM. Pharmacokinetics of chlorofluorocarbon and hydrofluoroalkane metered-dose inhaler formulations of beclomethasone dipropionate. Br J Clin Pharmacol 1999; 48(6): 866–8

    Article  PubMed  CAS  Google Scholar 

  49. Martin RJ, Szefler SJ, Chinchilli VM, et al. Systemic effect comparisons of six inhaled corticosteroid preparations. Am J Respir Crit Care Med 2002; 165(10): 1377–83

    Article  PubMed  Google Scholar 

  50. Brutsche MH, Brutsche IC, Munawar M, et al. Comparison of pharmacokinetics and systemic effects of inhaled fluticasone propionate in patients with asthma and healthy volunteers: a randomised crossover study. Lancet 2000; 356(9229): 556–61

    Article  PubMed  CAS  Google Scholar 

  51. Harrison TW, Tattersfield AE. Plasma concentrations of fluticasone propionate and budesonide following inhalation from dry powder inhalers by healthy and asthmatic subjects. Thorax 2003; 58(3): 258–60

    Article  PubMed  CAS  Google Scholar 

  52. Griffioen RW, de Jongh FH. Inhalation therapy in children younger than two years. Ned Tijdschr Geneeskd 1998; 142: 1484–8

    PubMed  CAS  Google Scholar 

  53. Hubner M, Hochhaus G, Derendorf H. Comparative pharmacology, bioavailability, pharmacokinetics, and pharmacodynamics of inhaled glucocorticosteroids. Immunol Allergy Clin North Am 2005; 25(3): 469–88

    Article  PubMed  Google Scholar 

  54. Hochhaus G. New developments in corticosteroids. Proc Am Thorac Soc 2004; 1(3): 269–74

    Article  PubMed  CAS  Google Scholar 

  55. Miller-Larsson A, Axelsson B-O, Brattsand R, et al. Relative lipophilicity of budesonide, fluticasone propionate, mometasone furoate, and ciclesonide: preference of variable lipophilicity in airways versus systemic compartment [abstract]. Am J Respir Crit Care Med 2003; 167(7): A773

    Google Scholar 

  56. Nave R, Fisher R, Zech K. In vitro metabolism of ciclesonide in human lung and liver precision-cut tissue slices. Biopharm Drug Dispos 2006; 27(4): 197–207

    Article  PubMed  CAS  Google Scholar 

  57. Tunek A, Sjodin K, Hallstrom G. Reversible formation of fatty acid esters of budesonide, an antiasthma glucocorticoid, in human lung and liver microsomes. Drug Metab Dispos 1997; 25(11): 1311–7

    PubMed  CAS  Google Scholar 

  58. Barnes PJ, Pedersen S, Busse WW. Efficacy and safety of inhaled corticosteroids: new developments. Am J Respir Crit Care Med 1998; 157 (3 Pt 2): S1–53

    PubMed  CAS  Google Scholar 

  59. Mollmann H, Wagner M, Meibohm B, et al. Pharmacokinetic and pharmacodynamic evaluation of fluticasone propionate after inhaled administration. Eur J Clin Pharmacol 1998; 53(6): 459–67

    Article  PubMed  CAS  Google Scholar 

  60. Wilson AM, Dempsey OJ, Coutie WJ, et al. Importance of drug-device interaction in determining systemic effects of inhaled corticosteroids. Lancet 1999; 353(9170): 2128

    Article  PubMed  CAS  Google Scholar 

  61. Derendorf HH, Machhaus G. The effect of protein binding on adrenal suppression potential of inhaled corticosteroids. J Allergy Clin Immunol 2006; 117(2): s94

    Article  Google Scholar 

  62. Schering-Plough Ltd. Asmanex twisthaler (mometasone furoate dry powder inhaler) SPC. Welwyn Garden City: Schering-Plough Ltd, 2004

    Google Scholar 

  63. Szefler SJ. Pharmacokinetics of intranasal corticosteroids. J Allergy Clin Immunol 2001; 108 (1 Suppl.): S26–31

    Article  PubMed  CAS  Google Scholar 

  64. Fardon TC, Lee DK, Haggart K, et al. Adrenal suppression with dry powder formulations of fluticasone propionate and mometasone furoate. Am J Respir Crit Care Med 2004; 170(9): 960–6

    Article  PubMed  Google Scholar 

  65. Hogger P, Rohdewald P. Binding kinetics of fluticasone propionate to the human glucocorticoid receptor. Steroids 1994; 59: 597–602

    Article  PubMed  CAS  Google Scholar 

  66. Masoli M, Weatherall M, Holt S, et al. Systematic review of the dose-response relation of inhaled fluticasone propionate. Arch Dis Child 2004; 89(10): 902–7

    Article  PubMed  CAS  Google Scholar 

  67. Evans WE, McLeod HL. Pharmacogenomics: drug disposition, drug targets, and side effects. N Engl J Med 2003; 348(6): 538–49

    Article  PubMed  CAS  Google Scholar 

  68. Weinshilboum R. Inheritance and drug response. N Engl J Med 2003; 348(6): 529–37

    Article  PubMed  Google Scholar 

  69. Szefler SJ, Martin RJ, King TS, et al. Significant variability in response to inhaled corticosteroids for persistent asthma. J Allergy Clin Immunol 2002; 109(3): 410–8

    Article  PubMed  CAS  Google Scholar 

  70. Drazen JM, Silverman EK, Lee TH. Heterogeneity of therapeutic responses in asthma. Br Med Bull 2000; 56(4): 1054–70

    Article  PubMed  CAS  Google Scholar 

  71. Weiss ST, Litonjua AA, Lange C, et al. Overview of the pharmacogenetics of asthma treatment. Pharmacogenomics J 2006; 6(5): 311–26

    PubMed  CAS  Google Scholar 

  72. Lazarus SC, Boushey HA, Fahy JV, et al. Long-acting beta2-agonist monotherapy vs continued therapy with inhaled corticosteroids in patients with persistent asthma: a randomized controlled trial. JAMA 2001; 285(20): 2583–93

    Article  PubMed  CAS  Google Scholar 

  73. Chowdhury B. Division director memorandum: overview of FDA background materials prepared for the meeting to discuss the implications of the available data related to the safety of long-acting beta-agonist bronchodilators, June 15, 2005 [online]. Available from URL: http://www.fda.gov/ohrms/dockets/ac/05/briefing/2005-4148B1_03_01-FDA-Div-Dir-Memo.pdf [Accessed 2006 Jun]

  74. The FDA safety information and adverse event reporting program: 2003 safety alert: Serevent (salmeterol xinofoate) [online]. Available from URL: http://www.fda.gov/medwatch/SAFETY/2003/serevent.htm [Accessed 2006 Jun]

  75. Bisgaard H. Effect of long-acting beta2 agonists on exacerbation rates of asthma in children. Pediatr Pulmonol 2003; 36(5): 391–8

    Article  PubMed  Google Scholar 

  76. Bisgaard H. Long-acting beta(2)-agonists in management of childhood asthma: a critical review of the literature. Pediatr Pulmonol 2000; 29(3): 221–34

    Article  PubMed  CAS  Google Scholar 

  77. Verberne AA, Frost C, Roorda RJ, et al. 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

    PubMed  CAS  Google Scholar 

  78. Simons FE. A comparison of beclomethasone, salmeterol, and placebo in children with asthma: Canadian Beclomethasone Dipropionate-Salmeterol Xinafoate Study Group. N Engl J Med 1997; 337(23): 1659–65

    Article  PubMed  CAS  Google Scholar 

  79. Reed CE, Offord KP, Nelson HS, et al. Aerosol beclomethasone dipropionate spray compared with theophylline as primary treatment for chronic mild-to-moderate asthma: the American Academy of Allergy, Asthma and Immunology Beclomethasone Dipropionate-Theophylline Study Group. J Allergy Clin Immunol 1998; 101 (1 Pt 1): 14–23

    Article  PubMed  CAS  Google Scholar 

  80. Leflein JG, Szefler SJ, Murphy KR, et al. Nebulized budesonide inhalation suspension compared with cromolyn sodium nebulizer solution for asthma in young children: results of a randomized outcomes trial. Pediatrics 2002; 109(5): 866–72

    Article  PubMed  Google Scholar 

  81. Garcia Garcia ML, Wahn U, Gilles L, et al. 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

    Article  PubMed  Google Scholar 

  82. National Institutes of Health, National Heart, Lung, and Blood Institute. National Asthma Education and Prevention Program: quick reference. NAEPP Expert Panel report guidelines for the diagnosis and management of asthma update on selected topics 2002. J Allergy Clin Immunol 2002; 110 (5 Suppl.): S141–219

    Article  Google Scholar 

  83. Lipworth BJ, Kaliner MA, LaForce CF, et al. Effect of ciclesonide and fluticasone on hypothalamic-pituitary-adrenal axis function in adults with mild-to-moderate persistent asthma. Ann Allergy Asthma Immunol 2005; 94(4): 465–72

    Article  PubMed  CAS  Google Scholar 

  84. Buhl R, Vinkler I, Magyar P, et al. Comparable efficacy of ciclesonide once daily versus fluticasone propionate twice daily in asthma. Pulm Pharmacol Ther 2006; 19(6): 404–12

    Article  PubMed  CAS  Google Scholar 

  85. Limb SL, Brown KC, Wood RA, et al. Irreversible lung function deficits in young adults with a history of childhood asthma. J Allergy Clin Immunol 2005; 116(6): 1213–9

    Article  PubMed  Google Scholar 

  86. O’Byrne PM, Pedersen S, Busse WW, et al. Effects of early intervention with inhaled budesonide on lung function in newly diagnosed asthma. Chest 2006; 129(6): 1478–85

    Article  PubMed  Google Scholar 

  87. Guilbert TW, Morgan WJ, Zeiger RS, et al. Long-term inhaled corticosteroids in preschool children at high risk for asthma. N Engl J Med 2006; 354(19): 1985–97

    Article  PubMed  CAS  Google Scholar 

  88. Brown PH, Blundell G, Greening AP, et al. Hypothalamo-pituitary-adrenal axis suppression in asthmatics inhaling high dose corticosteroids. Respir Med 1991; 85(6): 501–10

    Article  PubMed  CAS  Google Scholar 

  89. Bisgaard H, Damkjaer Nielsen M, Andersen B, et al. Adrenal function in children with bronchial asthma treated with beclomethasone dipropionate or budesonide. J Allergy Clin Immunol 1988; 81(6): 1088–95

    Article  PubMed  CAS  Google Scholar 

  90. Burch WM. Urine free-cortisol determination: a useful tool in the management of chronic hypoadrenal states. JAMA 1982; 247(14): 2002–4

    Article  PubMed  CAS  Google Scholar 

  91. Derendorf H, Hochhaus G. What is the best marker for inhaled corticosteroid safety? Allergy Asthma Proc 2005; 26(2): 89–93

    PubMed  CAS  Google Scholar 

  92. Nelson HS, Stricker W, Casale TB, et al. A comparison of methods for assessing hypothalamic-pituitary-adrenal (HPA) axis activity in asthma patients treated with inhaled corticosteroids. J Clin Pharmacol 2002; 42(3): 319–26

    Article  PubMed  CAS  Google Scholar 

  93. Dahl R. Systemic side effects of inhaled corticosteroids in patients with asthma. Respir Med 2006; 100(8): 1307–17

    Article  PubMed  Google Scholar 

  94. Oelkers W. Adrenal insufficiency. N Engl J Med 1996; 335(16): 1206–12

    Article  PubMed  CAS  Google Scholar 

  95. Todd GR, Acerini CL, Ross-Russell R, et al. Survey of adrenal crisis associated with inhaled corticosteroids in the United Kingdom. Arch Dis Child 2002; 87(6): 457–61

    Article  PubMed  CAS  Google Scholar 

  96. Reynolds NA, Scott LJ. Ciclesonide. Drugs 2004; 64(5): 511–9; discussion 520-1

    Article  PubMed  CAS  Google Scholar 

  97. Weinbrenner A, Huneke D, Zschiesche M, et al. Circadian rhythm of serum cortisol after repeated inhalation of the new topical steroid ciclesonide. J Clin Endocrinol Metab 2002; 87(5): 2160–3

    Article  PubMed  CAS  Google Scholar 

  98. Postma DS, Sevette C, Martinat Y, et al. Treatment of asthma by the inhaled corticosteroid ciclesonide given either in the morning or evening. Eur Respir J 2001; 17(6): 1083–8

    Article  PubMed  CAS  Google Scholar 

  99. Rees L, Rigden SP, Chantler C. The influence of steroid therapy and recombinant human erythropoietin on the growth of children with renal disease. Pediatr Nephrol 1991; 5(4): 556–8

    Article  PubMed  CAS  Google Scholar 

  100. Tanner JM, Whitehouse RH. Clinical longitudinal standards for height, weight, height velocity, weight velocity, and stages of puberty. Arch Dis Child 1976; 51(3): 170–9

    Article  PubMed  CAS  Google Scholar 

  101. Silverstein MD, Yunginger JW, Reed CE, et al. Attained adult height after childhood asthma: effect of glucocorticoid therapy. J Allergy Clin Immunol 1997; 99(4): 466–74

    Article  PubMed  CAS  Google Scholar 

  102. 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

    Article  PubMed  CAS  Google Scholar 

  103. Eid NS. Update on National Asthma Education and Prevention Program pediatric asthma treatment recommendations. Clin Pediatr (Phila) 2004; 43(9): 793–802

    Article  Google Scholar 

  104. Boulet LP. Perception of the role and potential side effects of inhaled corticosteroids among asthmatic patients. Chest 1998; 113(3): 587–92

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

No sources of funding were used to assist in the preparation of this review. N. Eid has received consultancies, honoraria, or grants from IVAX Research, Inc., AstraZeneca, Merck, Genetech, Chiron, Corus Pharma, and Schering-Plough; and R. Morton has received consultancies from AstraZeneca and MedImmune, and grants from Chiron and Corus Pharma.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Nemr Eid.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Gulliver, T., Morton, R. & Eid, N. Inhaled Corticosteroids in Children with Asthma. Pediatr-Drugs 9, 185–194 (2007). https://doi.org/10.2165/00148581-200709030-00007

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00148581-200709030-00007

Keywords

Navigation