Pediatric Drugs

, Volume 9, Issue 3, pp 185–194 | Cite as

Inhaled Corticosteroids in Children with Asthma

Pharmacologic Determinants of Safety and Efficacy and Other Clinical Considerations
  • Tanya Gulliver
  • Ronald Morton
  • Nemr Eid
Review Article


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.


Asthma Budesonide Fluticasone Propionate Beclomethasone Nedocromil 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



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.


  1. 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: 469–78PubMedCrossRefGoogle Scholar
  2. 2.
    National Center for Health Statistics. Faststats: asthma [online]. Available from URL: [Accessed 2007 Feb 9]
  3. 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.): S141–219CrossRefGoogle Scholar
  4. 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: 23–31PubMedCrossRefGoogle Scholar
  5. 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: 850–5PubMedCrossRefGoogle Scholar
  6. 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): 1346–53PubMedCrossRefGoogle Scholar
  7. 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): 155–61PubMedCrossRefGoogle Scholar
  8. 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): 379–85PubMedCrossRefGoogle Scholar
  9. 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): 525–30PubMedCrossRefGoogle Scholar
  10. 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): 400–9PubMedCrossRefGoogle Scholar
  11. 11.
    Ryrfeldt A, Andersson P, Edsbacker S, et al. Pharmacokinetics and metabolism of budesonide, a selective glucocorticoid. Eur J Respir Dis Suppl 1982; 122: 86–95PubMedGoogle Scholar
  12. 12.
    Mackie AE, Ventresca GP, Fuller RW, et al. Pharmacokinetics of intravenous fluticasone propionate in healthy subjects. Br J Clin Pharmacol 1996; 41(6): 539–42PubMedCrossRefGoogle Scholar
  13. 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): 479–86PubMedCrossRefGoogle Scholar
  14. 14.
    Rohatagi S, Arya V, Zech K, et al. Population pharmacokinetics and pharmacodynamics of ciclesonide. J Clin Pharmacol 2003; 43(4): 365–78PubMedCrossRefGoogle Scholar
  15. 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): 255–64PubMedCrossRefGoogle Scholar
  16. 16.
    Waugh J, Goa KL. Flunisolide HFA. Am J Respir Med 2002; 1(5): 369–72; discussion 373PubMedCrossRefGoogle Scholar
  17. 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: S10–6PubMedGoogle Scholar
  18. 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): 117–26PubMedCrossRefGoogle Scholar
  19. 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): 1839–44PubMedCrossRefGoogle Scholar
  20. 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): 146–52PubMedCrossRefGoogle Scholar
  21. 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): 510–6PubMedCrossRefGoogle Scholar
  22. 22.
    Boobis AR. Comparative physicochemical and pharmacokinetic profiles of inhaled beclomethasone dipropionate and budesonide. Respir Med 1998; 92Suppl. B: 2–6PubMedCrossRefGoogle Scholar
  23. 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): 1227–36PubMedGoogle Scholar
  24. 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): 528–32PubMedCrossRefGoogle Scholar
  25. 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): 1329–38PubMedCrossRefGoogle Scholar
  26. 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: 1483–93PubMedCrossRefGoogle Scholar
  27. 27.
    Schering-Plough Ltd. Asmanex twisthaler (mometasone furoate dry powder inhaler). Welwyn Garden City: Schering-Plough Ltd, 2004Google Scholar
  28. 28.
    Nolting A, Sista S, Abramowitz W. Flunisolide HFA vs flunisolide CFC: pharmacokinetic comparison in healthy volunteers. Biopharm Drug Dispos 2001; 22(9): 373–82PubMedCrossRefGoogle Scholar
  29. 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): 1339–54PubMedCrossRefGoogle Scholar
  30. 30.
    Kelly HW. Comparative potency and clinical efficacy of inhaled corticosteroids. Respir Care Clin N Am 1999; 5(4): 537–53PubMedGoogle Scholar
  31. 31.
    Derendorf H. Pharmacokinetic and pharmacodynamic properties of inhaled corticosteroids in relation to efficacy and safety. Respir Med 1997; 91Suppl. A: 22–8PubMedCrossRefGoogle Scholar
  32. 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: 91–3CrossRefGoogle Scholar
  33. 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): 405–11PubMedCrossRefGoogle Scholar
  34. 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): 764–70PubMedCrossRefGoogle Scholar
  35. 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): 58–63PubMedCrossRefGoogle Scholar
  36. 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): 45–55PubMedGoogle Scholar
  37. 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): 257–63PubMedCrossRefGoogle Scholar
  38. 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): 373–81PubMedCrossRefGoogle Scholar
  39. 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): 376–87PubMedCrossRefGoogle Scholar
  40. 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): 1054–63Google Scholar
  41. 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): 40–4PubMedGoogle Scholar
  42. 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): 511–6PubMedCrossRefGoogle Scholar
  43. 43.
    Lipworth BJ, Seckl JR. Measures for detecting systemic bioactivity with inhaled and intranasal corticosteroids. Thorax 1997; 52(5): 476–82PubMedCrossRefGoogle Scholar
  44. 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): 896–900PubMedCrossRefGoogle Scholar
  45. 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): 1340–5PubMedCrossRefGoogle Scholar
  46. 46.
    Howarth PH. Why particle size should affect clinical response to inhaled therapy. J Aerosol Med 2001; 14Suppl. 1: S27–34PubMedCrossRefGoogle Scholar
  47. 47.
    Lipworth BJ, Jackson CM. Safety of inhaled and intranasal corticosteroids: lessons for the new millennium. Drug Saf 2000; 23(1): 11–33PubMedCrossRefGoogle Scholar
  48. 48.
    Lipworth BJ, Jackson CM. Pharmacokinetics of chlorofluorocarbon and hydrofluoroalkane metered-dose inhaler formulations of beclomethasone dipropionate. Br J Clin Pharmacol 1999; 48(6): 866–8PubMedCrossRefGoogle Scholar
  49. 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): 1377–83PubMedCrossRefGoogle Scholar
  50. 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): 556–61PubMedCrossRefGoogle Scholar
  51. 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): 258–60PubMedCrossRefGoogle Scholar
  52. 52.
    Griffioen RW, de Jongh FH. Inhalation therapy in children younger than two years. Ned Tijdschr Geneeskd 1998; 142: 1484–8PubMedGoogle Scholar
  53. 53.
    Hubner M, Hochhaus G, Derendorf H. Comparative pharmacology, bioavailability, pharmacokinetics, and pharmacodynamics of inhaled glucocorticosteroids. Immunol Allergy Clin North Am 2005; 25(3): 469–88PubMedCrossRefGoogle Scholar
  54. 54.
    Hochhaus G. New developments in corticosteroids. Proc Am Thorac Soc 2004; 1(3): 269–74PubMedCrossRefGoogle Scholar
  55. 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): A773Google Scholar
  56. 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): 197–207PubMedCrossRefGoogle Scholar
  57. 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): 1311–7PubMedGoogle Scholar
  58. 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): S1–53PubMedGoogle Scholar
  59. 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): 459–67PubMedCrossRefGoogle Scholar
  60. 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): 2128PubMedCrossRefGoogle Scholar
  61. 61.
    Derendorf HH, Machhaus G. The effect of protein binding on adrenal suppression potential of inhaled corticosteroids. J Allergy Clin Immunol 2006; 117(2): s94CrossRefGoogle Scholar
  62. 62.
    Schering-Plough Ltd. Asmanex twisthaler (mometasone furoate dry powder inhaler) SPC. Welwyn Garden City: Schering-Plough Ltd, 2004Google Scholar
  63. 63.
    Szefler SJ. Pharmacokinetics of intranasal corticosteroids. J Allergy Clin Immunol 2001; 108 (1 Suppl.): S26–31PubMedCrossRefGoogle Scholar
  64. 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): 960–6PubMedCrossRefGoogle Scholar
  65. 65.
    Hogger P, Rohdewald P. Binding kinetics of fluticasone propionate to the human glucocorticoid receptor. Steroids 1994; 59: 597–602PubMedCrossRefGoogle Scholar
  66. 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): 902–7PubMedCrossRefGoogle Scholar
  67. 67.
    Evans WE, McLeod HL. Pharmacogenomics: drug disposition, drug targets, and side effects. N Engl J Med 2003; 348(6): 538–49PubMedCrossRefGoogle Scholar
  68. 68.
    Weinshilboum R. Inheritance and drug response. N Engl J Med 2003; 348(6): 529–37PubMedCrossRefGoogle Scholar
  69. 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): 410–8PubMedCrossRefGoogle Scholar
  70. 70.
    Drazen JM, Silverman EK, Lee TH. Heterogeneity of therapeutic responses in asthma. Br Med Bull 2000; 56(4): 1054–70PubMedCrossRefGoogle Scholar
  71. 71.
    Weiss ST, Litonjua AA, Lange C, et al. Overview of the pharmacogenetics of asthma treatment. Pharmacogenomics J 2006; 6(5): 311–26PubMedGoogle Scholar
  72. 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): 2583–93PubMedCrossRefGoogle Scholar
  73. 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: [Accessed 2006 Jun]
  74. 74.
    The FDA safety information and adverse event reporting program: 2003 safety alert: Serevent (salmeterol xinofoate) [online]. Available from URL: [Accessed 2006 Jun]
  75. 75.
    Bisgaard H. Effect of long-acting beta2 agonists on exacerbation rates of asthma in children. Pediatr Pulmonol 2003; 36(5): 391–8PubMedCrossRefGoogle Scholar
  76. 76.
    Bisgaard H. Long-acting beta(2)-agonists in management of childhood asthma: a critical review of the literature. Pediatr Pulmonol 2000; 29(3): 221–34PubMedCrossRefGoogle Scholar
  77. 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): 688–95PubMedGoogle Scholar
  78. 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): 1659–65PubMedCrossRefGoogle Scholar
  79. 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): 14–23PubMedCrossRefGoogle Scholar
  80. 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): 866–72PubMedCrossRefGoogle Scholar
  81. 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): 360–9PubMedCrossRefGoogle Scholar
  82. 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.): S141–219CrossRefGoogle Scholar
  83. 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): 465–72PubMedCrossRefGoogle Scholar
  84. 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): 404–12PubMedCrossRefGoogle Scholar
  85. 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): 1213–9PubMedCrossRefGoogle Scholar
  86. 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): 1478–85PubMedCrossRefGoogle Scholar
  87. 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): 1985–97PubMedCrossRefGoogle Scholar
  88. 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): 501–10PubMedCrossRefGoogle Scholar
  89. 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): 1088–95PubMedCrossRefGoogle Scholar
  90. 90.
    Burch WM. Urine free-cortisol determination: a useful tool in the management of chronic hypoadrenal states. JAMA 1982; 247(14): 2002–4PubMedCrossRefGoogle Scholar
  91. 91.
    Derendorf H, Hochhaus G. What is the best marker for inhaled corticosteroid safety? Allergy Asthma Proc 2005; 26(2): 89–93PubMedGoogle Scholar
  92. 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): 319–26PubMedCrossRefGoogle Scholar
  93. 93.
    Dahl R. Systemic side effects of inhaled corticosteroids in patients with asthma. Respir Med 2006; 100(8): 1307–17PubMedCrossRefGoogle Scholar
  94. 94.
    Oelkers W. Adrenal insufficiency. N Engl J Med 1996; 335(16): 1206–12PubMedCrossRefGoogle Scholar
  95. 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): 457–61PubMedCrossRefGoogle Scholar
  96. 96.
    Reynolds NA, Scott LJ. Ciclesonide. Drugs 2004; 64(5): 511–9; discussion 520-1PubMedCrossRefGoogle Scholar
  97. 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): 2160–3PubMedCrossRefGoogle Scholar
  98. 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): 1083–8PubMedCrossRefGoogle Scholar
  99. 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): 556–8PubMedCrossRefGoogle Scholar
  100. 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): 170–9PubMedCrossRefGoogle Scholar
  101. 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): 466–74PubMedCrossRefGoogle Scholar
  102. 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): 1064–9PubMedCrossRefGoogle Scholar
  103. 103.
    Eid NS. Update on National Asthma Education and Prevention Program pediatric asthma treatment recommendations. Clin Pediatr (Phila) 2004; 43(9): 793–802CrossRefGoogle Scholar
  104. 104.
    Boulet LP. Perception of the role and potential side effects of inhaled corticosteroids among asthmatic patients. Chest 1998; 113(3): 587–92PubMedCrossRefGoogle Scholar

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© Adis Data Information BV 2007

Authors and Affiliations

  1. 1.John Hunter Children’s HospitalNewcastleAustralia
  2. 2.University of Louisville School of MedicineLouisvilleUSA

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