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Safety of Inhaled and Intranasal Corticosteroids

Lessons for the New Millennium

  • Current Opinion
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Abstract

Although inhaled and intranasal corticosteroids are first-line therapy for asthma and allergic rhinitis, there has recently been an increasing awareness of their propensity to produce systemic adverse effects. The availability of more potent and lipophilic corticosteroids and new chlorofluorocarbon (CFC)-free formulations has focused attention on these safety issues.

The main determinant of systemic bioavailability of these drugs is direct absorption from the lung or nose, where there is no first-pass inactivation. Consequently, the systemic bioavailability of inhaled corticosteroids is greatly influenced by the efficiency of the inhaler device. Thus, when comparing different inhaled corticosteroids it is imperative to consider the unique drug/device interaction.

The pharmacokinetic profile is important in determining the systemic bioactivity of inhaled and intranasal corticosteroids. For highly lipophilic drugs, such as fluticasone propionate or mometasone furoate, there is preferential partitioning into the systemic tissue compartment, and consequently a large volume of distribution at steady state. In contrast, drugs with lower lipophilicity, such as triamcinolone acetonide or budesonide, have a smaller volume of distribution. The systemic tissue compartment may act as a slow release reservoir, resulting in a long elimination half-life for the lipophilic drugs.

For intranasal corticosteroids, a high degree of lipophilicity diminishes water solubility in mucosa and therefore increases the amount of drug swept away by mucociliary clearance before it can gain access to tissue receptor sites. This may reduce the anti-inflammatory efficacy in the nose, but might also reduce the propensity for direct systemic absorption from the nasal cavity.

The hydrofluoroalkane (HFA) formulations of beclomethasone dipropionate are solutions and exhibit a much higher respirable fine particle dose than do the CFC formulations. Dose-response studies with one of the HFA formulations have shown therapeutic equivalence at half the dosage, with little evidence of adrenal suppression at dosages up to 800 μg/day. A lack of similar studies for another of the available HFA formulations has led to a discrepancy in the recommendations for equivalence. Although in vitro studies have pointed to a similar fine particle distribution for the HFA and CFC formulations of fluticasone propionate, this is not supported by in vivo data for lung bioavailability, suggesting that care will be required when switching these formulations.

Prescribers of inhaled and intranasal corticosteroids should be aware of the potential for long term systemic effects. The safest way to use these drugs is to ‘step-down’ to achieve the lowest possible effective maintenance dosage.

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References

  1. Anonymous. National Asthma Education and Prevention Programme. Expert panel report II. Guidelines for the diagnosis and management of asthma. Bethesda (MD): National Institutes of Health Publication, 1997: 97–4051

  2. International consensus report on the diagnosis and management of rhinitis. International Rhinitis Working Group. Allergy 1994; 49 Suppl. 19: 1–34

    Google Scholar 

  3. Lipworth BJ. New perspectives on inhaled drug delivery and systemic bioactivity. Thorax 1995; 50: 105–10

    Article  PubMed  CAS  Google Scholar 

  4. Lipworth BJ, Seckl JL. Measures for detecting systemic bioactivity with inhaled and intranasal corticosteroids. Thorax 1997; 52: 476–82

    Article  PubMed  CAS  Google Scholar 

  5. Miller-Larsson A, Mattsson H, Hjertberg C, et al. Reversible fatty acid configuration of budesonide: novel mechanism for prolonged retention of topically applied steroid in airway tissue. Drug Metab Dispos 1998; 26: 623–30

    PubMed  CAS  Google Scholar 

  6. Lipworth BJ. Systemic adverse effects of inhaled corticosteroid therapy: a systematic review and meta-analysis. Arch Intern Med 1999; 159: 41–55

    Article  Google Scholar 

  7. Lipworth BJ, Wilson AM. Dose response to inhaled corticosteroids: benefits and risks. Semin Respir Crit Care Med 1998; 19: 625–46

    Article  Google Scholar 

  8. Johnson M. Development of fluticasone propionate and comparison with other inhaled corticosteroids. J Allergy Clin Immunol 1998; 101: S434–S439

    Article  PubMed  CAS  Google Scholar 

  9. Wieslander E, Delander EL, Jarkelid L, et al. Pharmacologic importance of reversible fatty acid configuration of budesonide studied in rat cell line in-vitro. Am J Respir Cell Mol Biol 1998; 19: 477–84

    PubMed  CAS  Google Scholar 

  10. Stellato C, Atsuta J, Bickel CA, et al. An in vitro comparison of commonly used topical glucocorticoid preparations. J Allergy Clin Immunol 1999; 104: 623–9

    Article  PubMed  CAS  Google Scholar 

  11. Ek A, Larsson K, Siljerud S, et al. Fluticasone and budesonide inhibit cytokine release in human lung epithelial cells and alveolar macrophages. Allergy 1999; 54: 691–9

    Article  PubMed  CAS  Google Scholar 

  12. Aksoy MO, Li X, Borenstern M, et al. Effects of topical corticosteroids on inflammatory mediator induced eicosanoid release by human airway epithelial cells. J Allergy Clin Immunol 1999; 103(6): 1081–91

    Article  PubMed  CAS  Google Scholar 

  13. Agertoft L, Pedersen S. A randomised double-blind dose reduction study to compare the minimal effective dose of budesonide turbuhaler and fluticasone propionate diskhaler. J Allergy Clin Immunol 1997; 99: 773–80

    Article  PubMed  CAS  Google Scholar 

  14. Ryrfeldt A, Andersson P, Edsbacker S, et al. Pharmacokinetics and metabolism of budesonide, a selective glucocorticoid. Eur J Respir Dis 1982; 63Suppl. 122: 86–95

    Google Scholar 

  15. Harding SM. The human pharmacology of fluticasone propionate. Respir Med 1990; 84Suppl. A: 25–9

    Article  PubMed  Google Scholar 

  16. Heald D, Argenti D, Jensen B, et al. The disposition of 14c triamcinolone acetonide administered as single oral dose of 100 μCi (800μg) to healthy volunteers. In: Proceedings of a joint meeting of the American Academy of Allergy, Asthma Immunology and the American Thoracic Society, in cooperation with the American College of Chest Physicians. Asthma 1995 Conference: Theory to Treatment; 1995 Jul 15-17; Chicago (IL), 14

  17. Mollman H, Rohdewald P, Schmidt EW, et al. Pharmacokinetics of triamcinolone acetonide and its phosphate ester. Eur J Clin Pharmacol 1985; 29: 85–9

    Article  Google Scholar 

  18. Asmanex Twisthaler: mometasone furoate anhydrous dry powder inhaler [clinical monograph]. Kennelworth (NJ): Schering-Plough, 1999. (Data on file)

  19. Andersson P, Ryrfeldt A. Biotransformation of the topical glucocorticoids, budesonide and beclomethasone, 17,21-dipropionate in human liver and lung homogenate. J Pharm Pharmacol 1984; 36: 763–5

    Article  PubMed  CAS  Google Scholar 

  20. Trescoli-Serrano C, Ward MJ, Rajput R, et al. Does swallowed charcoal affect gastrointestinal absorption of inhaled beclomethasone [abstract]. Eur Respir J 1995; 8Suppl. 19: 304

    Google Scholar 

  21. Foe K, Brown K, Seale JP. Metabolism of beclomethasone propionate esters in the homogenates of human lung and liver, whole blood and plasma in vitro. Annual Scientific Meeting of Thoracic Society of Australia and New Zealand; 1999 26 Feb-03 Mar; Canberra

  22. Agertoft L, Pedersen S, Harrison L. Lung deposition and basic pharmacokinetic parameters of beclomethasone dipropionate in asthmatic children after inhalation from a HFA-pMDI (Autohaler) and a CFC-pMDI with spacer [abstract]. Am J Respir Crit Care Med 1999; 159(Pt 2): A120

    Google Scholar 

  23. Harrison LI, Purrington A, Leitch C, et al. Beneficial effects of reduced particle size of CFC-free extrafine aerosol steroid on lung deposition, absorption, efficacy and safety [abstract]. Am J Respir Crit Care Med 1997; 155Suppl.: A666

    Google Scholar 

  24. Lipworth B. Pharmacokinetics of inhaled drugs. Br J Clin Pharmacol 1996; 42; 697–705

    Article  PubMed  CAS  Google Scholar 

  25. Thorsson L, Edsbacker S, Conradson TB. Lung deposition of budesonide from turbuhaler is twice that from a pressurised metered dose inhaler. Eur Respir J 1994; 7: 1839–44

    Article  PubMed  CAS  Google Scholar 

  26. Dempsey OJ, Coutie WR, Wilson AM, et al. Evaluation of the buccal component of systemic absorption with inhaled fluticasone propionate. Thorax 1999; 54: 614–7

    Article  PubMed  CAS  Google Scholar 

  27. Toogood JH, Baskerville J, Jennings B, et al. Use of spacers to facilitate inhaled corticosteroid treatment of asthma. Am Rev Respir Dis 1984; 129: 723–9

    PubMed  CAS  Google Scholar 

  28. Dempsey OJ, Wilson AM, Coutie WJ, et al. Evaluation and effect of a large volume spacer on the systemic bioactivity of fluticasone propionate and metered dose inhaler. Chest 1999; 116: 935–40

    Article  PubMed  CAS  Google Scholar 

  29. Wilson AM, Dempsey OJ, Coutie WJ, et al. Importance of drug-device interaction in determining systemic effects of inhaled corticosteroids [letter]. Lancet 1999; 353: 2128

    Article  PubMed  CAS  Google Scholar 

  30. Olsson B. Aerosol particle generation from dry-powder inhalers - can they equal pressurized metered dose inhalers? J Aerosol Med 1995; 8(3): S13–S19

    Article  PubMed  Google Scholar 

  31. Berg E. In vitro properties of pressurised metered dose inhalers with or without spacers. J Aerosol Med 1995; 8(3): S3–S11

    Article  PubMed  Google Scholar 

  32. Dempsey OJ, Humphries M, Coutie WJR, et al. Relative lung bioavailability of fluticasone propionate via large volume spacer or nebuliser in healthy volunteers [abstract]. Am J Respir Crit Care Med 2000; 161(3): A36

    Google Scholar 

  33. Meijer RJ, Kirstjens H, Arends LR, et al. Effects of inhaled fluticasone and oral prednisolone on clinical and inflammatory parameters in patients with asthma. Thorax 1999; 54: 894–9

    Article  PubMed  CAS  Google Scholar 

  34. Lipworth BJ. Therapeutic ratio of inhaled fluticasone. Thorax 2000; 55(3): 252–3

    Article  PubMed  CAS  Google Scholar 

  35. Edsbacker S, Kallen A. Differences in bioavailability of fluticasone propionate via dry powder inhaler and PMDI [abstract]. Eur Respir J 1999; 14Suppl. 30: 62S

    Google Scholar 

  36. Clark DJ, Lipworth BJ. Adrenal suppression with chronic dosing of fluticasone propionate compared with budesonide in adult asthmatic patients. Thorax 1997; 52: 55–8

    Article  PubMed  CAS  Google Scholar 

  37. Donnelly R, Williams KM, Baker B, et al. Effects of budesonide and fluticasone on 24 hour plasma cortisol: a dose response study. Am J Respir Crit Care Med 1997; 156: 1746–51

    PubMed  CAS  Google Scholar 

  38. Grahnen A, Jansson B, Brunden RM, et al. A dose response study comparing suppression of plasma cortisol induced by fluticasone propionate from Diskhaler and budesonide from turbuhaler. Eur J Clin Pharmacol 1997; 52: 261–7

    Article  PubMed  CAS  Google Scholar 

  39. Derom E, Van Schoor J, Verhaeghe W, et al. Systemic effects of inhaled fluticasone propionate and budesonide in adult patients with asthma. Am J Respir Crit Care Med 1999; 160: 157–61

    PubMed  CAS  Google Scholar 

  40. Wilson AM, Sims EJ, Orr LC, et al. Differences in lung bioavailability between different propellants for fluticasone propionate. Lancet 1999; 354: 1357–8

    Article  PubMed  CAS  Google Scholar 

  41. Wilson AM, McFarlane LC, Lipworth BJ. Effects of low and high doses of inhaled flunisolide and triamcinolone acetonide on basal and dynamic measures of adrenocortical activity in healthy volunteers. J Clin Endocrinol Metab 1998; 83: 922–5

    Article  PubMed  CAS  Google Scholar 

  42. Wilson AM, McFarlane LC, Lipworth BJ. Dose response effect for adrenal suppression with repeated twice daily inhaled fluticasone propionate and triamcinolone acetonide in adult asthmatics. Am J Respir Crit Care Med 1997; 156: 1274–7

    PubMed  CAS  Google Scholar 

  43. Weiner P, Berar-Yanay N, Davidovich A, et al. Nocturnal cortisol secretion in asthmatic patients after inhalation of fluticasone propionate. Chest 1999; 116(4): 931–4

    Article  PubMed  CAS  Google Scholar 

  44. Brutshe MH, Brutshe IC, Munavvar M, et al. Pharmacokinetics and systemic effects of inhaled fluticasone propionate are different in asthmatics and normal volunteers [abstract]. Eur Respir J 1999; 40Suppl. 30: 345S

    Google Scholar 

  45. Lofdahl GG, Thorsson L. Systemic availability of inhaled fluticasone propionate and budesonide in asthmatic patients and healthy subjects [abstract]. Eur Respir J 1999; 40Suppl. 30: 466S

    Google Scholar 

  46. Harrison TW, Wisniewski A, Honor JW, et al. Systemic activity of inhaled fluticasone propionate and budesonide in subjects with or without asthma [abstract]. Eur Respir J 1999; 40Suppl. 30: 466S

    Google Scholar 

  47. Argenti D, Colligon I, Heald D, et al. Nasal mucosal inflammation has no effect on the absorption of intranasal triamcinolone acetonide. J Clin Pharmacol 1994; 34: 854–8

    PubMed  CAS  Google Scholar 

  48. Grieff L, Ahlstrom-Emanuelsson C, Svensson C, et al. Dose efficacy comparison of mometasone and budesonide aqueous nasal spray in seasonal allergic rhinitis [abstract]. Allergy 1999; 54Suppl. 52: 156

    Google Scholar 

  49. Day J, Carrillo T. Comparison of the efficacy of budesonide and fluticasone propionate aqueous spray for once daily treatment of perennial allergic rhinitis. J Allergy Clin Immunol 1998; 102: 902–8

    Article  PubMed  CAS  Google Scholar 

  50. Creticos P, Fireman P, Stettipane G, et al. Intranasal budesonide aqueous pump spray (Rhinocort Aqua) for the treatment of seasonal allergic rhinitis. Allergy Asthma Proc 1998; 19: 285–94

    Article  PubMed  CAS  Google Scholar 

  51. Thorsson L, Borga O, Edsbacker S. Systemic availability of budesonide after nasal administration of three different formulations: pressurized aerosol, aqueous pump spray, and powder. Br J Clin Pharmacol 1999; 47: 619–24

    Article  PubMed  CAS  Google Scholar 

  52. Thonoor CM, Padhi D, Herron J, et al. Bioavailability and metabolism of mometasone furoate following administration of dry powder inhaler and metered dose inhaler in healthy human volunteers [abstract]. Eur Respir J 1999; 40Suppl. 30: 196S

    Google Scholar 

  53. Nasonex Aqueous Nasal Spray. Product datasheet. Welwyn Garden City: Schering-Plough, 1999

  54. Affrime M, Kosogloo T, Thonoor M. Mometasone furoate administered by dry powder inhaler has minimal systemic effects [abstract]. Chest 1999; 116Suppl. 2: 298S

    Google Scholar 

  55. 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: 155–61

    Article  PubMed  CAS  Google Scholar 

  56. Yang TT, Li S, Wyka B, et al. Analysis of particle size distribution with the new mometasone furoate dry powder inhaler [abstract]. Eur Respir J 1999; 40Suppl. 30: 63S

    Google Scholar 

  57. Isogai M, Shimizu H, Esumi Y, et al. Binding finites on mometasone furoate and related compounds including its metabolites for the glucocorticoids receptor of rat skin tissue. J Steroid Biochem Molec Biol 1993; 44: 141–5

    Article  PubMed  CAS  Google Scholar 

  58. Affrime MB, Kosogloo T, Thonoor CM. Comparison of hypothalamic-pituitary-adrenal axis suppression by mometasone furoate with that by fluticasone propionate [abstract]. Eur Respir J 1999; 14Suppl. 3: 196S

    Google Scholar 

  59. Derendorf H, Hochhaus G, Rohatagi S. Pharmacokinetics of triamcinolone acetonide after intravenous, oral and inhaled administration. J Clin Pharmacol 1995; 35: 302–5

    PubMed  CAS  Google Scholar 

  60. Kallen A, Thorsson L. The elimination rate of fluticasone propionate is not governed by uptake rate from the airways [abstract]. Eur Respir J 1999; 40Suppl. 30: 197S

    Google Scholar 

  61. Falcoz Z, Kergy SM, Smith J, et al. Pharmacokinetics and systemic exposure of inhaled beclomethasone dipropionate [abstract]. Eur Respir J 1996; 9Suppl. 23: 162S

    Google Scholar 

  62. Daley-Yates PT, Konka RL, Shen YY, et al. The relative systemic exposure to fluticasone propionate and mometasone furoate administered as aqueous nasal spray in healthy subjects [abstract]. J Allergy Clin Immunol 2000; 105: S201

    Article  Google Scholar 

  63. Knutsson PU, Stierna P, Marcus C, et al. Effects of intranasal glucocorticoids on endogenous glucocorticoid peripheral and central function. J Endocrinol 1995; 144: 301–10

    Article  PubMed  CAS  Google Scholar 

  64. Nayak AS, Ellis MH, Gross GN, et al. The effects of triamcinolone acetonide aqueous nasal spray on adrenocortical function in children with allergic rhinitis. J Allergy Clin Immunol 1998; 101: 157–62

    Article  PubMed  CAS  Google Scholar 

  65. Toogood JH, Jennings B, Hodsman AB, et al. Effects of dose and dosing schedule of inhaled budesonide on bone turnover. J Allergy Clin Immunol 1991; 88(4): 572–80

    Article  PubMed  CAS  Google Scholar 

  66. Wilson AM, Clark DJ, Devlin MM, et al. Adrenocortical activity with repeated administration of one-daily inhaled fluticasone propionate and budesonide in asthmatic adults. Eur J Clin Pharmacol 1998; 53(5): 317–20

    Article  PubMed  CAS  Google Scholar 

  67. McIntyre DH, Mitchell CA, Bowler SD, et al. Measuring the systemic effects of inhaled beclomethasone: timed morning urine collections compared with 24 hour specimens. Thorax 1995; 51: 281–4

    Google Scholar 

  68. Wilson AM, Lipworth BJ. 24 hour and fractionated profiles of adrenocortical activity in asthmatic patients receiving inhaled and intranasal corticosteroids. Thorax 1999; 54: 20–6

    Article  PubMed  CAS  Google Scholar 

  69. Andersson O, Cassel TM, Gronneberg R, et al. In vivo modulation of glucocorticoid receptor mRNA by inhaled fluticasone propionate in bronchial mucosa and blood lymphocytes in subjects with mild asthma. J Allergy Clin Immunol 1999; 103: 595–600

    Article  PubMed  CAS  Google Scholar 

  70. Wilson AM, McFarlane LC, Lipworth BJ. Effects of repeated once daily dosing with three intranasal corticosteroids on basal and dynamic measures of hypothalamic-pituitary-adrenal axis activity. J Allergy Clin Immunol 1998; 101: 470–4

    Article  PubMed  CAS  Google Scholar 

  71. Wilson AM, McFarlane LC, Lipworth BJ. Effects of intranasal corticosteroid on adrenal, bone and blood markers of systemic activity in allergic rhinitis. J Allergy Clin Immunol 1998; 102: 598–604

    Article  PubMed  CAS  Google Scholar 

  72. Foresi A, Pelucchi A, Gherson G, et al. Once daily intranasal fluticasone propionate (200μg) reduces nasal symptoms and inflammation but also attenuates the increase in bronchial responsiveness during the pollen season in allergic rhinitis. J Allergy Clin Immunol 1996; 98: 274–82

    Article  PubMed  CAS  Google Scholar 

  73. Vargas R, Dockhorn RJ, Findlay SR, et al. Effect of fluticasone propionate aqueous nasal spray versus oral prednisone on hypothalamic-pituitary-adrenal-axis. J Allergy Clin Immunol 1998; 102: 191–7

    Article  PubMed  CAS  Google Scholar 

  74. Crowley S, Hindmarsh PC, Hownia P, et al. The use of low doses of ACTH in the investigation of adrenal function in man. J Endocrinol 1991; 30: 475–9

    Article  Google Scholar 

  75. Broide J, Soferman R, Kivity S, et al. Low dose adrenocorticotropin test reveals impaired adrenal function in patients taking inhaled corticosteroids. J Clin Endocrinol Metab 1995; 80: 1243–6

    Article  PubMed  CAS  Google Scholar 

  76. Kannisto S, Korppi M, Remes K, et al. Adrenal suppression evaluated by a low dose adrenocorticotropin test and growth in asthmatic children treated with inhaled steroids. J Clin Endocrinol Metab 2000; 85: 652–7

    Article  PubMed  CAS  Google Scholar 

  77. Gazis AG, Horner JJ, Page S, et al. The effect of topical nasal betamethasone drops for nasal polyposis on adrenal function [letter]. Clin Otolaryngol 1998; 23: 280

    Article  Google Scholar 

  78. Findlay CS, MacDonald JF, Geddes N, et al. Childhood Cushings’syndrome induced by betamethasone nose drops and repeat prescriptions. BMJ 1998; 317: 739–40

    Article  PubMed  CAS  Google Scholar 

  79. Zwaan CM, Odink RJI, Delemarre-van dewall II A, et al. Acute adrenal insufficiency after discontinuation of inhaled corticosteroid therapy. Lancet 1992; 340: 1289–90

    Article  PubMed  CAS  Google Scholar 

  80. Wong J, Black P. Acute adrenal insufficiency associated with high dose inhaled steroids [letter]. BMJ 1992: 304: 1415

    Article  PubMed  CAS  Google Scholar 

  81. Chalkley SM, Chisholm DJ. Cushings’ syndrome from an inhaled glucocorticoid. Med J Aust 1994; 160: 611–5

    PubMed  CAS  Google Scholar 

  82. Carrel AL, Somers S, Lemanske RF, et al. Hypoglycaemia and cortisol deficiency associated with low dose corticosteroid therapy for asthma. Paediatrics 1996; 97: 921–4

    CAS  Google Scholar 

  83. Zimmerman B, Gold M, Wherrett D, et al. Adrenal suppression in two patients with asthma treated with low doses of the inhaled steroid fluticasone propionate. J Allergy Clin Immunol 1998; 101: 425–6

    Article  PubMed  CAS  Google Scholar 

  84. Duplantier JE, Nelson RP, Morelle AR, et al. Hypothalamicpituitary-adrenal axis suppression associated with the use of inhaled fluticasone propionate. J Allergy Clin Immunol 1998; 102: 699–700

    Article  PubMed  CAS  Google Scholar 

  85. Wilson AM, Blumsohn A, Yung RT, et al. Asthma and Cushing’s syndrome. Chest 2000; 117: 593–4

    Article  PubMed  CAS  Google Scholar 

  86. Todd GRG, Wright D, Ryan M. Acute adrenal insufficiency in a patient with asthma after changing from fluticasone propionate to budesonide. J Allergy Clin Immunol 1999; 103: 956–7

    Article  PubMed  CAS  Google Scholar 

  87. Taylor AV, Laiprosert N, Zimmerman D, et al. Adrenal suppression is secondary to inhaled fluticasone propionate. Ann Allergy Asthma Immunol 1999; 83: 68–70

    Article  PubMed  CAS  Google Scholar 

  88. Todd G, Dunlop K, McNaboe J, et al. Growth and adrenal suppression in asthmatic children treated with high dose fluticasone propionate. Lancet 1996; 348: 27–9

    Article  PubMed  CAS  Google Scholar 

  89. Roy A, Le Blanc C, Paquete L, et al. Skin bruising in asthmatic subjects treated with high doses of inhaled steroids: frequency in association with adrenal function. Eur Respir J 1996; 9: 226–31

    Article  PubMed  CAS  Google Scholar 

  90. Agertoft L, Pedersen S. Final height of asthmatic children treated for 7-11 years with inhaled budesonide [abstract]. Am J Respir Crit Care Med 1998; 157: A711

    Google Scholar 

  91. Kallen B, Rydhstroem H, Aberg A. Congenital malformations after the use of inhaled budesonide in early pregnancy. Obstet Gynecol 1999; 93: 392–5

    Article  PubMed  CAS  Google Scholar 

  92. Wong CA, Walsh LJ, Smith CJP, et al. Inhaled corticosteroid use and bone mineral density in patients with asthma. Lancet 2000; 355: 1399–403

    Article  PubMed  CAS  Google Scholar 

  93. Lipworth BJ. Modern drug treatment of chronic asthma. BMJ 1999; 318: 380–4

    Article  PubMed  CAS  Google Scholar 

  94. Brannan MD, Seibeiling M, Cutler DL, et al. Lack of systemic activity with intranasal mometasone furoate [abstract]. J Allergy Clin Immunol 1996; 97(Pt 3): 198

    Article  Google Scholar 

  95. Brannan MD, Herron JM, Reidenberg P, et al. Lack of HPA-axis suppression following 36 days of intranasal mometasone furoate [abstract]. Ann Allergy Asthma Immunol 1997; 78: 154

    Google Scholar 

  96. Brannan MD, Herron JM, Affrime MB. Safety and tolerability of once daily mometasone furoate aqueous nasal spray in children. Clin Ther 1997; 19: 1330–9

    Article  PubMed  CAS  Google Scholar 

  97. Leach CL, Davidson PJ, Brodre AU. Improved airway targeting with the CFC-free HFA-beclomethasone metered dose inhaler compared with CFC-beclomethasone. Eur Respir J 1998; 12: 1346–53

    Article  PubMed  CAS  Google Scholar 

  98. Harrison L, Dahl D, Cline A, et al. Pharmacokinetics and dose proportionality of beclomethasone from three strengths of a CFC-free beclomethasone dipropionate metered dose inhaler. Biopharm Drug Dispos 1997; 18: 635–43

    Article  PubMed  CAS  Google Scholar 

  99. Busse WW, Brazinsky S, Jacobsen K, et al. Efficacy response of inhaled beclomethasone dipropionate in asthma is proportional to dose and is improved by formulation with a new propellant. J Allergy Clin Immunol 1999; 104: 1215–22

    Article  PubMed  CAS  Google Scholar 

  100. Lipworth BJ, Jackson CM. Pharmacokinetics of chlorofluorocarbons and hydrofluoroalkane metered dose inhaled formulations of beclomethasone dipropionate. Br J Clin Pharmacol 1999; 48: 866–88

    Article  PubMed  CAS  Google Scholar 

  101. Milanowski J, Qualtrough G, Perrin DL. Inhaled beclomethasone dipropionate (BDP) with non-CFC propellant (HFA134a) is equivalent to BDP-CFC for the treatment of asthma. Respir Med 1999; 93: 235–41

    Article  Google Scholar 

  102. Lipworth BJ, Jackson CM. Equivalence of hydrofluoroalkane (HFA) and chlorofluorocarbons (CFC) formulations of inhaled beclomethasone [letter]. Respir Med 2000; 94(2): 177

    Article  PubMed  CAS  Google Scholar 

  103. Davies R, Leech C, Lipworth BJ, et al. Asthma management with HFA-BDP (QVAR™). Hosp Med 1999; 60: 263–70

    PubMed  CAS  Google Scholar 

  104. Cripps AL, Munro AJ, Boles MG, et al. Pharmaceutical evaluation of a new HFA-based metered dose inhaler for fluticasone propionate. J Aerosol Med 1997; 10: PD 6–5

    Google Scholar 

  105. Johnsson M. Fluticasone propionate: pharmacokinetics and pharmacodynamic implications of different aerosol delivery systems. In: Byron P, Dalby R, Farr SJ, editors. Respiratory drug delivery VI. Buffalo Grove (IL): Interpharm Press, 1998: 61–70

    Google Scholar 

  106. Schenkel EJ, Skoner DP, Bronsky EA, et al. Absence of growth retardation in children with perennial allergic rhinitis after one year of treatment with mometasone furoate aqueous nasal spray. Pediatrics 2000; 105(2): E22

    Article  PubMed  CAS  Google Scholar 

  107. McCowan C, Neville RG, Thomas GE, et al. Effect of asthma and its treatment on growth: four year follow up of cohort of children from general practices in Tayside, Scotland. BMJ 1998; 316(7132): 668–72

    Article  PubMed  CAS  Google Scholar 

  108. 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 

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Acknowledgements

The Asthma and Allergy Research Group has received funding support for clinical studies, giving lectures and attending postgraduate meetings from Aventis, AstraZeneca, Schering-Plough, 3M Healthcare and Glaxo Wellcome, all of whom manufacture inhaled and/or intranasal corticosteroids.

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  1. Asthma and Allergy Research Group, Department of Clinical Pharmacology & Therapeutics, Ninewells Hospital and Medical School, University of Dundee, Dundee, DD1 9SY, Scotland, UK

    Brian J. Lipworth & Catherine M. Jackson

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Lipworth, B.J., Jackson, C.M. Safety of Inhaled and Intranasal Corticosteroids. Drug-Safety 23, 11–33 (2000). https://doi.org/10.2165/00002018-200023010-00002

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