Glucocorticoids (Corticosteroids)

  • Christopher J. Corrigan
Chapter

Abstract

Inhaled glucocorticoids (GC) suppress the bronchial inflammation that is thought to underlie asthma and now form the mainstay of current antiasthma drug therapy (1). For the vast majority of patients with asthma, both adults and children, the benefits of this therapy substantially outweigh the risks. This chapter will consider clinical aspects of GC therapy, particularly inhaled therapy, for asthma, patterns of clinical response to GC therapy, GC-resistant asthma, and a summary of some of the mechanisms by which GC may exert their therapeutic effects.

Keywords

Fluticasone Propionate Allergy Clin Immunol cAMP Response Element Binding Beclomethasone Dipropionate Chronic Asthma 
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.

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References

  1. 1.
    National Heart und Lung and Blood Institute, National Institute of Health (1992) International consensus report on diagnosis and treatment of asthma. (Publication no. 92–3091). Eur Respir J 5: 601–641.Google Scholar
  2. 2.
    Summers QA (1991) Inhaled drugs and the lung. Clin Exp Allergy 21: 259–268.PubMedCrossRefGoogle Scholar
  3. 3.
    Newman SP, Moren F, Pavia D, Little F, Clarke SW (1981) Deposition of pressurized suspension aerosols inhaled through extension devices. Am Rev Respir Dis 124: 317–320.PubMedGoogle Scholar
  4. 4.
    Newhouse MT, Dolovich MB (1986) Control of asthma by aerosols. N Engl J Med 315: 870–874.PubMedCrossRefGoogle Scholar
  5. 5.
    Vidgren M, Paronen P, Vidgren P, Vainio P, Nuutinen J (1990) In vivo evaluation of the new multiple dose powder inhaler and the Rotahaler using gamma scintigraphy. Acta Pharm Nord 2: 3–10.PubMedGoogle Scholar
  6. 6.
    Barnes PJ (1989) A new approach to the treatment of asthma. N Engl J Med 321: 1517–1527.PubMedCrossRefGoogle Scholar
  7. 7.
    Wurthwein G, Rohdewald P (1990) Activation of beclomethasone dipropionate by hydrolysis to beclomethasone 17-monopropionate Biopharm Drug Dispos 11: 381–394.Google Scholar
  8. 8.
    Edsbacker S, Andersson P, Lindberg C, Ryrfeldt A, Thalen A (1987) Metabolic acetal splitting of budesonide. A novel inactivation pathway for topical glucocorticoids. Drug Metab Dispos 15: 412–417.Google Scholar
  9. 9.
    Harding SM (1990) The human pharmacology of fluticasone propionate. Respir Med 84 (Suppl A): 25–29.PubMedCrossRefGoogle Scholar
  10. 10.
    Barnes NC, Marone G, Di Maria GU, Visser S, Utama I, Payne SL (1993) A comparison of fluticasone propionate, 1 mg daily, with beclomethasone dipropionate, 2 mg daily, in the treatment of severe asthma. International study group. Eur Respir J 6: 877–885.Google Scholar
  11. 11.
    Toogood JH, Frankish CW, Jennings BH, Baskerville JC, Borga O, Lefcoe NM, Johansson SA (1990) A study of the mechanism of the antiasthmatic action of inhaled budesonide. J Allergy Clin Immunol 85: 872–880.PubMedCrossRefGoogle Scholar
  12. 12.
    Rafferty P, Tucker LG, Frame MH, Fergusson RI, Biggs BA, Crompton GK (1985) Comparison of budesonide and beclomethasone dipropionate in patients with severe chronic asthma: assessment of relative prednisolone-sparing effects. Br J Dis Chest 79: 244–250.PubMedCrossRefGoogle Scholar
  13. 13.
    Rosenhall L, Lundqvist G, Adelroth E, Glennow C (1982) Comparison between inhaled and oral corticosteroids in patients with chronic asthma. Eur J Respir Dis Suppl 122: 154–162.PubMedGoogle Scholar
  14. 14.
    Stiksa G, Glennow C (1985) Once daily inhalation of budesonide in the treatment of chronic asthma• a clinical comparison. Ann Allergy 55: 49–51.PubMedGoogle Scholar
  15. 15.
    Selroos O, Halme M (1991) Effect of a volumatic spacer and mouth rinsing on systemic absorption of inhaled corticosteroids from a metered dose inhaler and dry powder inhaler. Thorax 46: 891–894.PubMedCrossRefGoogle Scholar
  16. 16.
    Svendsen UG, Frolund L, Heinig JH, Madsen F, Nielsen NH, Weeke B (1992) High-dose inhaled steroids in the management of asthma. A comparison of the effects of budesonide and beclomethasone dipropionate on pulmonary function, symptoms, bronchial responsiveness and the adrenal function. Allergy 47 (2 pt 2): 174–180.PubMedCrossRefGoogle Scholar
  17. 17.
    Field HV, Jenkinson PM, Frame MH, Warner JO (1982) Asthma treatment with a new corticosteroid aerosol, budesonide, administered twice daily by spacer inhaler. Arch Dis Child 57: 864–866.PubMedCrossRefGoogle Scholar
  18. 18.
    Springer C, Avital A, Maayan C, Rosler A, Godfrey S (1987) Comparison of budesonide and beclomethasone dipropionate for treatment of asthma. Arch Dis Child 62: 815–819.PubMedCrossRefGoogle Scholar
  19. 19.
    Langdon CG, Capsey LJ (1994) Fluticasone propionate and budesonide in adult asthmatics: a comparison using dry-powder inhaler devices. Br J Clin Res 5: 85–99.Google Scholar
  20. 20.
    Langdon CG, Thompson J (1994) A multicentre study to compare the efficacy and safety of inhaled fluticasone propionate and budesonide via metered-dose inhalers in adults with mild to moderate asthma. Br J Clin Res 5: 73–84.Google Scholar
  21. 21.
    Leblanc P, Mink S, Keistinen T, Saarelainen PA, Ringdal N, Payne SL (1994) A comparison of fluticasone propionate 200 µg/day with beclomethasone 400 pg/day in adult asthma. Allergy 49: 380–385.PubMedCrossRefGoogle Scholar
  22. 22.
    Fabbri L, Burge PS, Croonenborgh L, Warlies F, Weeke B, Ciaccia A, Parker C (1993) Comparison of fluticasone propionate with beclomethasone dipropionate in moderate to severe asthma treated for one year. Thorax 48: 817–823.PubMedCrossRefGoogle Scholar
  23. 23.
    Mackenzie CA, Tsanakas J, Tabachnik E, Radford M, Berdel D, Gotz MH, Parker C (1994) An open study to assess the long term safety of fluticasone propionate in asthmatic children. Br J Clin Pract 48: 15–18.PubMedGoogle Scholar
  24. 24.
    Peretz A, Bourdoux PP (1991) Inhaled corticosteroids, bone formation, and osteocalcin. Lancet 338: 1340.PubMedCrossRefGoogle Scholar
  25. 25.
    Sorva R, Turpeinen M, Juntunen-Backman K, Karonen SL, Sorva A (1992) Effects of inhaled budesonide on serum markers of bone metabolism in children with asthma. J Allergy Clin Immunol 90: 808–815.PubMedCrossRefGoogle Scholar
  26. 26.
    Jennings BH, Andersson KE, Johansson SA (1991) The assessment of the systemic effects of inhaled glucocorticosteroids. The effects of inhaled budesonide vs oral prednisolone on calcium metabolism Eur J Clin Pharmacol 41: 11–16.Google Scholar
  27. 27.
    Toogood JH, Jennings B, Hodsman AB, Baskerville J, Fraher LJ (1991) Effects of dose and dosing schedule of inhaled budesonide on bone turnover. J Allergy Clin Immunol 88: 572–580.PubMedCrossRefGoogle Scholar
  28. 28.
    Leech JA, Hodder RV, Ooi DS, Gay J (1993) Effects of short-term inhaled budesonide and beclomethasone dipropionate on serum osteocalcin in premenopausal women. Am Rev Respir Dis 148: 113–115.PubMedGoogle Scholar
  29. 29.
    Balfour-Lynn L (1986) Growth and childhood asthma. Arch Dis Child 61: 1049–1055.PubMedCrossRefGoogle Scholar
  30. 30.
    Varsano I, Volovitz B, Malik H, Amir Y (1990) Safety of 1 year of treatment with budesonide in young children with asthma. J Allergy Clin Immunol 85: 914–920.PubMedCrossRefGoogle Scholar
  31. 31.
    Wolthers OD, Pedersen S (1992) Controlled study of linear growth in asthmatic children during treatment with inhaled glucocorticosteroids. Paediatrics 89: 839–842.Google Scholar
  32. 32.
    Nassif E, Weinberger M, Sherman B, Brown K (1987) Extrapulmonary effects of maintenance corticosteroid therapy with alternate-day prednisone and inhaled beclomethasone in children with chronic asthma. J Allergy Clin Immunol 80: 518–529.PubMedCrossRefGoogle Scholar
  33. 33.
    Turner-Warwick M (1977) On observing patterns of airflow obstruction in chronic asthma. Br J Dis Chest 71: 73–86.PubMedCrossRefGoogle Scholar
  34. 34.
    Clark TJH, Hetzel MR (1977) Diurnal variation of asthma. Br J Dis Chest 71: 87–92.PubMedCrossRefGoogle Scholar
  35. 35.
    Webb JR (1986) Dose response of patients to oral corticosteroid treatment during exacerbations of asthma. Br Med J 292: 1045–1047.CrossRefGoogle Scholar
  36. 36.
    Kamada AK, Leung DYM, Gleason MC, Hill MR, Stefler SJ (1992) High dose systemic glucocorticoid therapy in the treatment of asthma: a case of resistance and patterns. J Allergy Clin Immunol 90: 685–687.PubMedCrossRefGoogle Scholar
  37. 37.
    Woolcock AJ (1993) Steroid resistant asthma: what is the clinical definition? Eur Respir J 6: 743–747.PubMedGoogle Scholar
  38. 38.
    Corrigan CJ, Kay AB (1992) The role of T lymphocytes and eosinophils in the pathogenesis of asthma. Immunol Today 13: 501–507.PubMedCrossRefGoogle Scholar
  39. 39.
    Azzawi M, Bradley B, Jeffery PK, Frew M, Wardlaw AJ, Knowles G, Assoufi B, Collins JV, Durham SR, Kay AB (1990) Identification of activated T lymphocytes and eosinophils in bronchial biopsies in stable atopic asthma. Am Rev Respir Dis 142: 1410–1413.Google Scholar
  40. 40.
    Jeffery PK, Wardlaw AJ, Nelson FC, Collins JV, Kay AB (1989) Bronchial biopsies in asthma: an ultra-structural, quantitative study and correlation with hyperreactivity. Am Rev Respir Dis 140: 1745–1753.PubMedCrossRefGoogle Scholar
  41. 41.
    Bradley BL, Azzawi M, Assoufi B, Jacobson M, Collins JV, Irani A, Schwartz LB, Durham SR, Jeffery PK, Kay AB. (1991) Eosinophils, T-lymphocytes, mast cells, neutrophils and macrophages in bronchial biopsies from atopic asthmatics: comparison with atopic non-asthma and normal controls and relationship to bronchial hyperresponsiveness. J Allergy Clin Immunol 88: 661–674.PubMedCrossRefGoogle Scholar
  42. 42.
    Bentley AM, Maestrelli P, Saetta M, Fabbri LM, Robinson DR, Bradley BL, Jeffery PK, Durham SR, Kay AB (1992) Activated T-lymphocytes and eosinophils in the bronchial mucosa in isocyanate-induced asthma. J Allergy Clin Immunol 89: 821–829.PubMedCrossRefGoogle Scholar
  43. 43.
    Bentley AM, Menz G, Storz C, Robinson DR, Bradley B, Jeffery PK, Durham SR, Kay AB (1992) Identification of T-lymphocytes, macrophages and activated eosinophils in the bronchial mucosa in intrinsic asthma relationship to symptoms and bronchial responsiveness. Am Rev Respir Dis 146: 500–506.PubMedGoogle Scholar
  44. 44.
    Corrigan CJ, Hartnell A, Kay AB (1988) T-lymphocyte activation in acute severe asthma. Lancet i: 1129–1131.Google Scholar
  45. 45.
    Corrigan CJ, Kay AB (1990) CD4 T-lymphocyte activation in acute severe asthma. Relationship to disease severity and atopic status. Am Rev Respir Dis 141: 970–977.Google Scholar
  46. 46.
    Corrigan CJ, Haczku A, Gemou-Engesaeth V, Doi S, Kikuchi Y, Takatsu K, Durham SR, Kay AB (1993) CD4 T-lymphocyte activation in asthma is accompanied by increased concentrations of interleukin-5: effect of glucocorticoid therapy. Am Rev Respir Dis 147: 540–547.PubMedGoogle Scholar
  47. 47.
    Alexander AG, Barkans J, Moqbel R, Barnes NC, Kay AB, Corrigan CJ (1994) Serum interleukin-5 concentrations in atopic and non-atopic patients with glucocorticoid-dependent chronic severe asthma. Thorax 49: 1231–1233.PubMedCrossRefGoogle Scholar
  48. 48.
    Doi S, Gemou-Engesaeth V, Kay AB, Corrigan CJ (1994) Polymerase chain reaction quantification of cytokine messenger RNA expression in peripheral blood mononuclear cells of patients with severe asthma: effect of glucocorticoid therapy. Clin Exp Allergy 24: 854–687.PubMedCrossRefGoogle Scholar
  49. 49.
    Hamid Q, Azzawi M, Ying S, Moqbel R, Wardlaw AJ, Corrigan CJ, Bradley B, Durham SR, Collins JV, Jeffery PK, Quint DJ, Kay AB (1991) Expression of mRNA for interleukin-5 in mucosal bronchial biopsies from asthma. J Clin Invest 87: 1541–1546.PubMedCrossRefGoogle Scholar
  50. 50.
    Robinson DS, Hamid Q, Ying S, Tsicopoulos A, Barkans J, Bentley AM, Corrigan C, Durham SR, Kay AB (1992) Evidence for a predominant “Th2-type” bronchoalveolar lavage T-lymphocyte population in atopic asthma. N Engl J Med 326: 298–304.PubMedCrossRefGoogle Scholar
  51. 51.
    Ying S, Durham SR, Corrigan CJ, Hamid Q, Kay AB (1995) Phenotype of cells expressing mRNA for Th2-type (interleukin-4 and interleukin-5) and Thl-type (interleukin-2 and interferon-gamma) cytokines in bronchoalveolar lavage and bronchial biopsies from atopic asthmatics and normal control subjects. Am J Respir Cell Mol Biol 12: 477–487.PubMedGoogle Scholar
  52. 52.
    Robinson DS, Ying S, Bentley AM, Meng Q, North J, Durham SR, Kay AB (1993) Relationships among numbers of bronchoalveolar lavage cells expressing messenger ribonucleic acid for cytokines, asthma symptoms, and airway methacholine responsiveness in atopic asthma. J Allergy Clin Immunol 92: 397–403.PubMedCrossRefGoogle Scholar
  53. 53.
    Corrigan CJ, Hamid Q, North J, Barkans J, Moqbel R, Durham SR, Kay AB (1995) Peripheral blood CD4, but not CD8 T-lymphocytes in patients with exacerbation of asthma transcribe and translate messenger RNA encoding cytokines which prolong eosinophil survival in the context of a TH2-type pattern: effect of glucocorticoid therapy. Am J Respir Cell Mol Biol 12: 567–578.PubMedGoogle Scholar
  54. 54.
    Robinson DS, Hamid Q, Ying S, Bentley AM, Assoufi B, North J, Meng Q, Durham SR, Kay AB (1993) Prednisolone treatment in asthma is associated with modulation of bronchoalveolar lavage cell interleukin-4, interleukin-5 and interferon-gamma cytokine gene expression. Am Rev Respir Dis 148: 420–406.Google Scholar
  55. 55.
    Bentley AM, Meng Q, Robinson DS, Hamid Q, Kay AB, Durham SR (1993) Increases in activated T-lymphocytes, eosinophils and cytokine messenger RNA for IL-5 and GM-CSF in bronchial biopsies after allergen inhalation challenge in atopic asthmatics. Am J Respir Cell Mol Biol 8: 35–42.PubMedGoogle Scholar
  56. 56.
    Schwartz HL, Lowell FC, Melby JC (1968) Steroid resistance in bronchial asthma. Ann Intern Med 69: 493–499.PubMedGoogle Scholar
  57. 57.
    Carmichael J, Paterson IC, Diaz P, Crompton GK, Kay AB, Grant IWB (1981) Corticosteroid resistance in chronic asthma. Br Med J 282: 1419–1422.CrossRefGoogle Scholar
  58. 58.
    Kamada AK, Leung DY, Szefler SJ (1992) Steroid resistance in asthma• our current understanding. Pediatr Pulmonol 14: 180–186.PubMedCrossRefGoogle Scholar
  59. 59.
    Alvarez J, Surs W, Leung DYM, Iklé D, Gelfand EW, Szefler SJ (1992) Steroid resistant asthma: immunologic and phannacologic features. J Allergy Clin Immunol 89: 714–721.PubMedCrossRefGoogle Scholar
  60. 60.
    Kamada AK, Szefler SJ, Leung DYM (1993) The growing problem of steroid resistant asthma. Drug Ther 23: 55–68.Google Scholar
  61. 61.
    Poznansky MC, Gordon ACH, Douglas JG, Krajewski AS, Wyllie AH, Grant IWB (1984) Resistance to methylprednisolone in cultures of blood mononuclear cells from glucocorticoid-resistant asthmatic patients. Clin Sci 67: 639–645.PubMedGoogle Scholar
  62. 62.
    Corrigan CJ, Brown PH, Barnes NC, Szefler SJ, Tsai JJ, Frew AJ, Kay AB (1991) Glucocorticoid resistance in chronic asthma: glucocorticoid pharmacokinetics, glucocorticoid receptor characteristics and inhibition of peripheral blood T-cell proliferation by glucocorticoids in vitro. Am Rev Respir Dis 144: 1016–1025.PubMedCrossRefGoogle Scholar
  63. 63.
    Corrigan CJ, Brown PH, Barnes NC, Tsai JJ, Kay AB (1991) Glucocorticoid resistance in chronic asthma: peripheral blood T-lymphocyte activation and a comparison of the T-lymphocyte inhibitory effects of glucocorticoids and cyclosporin A. Am Rev Respir Dis 144: 1026–1032.PubMedCrossRefGoogle Scholar
  64. 64.
    Kamada AK, Spahn JD, Surs W, Brown E, Leung DY, Szefler SJ (1994) Coexistence of glucocorticoid receptor and pharmacokinetic abnormalities: factors that contribute to a poor response to treatment with glucocorticoids in children with asthma. J Pediatr 124: 984–986.PubMedCrossRefGoogle Scholar
  65. 65.
    Haczku A, Alexander A, Brown P, Assoufi B, Li B, Kay AB, Corrigan C (1994) The effect of dexamethasone, cyclosporine and rapamycin on T-lymphocyte proliferation in vitro: comparison of cells from patients with glucocorticoid-sensitive and glucocorticoid-resistant chronic asthma. J Allergy Clin Immunol 93: 510–519.PubMedCrossRefGoogle Scholar
  66. 66.
    Alexander AG, Barnes NC, Kay AB (1992) Trial of cyclosporin in corticosteroid-dependent chronic severe asthma. Lancet 339: 324–328.PubMedCrossRefGoogle Scholar
  67. 67.
    Leung DY, Martin RJ, Szefler SJ, Sher ER, Ying S, Kay AB, Hamid Q (1995) Dysregulation of inter-leukin 4, interleukin 5 and interferon gamma gene expression in steroid-resistant asthma. J Exp Med 181: 33–40.PubMedCrossRefGoogle Scholar
  68. 68.
    Spahn JD, Leung DY, Surs W, Harbeck RJ, Nimmagadda S, Szefler SJ (1995) Reduced glucocorticoid binding affinity in asthma is related to ongoing allergic inflammation. Am J Respir Crit Care Med 151: 1709–1714.PubMedGoogle Scholar
  69. 69.
    Sher ER, Leung DM, Surs W, Kam JC, Zieg G, Kamada AK, Szefler SJ (1994) Steroid-resistant asthma cellular mechanisms contributing to inadequate response to glucocorticoid therapy. J Clin Invest 93: 33–39.PubMedCrossRefGoogle Scholar
  70. 70.
    Kam JC, Szefler SJ, Surs W, Sher ER, Leung DY (1993) Combination IL-2 and IL-4 reduces glucocorticoid receptor-binding affinity and T cell response to glucocorticoids. J Immunol 151: 3460–3466.PubMedGoogle Scholar
  71. 71.
    Lane SJ, Arm JP, Staynov DZ, Lee TH (1994) Chemical mutational analysis of the human glucocorticoid receptor cDNA in glucocorticoid-resistant bronchial asthma. Am J Respir Cell Mol Biol 11: 42–48.PubMedGoogle Scholar
  72. 72.
    Adcock IM, Lane SJ, Brown CR, Peters MJ, Lee TH, Barnes PJ (1995) Differences in binding of glucocorticoid receptor to DNA in steroid-resistant asthma. J Immunol 154: 3500–3505.PubMedGoogle Scholar
  73. 73.
    Brown PH, Teelucksingh S, Matusiewicz SP, Greening AP, Crompton GK, Edwards CR (1991) Cutaneous vasoconstrictor response to glucocorticoids in asthma. Lancet 337: 576–580.PubMedCrossRefGoogle Scholar
  74. 74.
    Beato M (1989) Gene regulation by steroid hormones. Cell 56: 335–344.PubMedCrossRefGoogle Scholar
  75. 75.
    Kishimoto T, Taga T, Akira S (1994) Cytokine signal transduction. Cell 76: 253–262.PubMedCrossRefGoogle Scholar
  76. 76.
    Latchman DS (1990) Eukaryotic transcription factors. Biochem J 270: 281–289.PubMedGoogle Scholar
  77. 77.
    Yang-Yen HF, Chambard JC, Sun Y-L, Smeal T, Schmidt TJ, Drouin J, Karin M (1990) Transcriptional interference between c-Jun and the glucocorticoid receptor: mutual inhibition of DNA binding due to direct protein-protein interaction. Cell 62: 1205–1215.PubMedCrossRefGoogle Scholar
  78. 78.
    Barnes PJ, Adcock IM (1993) Anti-inflammatory actions of steroids: molecular mechanisms. Trends Pharmacol Sci 14: 436 141.Google Scholar
  79. 79.
    Yamamoto KK, Gonzalez GA, Biggs WH, Montminy MR (1989) Phosphorylation-induced binding and transcriptional efficacy of nuclear factor CREB. Nature 334: 494–498.CrossRefGoogle Scholar
  80. 80.
    Masquilier D, Sassone-Corsi P (1992) Transcriptional cross-talk: nuclear factors CREM and CREB bind to AP-1 sites and inhibit activation by Jun. J Biol Chem 267:22, 460–22, 466.Google Scholar

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© Springer Science+Business Media New York 1998

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  • Christopher J. Corrigan

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