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. 1992 Aug;47(8):616–621. doi: 10.1136/thx.47.8.616

Effects of corticosteroids on bronchodilator action in chronic obstructive lung disease.

J B Wempe 1, D S Postma 1, N Breederveld 1, E Kort 1, T W van der Mark 1, G H Koëter 1
PMCID: PMC463924  PMID: 1412119

Abstract

BACKGROUND: Short term treatment with corticosteroids does not usually reduce airflow limitation and airway responsiveness in patients with chronic obstructive lung disease. We investigated whether corticosteroids modulate the effects of inhaled salbutamol and ipratropium bromide. METHODS: Ten non-allergic subjects with stable disease were investigated; eight completed the randomised, double blind, three period cross over study. Treatment regimens consisted of 1.6 mg inhaled budesonide a day for three weeks, 40 mg oral prednisone a day for eight days, and placebo. After each period cumulative doubling doses of salbutamol, ipratropium, a combination of salbutamol and ipratropium, and placebo were administered on separate days until a plateau in FEV1 was reached. A histamine challenge was then performed. RESULTS: At the end of placebo treatment mean FEV1 was 55.5% predicted after inhaled placebo, 67.9% predicted after salbutamol and 64.0% predicted after ipratropium. Compared with the results after the placebo period the FEV1 with salbutamol increased by 0.7% predicted after treatment with budesonide and by 0.7% predicted after treatment with prednisone; the FEV1 with ipratropium increased by 0.7% predicted after budesonide and by 4.8% predicted after prednisone; none of these changes was significant. After placebo treatment the geometric mean PC20 was 0.55 mg/ml after placebo, 1.71 mg/ml after salbutamol and 0.97 mg/ml after ipratropium. Compared with the placebo period the PC20 with salbutamol was increased by 0.86 doubling concentrations after treatment with budesonide, and by 0.67 doubling concentrations after prednisone; the PC20 with ipratropium increased by 0.03 and 0.34 doubling concentrations after budesonide and after prednisone respectively compared with placebo; none of these changes was significant. CONCLUSIONS: In non-allergic subjects with chronic obstructive lung disease short term treatment with high doses of inhaled or oral corticosteroids does not modify the bronchodilator response to salbutamol or ipratropium or the protection provided by either drug against histamine. Salbutamol produces greater protection from histamine induced bronchoconstriction than ipratropium.

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Selected References

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  1. Auffarth B., Postma D. S., de Monchy J. G., van der Mark T. W., Boorsma M., Koëter G. H. Effects of inhaled budesonide on spirometric values, reversibility, airway responsiveness, and cough threshold in smokers with chronic obstructive lung disease. Thorax. 1991 May;46(5):372–377. doi: 10.1136/thx.46.5.372. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bandouvakis J., Cartier A., Roberts R., Ryan G., Hargreave F. E. The effect of ipratropium and fenoterol on methacholine-histamine-induced bronchoconstriction. Br J Dis Chest. 1981 Jul;75(3):295–305. doi: 10.1016/0007-0971(81)90009-7. [DOI] [PubMed] [Google Scholar]
  3. Britton J., Hanley S. P., Garrett H. V., Hadfield J. W., Tattersfield A. E. Dose related effects of salbutamol and ipratropium bromide on airway calibre and reactivity in subjects with asthma. Thorax. 1988 Apr;43(4):300–305. doi: 10.1136/thx.43.4.300. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Britton J., Tattersfield A. Comparison of cumulative and non-cumulative techniques to measure dose-response curves for beta agonists in patients with asthma. Thorax. 1984 Aug;39(8):597–599. doi: 10.1136/thx.39.8.597. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Cockcroft D. W., Killian D. N., Mellon J. J., Hargreave F. E. Bronchial reactivity to inhaled histamine: a method and clinical survey. Clin Allergy. 1977 May;7(3):235–243. doi: 10.1111/j.1365-2222.1977.tb01448.x. [DOI] [PubMed] [Google Scholar]
  6. Cockcroft D. W., Killian D. N., Mellon J. J., Hargreave F. E. Protective effect of drugs on histamine-induced asthma. Thorax. 1977 Aug;32(4):429–437. doi: 10.1136/thx.32.4.429. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Curzon P. G., Martin M. A., Cooke N. J., Muers M. F. Effect of oral prednisolone on response to salbutamol and ipratropium bromide aerosols in patients with chronic airflow obstruction. Thorax. 1983 Aug;38(8):601–604. doi: 10.1136/thx.38.8.601. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Easton J. G. Effect of an inhaled corticosteroid on methacholine airway reactivity. J Allergy Clin Immunol. 1981 May;67(5):388–390. doi: 10.1016/0091-6749(81)90084-1. [DOI] [PubMed] [Google Scholar]
  9. Easton P. A., Jadue C., Dhingra S., Anthonisen N. R. A comparison of the bronchodilating effects of a beta-2 adrenergic agent (albuterol) and an anticholinergic agent (ipratropium bromide), given by aerosol alone or in sequence. N Engl J Med. 1986 Sep 18;315(12):735–739. doi: 10.1056/NEJM198609183151205. [DOI] [PubMed] [Google Scholar]
  10. Eliasson O., Hoffman J., Trueb D., Frederick D., McCormick J. R. Corticosteroids in COPD. A clinical trial and reassessment of the literature. Chest. 1986 Apr;89(4):484–490. doi: 10.1378/chest.89.4.484. [DOI] [PubMed] [Google Scholar]
  11. Ellul-Micallef R., Fenech F. F. Effect of intravenous prednisolone in asthmatics with diminished adrenergic responsiveness. Lancet. 1975 Dec 27;2(7948):1269–1271. doi: 10.1016/s0140-6736(75)90608-x. [DOI] [PubMed] [Google Scholar]
  12. Engel T., Heinig J. H., Madsen O., Hansen M., Weeke E. R. A trial of inhaled budesonide on airway responsiveness in smokers with chronic bronchitis. Eur Respir J. 1989 Nov;2(10):935–939. [PubMed] [Google Scholar]
  13. Fraser C. M., Venter J. C. The synthesis of beta-adrenergic receptors in cultured human lung cells: induction by glucocorticoids. Biochem Biophys Res Commun. 1980 May 14;94(1):390–397. doi: 10.1016/s0006-291x(80)80233-6. [DOI] [PubMed] [Google Scholar]
  14. Grandordy B. M., Thomas V., de Lauture D., Marsac J. Cumulative dose-response curves for assessing combined effects of salbutamol and ipratropium bromide in chronic asthma. Eur Respir J. 1988 Jun;1(6):531–535. [PubMed] [Google Scholar]
  15. Harding S. M., Freedman S. A comparison of oral and inhaled steroids in patients with chronic airways obstruction: features determining response. Thorax. 1978 Apr;33(2):214–218. doi: 10.1136/thx.33.2.214. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Higgins B. G., Powell R. M., Cooper S., Tattersfield A. E. Effect of salbutamol and ipratropium bromide on airway calibre and bronchial reactivity in asthma and chronic bronchitis. Eur Respir J. 1991 Apr;4(4):415–420. [PubMed] [Google Scholar]
  17. Holgate S. T., Baldwin C. J., Tattersfield A. E. beta-adrenergic agonist resistance in normal human airways. Lancet. 1977 Aug 20;2(8034):375–377. doi: 10.1016/s0140-6736(77)90304-x. [DOI] [PubMed] [Google Scholar]
  18. Hui K. K., Conolly M. E., Tashkin D. P. Reversal of human lymphocyte beta-adrenoceptor desensitization by glucocorticoids. Clin Pharmacol Ther. 1982 Nov;32(5):566–571. doi: 10.1038/clpt.1982.204. [DOI] [PubMed] [Google Scholar]
  19. Jenkins C. R., Chow C. M., Fisher B. L., Marlin G. E. Comparison of ipratropium bromide and salbutamol by aerosolized solution. Aust N Z J Med. 1981 Oct;11(5):513–516. doi: 10.1111/j.1445-5994.1981.tb04621.x. [DOI] [PubMed] [Google Scholar]
  20. Kraan J., Koëter G. H., van der Mark T. W., Boorsma M., Kukler J., Sluiter H. J., De Vries K. Dosage and time effects of inhaled budesonide on bronchial hyperreactivity. Am Rev Respir Dis. 1988 Jan;137(1):44–48. doi: 10.1164/ajrccm/137.1.44. [DOI] [PubMed] [Google Scholar]
  21. Lightbody I. M., Ingram C. G., Legge J. S., Johnston R. N. Ipratropium bromide, salbutamol and prednisolone in bronchial asthma and chronic bronchitis. Br J Dis Chest. 1978 Jul;72(3):181–186. doi: 10.1016/0007-0971(78)90039-6. [DOI] [PubMed] [Google Scholar]
  22. Mendella L. A., Manfreda J., Warren C. P., Anthonisen N. R. Steroid response in stable chronic obstructive pulmonary disease. Ann Intern Med. 1982 Jan;96(1):17–21. doi: 10.7326/0003-4819-96-1-17. [DOI] [PubMed] [Google Scholar]
  23. Molema J., Lammers J. W., van Herwaarden C. L., Folgering H. T. Effects of inhaled beclomethasone dipropionate on beta 2-receptor function in the airways and adrenal responsiveness in bronchial asthma. Eur J Clin Pharmacol. 1988;34(6):577–583. doi: 10.1007/BF00615220. [DOI] [PubMed] [Google Scholar]
  24. Petrie G. R., Palmer K. N. Comparison of aerosol ipratropium bromide and salbutamol in chronic bronchitis and asthma. Br Med J. 1975 Feb 22;1(5955):430–432. doi: 10.1136/bmj.1.5955.430. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Ramsdale E. H., Morris M. M., Roberts R. S., Hargreave F. E. Bronchial responsiveness to methacholine in chronic bronchitis: relationship to airflow obstruction and cold air responsiveness. Thorax. 1984 Dec;39(12):912–918. doi: 10.1136/thx.39.12.912. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Ryan G., Latimer K. M., Juniper E. F., Roberts R. S., Hargreave F. E. Effect of beclomethasone dipropionate on bronchial responsiveness to histamine in controlled nonsteroid-dependent asthma. J Allergy Clin Immunol. 1985 Jan;75(1 Pt 1):25–30. doi: 10.1016/0091-6749(85)90007-7. [DOI] [PubMed] [Google Scholar]
  27. Shenfield G. M., Hodson M. E., Clarke S. W., Paterson J. W. Interaction of corticosteroids and catecholamines in the treatment of asthma. Thorax. 1975 Aug;30(4):430–435. doi: 10.1136/thx.30.4.430. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Shim C., Stover D. E., Williams M. H., Jr Response to corticosteroids in chronic bronchitis. J Allergy Clin Immunol. 1978 Dec;62(6):363–367. doi: 10.1016/0091-6749(78)90137-9. [DOI] [PubMed] [Google Scholar]
  29. Ullah M. I., Newman G. B., Saunders K. B. Influence of age on response to ipratropium and salbutamol in asthma. Thorax. 1981 Jul;36(7):523–529. doi: 10.1136/thx.36.7.523. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Wardman A. G., Simpson F. G., Knox A. J., Page R. L., Cooke N. J. The use of high dose inhaled beclomethasone dipropionate as a means of assessing steroid responsiveness in obstructive airways disease. Br J Dis Chest. 1988 Apr;82(2):168–171. doi: 10.1016/0007-0971(88)90038-1. [DOI] [PubMed] [Google Scholar]
  31. Webb J., Clark T. J., Chilvers C. Time course of response to prednisolone in chronic airflow obstruction. Thorax. 1981 Jan;36(1):18–21. doi: 10.1136/thx.36.1.18. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Weir D. C., Gove R. I., Robertson A. S., Burge P. S. Corticosteroid trials in non-asthmatic chronic airflow obstruction: a comparison of oral prednisolone and inhaled beclomethasone dipropionate. Thorax. 1990 Feb;45(2):112–117. doi: 10.1136/thx.45.2.112. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Weir D. C., Robertson A. S., Gove R. I., Burge P. S. Time course of response to oral and inhaled corticosteroids in non-asthmatic chronic airflow obstruction. Thorax. 1990 Feb;45(2):118–121. doi: 10.1136/thx.45.2.118. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Yan K., Salome C. M., Woolcock A. J. Prevalence and nature of bronchial hyperresponsiveness in subjects with chronic obstructive pulmonary disease. Am Rev Respir Dis. 1985 Jul;132(1):25–29. doi: 10.1164/arrd.1985.132.1.25. [DOI] [PubMed] [Google Scholar]

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