Abstract
BACKGROUND: It has been suggested that inhaled corticosteroids may provide greater protection against constrictor stimuli that act indirectly such as exercise than those that act directly such as histamine. METHODS: The effects of six weeks treatment with inhaled budesonide (800 micrograms twice daily) on bronchial reactivity to histamine, exercise, and eucapnic voluntary hyperventilation of dry air were compared in a double blind, placebo controlled, non-crossover study in 40 subjects with asthma. Change in bronchial reactivity to histamine and eucapnic hyperventilation over the six weeks was measured as change in the provocative dose of histamine or dry air causing a 20% fall in FEV1 (PD20 histamine and PV20 eucapnic hyperventilation (EVH) of dry air); this was not possible for exercise because of the development of refractoriness. To enable the change in response to all three stimuli to be compared, the response (percent fall in FEV1) to a fixed dose was measured for all three challenge tests. RESULTS: After budesonide there was an increase in PD20 histamine from 0.48 to 2.81 mumol and in PV20 EVH from 364 to 639 litres, and a significant correlation between the changes in PD20 histamine and PV20 EVH (r = 0.63). The median percentage fall in FEV1 in response to eucapnic hyperventilation, exercise, and histamine was similar before budesonide (25.5%, 26.6%, and 24.5%); the reduction in the percentage fall in FEV1 with budesonide was also similar for the three challenges (18.9%, 17.5%, and 16.6%), and all differed significantly from the changes following placebo. There was a significant correlation between change in percentage fall in FEV1 after budesonide with the three stimuli (histamine v exercise: r = 0.48; histamine v eucapnic hyperventilation: r = 0.46; exercise v eucapnic hyperventilation: r = 0.63). CONCLUSION: The similar magnitude of change in bronchial reactivity to all three stimuli after budesonide and the within subject correlation obtained between these changes suggest that corticosteroids act by a common mechanism to protect against eucapnic hyperventilation, exercise, and histamine.
Full text
PDF





Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Anderson S. D. Recent advances in the understanding of exercise-induced asthma. Eur J Respir Dis Suppl. 1983;128(Pt 1):225–236. [PubMed] [Google Scholar]
- Anderson S. D., Schoeffel R. E. Respiratory heat and water loss during exercise in patients with asthma. Effect of repeated exercise challenge. Eur J Respir Dis. 1982 Sep;63(5):472–480. [PubMed] [Google Scholar]
- Bianco S., Vaghi A., Robuschi M., Pasargiklian M. Prevention of exercise-induced bronchoconstriction by inhaled frusemide. Lancet. 1988 Jul 30;2(8605):252–255. doi: 10.1016/s0140-6736(88)92540-8. [DOI] [PubMed] [Google Scholar]
- Breslin F. J., McFadden E. R., Jr, Ingram R. H., Jr The effects of cromolyn sodium on the airway response to hyperpnea and cold air in asthma. Am Rev Respir Dis. 1980 Jul;122(1):11–16. doi: 10.1164/arrd.1980.122.1.11. [DOI] [PubMed] [Google Scholar]
- Cochrane C. G. The enhancement of inflammatory injury. Am Rev Respir Dis. 1987 Jul;136(1):1–2. doi: 10.1164/ajrccm/136.1.1. [DOI] [PubMed] [Google Scholar]
- Dahl R., Johansson S. A. Importance of duration of treatment with inhaled budesonide on the immediate and late bronchial reaction. Eur J Respir Dis Suppl. 1982;122:167–175. [PubMed] [Google Scholar]
- De Baets F. M., Goeteyn M., Kerrebijn K. F. The effect of two months of treatment with inhaled budesonide on bronchial responsiveness to histamine and house-dust mite antigen in asthmatic children. Am Rev Respir Dis. 1990 Sep;142(3):581–586. doi: 10.1164/ajrccm/142.3.581. [DOI] [PubMed] [Google Scholar]
- Debelić M., Hertel G., König J. Double-blind crossover study comparing sodium cromoglycate, reproterol, reproterol plus sodium cromoglycate, and placebo in exercise-induced asthma. Ann Allergy. 1988 Jul;61(1):25–29. [PubMed] [Google Scholar]
- Dixon C. M., Ind P. W. Inhaled sodium metabisulphite induced bronchoconstriction: inhibition by nedocromil sodium and sodium cromoglycate. Br J Clin Pharmacol. 1990 Sep;30(3):371–376. doi: 10.1111/j.1365-2125.1990.tb03786.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Eggleston P. A., Guerrant J. L. A standardized method of evaluating exercise-induced asthma. J Allergy Clin Immunol. 1976 Sep;58(3):414–425. doi: 10.1016/0091-6749(76)90122-6. [DOI] [PubMed] [Google Scholar]
- Hartley J. P., Charles T. J., Seaton A. Betamethasone valerate inhalation and exercise-induced asthma in adults. Br J Dis Chest. 1977 Oct;71(4):253–258. [PubMed] [Google Scholar]
- Holgate S. T., Finnerty J. P. Antihistamines in asthma. J Allergy Clin Immunol. 1989 Feb;83(2 Pt 2):537–547. doi: 10.1016/0091-6749(89)90035-3. [DOI] [PubMed] [Google Scholar]
- James A. L., Paré P. D., Hogg J. C. The mechanics of airway narrowing in asthma. Am Rev Respir Dis. 1989 Jan;139(1):242–246. doi: 10.1164/ajrccm/139.1.242. [DOI] [PubMed] [Google Scholar]
- Juniper E. F., Kline P. A., Vanzieleghem M. A., Ramsdale E. H., O'Byrne P. M., Hargreave F. E. Effect of long-term treatment with an inhaled corticosteroid (budesonide) on airway hyperresponsiveness and clinical asthma in nonsteroid-dependent asthmatics. Am Rev Respir Dis. 1990 Oct;142(4):832–836. doi: 10.1164/ajrccm/142.4.832. [DOI] [PubMed] [Google Scholar]
- Kang B., Townley R. G., Lee C. K., Miller Kolotkin B. Bronchial reactivity to histamine before and after sodium cromoglycate in bronchial asthma. Br Med J. 1976 Apr 10;1(6014):867–870. doi: 10.1136/bmj.1.6014.867. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kraan J., Koëter G. H., vd Mark T. W., Sluiter H. J., de Vries K. Changes in bronchial hyperreactivity induced by 4 weeks of treatment with antiasthmatic drugs in patients with allergic asthma: a comparison between budesonide and terbutaline. J Allergy Clin Immunol. 1985 Oct;76(4):628–636. doi: 10.1016/0091-6749(85)90786-9. [DOI] [PubMed] [Google Scholar]
- Kraemer R., Sennhauser F., Reinhardt M. Effects of regular inhalation of beclomethasone dipropionate and sodium cromoglycate on bronchial hyperreactivity in asthmatic children. Acta Paediatr Scand. 1987 Jan;76(1):119–123. doi: 10.1111/j.1651-2227.1987.tb10426.x. [DOI] [PubMed] [Google Scholar]
- Lee T. H., Assoufi B. K., Kay A. B. The link between exercise, respiratory heat exchange, and the mast cell in bronchial asthma. Lancet. 1983 Mar 5;1(8323):520–522. doi: 10.1016/s0140-6736(83)92204-3. [DOI] [PubMed] [Google Scholar]
- Molema J., van Herwaarden C. L., Folgering H. T. Effects of long-term treatment with inhaled cromoglycate and budesonide on bronchial hyperresponsiveness in patients with allergic asthma. Eur Respir J. 1989 Apr;2(4):308–316. [PubMed] [Google Scholar]
- Nichol G. M., Alton E. W., Nix A., Geddes D. M., Chung K. F., Barnes P. J. Effect of inhaled furosemide on metabisulfite- and methacholine-induced bronchoconstriction and nasal potential difference in asthmatic subjects. Am Rev Respir Dis. 1990 Sep;142(3):576–580. doi: 10.1164/ajrccm/142.3.576. [DOI] [PubMed] [Google Scholar]
- O'Byrne P. M., Morris M., Roberts R., Hargreave F. E. Inhibition of the bronchial response to respiratory heat exchange by increasing doses of terbutaline sulphate. Thorax. 1982 Dec;37(12):913–917. doi: 10.1136/thx.37.12.913. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Phillips Y. Y., Jaeger J. J., Laube B. L., Rosenthal R. R. Eucapnic voluntary hyperventilation of compressed gas mixture. A simple system for bronchial challenge by respiratory heat loss. Am Rev Respir Dis. 1985 Jan;131(1):31–35. doi: 10.1164/arrd.1985.131.1.31. [DOI] [PubMed] [Google Scholar]
- Roche W. R., Beasley R., Williams J. H., Holgate S. T. Subepithelial fibrosis in the bronchi of asthmatics. Lancet. 1989 Mar 11;1(8637):520–524. doi: 10.1016/s0140-6736(89)90067-6. [DOI] [PubMed] [Google Scholar]
- Rossing T. H., Weiss J. W., Breslin F. J., Ingram R. H., Jr, McFadden E. R., Jr Effects of inhaled sympathomimetics on obstructive response to respiratory heat loss. J Appl Physiol Respir Environ Exerc Physiol. 1982 May;52(5):1119–1123. doi: 10.1152/jappl.1982.52.5.1119. [DOI] [PubMed] [Google Scholar]
- 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]
- Salome C. M., Schoeffel R. E., Woolcock A. J. Effect of aerosol and oral fenoterol on histamine and methacholine challenge in asthmatic subjects. Thorax. 1981 Aug;36(8):580–584. doi: 10.1136/thx.36.8.580. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sampson S. R., Vidruk E. H. Properties of 'irritant' receptors in canine lung. Respir Physiol. 1975 Oct;25(1):9–22. doi: 10.1016/0034-5687(75)90047-x. [DOI] [PubMed] [Google Scholar]
- Schoeffel R. E., Anderson S. D., Gillam I., Lindsay D. A. Multiple exercise and histamine challenge in asthmatic patients. Thorax. 1980 Mar;35(3):164–170. doi: 10.1136/thx.35.3.164. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tattersfield A. E. Effect of beta-agonists and anticholinergic drugs on bronchial reactivity. Am Rev Respir Dis. 1987 Oct;136(4 Pt 2):S64–S68. doi: 10.1164/ajrccm/136.4_Pt_2.S64. [DOI] [PubMed] [Google Scholar]
- Vathenen A. S., Knox A. J., Wisniewski A., Tattersfield A. E. Time course of change in bronchial reactivity with an inhaled corticosteroid in asthma. Am Rev Respir Dis. 1991 Jun;143(6):1317–1321. doi: 10.1164/ajrccm/143.6.1317. [DOI] [PubMed] [Google Scholar]
- Yan K., Salome C., Woolcock A. J. Rapid method for measurement of bronchial responsiveness. Thorax. 1983 Oct;38(10):760–765. doi: 10.1136/thx.38.10.760. [DOI] [PMC free article] [PubMed] [Google Scholar]
