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. 1988 Apr;43(4):300–305. doi: 10.1136/thx.43.4.300

Dose related effects of salbutamol and ipratropium bromide on airway calibre and reactivity in subjects with asthma.

J Britton 1, S P Hanley 1, H V Garrett 1, J W Hadfield 1, A E Tattersfield 1
PMCID: PMC461217  PMID: 2970125

Abstract

The relationship between change in airway calibre and change in airway reactivity after administration of bronchodilator drugs has been investigated by comparing the effect of increasing doses of inhaled salbutamol and ipratropium bromide on the forced expiratory volume in one second (FEV1), specific airways conductance (sGaw), and the dose of histamine causing a 20% fall in FEV1 (PD20) in six subjects with mild asthma. On each of 10 occasions measurements were made of baseline FEV1, sGaw, and PD20 after 15 minutes' rest, and followed one hour later, when the FEV1 had returned to baseline, by a single nebulised dose of salbutamol (placebo, 5, 30, 200 and 1000 micrograms) or ipratropium (placebo, 5, 30, 200 and 1000 micrograms) given in random order. Measurements of FEV1, sGaw, and PD20 were repeated 15 minutes after salbutamol and 40 minutes after ipratropium. Salbutamol and ipratropium caused a similar dose related increase in FEV1 and sGaw, with a mean increase after the highest doses of 0.76 and 0.69 litres for FEV1 and 1.15 and 0.96 s-1 kPa-1 for sGaw. Salbutamol also caused a dose related increase in PD20 to a maximum of 2.87 (95% confidence interval 2.18-3.55) doubling doses of histamine after the 1000 micrograms dose, but ipratropium bromide caused no significant change in PD20 (maximum increase 0.24 doubling doses, 95% confidence interval -0.73 to 1.22). Thus bronchodilatation after salbutamol was associated with a significantly greater change in airway reactivity than a similar amount of bronchodilatation after ipratropium bromide. This study shows that the relation between change in airway reactivity and bronchodilatation is different for two drugs with different mechanisms of action, suggesting that change in airway calibre is not a major determinant of change in airway reactivity with bronchodilator drugs.

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Selected References

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  1. Ahrens R. C., Harris J. B., Milavetz G., Annis L., Ries R. Use of bronchial provocation with histamine to compare the pharmacodynamics of inhaled albuterol and metaproterenol in patients with asthma. J Allergy Clin Immunol. 1987 Jun;79(6):876–882. doi: 10.1016/0091-6749(87)90235-1. [DOI] [PubMed] [Google Scholar]
  2. Bahous J., Cartier A., Ouimet G., Pineau L., Malo J. L. Nonallergic bronchial hyperexcitability in chronic bronchitis. Am Rev Respir Dis. 1984 Feb;129(2):216–220. [PubMed] [Google Scholar]
  3. Barnes P. J. Neural control of human airways in health and disease. Am Rev Respir Dis. 1986 Dec;134(6):1289–1314. doi: 10.1164/arrd.1986.134.5.1289. [DOI] [PubMed] [Google Scholar]
  4. Beasley C. R., Rafferty P., Holgate S. T. Bronchoconstrictor properties of preservatives in ipratropium bromide (Atrovent) nebuliser solution. Br Med J (Clin Res Ed) 1987 May 9;294(6581):1197–1198. doi: 10.1136/bmj.294.6581.1197-a. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Benson M. K. Bronchial hyperreactivity. Br J Dis Chest. 1975 Oct;69(0):227–239. doi: 10.1016/0007-0971(75)90090-x. [DOI] [PubMed] [Google Scholar]
  6. Casterline C. L., Evans R., 3rd, Ward G. W., Jr The effect of atropine and albuterol aerosols on the human bronchial response to histamine. J Allergy Clin Immunol. 1976 Nov;58(5):607–613. doi: 10.1016/0091-6749(76)90207-4. [DOI] [PubMed] [Google Scholar]
  7. Casterline C. L., Evans R., 3rd, Ward G. W., Jr The effect of atropine and albuterol aerosols on the human bronchial response to histamine. J Allergy Clin Immunol. 1976 Nov;58(5):607–613. doi: 10.1016/0091-6749(76)90207-4. [DOI] [PubMed] [Google Scholar]
  8. Chung K. F., Morgan B., Keyes S. J., Snashall P. D. Histamine dose-response relationships in normal and asthmatic subjects. The importance of starting airway caliber. Am Rev Respir Dis. 1982 Nov;126(5):849–854. doi: 10.1164/arrd.1982.126.5.849. [DOI] [PubMed] [Google Scholar]
  9. Chung K. F., Snashall P. D. Effect of prior bronchoconstriction on the airway response to histamine in normal subjects. Thorax. 1984 Jan;39(1):40–45. doi: 10.1136/thx.39.1.40. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Chung K. F., Snashall P. D. Methacholine dose-response curves in normal and asthmatic man: effect of starting conductance and pharmacological antagonism. Clin Sci (Lond) 1984 Jun;66(6):665–673. doi: 10.1042/cs0660665. [DOI] [PubMed] [Google Scholar]
  11. 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]
  12. Crompton G. K. A comparison of responses to bronchodilator drugs in chronic bronchitis and chronic asthma. Thorax. 1968 Jan;23(1):46–55. doi: 10.1136/thx.23.1.46. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Fuller R. W., Dixon C. M., Dollery C. T., Barnes P. J. Prostaglandin D2 potentiates airway responsiveness to histamine and methacholine. Am Rev Respir Dis. 1986 Feb;133(2):252–254. doi: 10.1164/arrd.1986.133.2.252. [DOI] [PubMed] [Google Scholar]
  14. Gomm S. A., Keaney N. P., Hunt L. P., Allen S. C., Stretton T. B. Dose-response comparison of ipratropium bromide from a metered-dose inhaler and by jet nebulisation. Thorax. 1983 Apr;38(4):297–301. doi: 10.1136/thx.38.4.297. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Hardy C. C., Bradding P., Robinson C., Holgate S. T. The combined effects of two pairs of mediators, adenosine with methacholine and prostaglandin D2 with histamine, on airway calibre in asthma. Clin Sci (Lond) 1986 Oct;71(4):385–392. doi: 10.1042/cs0710385. [DOI] [PubMed] [Google Scholar]
  16. Heaton R. W., Henderson A. F., Dunlop L. S., Costello J. F. The influence of pretreatment with prostaglandin F2 alpha on bronchial sensitivity to inhaled histamine and methacholine in normal subjects. Br J Dis Chest. 1984 Apr;78(2):168–173. [PubMed] [Google Scholar]
  17. Hockley B., Johnson N. M. A comparison of three high doses of ipratropium bromide in chronic asthma. Br J Dis Chest. 1985 Oct;79(4):379–384. doi: 10.1016/0007-0971(85)90072-5. [DOI] [PubMed] [Google Scholar]
  18. Klein R. C., Salvaggio J. E. Nonspecificity of the bronchoconstricting effect of histamine and acetyl-beta-methylcholine in patients with obstructive airway disease. J Allergy. 1966 Mar;37(3):158–168. doi: 10.1016/0021-8707(66)90090-6. [DOI] [PubMed] [Google Scholar]
  19. Lenney W., Evans N. A. Nebulized salbutamol and ipratropium bromide in asthmatic children. Br J Dis Chest. 1986 Jan;80(1):59–65. doi: 10.1016/0007-0971(86)90011-2. [DOI] [PubMed] [Google Scholar]
  20. Levene S., McKenzie S. A. Protective effect of theophylline on histamine-induced bronchoconstriction in asthmatic children. Br J Clin Pharmacol. 1986 Apr;21(4):445–449. doi: 10.1111/j.1365-2125.1986.tb05220.x. [DOI] [PMC free article] [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. McWilliams B. C., Menendez R., Kelly H. W., Howick J. Effects of theophylline on inhaled methacholine and histamine in asthmatic children. Am Rev Respir Dis. 1984 Aug;130(2):193–197. doi: 10.1164/arrd.1984.130.2.193. [DOI] [PubMed] [Google Scholar]
  23. PARKER C. D., BILBO R. E., REED C. E. METHACHOLINE AEROSOL AS TEST FOR BRONCHIAL ASTHMA. Arch Intern Med. 1965 Apr;115:452–458. doi: 10.1001/archinte.1965.03860160078013. [DOI] [PubMed] [Google Scholar]
  24. Patakas D., Maniki E., Tsara V., Dascalopoulou E. Nifedipine treatment of patients with bronchial asthma. J Allergy Clin Immunol. 1987 Jun;79(6):959–963. doi: 10.1016/0091-6749(87)90247-8. [DOI] [PubMed] [Google Scholar]
  25. Peters S. P., Schulman E. S., Schleimer R. P., MacGlashan D. W., Jr, Newball H. H., Lichtenstein L. M. Dispersed human lung mast cells. Pharmacologic aspects and comparison with human lung tissue fragments. Am Rev Respir Dis. 1982 Dec;126(6):1034–1039. doi: 10.1164/arrd.1982.126.6.1034. [DOI] [PubMed] [Google Scholar]
  26. 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]
  27. 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]
  28. Ramsdell J. W., Nachtwey F. J., Moser K. M. Bronchial hyperreactivity in chronic obstructive bronchitis. Am Rev Respir Dis. 1982 Nov;126(5):829–832. doi: 10.1164/arrd.1982.126.5.829. [DOI] [PubMed] [Google Scholar]
  29. 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]
  30. Salome C. M., Schoeffel R. E., Yan K., Woolcock A. J. Effect of aerosol fenoterol on the severity of bronchial hyperreactivity in patients with asthma. Thorax. 1983 Nov;38(11):854–858. doi: 10.1136/thx.38.11.854. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. 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]
  32. Taylor R. G., Joyce H., Gross E., Holland F., Pride N. B. Bronchial reactivity to inhaled histamine and annual rate of decline in FEV1 in male smokers and ex-smokers. Thorax. 1985 Jan;40(1):9–16. doi: 10.1136/thx.40.1.9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Woenne R., Kattan M., Orange R. P., Levison H. Bronchial hyperreactivity to histamine and methacholine in asthmatic children after inhalation of SCH 1000 and chlorpheniramine maleate. J Allergy Clin Immunol. 1978 Aug;62(2):119–124. doi: 10.1016/0091-6749(78)90089-1. [DOI] [PubMed] [Google Scholar]
  34. 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]
  35. van der Lende R., Visser B. F., Wever-Hess J., de Vries K., Orie N. G. Distribution of histamine threshold values in a random population. Rev Inst Hyg Mines (Hasselt) 1973;28(4):186–190. [PubMed] [Google Scholar]

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