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. 1988 Sep;26(3):295–301. doi: 10.1111/j.1365-2125.1988.tb05280.x

The influence of ipratropium bromide and sodium cromoglycate on benzalkonium chloride-induced bronchoconstriction in asthma.

K A Miszkiel 1, R Beasley 1, S T Holgate 1
PMCID: PMC1386542  PMID: 2972308

Abstract

1. Benzalkonium chloride, an antibacterial preservative that is added to nebuliser solutions, has been shown to cause bronchoconstriction when inhaled by asthmatic subjects. 2. To investigate the potential role of reflex and mast cell-dependent mechanisms in the pathogenesis of bronchoconstriction produced by benzalkonium chloride we examined the effects of ipratropium bromide and sodium cromoglycate on this response in both concentration-response and time-course studies in nine asthmatic subjects. 3. Pretreatment with inhaled ipratropium bromide (1 mg) and sodium cromoglycate (40 mg) displaced the benzalkonium chloride concentration-response curves to the right by a mean 2.2 fold and 3.1 fold respectively. 4. Ipratropium bromide and sodium cromoglycate markedly attenuated the airway response to benzalkonium chloride throughout the 45 min time course period, inhibiting the overall response by 56% and 78% respectively. 5. We conclude that benzalkonium chloride provokes bronchoconstriction in asthmatic subjects through a combination of mast cell activation and stimulation of peripheral and central neural pathways.

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Selected References

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  1. Allen C. J., Campbell A. H. Dose response of ipratropium assessed by two methods. Thorax. 1980 Feb;35(2):137–139. doi: 10.1136/thx.35.2.137. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Barnes P. J. Asthma as an axon reflex. Lancet. 1986 Feb 1;1(8475):242–245. doi: 10.1016/s0140-6736(86)90777-4. [DOI] [PubMed] [Google Scholar]
  3. 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]
  4. Beasley R., Varley J., Robinson C., Holgate S. T. Cholinergic-mediated bronchoconstriction induced by prostaglandin D2, its initial metabolite 9 alpha,11 beta-PGF2, and PGF2 alpha in asthma. Am Rev Respir Dis. 1987 Nov;136(5):1140–1144. doi: 10.1164/ajrccm/136.5.1140. [DOI] [PubMed] [Google Scholar]
  5. Bisgaard H., Groth S., Madsen F. Bronchial hyperreactivity to leucotriene D4 and histamine in exogenous asthma. Br Med J (Clin Res Ed) 1985 May 18;290(6480):1468–1471. doi: 10.1136/bmj.290.6480.1468. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Britton J., Mortagy A., Tattersfield A. Histamine challenge testing: comparison of three methods. Thorax. 1986 Feb;41(2):128–132. doi: 10.1136/thx.41.2.128. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Chai H., Farr R. S., Froehlich L. A., Mathison D. A., McLean J. A., Rosenthal R. R., Sheffer A. L., Spector S. L., Townley R. G. Standardization of bronchial inhalation challenge procedures. J Allergy Clin Immunol. 1975 Oct;56(4):323–327. doi: 10.1016/0091-6749(75)90107-4. [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. Coleman J. W., Holgate S. T., Church M. K., Godfrey R. C. Immunoglobulin E decapeptide-induced 5-hydroxytryptamine release from rat peritoneal mast cells. Comparison with corticotropin-(1-24)-peptide, polyarginine, polylysine and antigen. Biochem J. 1981 Sep 15;198(3):615–619. doi: 10.1042/bj1980615. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Compton L. J., Steinberg A. D., Sano H. Nuclear DNA degradation in lymphocytes of patients with systemic lupus erythematosus. J Immunol. 1984 Jul;133(1):213–216. [PubMed] [Google Scholar]
  11. Dixon M., Jackson D. M., Richards I. M. The action of sodium cromoglycate on 'C' fibre endings in the dog lung. Br J Pharmacol. 1980 Sep;70(1):11–13. doi: 10.1111/j.1476-5381.1980.tb10898.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Fuller R. W., Dixon C. M., Cuss F. M., Barnes P. J. Bradykinin-induced bronchoconstriction in humans. Mode of action. Am Rev Respir Dis. 1987 Jan;135(1):176–180. doi: 10.1164/arrd.1987.135.1.176. [DOI] [PubMed] [Google Scholar]
  13. Mann J. S., Cushley M. J., Holgate S. T. Adenosine-induced bronchoconstriction in asthma. Role of parasympathetic stimulation and adrenergic inhibition. Am Rev Respir Dis. 1985 Jul;132(1):1–6. doi: 10.1164/arrd.1985.132.1.1. [DOI] [PubMed] [Google Scholar]
  14. Miszkiel K. A., Beasley R., Rafferty P., Holgate S. T. The contribution of histamine release to bronchoconstriction provoked by inhaled benzalkonium chloride in asthma. Br J Clin Pharmacol. 1988 Feb;25(2):157–163. doi: 10.1111/j.1365-2125.1988.tb03286.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. NADEL J. A., SALEM H., TAMPLIN B., TOKIWA Y. MECHANISM OF BRONCHOCONSTRICTION DURING INHALATION OF SULFUR DIOXIDE. J Appl Physiol. 1965 Jan;20:164–167. doi: 10.1152/jappl.1965.20.1.164. [DOI] [PubMed] [Google Scholar]
  16. Omini C., Brunelli G., Daffonchio L., Mapp C., Fabbri L., Berti F. Prostaglandin D2 (PGD2) potentiates cholinergic responsiveness in guinea-pig trachea. J Auton Pharmacol. 1986 Sep;6(3):181–186. doi: 10.1111/j.1474-8673.1986.tb00643.x. [DOI] [PubMed] [Google Scholar]
  17. Read G. W., Hong S. M., Kiefer E. F. Competitive inhibition of 48/80-induced histamine release by benzalkonium chloride and its analogs and the polyamine receptor in mast cells. J Pharmacol Exp Ther. 1982 Sep;222(3):652–657. [PubMed] [Google Scholar]
  18. Read G. W., Kiefer E. F. Benzalkonium chloride: selective inhibitor of histamine release induced by compound 48/80 and other polyamines. J Pharmacol Exp Ther. 1979 Dec;211(3):711–715. [PubMed] [Google Scholar]
  19. Snashall P. D., Baldwin C. Mechanisms of sulphur dioxide induced bronchoconstriction in normal and asthmatic man. Thorax. 1982 Feb;37(2):118–123. doi: 10.1136/thx.37.2.118. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Widdicombe J. The neural reflexes in the airways. Eur J Respir Dis Suppl. 1986;144:1–33. [PubMed] [Google Scholar]

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