Skip to main content
NCBI home page
Thorax logoLink to Thorax
. 1987 Dec;42(12):946–952. doi: 10.1136/thx.42.12.946

Effects of a cyclo-oxygenase inhibitor, flurbiprofen, and an H1 histamine receptor antagonist, terfenadine, alone and in combination on allergen induced immediate bronchoconstriction in man.

N Curzen 1, P Rafferty 1, S T Holgate 1
PMCID: PMC461056  PMID: 2894081

Abstract

The effect of flurbiprofen, a potent cyclo-oxygenase inhibitor, on histamine and methacholine reactivity was assessed in seven atopic subjects with asthma. Flurbiprofen 150 mg daily for three days displaced the histamine-FEV1 concentration-response curve to the right by 1.5 doubling doses, whereas no effect was observed on the response to methacholine. Subsequently the effects of flurbiprofen and terfenadine, a specific H1 histamine receptor antagonist, on allergen induced bronchoconstriction were studied in seven atopic but non-asthmatic subjects. The subjects inhaled the concentration of grass pollen allergen that had previously been shown to produce a 20% fall in FEV1 on separate occasions after prior treatment with placebo, flurbiprofen 150 mg daily for three days, terfenadine 180 mg three hours before challenge, and the combination of flurbiprofen and terfenadine. After placebo, allergen challenge caused a mean (SEM) maximum fall in FEV1 of 37.6% (2.6%) after 20 (3.7) minutes, followed by a gradual recovery to within 15% of baseline at 60 minutes. Terfenadine reduced the maximum allergen provoked fall in FEV1 to 21.5% (2.2%) and reduced the area under the time-response curve (AUC) by 50% (6%). Flurbiprofen alone reduced the mean maximum fall in FEV1 to 29.6% (3.2%) and reduced the AUC by 26%. The effect of the combination of flurbiprofen and terfenadine did not differ significantly from that of terfenadine alone. We conclude that histamine and prostaglandins contribute to immediate allergen induced bronchoconstriction and that a complex interaction occurs between the two classes of mediators.

Full text

PDF
946

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Adams G. K., 3rd, Lichtenstein L. M. Indomethacin enhances response of human bronchus to antigen. Am Rev Respir Dis. 1985 Jan;131(1):8–10. doi: 10.1164/arrd.1985.131.1.8. [DOI] [PubMed] [Google Scholar]
  2. 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]
  3. Crook D., Collins A. J., Rose A. J. A comparison of the effect of flurbiprofen on prostaglandin synthetase from human rheumatoid synovium and enzymatically active animal tissues. J Pharm Pharmacol. 1976 Jun;28(6):535–535. doi: 10.1111/j.2042-7158.1976.tb02787.x. [DOI] [PubMed] [Google Scholar]
  4. Dahlén S. E., Björk J., Hedqvist P., Arfors K. E., Hammarström S., Lindgren J. A., Samuelsson B. Leukotrienes promote plasma leakage and leukocyte adhesion in postcapillary venules: in vivo effects with relevance to the acute inflammatory response. Proc Natl Acad Sci U S A. 1981 Jun;78(6):3887–3891. doi: 10.1073/pnas.78.6.3887. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Fairfax A. J., Hanson J. M., Morley J. The late reaction following bronchial provocation with house dust mite allergen. Dependence on arachidonic acid metabolism. Clin Exp Immunol. 1983 May;52(2):393–398. [PMC free article] [PubMed] [Google Scholar]
  6. Gréen K., Hedqvist P., Svanborg N. Increased plasma levels of 15-keto-13,14-dihydro-prostaglandin F2X after allergen-provoked asthma in man. Lancet. 1974 Dec 14;2(7894):1419–1421. doi: 10.1016/s0140-6736(74)90075-0. [DOI] [PubMed] [Google Scholar]
  7. Hardy C. C., Robinson C., Tattersfield A. E., Holgate S. T. The bronchoconstrictor effect of inhaled prostaglandin D2 in normal and asthmatic men. N Engl J Med. 1984 Jul 26;311(4):209–213. doi: 10.1056/NEJM198407263110401. [DOI] [PubMed] [Google Scholar]
  8. Harvey J., Holgate S. T., Peters B. J., Robinson C., Walker J. R. Oxidative transformations of arachidonic acid in human dispersed lung cells: disparity between the utilization of endogenous and exogenous substrate. Br J Pharmacol. 1985 Oct;86(2):417–426. doi: 10.1111/j.1476-5381.1985.tb08911.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Holgate S. T., Benyon R. C., Howarth P. H., Agius R., Hardy C., Robinson C., Durham S. R., Kay A. B., Church M. K. Relationship between mediator release from human lung mast cells in vitro and in vivo. Int Arch Allergy Appl Immunol. 1985;77(1-2):47–56. doi: 10.1159/000233752. [DOI] [PubMed] [Google Scholar]
  10. Holgate S. T., Burns G. B., Robinson C., Church M. K. Anaphylactic- and calcium-dependent generation of prostaglandin D2 (PGD2), thromboxane B2, and other cyclooxygenase products of arachidonic acid by dispersed human lung cells and relationship to histamine release. J Immunol. 1984 Oct;133(4):2138–2144. [PubMed] [Google Scholar]
  11. Howarth P. H., Durham S. R., Lee T. H., Kay A. B., Church M. K., Holgate S. T. Influence of albuterol, cromolyn sodium and ipratropium bromide on the airway and circulating mediator responses to allergen bronchial provocation in asthma. Am Rev Respir Dis. 1985 Nov;132(5):986–992. doi: 10.1164/arrd.1985.132.5.986. [DOI] [PubMed] [Google Scholar]
  12. Joubert J. R., Shephard E., Mouton W., Van Zyl L., Viljoen I. Non-steroid anti-inflammatory drugs in asthma: dangerous or useful therapy? Allergy. 1985 Apr;40(3):202–207. doi: 10.1111/j.1398-9995.1985.tb00217.x. [DOI] [PubMed] [Google Scholar]
  13. Knauer K. A., Lichtenstein L. M., Adkinson N. F., Jr, Fish J. E. Platelet activation during antigen-induced airway reactions in asthmatic subjects. N Engl J Med. 1981 Jun 4;304(23):1404–1407. doi: 10.1056/NEJM198106043042307. [DOI] [PubMed] [Google Scholar]
  14. Lewis R. A., Soter N. A., Diamond P. T., Austen K. F., Oates J. A., Roberts L. J., 2nd Prostaglandin D2 generation after activation of rat and human mast cells with anti-IgE. J Immunol. 1982 Oct;129(4):1627–1631. [PubMed] [Google Scholar]
  15. MacGlashan D. W., Jr, Schleimer R. P., Peters S. P., Schulman E. S., Adams G. K., 3rd, Newball H. H., Lichtenstein L. M. Generation of leukotrienes by purified human lung mast cells. J Clin Invest. 1982 Oct;70(4):747–751. doi: 10.1172/JCI110670. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Marone G., Kagey-Sobotka A., Lichtenstein L. M. Effects of arachidonic acid and its metabolites on antigen-induced histamine release from human basophils in vitro. J Immunol. 1979 Oct;123(4):1669–1677. [PubMed] [Google Scholar]
  17. Morris H. G., Sherman N. A., Shepperdson F. T., Selner J. C. Radioimmunoassay of thromboxane B2 in plasma of normal and asthmatic subjects. Adv Prostaglandin Thromboxane Res. 1980;8:1759–1764. [PubMed] [Google Scholar]
  18. Pepys J., Hargreave F. E., Chan M., McCarthy D. S. Inhibitory effects of disodium cromoglycate on allergen-inhalation tests. Lancet. 1968 Jul 20;2(7560):134–137. doi: 10.1016/s0140-6736(68)90419-4. [DOI] [PubMed] [Google Scholar]
  19. Peters S. P., MacGlashan D. W., Jr, Schleimer R. P., Hayes E. C., Adkinson N. F., Jr, Lichtenstein L. M. The pharmacologic modulation of the release of arachidonic acid metabolites from purified human lung mast cells. Am Rev Respir Dis. 1985 Aug;132(2):367–373. doi: 10.1164/arrd.1985.132.2.367. [DOI] [PubMed] [Google Scholar]
  20. Platshon L. F., Kaliner M. The effects of the immunologic release of histamine upon human lung cyclic nucleotide levels and prostaglandin generation. J Clin Invest. 1978 Dec;62(6):1113–1121. doi: 10.1172/JCI109230. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Shephard E. G., Malan L., Macfarlane C. M., Mouton W., Joubert J. R. Lung function and plasma levels of thromboxane B2, 6-ketoprostaglandin F1 alpha and beta-thromboglobulin in antigen-induced asthma before and after indomethacin pretreatment. Br J Clin Pharmacol. 1985 Apr;19(4):459–470. doi: 10.1111/j.1365-2125.1985.tb02671.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Smith A. P., Dunlop L. Letter: Prostaglandins and asthma. Lancet. 1975 Jan 4;1(7897):39–39. doi: 10.1016/s0140-6736(75)92400-9. [DOI] [PubMed] [Google Scholar]
  23. Smith A. P. Effect of indomethacin in asthma: evidence against a role for prostaglandins in its pathogenesis. Br J Clin Pharmacol. 1975 Aug;2(4):307–309. doi: 10.1111/j.1365-2125.1975.tb02775.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Walters E. H., Parrish R. W., Bevan C., Smith A. P. Induction of bronchial hypersensitivity: evidence for a role for prostaglandins. Thorax. 1981 Aug;36(8):571–574. doi: 10.1136/thx.36.8.571. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Walters E. H. Prostaglandins and the control of airways responses to histamine in normal and asthmatic subjects. Thorax. 1983 Mar;38(3):188–194. doi: 10.1136/thx.38.3.188. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Thorax are provided here courtesy of BMJ Publishing Group

RESOURCES