Skip to main content
Thorax logoLink to Thorax
. 1989 Feb;44(2):102–107. doi: 10.1136/thx.44.2.102

Effects of salbutamol on bronchoconstriction, bronchial hyperresponsiveness, and leucocyte responses induced by platelet activating factor in man.

K F Chung 1, G Dent 1, P J Barnes 1
PMCID: PMC461702  PMID: 2648645

Abstract

Platelet activating factor, a potent mediator of inflammation, causes a sustained increase in airway responsiveness to methacholine in man and has been implicated in asthma. The effect of the beta 2 agonist salbutamol (200 micrograms by inhalation) on platelet activating factor induced bronchoconstriction and airway hyperresponsiveness was studied in seven normal subjects in a double blind, crossover study. Salbutamol only partially inhibited the platelet activating factor induced fall in partial flow at 30% of vital capacity (Vp30) (mean percentage fall 47.6 (SEM 7.9); p less than 0.001), whereas it completely blocked a similar degree of bronchoconstriction induced by methacholine. Salbutamol did not prevent the accompanying transient flushing and chest irritation and did not affect the transient neutropenia (mean % fall 69.5 (13.6); p less than 0.01) or the rebound neutrophilia (mean % increase 84.7 (24.7); p less than 0.05) that followed platelet activating factor. There was an increase in the airway responsiveness to methacholine following inhalation of platelet activating factor, the maximum mean change being a three fold increase in PC40 (the provocative concentration of methacholine causing a 40% fall in Vp30) on day 3 (p less than 0.01). Salbutamol caused a significant attenuation of this response on day 3 (p less than 0.02) but had no significant effect on days 1 and 7. Thus a therapeutic dose of salbutamol caused partial inhibition of platelet activating factor induced bronchoconstriction and had a minimal effect on the increased bronchial responsiveness following platelet activating factor.

Full text

PDF
106

Selected References

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

  1. Adelroth E., Morris M. M., Hargreave F. E., O'Byrne P. M. Airway responsiveness to leukotrienes C4 and D4 and to methacholine in patients with asthma and normal controls. N Engl J Med. 1986 Aug 21;315(8):480–484. doi: 10.1056/NEJM198608213150803. [DOI] [PubMed] [Google Scholar]
  2. Barnes P. J., Gribbin H. R., Osmanliev D., Pride N. B. Partial flow-volume curves to measure bronchodilator dos-response curves in normal humans. J Appl Physiol Respir Environ Exerc Physiol. 1981 Jun;50(6):1193–1197. doi: 10.1152/jappl.1981.50.6.1193. [DOI] [PubMed] [Google Scholar]
  3. Boushey H. A., Holtzman M. J., Sheller J. R., Nadel J. A. Bronchial hyperreactivity. Am Rev Respir Dis. 1980 Feb;121(2):389–413. doi: 10.1164/arrd.1980.121.2.389. [DOI] [PubMed] [Google Scholar]
  4. Chung K. F., Aizawa H., Leikauf G. D., Ueki I. F., Evans T. W., Nadel J. A. Airway hyperresponsiveness induced by platelet-activating factor: role of thromboxane generation. J Pharmacol Exp Ther. 1986 Mar;236(3):580–584. [PubMed] [Google Scholar]
  5. Chung K. F., Minette P., McCusker M., Barnes P. J. Ketotifen inhibits the cutaneous but not the airway responses to platelet-activating factor in man. J Allergy Clin Immunol. 1988 Jun;81(6):1192–1198. doi: 10.1016/0091-6749(88)90890-1. [DOI] [PubMed] [Google Scholar]
  6. Chung K. F. Role of inflammation in the hyperreactivity of the airways in asthma. Thorax. 1986 Sep;41(9):657–662. doi: 10.1136/thx.41.9.657. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Cockcroft D. W., Murdock K. Y. Comparative effects of inhaled salbutamol, sodium cromoglycate, and beclomethasone dipropionate on allergen-induced early asthmatic responses, late asthmatic responses, and increased bronchial responsiveness to histamine. J Allergy Clin Immunol. 1987 May;79(5):734–740. doi: 10.1016/0091-6749(87)90204-1. [DOI] [PubMed] [Google Scholar]
  8. Cuss F. M., Dixon C. M., Barnes P. J. Effects of inhaled platelet activating factor on pulmonary function and bronchial responsiveness in man. Lancet. 1986 Jul 26;2(8500):189–192. doi: 10.1016/s0140-6736(86)92489-x. [DOI] [PubMed] [Google Scholar]
  9. Evans T. W., Chung K. F., Rogers D. F., Barnes P. J. Effect of platelet-activating factor on airway vascular permeability: possible mechanisms. J Appl Physiol (1985) 1987 Aug;63(2):479–484. doi: 10.1152/jappl.1987.63.2.479. [DOI] [PubMed] [Google Scholar]
  10. Freedman B. J. The functional geometry of the bronchi. The relationship between changes in external diameter and calibre, and a consideration of the passive role played by the mucosa in bronchoconstriction. Bull Physiopathol Respir (Nancy) 1972 May-Jun;8(3):545–552. [PubMed] [Google Scholar]
  11. Griffin M., Weiss J. W., Leitch A. G., McFadden E. R., Jr, Corey E. J., Austen K. F., Drazen J. M. Effects of leukotriene D on the airways in asthma. N Engl J Med. 1983 Feb 24;308(8):436–439. doi: 10.1056/NEJM198302243080807. [DOI] [PubMed] [Google Scholar]
  12. Henocq E., Vargaftig B. B. Skin eosinophilia in atopic patients. J Allergy Clin Immunol. 1988 Apr;81(4):691–695. doi: 10.1016/0091-6749(88)91040-8. [DOI] [PubMed] [Google Scholar]
  13. Lellouch-Tubiana A., Lefort J., Simon M. T., Pfister A., Vargaftig B. B. Eosinophil recruitment into guinea pig lungs after PAF-acether and allergen administration. Modulation by prostacyclin, platelet depletion, and selective antagonists. Am Rev Respir Dis. 1988 Apr;137(4):948–954. doi: 10.1164/ajrccm/137.4.948. [DOI] [PubMed] [Google Scholar]
  14. O'Donnell S. R., Persson C. G. Beta-adrenoceptor mediated inhibition by terbutaline of histamine effects on vascular permeability. Br J Pharmacol. 1978 Mar;62(3):321–324. doi: 10.1111/j.1476-5381.1978.tb08463.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. 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]
  16. Wardlaw A. J., Moqbel R., Cromwell O., Kay A. B. Platelet-activating factor. A potent chemotactic and chemokinetic factor for human eosinophils. J Clin Invest. 1986 Dec;78(6):1701–1706. doi: 10.1172/JCI112765. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Wong K., Freund K. Inhibition of the n-formylmethionyl-leucyl-phenylalanine induced respiratory burst in human neutrophils by adrenergic agonists and prostaglandins of the E series. Can J Physiol Pharmacol. 1981 Sep;59(9):915–920. doi: 10.1139/y81-141. [DOI] [PubMed] [Google Scholar]

Articles from Thorax are provided here courtesy of BMJ Publishing Group

RESOURCES