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. 1984 Nov;39(11):837–843. doi: 10.1136/thx.39.11.837

Comparison of in vivo airway responsiveness and in vitro smooth muscle sensitivity to methacholine in man.

J A Roberts, D Raeburn, I W Rodger, N C Thomson
PMCID: PMC459934  PMID: 6390773

Abstract

Airway responsiveness to methacholine varies between normal people and is increased in patients with asthma. The importance of airway smooth muscle sensitivity in determining in vivo responsiveness is unknown. We have examined this question by comparing in vivo airway responsiveness with in vitro airway smooth muscle sensitivity to methacholine in 10 patients undergoing thoracic surgery. In vivo responsiveness was determined by administration of inhalations of doubling concentrations of methacholine. Results were expressed as the provocation concentration (PC) causing a decrease in forced expiratory volume in one second of 20% (PC20FEV1), specific airway conductance of 35% (PC35SGaw), and maximal expiratory flow at 35% vital capacity, measured for the partial (V35(p)) and complete (V35(c)) flow volume curves, of 35% (PC35V35(p); PC35V35(c)). In vitro airway smooth muscle sensitivity was determined from specimens obtained at thoracotomy. Log dose-response curves to methacholine were constructed and the concentration causing a 50% maximum contraction (EC50) was derived. There were differences between patients for both in vivo airway responsiveness and in vitro smooth muscle sensitivity to methacholine. There were no significant relationships between the in vivo and in vitro measurements. The results suggest that factors other than solely the sensitivity of smooth muscle must determine in vivo airway responsiveness to methacholine.

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Selected References

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  1. BLAKEMORE W. S., FORSTER R. E., MORTON J. W., OGILVIE C. M. A standardized breath holding technique for the clinical measurement of the diffusing capacity of the lung for carbon monoxide. J Clin Invest. 1957 Jan;36(1 Pt 1):1–17. doi: 10.1172/JCI103402. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. 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]
  3. Brink C., Grimaud C., Guillot C., Orehek J. The interaction between indomethacin and contractile agents on human isolated airway muscle. Br J Pharmacol. 1980 Jul;69(3):383–388. doi: 10.1111/j.1476-5381.1980.tb07026.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cockcroft D. W., Killian D. N., Mellon J. J., Hargreave F. E. Bronchial reactivity to inhaled histamine: a method and clinical survey. Clin Allergy. 1977 May;7(3):235–243. doi: 10.1111/j.1365-2222.1977.tb01448.x. [DOI] [PubMed] [Google Scholar]
  5. DUBOIS A. B., BOTELHO S. Y., COMROE J. H., Jr A new method for measuring airway resistance in man using a body plethysmograph: values in normal subjects and in patients with respiratory disease. J Clin Invest. 1956 Mar;35(3):327–335. doi: 10.1172/JCI103282. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Dahlén S. E., Hansson G., Hedqvist P., Björck T., Granström E., Dahlén B. Allergen challenge of lung tissue from asthmatics elicits bronchial contraction that correlates with the release of leukotrienes C4, D4, and E4. Proc Natl Acad Sci U S A. 1983 Mar;80(6):1712–1716. doi: 10.1073/pnas.80.6.1712. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Fish J. E., Ankin M. G., Kelly J. F., Peterman V. I. Regulation of bronchomotor tone by lung inflation in asthmatic and nonasthmatic subjects. J Appl Physiol Respir Environ Exerc Physiol. 1981 May;50(5):1079–1086. doi: 10.1152/jappl.1981.50.5.1079. [DOI] [PubMed] [Google Scholar]
  8. Goldie R. G., Paterson J. W., Wale J. L. Pharmacological responses of human and porcine lung parenchyma, bronchus and pulmonary artery. Br J Pharmacol. 1982 Aug;76(4):515–521. doi: 10.1111/j.1476-5381.1982.tb09248.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. HAWKINS D. F., SCHILD H. O. The action of drugs on isolated human bronchial chains. Br J Pharmacol Chemother. 1951 Dec;6(4):682–690. doi: 10.1111/j.1476-5381.1951.tb00680.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hargreave F. E., Ryan G., Thomson N. C., O'Byrne P. M., Latimer K., Juniper E. F., Dolovich J. Bronchial responsiveness to histamine or methacholine in asthma: measurement and clinical significance. J Allergy Clin Immunol. 1981 Nov;68(5):347–355. doi: 10.1016/0091-6749(81)90132-9. [DOI] [PubMed] [Google Scholar]
  11. Higenbottam T. Narrowing of glottis opening in humans associated with experimentally induced bronchoconstriction. J Appl Physiol Respir Environ Exerc Physiol. 1980 Sep;49(3):403–407. doi: 10.1152/jappl.1980.49.3.403. [DOI] [PubMed] [Google Scholar]
  12. Hogg J. C. Bronchial mucosal permeability and its relationship to airways hyperreactivity. J Allergy Clin Immunol. 1981 Jun;67(6):421–425. doi: 10.1016/0091-6749(81)90094-4. [DOI] [PubMed] [Google Scholar]
  13. Kaliner M., Orange R. P., Austen K. F. Immunological release of histamine and slow reacting substance of anaphylaxis from human lung. J Exp Med. 1972 Sep 1;136(3):556–567. doi: 10.1084/jem.136.3.556. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Nadel J. A. Regulation of fluid and mucous secretions in airways. J Allergy Clin Immunol. 1981 Jun;67(6):417–420. doi: 10.1016/0091-6749(81)90093-2. [DOI] [PubMed] [Google Scholar]
  15. 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]
  16. Richardson J. B. Nerve supply to the lungs. Am Rev Respir Dis. 1979 May;119(5):785–802. doi: 10.1164/arrd.1979.119.5.785. [DOI] [PubMed] [Google Scholar]
  17. Ryan G., Dolovich M. B., Obminski G., Cockcroft D. W., Juniper E., Hargreave F. E., Newhouse M. T. Standardization of inhalation provocation tests: influence of nebulizer output, particle size, and method of inhalation. J Allergy Clin Immunol. 1981 Feb;67(2):156–161. doi: 10.1016/0091-6749(81)90012-9. [DOI] [PubMed] [Google Scholar]
  18. Thomson N. C. Neurogenic and myogenic mechanisms of nonspecific bronchial hyperresponsiveness. Eur J Respir Dis Suppl. 1983;128(Pt 1):206–212. [PubMed] [Google Scholar]
  19. Vidruk E. H., Hahn H. L., Nadel J. A., Sampson S. R. Mechanisms by which histamine stimulates rapidly adapting receptors in dog lungs. J Appl Physiol Respir Environ Exerc Physiol. 1977 Sep;43(3):397–402. doi: 10.1152/jappl.1977.43.3.397. [DOI] [PubMed] [Google Scholar]
  20. Vincenc K. S., Black J. L., Yan K., Armour C. L., Donnelly P. D., Woolcock A. J. Comparison of in vivo and in vitro responses to histamine in human airways. Am Rev Respir Dis. 1983 Nov;128(5):875–879. doi: 10.1164/arrd.1983.128.5.875. [DOI] [PubMed] [Google Scholar]
  21. WIDDICOMBE J. G. Regulation of tracheobronchial smooth muscle. Physiol Rev. 1963 Jan;43:1–37. doi: 10.1152/physrev.1963.43.1.1. [DOI] [PubMed] [Google Scholar]
  22. Westfall T. C. Neuroeffector mechanisms. Annu Rev Physiol. 1980;42:383–397. doi: 10.1146/annurev.ph.42.030180.002123. [DOI] [PubMed] [Google Scholar]

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