Abstract
Bronchial hyperresponsiveness (BHR) is a common feature in the majority of asthmatic subjects and methacholine is the most frequently used agent for the test. The influence of 3 or 5 min time intervals between doses steps in a double methacholine challenge test (MCH-3′ or MCH-5′) was investigated. Using the MCH-3′ challenge, 52 intermittent asthmatics were classified as having moderate (BHR-M; 18 subjects), mild (BHR-m; 19 subjects), or bordeline (BHR-B; 15 subjects) BHR. The cumulative dose and the PD20FEV1 were higher for MCH-5′ compared with MCH-3′ in BHR-m (p < 0.05) and BHR-B (p < 0.05) but not in the BHR-M group. Also the dose response slopes, FEV1% decline/cumulative methacholine dose, calculated for the two challenge tests were statistically different only in BHR-m (p < 0.05) and BHR-B (p < 0.01). At MCH-5′, there were 16 subjects with BHR-M, 18 with BHR-m, 12 with BHR-B and 6 subjects with normal reactivity. Results may suggest that in the group of BHR-m and BHR-B subjects, at MCH-5′ compared with MCH-3′, the cumulative effect of the administered drug, quickly metabolized by cholinesterase, is not complete, thus leading to an incorrect estimation of bronchial hyperresponsiveness degree. It is hoped that time interval between doses be standardized to ensure maximum comparability within and between subjects in challenge tests.
Similar content being viewed by others
References
HA Boushey MK Holtzmann JR Sheller JA Nadel (1980) ArticleTitleBronchial hyperreactivity Am Rev Respir Dis 121 389–413
ST Holgate R Beasley OP Twentyman (1987) ArticleTitleThe pathogenesis and significance of bronchial hyperresponsiveness in airways diseases Clin Sci 73 561–572
J Orehek P Gayrard (1976) ArticleTitleLes tests de provocation bronchique non-specifique dans l’asthme Bull Eur Phisiopathol Respir 2 565–598
PJ Sterk EH Bel (1989) ArticleTitleBronchial hyperresponsiveness: the need for a distinction between hypersensitivity and excessive airway narrowing Eur Resp J 2 267–274
American Thoracic Society (2000) ArticleTitleGuidelines for Methacholine and Exercise Challenge Testing-1999 Am J Respir Crit Care Med 161 309–329
H Chai RS Fair LA, Froehlich et al. (1975) ArticleTitleStandardization of bronchial inhalation procedures J Allergy Clin Immunol 56 323–327
PJ Sterk LM Fabbri PH Quanjer et al. (1993) ArticleTitleAirway responsiveness. Standardized challenge testing with pharmacological, physical and sensitizing stimuli in adults. Report Working Party Standardization of Lung Function Tests, European Community for Steel and Coal. Official Statement of the European Respiratory Society Eur Resp J (suppl) 16 53–83
P Malmberg K Larsson BM Sundblad W Zhiping (1993) ArticleTitleImportance of the time interval between FEV1 measurements in a methacholine provocation test Eur Resp J 6 680–686
R Pellegrino PJ Sterk JK Sont V Brusasco (1998) ArticleTitleAssessing the effect of deep inhalation on airway calibre: a novel approach to lung function in bronchial asthma and COPD Eur Respir J 12 1219–1227
R Pellegrino B Violante V Brusasco (1996) ArticleTitleMaximal bronchoconstriction in humans. Relationship to deep inhalation and airway sensitivity Am J Respir Crit Care Med 153 115–121
JR Beach SC Stenton MJ Connolly EH Walters DJ Hendrick (1995) ArticleTitleEffects of diurnal variation and prolonged refractoriness on repeated measurements of airways responsiveness to methacholine Thorax 50 235–239
JH Brown P Taylor (1996) Muscarinic receptor agonists and antagonists. In: Goodman and Gilman’s, The Pharmacological Basis of Therapeutics Mc Graw Hill, New York 141–160
A Cartier JL Malo P Begin M Sestier RR Martin (1983) ArticleTitleTime course of the bronchoconstriction induced by inhaled histamine and methacholine J Appl Physiol 54 821–826
JL Malo J L’Archeveque H Ghezzo A Cartier (1995) ArticleTitleThe reversibility of airway obstruction to an inhaled beta-adrenergic agent is less satisfactory after methacholine testing in asthmatic subjects Chest 107 1370–1374
F Mannino S Anticoli A Luca ParticleDe C Terzano (1996) ArticleTitleTime course of methacholine-induced broncoconstriction during drug and spontaneous resolution Allergol et Immunopathol 24 70–74
F Mannino B Sposato A, Ricci et al. (2001) ArticleTitleInduction and recovery phases of methacholine-induced broncoconstriction using FEV1 according to the degree of bronchial hyperresponsiveness Lung 179 137–145
PJ Merkus HM Rooda EE Essen-Zandvliet Particlevan et al. (1992) ArticleTitleAssessment of bronchodilatation after spontaneous recovery from a histamine challenge in asthmatic children Thorax 47 355–359
X Norel M Angrisani C, Labat et al. (1993) ArticleTitleDegradation of acethylcholine in human airways: role of butyrylcholinesterase Br J Pharmacol 108 914–919
G O’Connor D Sparrow D Taylor et al. (1987) ArticleTitleAnalysis of dose-response curves to methacholine Am Rev Respir Dis 136 1412–1417
SC Wu J Hildebrandt PD Isner et al. (1993) ArticleTitleEfficacy of anticholinergic and beta-adrenergic agonist. Treatment of maximal cholinergic bronchospasm in tracheally intubated rabbits Anest Analg 75 777–783
National Asthma Education, Prevention Program (1997) Expert panel report 2: guidelines for the diagnosis and management of asthma. National Institutes of Health, Bethesda. NHI Publication No. 97-4051
AS Glantz (1997) Primer of Biostatistics McGraw Hill Inc New York
EF Juniper PA Frith C, Dunnett et al. (1978) ArticleTitleReproducibility and comparison of responses to inhaled histamine and methacholine Thorax 33 705–710
K Yan C Salome AJ Woolcock (1983) ArticleTitleRapid method for measurement of bronchial responsiveness Thorax 38 760–765
Y Yagi M Kuwahara M Maeda et al. (1998) ArticleTitleAirway responsiveness to acetylcholine in congenitally bronchial-hypersensitive (BHS) and bronchial-hyposensitive (BHR) guinea pigs in vivo and in vitro Exp Anim 47 173–181
H Kadota M Kuwahara R Nishibata et al. (2001) ArticleTitleEffect of acetylcholinesterase activity on pathogenesis of airway hyperresponsiveness in guinea pigs Exp Anim 50 91–95
BM Sundblad K Larsson (2002) ArticleTitleEffect of deep inhalation after a bronchial methacholine pro-vocation in asthmatic and in non-asthmatic subjects Respir Med 96 477–481
Acknowledgment
This work as supported by grant no. 8111111 from the University La Sapienza, Rome
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Mariotta, S., Sposato, B., Ricci, A. et al. Time Intervals (3′ or 5′) Between Dose Steps Can Influence Methacholine Challenge Test. Lung 183, 1–11 (2005). https://doi.org/10.1007/s00408-004-2514-3
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/s00408-004-2514-3