Smooth muscle in the maintenance of increased airway resistance elicited by methacholine in humans

Chapman, DG; Pascoe, CD; Lee-Gosselin, A; Couture, C; Seow, CY; Paré, PD; Salome, CM; King, GG; Bossé, Y

Smooth muscle in the maintenance of increased airway resistance elicited by methacholine in humans

Chapman, DG

Pascoe, CD Lee-Gosselin, A Couture, C Seow, CY Paré, PD Salome, CM King, GG Bossé, Y

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Publication Type:: Journal Article
Citation:: American Journal of Respiratory and Critical Care Medicine, 2014, 190 (8), pp. 879 - 885
Issue Date:: 2014-01-01

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Field	Value	Language
dc.contributor.author	Chapman, DG https://orcid.org/0000-0002-8211-1817	en_US
dc.contributor.author	Pascoe, CD	en_US
dc.contributor.author	Lee-Gosselin, A	en_US
dc.contributor.author	Couture, C	en_US
dc.contributor.author	Seow, CY	en_US
dc.contributor.author	Paré, PD	en_US
dc.contributor.author	Salome, CM	en_US
dc.contributor.author	King, GG	en_US
dc.contributor.author	Bossé, Y	en_US
dc.date.issued	2014-01-01	en_US
dc.identifier.citation	American Journal of Respiratory and Critical Care Medicine, 2014, 190 (8), pp. 879 - 885	en_US
dc.identifier.issn	1073-449X	en_US
dc.identifier.uri	http://hdl.handle.net/10453/118811
dc.description.abstract	Copyright © 2014 by the American Thoracic Society. Rationale: Airway narrowing is maintained for a prolonged period after acute bronchoconstriction in humans in the absence of deep inspirations (DIs). Objectives: To determine whether maintenance of airway smooth muscle (ASM) shortening is responsible for the persistence of airway narrowing in healthy subjects following transient methacholine (MCh)-induced bronchoconstriction. Methods: On two separate visits, five healthy subjects underwent MCh challenges until respiratory system resistance (Rrs) had increased by approximately 1.5 cm H<inf>2</inf>O/L/s. Subjects took a DI either immediately after or 30 minutes after the last dose. The extent of renarrowing following the bronchodilator effect of DI was used to assess the continued action of MCh (calculated as percent change in Rrs from the pre-DI Rrs). We then used human bronchial rings to determine whether ASM can maintain shortening during a progressive decrease of carbachol concentration. Measurements and Main Results: The increased Rrs induced by MCh was maintained for 30 minutes despite waning of MCh concentration over that period, measured as attenuated renarrowing when the DI was taken 30 minutes after compared with immediately after the last dose (7 min post-DI, -36.2 ± 11.8 vs. 14.4 ± 13.2%; 12 min post-DI, -39.5 ± 9.8 vs. 15.2 ± 17.8%). Ex vivo, ASMshortening was largely maintained during a progressive decrease of carbachol concentration, even down to concentrations that would not be expected to induce shortening. Conclusions: The maintenance of airway narrowing despite MCh clearance in humans is attributed to an intrinsic ability of ASM to maintain shortening during a progressive decrease of contractile stimulation.	en_US
dc.relation.ispartof	American Journal of Respiratory and Critical Care Medicine	en_US
dc.relation.isbasedon	10.1164/rccm.201403-0502OC	en_US
dc.subject.classification	Respiratory System	en_US
dc.subject.mesh	Muscle, Smooth	en_US
dc.subject.mesh	Bronchi	en_US
dc.subject.mesh	Humans	en_US
dc.subject.mesh	Methacholine Chloride	en_US
dc.subject.mesh	Bronchoconstrictor Agents	en_US
dc.subject.mesh	Airway Resistance	en_US
dc.subject.mesh	Bronchial Provocation Tests	en_US
dc.subject.mesh	Bronchoconstriction	en_US
dc.subject.mesh	Inhalation	en_US
dc.subject.mesh	Adult	en_US
dc.subject.mesh	Middle Aged	en_US
dc.subject.mesh	Male	en_US
dc.subject.mesh	Healthy Volunteers	en_US
dc.title	Smooth muscle in the maintenance of increased airway resistance elicited by methacholine in humans	en_US
dc.type	Journal Article
utslib.citation.volume	8	en_US
utslib.citation.volume	190	en_US
utslib.for	1102 Cardiorespiratory Medicine and Haematology	en_US
utslib.for	1103 Clinical Sciences	en_US
utslib.for	11 Medical and Health Sciences	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
utslib.copyright.status	closed_access
pubs.issue	8	en_US
pubs.publication-status	Published	en_US
pubs.volume	190	en_US

Abstract:

Copyright © 2014 by the American Thoracic Society. Rationale: Airway narrowing is maintained for a prolonged period after acute bronchoconstriction in humans in the absence of deep inspirations (DIs). Objectives: To determine whether maintenance of airway smooth muscle (ASM) shortening is responsible for the persistence of airway narrowing in healthy subjects following transient methacholine (MCh)-induced bronchoconstriction. Methods: On two separate visits, five healthy subjects underwent MCh challenges until respiratory system resistance (Rrs) had increased by approximately 1.5 cm H2O/L/s. Subjects took a DI either immediately after or 30 minutes after the last dose. The extent of renarrowing following the bronchodilator effect of DI was used to assess the continued action of MCh (calculated as percent change in Rrs from the pre-DI Rrs). We then used human bronchial rings to determine whether ASM can maintain shortening during a progressive decrease of carbachol concentration. Measurements and Main Results: The increased Rrs induced by MCh was maintained for 30 minutes despite waning of MCh concentration over that period, measured as attenuated renarrowing when the DI was taken 30 minutes after compared with immediately after the last dose (7 min post-DI, -36.2 ± 11.8 vs. 14.4 ± 13.2%; 12 min post-DI, -39.5 ± 9.8 vs. 15.2 ± 17.8%). Ex vivo, ASMshortening was largely maintained during a progressive decrease of carbachol concentration, even down to concentrations that would not be expected to induce shortening. Conclusions: The maintenance of airway narrowing despite MCh clearance in humans is attributed to an intrinsic ability of ASM to maintain shortening during a progressive decrease of contractile stimulation.

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http://hdl.handle.net/10453/118811