Airway smooth muscle tone increases airway responsiveness in healthy young adults

Gazzola, M; Lortie, K; Henry, C; Mailhot-Larouche, S; Chapman, DG; Couture, C; Seow, CY; Paré, PD; King, GG; Boulet, LP; Bossé, Y

Airway smooth muscle tone increases airway responsiveness in healthy young adults

Gazzola, M Lortie, K Henry, C Mailhot-Larouche, S Chapman, DG

Couture, C Seow, CY Paré, PD King, GG Boulet, LP Bossé, Y

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Publication Type:: Journal Article
Citation:: American Journal of Physiology - Lung Cellular and Molecular Physiology, 2017, 312 (3), pp. L348 - L357
Issue Date:: 2017-03-01

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Field	Value	Language
dc.contributor.author	Gazzola, M	en_US
dc.contributor.author	Lortie, K	en_US
dc.contributor.author	Henry, C	en_US
dc.contributor.author	Mailhot-Larouche, S	en_US
dc.contributor.author	Chapman, DG https://orcid.org/0000-0002-8211-1817	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	King, GG	en_US
dc.contributor.author	Boulet, LP	en_US
dc.contributor.author	Bossé, Y	en_US
dc.date.available	2020-05-25T19:07:20Z
dc.date.issued	2017-03-01	en_US
dc.identifier.citation	American Journal of Physiology - Lung Cellular and Molecular Physiology, 2017, 312 (3), pp. L348 - L357	en_US
dc.identifier.issn	1040-0605	en_US
dc.identifier.uri	http://hdl.handle.net/10453/111977
dc.description.abstract	© 2017 the American Physiological Society. Force adaptation, a process whereby sustained spasmogenic activation (viz., tone) of airway smooth muscle (ASM) increases its contractile capacity, has been reported in isolated ASM tissues in vitro, as well as in mice in vivo. The objective of the present study was to assess the effect of tone on airway responsiveness in humans. Ten healthy volunteers underwent methacholine challenge on two occasions. One challenge consisted of six serial doses of saline followed by a single high dose of methacholine. The other consisted of six low doses of methacholine 5 min apart followed by a higher dose. The cumulative dose was identical for both challenges. After both methacholine challenges, subjects took a deep inspiration (DI) to total lung capacity as another way to probe ASM mechanics. Responses to methacholine and the DI were measured using a multifrequency forced oscillation technique. Compared with a single high dose, the challenge preceded by tone led to an elevated response measured by respiratory system resistance (Rrs) and reactance at 5 Hz. However, there was no difference in the increase in Rrs at 19 Hz, suggesting a predominant effect on smaller airways. Increased tone also reduced the efficacy of DI, measured by an attenuated maximal dilation during the DI and an increased renarrowing post-DI. We conclude that ASM tone increases small airway responsiveness to inhaled methacholine and reduces the effectiveness of DI in healthy humans. This suggests that force adaptation may contribute to airway hyperresponsiveness and the reduced bronchodilatory effect of DI in asthma.	en_US
dc.relation.ispartof	American Journal of Physiology - Lung Cellular and Molecular Physiology	en_US
dc.relation.isbasedon	10.1152/ajplung.00400.2016	en_US
dc.subject.classification	Respiratory System	en_US
dc.subject.mesh	Muscle, Smooth	en_US
dc.subject.mesh	Lung	en_US
dc.subject.mesh	Bronchi	en_US
dc.subject.mesh	Humans	en_US
dc.subject.mesh	Respiratory Hypersensitivity	en_US
dc.subject.mesh	Methacholine Chloride	en_US
dc.subject.mesh	Spirometry	en_US
dc.subject.mesh	Oscillometry	en_US
dc.subject.mesh	Respiratory Mechanics	en_US
dc.subject.mesh	Inhalation	en_US
dc.subject.mesh	Muscle Tonus	en_US
dc.subject.mesh	Adult	en_US
dc.subject.mesh	Health	en_US
dc.subject.mesh	Female	en_US
dc.subject.mesh	Male	en_US
dc.subject.mesh	Young Adult	en_US
dc.title	Airway smooth muscle tone increases airway responsiveness in healthy young adults	en_US
dc.type	Journal Article
utslib.citation.volume	3	en_US
utslib.citation.volume	312	en_US
utslib.for	0606 Physiology	en_US
utslib.for	1116 Medical Physiology	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	open_access
pubs.issue	3	en_US
pubs.publication-status	Published	en_US
pubs.volume	312	en_US

Abstract:

© 2017 the American Physiological Society. Force adaptation, a process whereby sustained spasmogenic activation (viz., tone) of airway smooth muscle (ASM) increases its contractile capacity, has been reported in isolated ASM tissues in vitro, as well as in mice in vivo. The objective of the present study was to assess the effect of tone on airway responsiveness in humans. Ten healthy volunteers underwent methacholine challenge on two occasions. One challenge consisted of six serial doses of saline followed by a single high dose of methacholine. The other consisted of six low doses of methacholine 5 min apart followed by a higher dose. The cumulative dose was identical for both challenges. After both methacholine challenges, subjects took a deep inspiration (DI) to total lung capacity as another way to probe ASM mechanics. Responses to methacholine and the DI were measured using a multifrequency forced oscillation technique. Compared with a single high dose, the challenge preceded by tone led to an elevated response measured by respiratory system resistance (Rrs) and reactance at 5 Hz. However, there was no difference in the increase in Rrs at 19 Hz, suggesting a predominant effect on smaller airways. Increased tone also reduced the efficacy of DI, measured by an attenuated maximal dilation during the DI and an increased renarrowing post-DI. We conclude that ASM tone increases small airway responsiveness to inhaled methacholine and reduces the effectiveness of DI in healthy humans. This suggests that force adaptation may contribute to airway hyperresponsiveness and the reduced bronchodilatory effect of DI in asthma.

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http://hdl.handle.net/10453/111977