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Assessment of airway response distribution and paradoxical airway dilation in mice during methacholine challenge


Dubsky, S and Zosky, GR and Perks, K and Samarage, CR and Henon, Y and Hooper, SB and Fouras, A, Assessment of airway response distribution and paradoxical airway dilation in mice during methacholine challenge, Journal of Applied Physiology, 122, (3) pp. 503-510. ISSN 8750-7587 (2017) [Refereed Article]

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Copyright 2017 the American Physiological Society

DOI: doi:10.1152/japplphysiol.00476.2016


Detailed information on the distribution of airway diameters during bronchoconstriction in situ is required in order to understand the regional response of the lungs. Imaging studies using computed tomography (CT) have previously measured airway diameters and changes in response to bronchoconstricting agents, but the manual measurements used have severely limited the number of airways measured per subject. Hence, the detailed distribution and heterogeneity of airway responses is unknown. We have developed and applied dynamic imaging and advanced image-processing methods to quantify and compare hundreds of airways in vivo. The method, based on CT, was applied to house-dust-mite sensitized and control mice during intravenous methacholine infusion. Airway diameters were measured pre- and post-methacholine challenge, and the results compared to demonstrate the distribution of airway response throughout the lungs during mechanical ventilation. Forced oscillation testing was used to measure the global response in lung mechanics. We found marked heterogeneity in the response, with paradoxical dilation of airways present at all airway sizes. The probability of paradoxical dilation decreased with decreasing baseline airway diameter and was not affected by pre-existing inflammation. The results confirm the importance of considering the lung as an entire interconnected system, rather than a collection of independent units. It is hoped that the response distribution measurements can help to elucidate the mechanisms that lead to heterogeneous airway response in vivo.

Item Details

Item Type:Refereed Article
Keywords:airway heterogeneity, 4DCT, methacholine challenge, mice
Research Division:Biomedical and Clinical Sciences
Research Group:Cardiovascular medicine and haematology
Research Field:Respiratory diseases
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Zosky, GR (Professor Graeme Zosky)
ID Code:113703
Year Published:2017 (online first 2016)
Funding Support:National Health and Medical Research Council (1077905)
Web of Science® Times Cited:21
Deposited By:Medicine
Deposited On:2017-01-16
Last Modified:2018-11-19
Downloads:60 View Download Statistics

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