Airway remodelling and allergic inflammation are key features of airway hyperresponsiveness (AHR) in asthma; however, their interrelationships are unclear. The present study investigated the separate and combined effects of increased airway smooth muscle (ASM) layer thickness and allergy on AHR. We integrated a protocol of ovalbumin (OVA)-induced allergy into a non-inflammatory mouse model of ASM remodelling induced by conditional and airway-specific expression of transforming growth factor-α (TGF-α) in early growth response-1 (Egr-1)-deficient transgenic mice, which produced thickening of the ASM layer following ingestion of doxycycline. Mice were sensitised to OVA and assigned to one of four treatment groups: Allergy – normal chow diet and OVA challenge; Remodelling – doxycycline in chow and saline challenge; Allergy and Remodelling – doxycycline in chow and OVA challenge; and Control – normal chow diet and saline challenge. Airway responsiveness to methacholine (MCh) and histology were assessed. Compared with the Control group, airway responsiveness to MCh was increased in the Allergy group, independent of changes in wall structure, whereas airway responsiveness in the Remodelling group was increased independent of exposure to aeroallergen. The combined effects of allergy and remodelling on airway responsiveness were greater than either of them alone. There was a positive relationship between the thickness of the ASM layer with airway responsiveness, which was shifted upward in the presence of allergy. These findings support allergy and airway remodelling as independent causes of variable and excessive airway narrowing.
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February 2018
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Cover Image
Cover Image
A representative image of an airway from a mouse sensitized and challenged with an allergen. The histological image was captured 24 hours after allergen exposure at which point airway hyperresponsiveness persists without any discernible change to wall structure. In Clinical Science volume 132, issue 3, Wang et al. report on the effects of airway remodelling and allergy on airway responsiveness; for details see pages 327–338. Image kindly provided by Kimberley C.W. Wang (The University of Western Australia).
Research Article|
February 02 2018
Independent and combined effects of airway remodelling and allergy on airway responsiveness
Kimberley C.W. Wang
;
1Telethon Kids Institute, The University of Western Australia, Subiaco, Western Australia, Australia
2School of Human Sciences, The University of Western Australia, Crawley, Western Australia, Australia
Correspondence: Kimberley C.W. Wang ([email protected])
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Timothy D. Le Cras;
Timothy D. Le Cras
3Division of Pulmonary Biology, Cincinnati Children’s Hospital Medical Center and Department of Pediatrics, University of Cincinnati School of Medicine, Cincinnati, OH, U.S.A.
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Alexander N. Larcombe;
Alexander N. Larcombe
1Telethon Kids Institute, The University of Western Australia, Subiaco, Western Australia, Australia
4School of Public Health, Curtin University, Perth, Western Australia, Australia
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Graeme R. Zosky;
Graeme R. Zosky
1Telethon Kids Institute, The University of Western Australia, Subiaco, Western Australia, Australia
5School of Medicine, University of Tasmania, Hobart, Tasmania, Australia
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John G. Elliot;
John G. Elliot
6Department of Pulmonary Physiology and Sleep Medicine, West Australian Sleep Disorders Research Institute, Sir Charles Gairdner Hospital, Nedlands, Australia
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Alan L. James;
Alan L. James
6Department of Pulmonary Physiology and Sleep Medicine, West Australian Sleep Disorders Research Institute, Sir Charles Gairdner Hospital, Nedlands, Australia
7School of Medicine and Pharmacology, The University of Western Australia, Crawley, Western Australia, Australia
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Peter B. Noble
Peter B. Noble
1Telethon Kids Institute, The University of Western Australia, Subiaco, Western Australia, Australia
2School of Human Sciences, The University of Western Australia, Crawley, Western Australia, Australia
8Centre for Neonatal Research and Education, School of Paediatrics and Child Health, The University of Western Australia, Perth, Western Australia, Australia
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Publisher: Portland Press Ltd
Received:
September 26 2017
Revision Received:
December 08 2017
Accepted:
December 21 2017
Accepted Manuscript online:
December 22 2017
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society
2018
Clin Sci (Lond) (2018) 132 (3): 327–338.
Article history
Received:
September 26 2017
Revision Received:
December 08 2017
Accepted:
December 21 2017
Accepted Manuscript online:
December 22 2017
Citation
Kimberley C.W. Wang, Timothy D. Le Cras, Alexander N. Larcombe, Graeme R. Zosky, John G. Elliot, Alan L. James, Peter B. Noble; Independent and combined effects of airway remodelling and allergy on airway responsiveness. Clin Sci (Lond) 14 February 2018; 132 (3): 327–338. doi: https://doi.org/10.1042/CS20171386
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