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Independent and combined effects of airway remodelling and allergy on airway responsiveness


Wang, KCW and Le Cras, TD and Larcombe, AN and Zosky, GR and Elliot, JG and James, AL and Noble, PB, Independent and combined effects of airway remodelling and allergy on airway responsiveness, Clinical Science, 132, (3) pp. 327-338. ISSN 0143-5221 (2018) [Refereed Article]

Copyright Statement

Copyright 2018 the Authors

DOI: doi:10.1042/CS20171386


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.

Item Details

Item Type:Refereed Article
Keywords:asthma, airway smooth muscle, allergy, airway hyperresponsiveness
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:125424
Year Published:2018
Web of Science® Times Cited:17
Deposited By:Medicine
Deposited On:2018-04-17
Last Modified:2022-08-25

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