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

Kimberley Cw Wang, Timothy D Le Cras, Alexander N Larcombe, Graeme R Zosky, John G Elliot, Alan L James, Peter B Noble

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Airway remodelling and allergic inflammation are key features of airway hyperresponsiveness in asthma, however their interrelationships are unclear. This study investigated the separate and combined effects of increased airway smooth muscle (ASM) layer thickness and allergy on airway hyperresponsiveness. 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 TGF-α in 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 and histology were assessed. Compared with the Control group, airway responsiveness to methacholine was increased in the Allergy group, independently 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 alone. There was a positive relationship between the thickness of the ASM layer with airway responsiveness, which was upward shifted in the presence of allergy. These findings support allergy and airway remodelling as independent causes of variable and excessive airway narrowing.

Original languageEnglish
Article numberCS20171386
Pages (from-to)327-338
JournalClinical Science
Volume132
Issue number3
DOIs
Publication statusPublished - 14 Feb 2018

Fingerprint

Airway Remodeling
Hypersensitivity
Ovalbumin
Smooth Muscle
Doxycycline
Methacholine Chloride
Diet
Transgenic Mice
Histology
Asthma
Eating
Inflammation
Control Groups

Cite this

@article{3b9a6310c1384a3b9c0a8064c97cad2a,
title = "Independent and combined effects of airway remodelling and allergy on airway responsiveness",
abstract = "Airway remodelling and allergic inflammation are key features of airway hyperresponsiveness in asthma, however their interrelationships are unclear. This study investigated the separate and combined effects of increased airway smooth muscle (ASM) layer thickness and allergy on airway hyperresponsiveness. 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 TGF-α in 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 and histology were assessed. Compared with the Control group, airway responsiveness to methacholine was increased in the Allergy group, independently 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 alone. There was a positive relationship between the thickness of the ASM layer with airway responsiveness, which was upward shifted in the presence of allergy. These findings support allergy and airway remodelling as independent causes of variable and excessive airway narrowing.",
keywords = "Journal Article",
author = "Wang, {Kimberley Cw} and {Le Cras}, {Timothy D} and Larcombe, {Alexander N} and Zosky, {Graeme R} and Elliot, {John G} and James, {Alan L} and Noble, {Peter B}",
note = "{\circledC}2017 The Author(s).",
year = "2018",
month = "2",
day = "14",
doi = "10.1042/CS20171386",
language = "English",
volume = "132",
pages = "327--338",
journal = "Clinical Science",
issn = "0143-5221",
publisher = "Portland Press Ltd.",
number = "3",

}

Independent and combined effects of airway remodelling and allergy on airway responsiveness. / Wang, Kimberley Cw; Le Cras, Timothy D; Larcombe, Alexander N; Zosky, Graeme R; Elliot, John G; James, Alan L; Noble, Peter B.

In: Clinical Science, Vol. 132, No. 3, CS20171386, 14.02.2018, p. 327-338.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Independent and combined effects of airway remodelling and allergy on airway responsiveness

AU - Wang, Kimberley Cw

AU - Le Cras, Timothy D

AU - Larcombe, Alexander N

AU - Zosky, Graeme R

AU - Elliot, John G

AU - James, Alan L

AU - Noble, Peter B

N1 - ©2017 The Author(s).

PY - 2018/2/14

Y1 - 2018/2/14

N2 - Airway remodelling and allergic inflammation are key features of airway hyperresponsiveness in asthma, however their interrelationships are unclear. This study investigated the separate and combined effects of increased airway smooth muscle (ASM) layer thickness and allergy on airway hyperresponsiveness. 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 TGF-α in 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 and histology were assessed. Compared with the Control group, airway responsiveness to methacholine was increased in the Allergy group, independently 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 alone. There was a positive relationship between the thickness of the ASM layer with airway responsiveness, which was upward shifted in the presence of allergy. These findings support allergy and airway remodelling as independent causes of variable and excessive airway narrowing.

AB - Airway remodelling and allergic inflammation are key features of airway hyperresponsiveness in asthma, however their interrelationships are unclear. This study investigated the separate and combined effects of increased airway smooth muscle (ASM) layer thickness and allergy on airway hyperresponsiveness. 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 TGF-α in 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 and histology were assessed. Compared with the Control group, airway responsiveness to methacholine was increased in the Allergy group, independently 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 alone. There was a positive relationship between the thickness of the ASM layer with airway responsiveness, which was upward shifted in the presence of allergy. These findings support allergy and airway remodelling as independent causes of variable and excessive airway narrowing.

KW - Journal Article

U2 - 10.1042/CS20171386

DO - 10.1042/CS20171386

M3 - Article

VL - 132

SP - 327

EP - 338

JO - Clinical Science

JF - Clinical Science

SN - 0143-5221

IS - 3

M1 - CS20171386

ER -