Airway hyperresponsiveness is dissociated from airway wall structural remodeling.

BACKGROUND: Nonasthmatic eosinophilic bronchitis (EB) has emerged as a useful tool to study the structural and inflammatory mechanisms of airway hyperresponsiveness (AHR) in asthma. We have previously shown that vascular remodeling and reticular basement membrane (RBM) thickening are present in EB....

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Main Authors: Siddiqui, S, Mistry, V, Doe, C, Roach, K, Morgan, A, Wardlaw, A, Pavord, I, Bradding, P, Brightling, C
Format: Journal article
Language:English
Published: 2008
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author Siddiqui, S
Mistry, V
Doe, C
Roach, K
Morgan, A
Wardlaw, A
Pavord, I
Bradding, P
Brightling, C
author_facet Siddiqui, S
Mistry, V
Doe, C
Roach, K
Morgan, A
Wardlaw, A
Pavord, I
Bradding, P
Brightling, C
author_sort Siddiqui, S
collection OXFORD
description BACKGROUND: Nonasthmatic eosinophilic bronchitis (EB) has emerged as a useful tool to study the structural and inflammatory mechanisms of airway hyperresponsiveness (AHR) in asthma. We have previously shown that vascular remodeling and reticular basement membrane (RBM) thickening are present in EB. However, it is not known whether other features of structural remodeling including increased airway smooth muscle (ASM) mass, matrix deposition, and glandular hyperplasia are also present in EB. OBJECTIVES: We sought to determine whether structural remodeling occurs in EB and is associated with AHR and airflow limitation. METHODS: Forty-two patients with asthma, 21 patients with EB, and 19 healthy volunteers were recruited. ASM area, RBM thickness, collagen 3 deposition, glandular area, mast cells, and granulocytes were assessed in bronchial biopsy samples. RESULTS: Nonasthmatic eosinophilic bronchitis and asthma were associated with a significant increase in ASM mass and RBM thickness compared with healthy subjects. In contrast, we did not observe any significant differences in collagen 3 deposition in the lamina propria and ASM or the % area of glands in the lamina propria. Univariate analysis demonstrated that mast cell numbers in the ASM were the only feature of remodeling associated with AHR (beta = -0.51; P = .004). Stepwise linear regression revealed that a combination of mast cell numbers in the ASM (beta = -0.43) and disease duration (beta = -0.25; model-adjusted R(2) = 0.26; P = .027) best modeled AHR. CONCLUSION: Mast cell localization to the ASM bundle, but not structural remodeling of the airway wall, is associated with AHR in asthma.
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spelling oxford-uuid:a11d96cc-727a-4a56-8b31-c2c3fee3f48b2022-03-27T02:10:43ZAirway hyperresponsiveness is dissociated from airway wall structural remodeling.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:a11d96cc-727a-4a56-8b31-c2c3fee3f48bEnglishSymplectic Elements at Oxford2008Siddiqui, SMistry, VDoe, CRoach, KMorgan, AWardlaw, APavord, IBradding, PBrightling, CBACKGROUND: Nonasthmatic eosinophilic bronchitis (EB) has emerged as a useful tool to study the structural and inflammatory mechanisms of airway hyperresponsiveness (AHR) in asthma. We have previously shown that vascular remodeling and reticular basement membrane (RBM) thickening are present in EB. However, it is not known whether other features of structural remodeling including increased airway smooth muscle (ASM) mass, matrix deposition, and glandular hyperplasia are also present in EB. OBJECTIVES: We sought to determine whether structural remodeling occurs in EB and is associated with AHR and airflow limitation. METHODS: Forty-two patients with asthma, 21 patients with EB, and 19 healthy volunteers were recruited. ASM area, RBM thickness, collagen 3 deposition, glandular area, mast cells, and granulocytes were assessed in bronchial biopsy samples. RESULTS: Nonasthmatic eosinophilic bronchitis and asthma were associated with a significant increase in ASM mass and RBM thickness compared with healthy subjects. In contrast, we did not observe any significant differences in collagen 3 deposition in the lamina propria and ASM or the % area of glands in the lamina propria. Univariate analysis demonstrated that mast cell numbers in the ASM were the only feature of remodeling associated with AHR (beta = -0.51; P = .004). Stepwise linear regression revealed that a combination of mast cell numbers in the ASM (beta = -0.43) and disease duration (beta = -0.25; model-adjusted R(2) = 0.26; P = .027) best modeled AHR. CONCLUSION: Mast cell localization to the ASM bundle, but not structural remodeling of the airway wall, is associated with AHR in asthma.
spellingShingle Siddiqui, S
Mistry, V
Doe, C
Roach, K
Morgan, A
Wardlaw, A
Pavord, I
Bradding, P
Brightling, C
Airway hyperresponsiveness is dissociated from airway wall structural remodeling.
title Airway hyperresponsiveness is dissociated from airway wall structural remodeling.
title_full Airway hyperresponsiveness is dissociated from airway wall structural remodeling.
title_fullStr Airway hyperresponsiveness is dissociated from airway wall structural remodeling.
title_full_unstemmed Airway hyperresponsiveness is dissociated from airway wall structural remodeling.
title_short Airway hyperresponsiveness is dissociated from airway wall structural remodeling.
title_sort airway hyperresponsiveness is dissociated from airway wall structural remodeling
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AT morgana airwayhyperresponsivenessisdissociatedfromairwaywallstructuralremodeling
AT wardlawa airwayhyperresponsivenessisdissociatedfromairwaywallstructuralremodeling
AT pavordi airwayhyperresponsivenessisdissociatedfromairwaywallstructuralremodeling
AT braddingp airwayhyperresponsivenessisdissociatedfromairwaywallstructuralremodeling
AT brightlingc airwayhyperresponsivenessisdissociatedfromairwaywallstructuralremodeling