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. 2008 Aug;122(2):335-41, 341.e1-3.
doi: 10.1016/j.jaci.2008.05.020. Epub 2008 Jun 24.

Airway hyperresponsiveness is dissociated from airway wall structural remodeling

Salman Siddiqui  1 , Vijay Mistry, Camille Doe, Katy Roach, Angela Morgan, Andrew Wardlaw, Ian Pavord, Peter Bradding, Christopher Brightling
Affiliations

Airway hyperresponsiveness is dissociated from airway wall structural remodeling

Salman Siddiqui et al. J Allergy Clin Immunol. 2008 Aug.

Abstract

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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Figures

FIG E1
FIG E1
Correlation between SQS (x-axis) and thresholded collagen 3 deposition (y-axis) in the lamina propria. The regression line crosses the x-axis at 1, suggesting that the threshold appropriately excluded weak or absent staining assessed visually as noise.
FIG 1
FIG 1. Increased ASM area in asthma and EB.
Representative photomicrographs of smooth muscle actin–immunostained mucosal biopsies (×100 magnification) in healthy subject (A), EB (B), and refractory asthma (C). D, Dot plot of percentage ASM in subjects with asthma with severity defined according to GINA, subjects with EB, and healthy subjects.
FIG 2
FIG 2. Reduced collagen 3 deposition in the lamina propria in moderate asthma.
Representative photomicrographs of collagen 3 staining (left) and corresponding thresholded collagen 3 (right) in the lamina propria in mucosal biopsies in healthy subject (A and B), EB (C and D), and asthma (E and F) (×25 magnification). G, Dot plot of percent collagen 3 expression in the lamina propria in subjects with asthma with severity defined according to GINA, subjects with EB, and healthy controls.
FIG 3
FIG 3. Mast cell numbers in the ASM in asthma correlate with AHR.
A, Dot plot of mast cell numbers (horizontal bar, mean) in the ASM in controls, subjects with asthma with severity defined according to GINA, subjects with refractory asthma, and patients with EB. B, Correlation of mast cell numbers in the ASM (x-axis) and methacholine PC20 in asthma (y-axis).
See this image and copyright information in PMC

Comment in

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