Literature DB >> 18572228

Airway hyperresponsiveness is dissociated from airway wall structural remodeling.

Salman Siddiqui1, Vijay Mistry, Camille Doe, Katy Roach, Angela Morgan, Andrew Wardlaw, Ian Pavord, Peter Bradding, Christopher Brightling.   

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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Year:  2008        PMID: 18572228      PMCID: PMC3992373          DOI: 10.1016/j.jaci.2008.05.020

Source DB:  PubMed          Journal:  J Allergy Clin Immunol        ISSN: 0091-6749            Impact factor:   10.793


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