Airway hyperresponsiveness is dissociated from airway structural remodeling

Institute of Lung Health, Leicester, United Kingdom.
The Journal of allergy and clinical immunology (Impact Factor: 11.48). 07/2008; 122(2):335-41, 341.e1-3. DOI: 10.1016/j.jaci.2008.05.020
Source: PubMed


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.
We sought to determine whether structural remodeling occurs in EB and is associated with AHR and airflow limitation.
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.
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.
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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Available from: Katy M Roach, Mar 31, 2015
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    • "Though it is difficult to associate aspects of remodeling with disease severity or degree of airways obstruction and hyperresponsiveness (Mauad et al., 2007), some investigators indicated that smooth muscle remodeling is related to the severity of asthma (James et al., 2009). It has shown that the clinical expression of asthma (Brightling et al., 2002), AHR (Siddiqui et al., 2008) and impaired airway relaxation (Slats et al., 2007) are associated with mast cell counts in the ASM layer in asthma. The deposition of extracellular matrix inside and outside the smooth muscle layer in asthma also seems to be related to its clinical severity and is altered as compared to healthy controls (Araujo et al., 2008; Klagas et al., 2009). "
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    • "Airway smooth muscle cells are the major effector cells regulating bronchomotor tone in response to several mediators [98]. Some authors have reported that increased vascularity, reticular basement membrane thickening, and increased airway smooth muscle mass are features of both diseases [99, 100]. However, the same authors have recently reported that patients with asthma had airway wall thickening, as opposed to subjects with NAEB, who maintained airway patency without wall thickening [101]. "
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