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. 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.


OBJECTIVE
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.


CONCLUSIONS
Mast cell localization to the ASM bundle, but not structural remodeling of the airway wall, is associated with AHR in asthma.
Institute of Lung Health, Leicester, United Kingdom.
Salman
S
Siddiqui
Vijay
V
Mistry
Camille
C
Doe
Katy
K
Roach
Angela
A
Morgan
Andrew
A
Wardlaw
Ian
I
Pavord
Peter
P
Bradding
Christopher
C
Brightling
D000328:Adult; D001249:Asthma / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D001485:Basement Membrane / Q000737:chemistry / Q000276:immunology / Q000473:pathology; D001980:Bronchi / Q000737:chemistry / Q000276:immunology / Q000473:pathology*; D016535:Bronchial Hyperreactivity / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D001991:Bronchitis / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D003094:Collagen / Q000032:analysis / Q000276:immunology; D004804:Eosinophils / Q000276:immunology; D005260:Female; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D008297:Male; D008407:Mast Cells / Q000276:immunology; D008875:Middle Aged; D009130:Muscle, Smooth / Q000276:immunology / Q000473:pathology*; D020545:Respiratory Mucosa / Q000737:chemistry / Q000276:immunology / Q000473:pathology*
D003094:Collagen