Bronchial hyper-responsiveness, subepithelial fibrosis, and transforming growth factor-beta(1) expression in patients with long-standing and recently diagnosed asthma.
BACKGROUND
Chronic inflammation in asthmatic airways leads to bronchial hyper-responsiveness (BHR) and the development of structural changes. Important features of remodeling include the formation of subepithelial fibrosis due to increased collagen deposition in the reticular basement membrane. Transforming growth factor (TGF)-beta might be a central mediator of tissue fibrosis and remodeling.


METHODS
Immunohistochemistry was used to measure collagen III deposition and TGF-beta(1) expression in biopsies from patients with long-standing asthma treated with inhaled corticosteroids, patients with recently diagnosed asthma, and control subjects. Computer-assisted image analysis was used to evaluate total basement membrane (TBM) thickness.


RESULTS
Asthmatics, particularly those with long-standing asthma, had thicker TBMs than healthy subjects. Collagen III deposition was comparable in the studied groups. BHR was not correlated with features of mucosal inflammation and was lower in steroid-treated patients with long-standing asthma than in subjects with newly diagnosed asthma untreated with steroids. Epithelial TGF-beta(1) expression negatively correlated with collagen III deposition and TBM thickness.


CONCLUSIONS
The study showed that TBM thickness, but not collagen III deposition, could be a differentiating marker of asthmatics of different disease duration and treatment. The lack of correlation between BHR and features of mucosal inflammation suggests the complexity of BHR development. Corticosteroids can reduce BHR in asthmatics, but it seems to be less effective in reducing subepithelial fibrosis. The role of epithelial TGF-beta(1) needs to be further investigated since the possibility that it plays a protective and anti-inflammatory role in asthmatic airways cannot be excluded.
Tomkowicz
Aneta
A
Department of Dietetics, Faculty of Public Health, Wrocław Medical University, Bartla 5, 51-618 Wrocław, Poland. anewla@wp.pl
Kraus-Filarska
Maria
M
Bar
Julia
J
Rabczyński
Jerzy
J
Jeleń
Michał
M
Piesiak
Paweł
P
Fal
Andrzej
A
Panaszek
Bernard
B
D000328:Adult; D000368:Aged; D001249:Asthma / Q000378:metabolism*; D001980:Bronchi / Q000378:metabolism*; D003094:Collagen / Q000378:metabolism; D005260:Female; D005355:Fibrosis / Q000473:pathology; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry / Q000379:methods; D007249:Inflammation / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
D053773:Transforming Growth Factor beta1; D003094:Collagen