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Basic fibroblast growth factor in asthma: Measurement in bronchoalveolar lavage fluid basally and following allergen challenge

https://doi.org/10.1067/mai.2001.112268Get rights and content

Abstract

Airway remodeling in asthma refers to a collection of chronic structural changes including subepithelial fibrosis, airway smooth muscle hypertrophy/hyperplasia, and possibly angiogenesis. The mechanisms leading to remodeling are not well defined. One molecule of possible relevance is basic fibroblast growth factor (bFGF), which is a potent mitogen for fibro-blasts, airway smooth muscle cells, and endothelial cells. To test the hypothesis that bFGF expression is increased in asthma, we measured levels of the growth factor in bronchoalveolar lavage (BAL) fluid. Basally, BAL fluid bFGF concentrations were significantly higher in subjects with atopic asthma than in control subjects without asthma (median 0.22 vs 0.06 pg/mL, P = .003). The effect of acute allergen exposure was examined with a segmental bronchoprovocation model in a separate group of subjects with atopic asthma. Ten minutes after segmental bronchoprovocation there was a 5-fold increase in bFGF levels in BAL fluid recovered from allergen-challenged sites compared with control saline-challenged sites (1.52 vs 0.30 pg/mL, P < .002). We conclude that basal levels of BAL fluid bFGF are increased in atopic asthma and that a further increase occurs in response to acute allergen exposure. These findings lend support to the hypothesis that bFGF is implicated in airway remodeling in asthma. (J Allergy Clin Immunol 2001;107:384-7.)

Section snippets

Subjects

For basal measurements, we studied 7 mildly symptomatic subjects with atopic asthma (all men, aged 22.3 ± 1.0 years) and 8 control subjects without asthma (1 man and 7 women, aged 30.9 ± 5.0 years, 2 atopic). The subjects with asthma were all treated with short-acting β2-agonists as required, but none had received oral or inhaled corticosteroids for at least 3 months. Control subjects were taking no regular medication. To examine bFGF release, we performed segmental allergen bronchoprovocation

Subject comparisons

Control subjects and subjects with asthma undergoing basal measurements did not differ significantly in age (P = .11), but FEV1% measurements were significantly lower for the subjects with asthma (85.2% ± 3.9% vs 103.6% ± 2.9%, P = .002). The subjects with asthma in this part of the study had varying degrees of airway hyperreactivity (geometric mean PC20 [provocative concentration of agonist producing a 20% fall in FEV1] methacholine, 0.88 mg/mL; range, 0.31-8.34 mg/mL), whereas the control

Discussion

In this study we have shown that basal levels of bFGF in BAL fluid are increased in atopic asthma and that a further increase occurs in response to allergen exposure. To our knowledge this report represents the first description of the in vivo expression of this growth factor in asthma.

One potential explanation for the rapid rise in BAL fluid bFGF after segmental allergen challenge would be release of the growth factor from mast cells. The immediate airway response to allergen is considered to

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Reprint requests: A. E. Redington, MD, Department of Respiratory Medicine, 2nd Floor, Thomas Guy House, Guy's Hospital, London SE1 9RT, England, UK.

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