Involvement of vascular endothelial growth factor in exercise induced bronchoconstriction in asthmatic patients.
BACKGROUND
There is evidence that the bronchial microcirculation has the potential to contribute to the pathophysiological mechanisms of exercise induced bronchoconstriction (EIB) in asthmatic subjects. Vascular endothelial growth factor (VEGF), which is highly expressed in asthmatic airways, increases vascular permeability. The relationship between VEGF levels in induced sputum and the severity of EIB in asthmatic subjects was studied.


METHODS
The concentration of VEGF in induced sputum was examined in 23 asthmatic subjects and 11 normal controls. The asthmatic subjects performed an exercise test and the % maximal fall in forced expiratory volume in 1 second (FEV(1)) was measured. Beclomethasone dipropionate (BDP) 400 micro g twice daily was administered to the asthmatic subjects for 8 weeks and the exercise test and sputum induction were repeated.


RESULTS
The concentration of VEGF in induced sputum was significantly higher in asthmatic subjects than in normal controls. There was a significant correlation between the concentration of VEGF and the % maximal fall in FEV(1) (r=0.826, p=0.0001) and between the concentration of VEGF and airway vascular permeability index (r=0.621, p=0.0037). After treatment with inhaled BDP there was a significant decrease in the concentration of VEGF in the asthmatic subjects (before treatment: 7051 (2361) pg/ml, after treatment: 4498 (2135) pg/ml, p<0.0001). The change in the concentration of VEGF was significantly correlated with the change in the % maximal fall in FEV(1) (r=0.463, p=0.031).


CONCLUSIONS
Excessive production of VEGF in asthmatic airways may contribute to the pathogenesis of EIB via increased airway vascular permeability.
D000280:Administration, Inhalation; D000328:Adult; D000420:Albuterol / Q000008:administration & dosage; D001250:Asthma, Exercise-Induced / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D016084:Bronchoconstriction / Q000187:drug effects*; D016085:Bronchoconstrictor Agents; D001993:Bronchodilator Agents / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D016228:Endothelial Growth Factors / Q000502:physiology*; D015444:Exercise / Q000502:physiology*; D005260:Female; D005541:Forced Expiratory Volume / Q000502:physiology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000502:physiology*; D008222:Lymphokines / Q000502:physiology*; D008297:Male; D016210:Methacholine Chloride; D013183:Sputum / Q000737:chemistry; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016085:Bronchoconstrictor Agents; D001993:Bronchodilator Agents; D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D016210:Methacholine Chloride; D000420:Albuterol