Relationships of methacholine and adenosine monophosphate responsiveness with serum vascular endothelial growth factor in children with asthma

Background: Airway hyperresponsiveness, which is a characteristic feature of asthma, is usually measured by means of bronchial challenge with direct or indirect stimuli. Vascular endothelial growth factor (VEGF) increases vascular permeability and angiogenesis, leads to mucosal edema, narrows the airway diameter, and reduces airway flow. Objective: To examine the relationships between serum VEGF level and airway responsiveness to methacholine and adenosine monophosphate (AMP) in children with asthma. Methods: Peripheral blood eosinophil counts, serum eosinophil cationic protein (ECP) concentrations, and serum VEGF concentrations were measured in 31 asthmatic children and 26 control subjects. Methacholine and AMP bronchial challenges were performed on children with asthma. Results: Children with asthma had a significantly higher mean (SD) level of VEGF than controls (361.2 [212.0] vs 102.7 [50.0] pg/mL; P < .001). Blood eosinophil counts and serum ECP levels significantly correlated inversely with AMP provocation concentration that caused a decrease in forced expiratory volume in 1 second of 20% (PC₂₀) (r = -0.474, P =.01; r = -0.442, P =.03, respectively), but not with methacholine PC₂₀ (r=-0.228, P = .26; r=-0.338, P =.10, respectively). Serum VEGF levels significantly correlated with airway responsiveness to AMP (r=-0.462; P = .009) but not to methacholine (r=-0.243; P = .19). Conclusions: Serum VEGF levels were increased in children with asthma and were related to airway responsiveness to AMP but not to methacholine. Increased VEGF levels in asthmatic children may result in increased airway responsiveness by mechanisms related to airway inflammation or increased permeability of airway vasculature.