Analysis of Growth Factors and Inflammatory Cytokines in Exhaled Breath Condensate from Asthmatic Children

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Abstract
Vascular endothelial growth factor (VEGF), AA isoform of platelet-derived growth factor (PDGF-AA), and epidermal growth factor (EGF) are involved in the pathogenesis of airway inflammation in asthma. These molecules are closely associated with cytokines such as tumor necrosis factor-alpha (TNF-alpha) and interleukin (IL)-4. This study investigates the relation between childhood asthma and levels of these mediators in exhaled breath condensate (EBC). EBC was collected from asthmatic children and controls using a disposable collection kit, and the concentrations of VEGF, PDGF-AA, EGF, TNF-alpha and IL-4 in EBC were measured using sandwich enzyme immunoassays. Exhaled nitric oxide concentration was measured by a chemiluminescence analyzer. Thirty-five asthmatic patients aged between 7 and 18 years and 11 controls were recruited. Sixteen patients had intermittent asthma (IA) whereas 19 of them suffered from persistent asthma (PA). A significant correlation was found between IL-4 and TNF-alpha in EBC (rho = 0.374, p = 0.010). PDGF-AA levels in EBC were higher in subjects with diminished FEV1 (p = 0.023) whereas IL-4 concentrations were increased in asthmatics (p = 0.007) as well as subjects with increased plasma total IgE (p = 0.033). Patients with PA receiving high-dose inhaled corticosteroid (ICS) had higher EBC IL-4 concentration than those on low-dose ICS (p = 0.007). Linear regression revealed that PDGF-AA levels in EBC were negatively associated with FEV1 percentage (beta = -0.459, p = 0.006) among the asthmatic patients. IL-4 in EBC is increased in childhood asthma, and growth factors are detectable in a significant proportion of these children. Increased PDGF-AA is found in asthmatics with more severe airflow limitation.