A. Nakonechna 1 , J. Antipkin 2 ,T. Umanets 2 , V. Lapshyn 2 , N. Goncharenko 2

1. The impact of endothelial dysfunction on airway responsiveness and asthma severity in children A. Nakonechna1, J. Antipkin2,T. Umanets2, V. Lapshyn2, N. Goncharenko2 Poster 1477 1) Royal Liverpool and Broadgreen University Hospitals NHS Trust, Liverpool, United Kingdom 2) Institute of Pediatry, Obstetrics and Gynaecology, Kiev, Ukraine E-mail: allergy@novidec.com INTRODUCTION MATERIALS AND METHODS Airway remodelling in asthma include specific changes to the vasculature. However, the definite evidences on whether structural endothelial alterations can link with persistent airway hyperresponsiveness and severity of childhood asthma are still unclear. We investigated the impact of endothelial dysfunction on airway responsiveness and asthma severity in children. • 185 children aged 6-12 years with bronchial asthma (BA) • 52 age-matched healthy controls were observed • Diagnosis and assessment of asthma based on: • Clinical questionnaire (respiratory symptoms, frequency of episodes of asthma, family history, medication, duration of asthma) • Physical examination • Allergy skin prick tests (SPTs) - cat, dog, house dust mite, D. pharine, D.pteronissinus, grass mix, tree mix, Alternaria, Aspergilus, Cladosporium, food allergens (egg, milk, wheat, fish, soya, meat, nuts) • Total IgE and antigen specific IgE • Lung functions • Bronchial hyperreactivity (BHR) test with methacholine - provocation concentration of methacholine needed to produce a 20% fall in FEV1 (PC20, FEV1) • Endothelial cell function - measure of endothelial cell response to stimulation • Endothelium-dependent dilatation (EDD) - was assessed in the flow-mediated vasodilation (FMD) test during reactive hyperaemia by high-frequency ultrasonography of the brachial artery. Graphs • All children with bronchial asthma (185) were divided in 2 groups according to asthma severity, that was assessed by: FEV1, Peak Expiratory Flow (PEF) variability and daily symptom scores (Pic.1): • Group I – children with mild asthma (52 pat.) - 28,2% • Group II- children with moderate asthma (133 pat.) - 71,8% • Diagnosis of BA was confirmed by positive SPT and increased total IgE (376 ±12 KU/l in Gr.I and 498±10 KU/l in Gr.II )and specific IgE levels, that were more expressive in a group with moderate asthma (Pic.2) • The provocative concentration of methacholine causing a 20% fall in FEV1 (PC20, FEV1) was decreased in all asthmatic children, but more significant in moderate asthma. • Remarkable, that decreasing of PC20 associated with: • lower levels of lung function (percent predicted FEV1 and percent predicted FVC) • the occurrence of asthma symptoms (shortness of breath, persistent wheezing, or exercise-induced cough and wheeze) • longer duration of asthma • This relationship was such that the lower the PC20 - the lower were the level of FEV1 percent predicted, the higher number of symptoms and the longer the duration of asthma (p<0,001). • The investigation of the endothelial cells function shown : • 1)The outlet diameter of arteria brachialis was expressively bigger in asthmatic children compared with control group, and more significant was in Gr.II (Pic.4a) • 2)Calculations of Doppler parameters shown that: • a) The peak systolic velocity (PSV) in asthmatic children was reliably higher than in control group and more elevated in moderate asthma children (Gr.II). (Pic.4b) • b) Resistive index (RI) and pulsatility index (PI) reduced in all asthmatic children, but more convincing in Gr.II with moderate asthma (Pic.4c). • The elevating of PSV together with the reduction of resistive index (RI) and pulsatility index (PI) testify to the weakening of the vascular resistance and increasing of blood flow and vascularity, which are the pathomorphological markers of vascular changes by endothelial dysfunction in asthmatic children. • 3) Flow-mediated vasodilatation (FMD) test confirmed, that in patients with BA, endothelial dysfunction becomes apparent by decreased responses to endothelium-dependent stimuli (flow) (Pic.5). • Asthmatic children presented lower endothelium-dependent vasodilatation (EDD) compared with control group (7,4±1,8% vs. 14,6±0,4%) (p<0,001). • More of that EDD values in patients with moderate asthma were significantly lower than those in patients with mild asthma (6,2±0,7% vs 9,3±1,1%)(Pic.6). • Asthma severity and methacholine airways responsiveness were related to endothelial dysfunction (p<0,001): • direct correlation between EDD and airway hyperresponsiveness - the lower the PC20 the lower was the EDD • direct correlation between EDD and severity of asthma in children (EDD correlated with predicted value of FEV1 and PEF variability as well with symptoms in asthmatic children) (p=0,005) RESULTS A B Pic.5 Flow-mediated vasodilatation (FMD) test – Ultrasound image of the brachial artery at (A) baseline and (B) 60 sec. after hyperemic stimulus CONCLUSIONS • Children with BA have an evident endothelial dysfunction that was shown in decreased vasodilatatory response to shear stress (EDD) • Level of endothelial dysfunction is linked to degree of airway responsiveness and disease severity in children with mild to moderate asthma