Airway angiogenesis may be an important part of structural remodeling in the pathogenesis of asthma. We analysed the induced sputum of rhinitis and controlled asthma patients for angiogenin, vascular endothelial growth factor (VEGF), IL-8, fibroblast growth factor and TNF-alpha. We found significantly increased angiogenin and VEGF concentrations in the induced sputum of corticosteroid-treated and well-controlled asthma patients. These results suggest that standard therapy does not sufficiently effect lung remodelling, therefore new therapies are needed. We further demonstrated that increased airway angiogenesis already started in rhinitis patients without asthma.
COBISS.SI-ID: 25417689
Polymorphisms in the vascular endothelial growth factor A (VEGFA) gene might be associated with asthma treatment response. This study enrolled 131 children with asthma treated with different therapies - specifically, the inhaled corticosteroid (ICS) fluticasone propionate or the leukotriene receptor antagonist (LTRA) montelukast. We performed an association analysis between improvement of lung function - assessed by measurement of the percentage of the predicted forced expiratory volume in 1 second (%predicted FEV(1)), the ratio between the FEV(1) and the forced vital capacity (FEV(1)/FVC) after 6 and 12 months of treatment, and asthma control after 12 months of treatment - and two polymorphisms, rs2146323 and rs833058, in the VEGFA gene Our results showed that treatment response to commonly used asthma therapies (ICS or LTRA) is associated with polymorphisms rs2146323 and rs833058 in VEGFA. With additional replication, our findings could contribute to the development of individualized asthma therapy.
COBISS.SI-ID: 29912793
Asthma is one of the most common chronic diseases in childhood. It is well known that genetic variability contributes to asthma risk. One of the most replicated asthma candidate genes is ORM1like 3 (ORMDL3), which has been associated with asthma susceptibility. Another asthma candidate gene is signal transducer and activator of transcription 6 (STAT6), a regulator of IgE class switching. Gene coding thromboxane A2 receptor (TBXA2R), involved in chronic airway inflammation, has been associated with asthma in several genetic studies. The study group consisted of 154 children with asthma, in whom clinical parameters were measured and whose asthma control and atopic status were determined. A control group comprised of 71 healthy children. Genotyping was performed using an allelic discrimination assay. The ORMDL3 polymorphism rs4795405 was suggestively associated with asthma risk. Furthermore, it was significantly associated with non atopic asthma and asthma without rhinitis. No association was detected between the STAT6 polymorphism rs324011 or the TBXA2R polymorphisms rs8113232 and rs3786989 and asthma susceptibility. However, an association between rs324011 in STAT6 with recurrent wheezing in early childhood and a suggestive association between rs8113232 in TBXA2R with rhinitis in children with asthma were observed. Our results confirmed ORMDL3 as a candidate gene for childhood asthma susceptibility. STAT6 and TBXA2R polymorphisms were not associated with asthma risk, but they were associated with asthma related symptoms.
COBISS.SI-ID: 28983257
Angiogenesis is a prominent feature of structural tissue remodeling that occurs in chronic airway diseases, including chronic obstructive pulmonary disease (COPD). The aim of this study was to evaluate the airway levels of VEGF, angiogenin, IL8 and TNFα in patients with COPD during the stable phase and during acute exacerbation of the disease. We analysed induced sputum samples from 28 patients with COPD. Thirteen of these patients were followed up and second samples of sputum were obtained during acute exacerbation of the disease. The two control groups consisted of 12 healthy smokers and seven healthy nonsmokers, all with normal lung function tests. Concentrations of VEGF, angiogenin, IL8, TNFα and bFGF were measured by cytometric bead array. In the induced sputum of patients with stable COPD, concentrations of VEGF (P ( 0.001, P = 0.02), angiogenin (P ( 0.0001, P ( 0.0001), IL8 (P ( 0.0001, P = 0.0021) and TNFα (P (0.001, P = 0.03) were significantly elevated in comparison with healthy smokers and nonsmokers. No additional elevation of angiogenic factors was demonstrated at the time of exacerbation. There was a significant negative correlation between FEV1 and VEGF (P ( 0.05, r = 0.38), angiogenin (P ( 0.0001, r = 0.68) and IL8 (P ( 0.001, r = 0.54) among smokers (smoking COPD patients and healthy smokers). No significant differences were observed between groups of healthy smokers and nonsmokers. These results showed increased airway angiogenesis in patients with COPD. Moreover, VEGF, IL8 and angiogenin negatively correlated with pulmonary function, which suggests their important role in COPD airway remodeling. However, no additional angiogenic activation was found during exacerbation of COPD.
COBISS.SI-ID: 29451737
The mechanisms responsible for the difference between clinically irrelevant IgE sensitization and allergic rhinitis are not fully understood. Therefore we evaluated the humoral and cellular mechanisms that may be associated with the presence of allergic rhinitis symptoms. We selected 26 subjects with positive grass pollen skin tests and IgE antibodies to Timothy (g6) and the major grass allergens rPhl p 1, 5b. Fourteen of those patients reported a history of allergic rhinitis. During winter, we performed a grass pollen CD63 basophile activation test using four log allergen concentrations, followed by a grass nasal provocation test (NPT). We obtained symptom scores in the subsequent pollination season. We showed that subjects with a positive NPT have significantly higher CD63 basophile grass pollen responsiveness than NPT negative subjects, preferably at submaximal allergen concentrations, which represent cellular sensitivity. Moreover, basophile sensitivity positively correlated with the size of the grass specific IgE fraction in relation to total IgE, and it was highly predictive of allergic rhinitis symptoms in the following pollination season. In conclusion allergic rhinitis symptoms are significantly associated with allergen specific basophile sensitivity. In vitro evaluation of basophile sensitivity should prove useful for distinguishing clinical phenotype of allergic sensitization.
COBISS.SI-ID: 28743129