Phd ceremony D. Ierodiakonou: Genetic and environmental interplay in asthma severity and its underlying airway pathology
|When:||Mo 03-03-2014 17:00 - 18:00|
Asthma is a chronic inflammatory disorder of the airways that affects children and adults of all ages. With this thesis we aimed to better understand the underlying mechanisms of asthma severity. We investigated the role of genes encoding proteins involved in epithelial integrity, chronic airway inflammation and airway remodeling in asthma. The results show that genetic variation determines epithelial integrity, the extent of the airway inflammation and remodeling, as well as the subsequent clinical severity (i.e. airway hyper-responsiveness, lung function level and decline over time) of adult individuals with asthma. We showed that gene by inhaled corticosteroids and gene by smoking interactions also play a role in the clinico-pathological expression of the disease. We further focused on the susceptibility of asthmatic children to ambient air pollution, an unavoidable environmental exposure of the modern world. We showed associations of long-term air pollution (carbon monoxide and nitrogen dioxide) exposure with severity of airflow obstruction and airway hyper-responsiveness in children with asthma. We did not find strong evidence of modification of pollution effects by controller medication used in a clinical trial. However, we showed that genetics play a role in the respiratory response of asthmatic children to air pollution by potentially regulating oxidant/anti-oxidant cellular mechanisms and inflammation. Uunderstanding the underlying mechanisms of asthma severity and adding to the current knowledge of asthma pathophysiology may ultimately offer better targets for drug development for either prevention or cure of asthma.