Risk factors and treatment of pediatric chronic diseases: Type 1 diabetes, asthma and allergy

Chronic diseases such as type 1 diabetes (T1DM) and asthma are leading causes of morbidity and mortality worldwide. The increase in the number of children with chronic diseases is a major concern. Early detection through improved screening and diagnostic tests, better diagnosis based on updated guidelines, and improved drug therapy have led to more effective treatment of chronic illnesses.The studies included in this thesis focused on different aspects related to pediatric chronic disorders including T1DM, asthma and allergy. We have investigated the trends in prevalence and incidence rates of cardiovascular disease (CVD) risk factors, asthma and related-medications use in children with T1DM and evaluated genetic and environmental risk factors associated with the occurrence of childhood asthma, asthma exacerbations and allergy.Our studies in children with T1DM demonstrated that these children have higher prevalence rates of CVD risk factors and use of CV medication compared with age and gender-matched children without diabetes. The higher risk was already present one year before the onset of diabetes and further increased over the years of follow-up. However, there was substantial under-treatment of hypertension and hypercholesterolemia in children with T1DM. Our studies also showed a high rate of poor glycemic control (HbA1c>7.5% (58 mmol/mol)) in the pediatric population with T1DM. There are strong indications that genetic and environmental factors increase the risk of developing asthma and allergy in children. Our findings showed that a genetic risk score developed in adults with asthma also predicts asthma in children. The results of our meta-analysis including 34 published studies on the association between early life antibiotics use and the risk of long-term allergy suggested thatexposure to antibiotics during the first two years of life is associated with an increased risk of allergic symptoms including hay fever, eczema and food allergy later in life. Moreover, our thesis suggested a long-term protective effect of breast-feeding on asthma exacerbations. It is known that gut microbiome is influenced by environmental factors. The healthy gut microbiome is highly diverse and can be disturbed by environmental factors e.g. early life antibiotic therapy and breast-feeding. Reduced gut microbiome diversity during the first months of life might influence the immune system and might lead to increased risk of asthma and allergy. However, the role of early life factors on risk of later asthma, asthma exacerbations and allergies needs further elucidation.