Endotyping Childhood Asthma

In this thesis, different endotypes of asthma were investigated. Asthma is the most common chronic disease in childhood – it represents a great burden to the affected families and has huge expenses for the health care system. However, we have limited knowledge of specific endotypes of childhood asthma – a very heterogeneous disease – and asthma is still treated as one disease with limited possibilities for targeted and personalized treatment. Therefore, enlightening different endotypes of childhood asthma can help us unravel different mechanisms and identify useful predictive biomarkers of disease, which are in urgent need – especially during early childhood. Genetic markers and polygenic risk scores (PRS) could constitute a change in paradigm trying to reach this goal. This thesis focused on 1) the role of blood eosinophils – a well-established biomarker in later life atopic disease – throughout early childhood atopic disease, 2) genetic risk of asthma as a predictor of course of disease and disease subtypes, and 3) genetic risk of high body mass index (BMI) and early-life mechanisms of childhood asthma. We delved into this by investigating different cohorts. First, we leveraged the deep data layers within the two COpenhagen Prospective Studies on Athma in Childhood (COPSAC) motherchild cohorts. The COPSAC2000 cohort is a high-risk cohort consisting of 411 children born by mothers with asthma, and the COPSAC2010 cohort is an unselected, population-based cohort consisting of 700 children. The children were followed intensively from birth and throughout childhood with extensive examinations. All procedures and diagnoses adhered to strictly followed standard operational procedures, therefore securing homogeneity in the data. Secondly, we investigated the extensive register-based cohort established by The Integrative Psychiatric Research (iPSYCH) consortium combined with registries on prescriptions and hospitalizations.