Professor, PhD, MD
Klaus Bønnelykke
Copenhagen Prosepective Studies on Asthma in Childhood
| Project management | ||
| Project status | Open | |
| Data collection dates | ||
| Start | 01.10.2020 | |
| End | 30.06.2025 | |
Severe childhood asthma - a national cohort study
Short summary
Some children with asthma have many symptoms despite relevant treatment. The aim of the Severe Childhood Asthma study is to understand the underlying disease mechanisms to help improve treatment. We wish to investigate disease mechanisms in terms of genetic regulation, the microbiome composition of the child, and metabolites in blood. The project aim to contribute towards a more personalized and and targeted treatment of the individual child suffering from severe or exacerbation prone asthma.
Rationale
The aim of this project is to understand the underlying mechanisms of severe asthma in childhood in order to identify novel treatment targets, predict disease course, and allow personalized and improved treatment. We want to understand genetic regulation and pathways of importance for disease development and disease control, understand functional subtypes of disease, and improve prediction and treatment of exacerbations. The project will increase our understanding of severe and exacerbation prone childhood asthma with the potential to improve prevention and treatment of this clinically important disease entity. The aim of the study is - To establish a national Danish cohort of 150 children with severe asthma, and 75 healthy children, by a joint effort from all the Danish pediatric departments. - To conduct a cross-sectional global multi-omics assessment of genetics, epigenetics, gene expression and metabolomics to understand the disease pathways of severe and difficult-to-treat asthma in childhood and allow improved treatment of disease. - To analyze the gut and airway microbiome composition involved in severe and difficult-to-treat asthma in order to identify disease-modifying bacteria and viruses, which might provide novel preventative and therapeutic options. - To predict and understand exacerbations using gene expression, epigenetics, airway immunology, microbiome and metabolomics in order to optimize treatment and prevent exacerbations.
Description of the cohort
We will establish a national Danish clinical cohort of approximately 300 children aged 6-18 years with severe or exacerbation prone asthma, as well as 200 healthy children. This will be done as a joint effort by a national collaboration between all pediatric departments in Denmark in a prospective observational study. The children with asthma will be thoroughly clinically examined to distinguish between cases with severe asthma vs. cases with difficult to treat asthma due to other causes (adherence, comorbidity, etc.) and assessed with multi-omics approaches at a cross-sectional visit. The severe and exacerbation prone asthma cohort will be compared internally to identify disease subtypes and also to healthy controls in order to identify novel disease mechanisms. We wish to include approximately 150 healthy age-matched controls as we aim to have one control per two severe asthma cases .
Data and biological material
A major effort will be put into detailed clinical phenotyping of asthma and intermediate traits, such as lung function, which will be combined with advanced research methodologies within genetics, epigenetics, gene expression, microbiome, metabolome and immune profiles. The objective is to identify underlying specific disease mechanisms (endotypes) that can be targeted in order to personalize and improve treatment. Furthermore, assessment (clinical assessment and sampling of biological material) will be performed in children with asthma at the baseline visit to the COPSAC clinic and during acute asthma exacerbations during a 1-year follow-up in order to study the basis of exacerbation to develop tools to predict exacerbations, understand underlying mechanisms and predict treatment response during exacerbations. Furthermore, the children and families fill out detailed questionnaires, and we collect health related information from the patient journals.
Collaborating researchers and departments
Department of pediatrics, Herlev and Gentofte Hospital