By Trine Mølbæk-Engbjerg
Principal supervisor: Bo Lund Krogsgaard Chawes, MD, PhD, DMSc, Professor
Co-supervisors: Klaus Bønnelykke, MD, PhD, Professor, Susanne Brix Pedersen, MSc, PhD and Morten Arendt Rasmussen, MSc, PhD
Chairperson: Kim Gjerum Nielsen, MD, DMSc, Professor, Department of Clinical Medicine, University of Copenhagen, Denmark
Opponent: Ingvild Bruun Mikalsen, MD, PhD, Professor, University of Bergen, Norway
Opponent: Signe Vahlkvist, MD, PhD, Associate Professor, University of Southern Denmark, Denmark
Summary
Background
Asthma is an inflammatory disease in the airways that often debuts in childhood or adolescence. The disease is the most common chronic disease in childhood and represents a large burden to the affected families and society. Living with asthmatic disease may also increase the risk of other health conditions. Several studies found that adolescents with chronic diseases have an increased risk of developing depression and anxiety, and a connection between asthma and neurodevelopmental disorders has been identified. Finally, other studies have observed an association between dyslipidaemia, obesity, and asthma. It is not clear why these relations are observed, but one hypothesis is that asthma and other non-communicable diseases share genetic and environmental risk factors, leading to low-grade systemic inflammation that drives these diseases.
In this PhD thesis, we explore the following:
- We outline the design of the 18-year follow-up visit from the COPSAC2000 cohort
- We investigate associations between asthma, risk behaviours, and non-atopic comorbidity.
- We explore associations between systemic inflammatory biomarkers collected through childhood and adolescence and asthma status at 18 years.
Methods and results
This PhD thesis is based on data from the Copenhagen Prospective Study on Asthma in Childhood (COPSAC2000), a high-risk cohort comprising 411 children born to mothers with asthma. The children were followed closely from one month of age to 18 years with extensive examinations and data collection.
Paper I. Design of the 18-year follow-up of the Danish COPSAC2000 birth cohort, BMJ Paediatrics Open, published
In Paper I, we outline the design of the 18-year follow-up visit for the COPSAC2000 cohort, in which risk factors for atopic diseases, obesity, and neuropsychiatric disorders are identified through extensive environmental characterisation, deep clinical phenotyping, and 8longitudinal biosampling. This paper outlines the data that serve as the basis for the analyses conducted in Papers II and Paper III.
Paper II. Risk behaviours and non-atopic comorbidities of adolescents with asthma, World Allergy Organization Journal, published
In Paper II, we investigate the association between asthma status at the 18-year follow-up visit of the COPSAC2000 cohort and risk behaviours and non-atopic comorbidities. We include obesity and neuropsychiatric diseases captured from medical records and electronic questionnaires on behavioural traits and psychopathology. The study shows that neuropsychiatric comorbidity and self-destructive behaviour are associated with asthma at 18 years of age.
Paper III. Longitudinal trajectories of inflammatory biomarkers and their association with asthma, manuscript prepared for submission
In Paper III, we longitudinally examine inflammatory biomarkers across childhood and adolescence in COPSAC2000 to identify associations between trajectories of these biomarkers and asthma, and asthma-related outcomes at 18 years. We found an association among platelet trajectories, airway obstruction (FEV1), and airway hyperresponsiveness (PD20), suggesting that platelet levels over time are involved in the pathophysiology of asthma.
Conclusion
To conclude, Paper I provides knowledge of the cohort used in the thesis. Paper II identifies risk behaviours and non-atopic comorbidities associated with asthma and contributes to knowledge of the general health of adolescents living with asthma. Paper III explores biomarkers of systemic inflammation across childhood and adolescence and their association with asthma at 18 years, advancing our understanding of asthma pathogenesis and the role of platelets.
