By Fredreikke Skov
Principal supervisor: Ann-Marie Malby Schoos, MD, PhD, DMSc
Principal co-supervisor: Bo Chawes, MD, PhD, DMSc
Co-supervisors: Klaus Bønnelykke, MD, PhD and Rikke Bjergsand Sunde, MD, PhD
Chairperson: Allan Linneberg, Professor, University of Copenhagen
Opponent: Mohamed Shamji, Professor in Immunology and Allergy, Imperial College London, NHLI, United Kingdom
Opponent: Wojciech Feleszko, Associate professor, Department of Pediatric Pulmonology and Allergology, Medical University of Warsawa, Poland
Summary
Asthma and allergy are among the most common chronic diseases in childhood and have a significant impact on the children’s quality of life and health. Despite extensive research, the development of these “atopic diseases” and their progression remain incompletely understood. Why some children outgrow their asthma and allergy while others develop a more severe and persistent course remains an unanswered question.
We know from previous research that the risk of developing persistent asthma and allergies in childhood is shaped by a complex interplay of genetic predisposition, environmental exposures, infection history, and immune system maturation – often characterized by considerable individual variability. Furthermore, increasing attention has also been directed toward identifying and characterizing distinct asthma phenotypes, as disease progression and treatment response are likely to differ according to the underlying inflammatory profile. Asthma is frequently classified based on immunological patterns, with particular focus on type 2 (T2) inflammation – an immune response closely associated with allergic sensitization and eosinophilic activation. So-called “T2- high” asthma is typically linked to a higher disease burden and more severe outcomes in adults, but knowledge regarding the clinical significance of the phenotype in childhood remains limited.
A new technology in allergy diagnostics, component resolved diagnostics (CRD), has enabled a more in-depth understanding of allergic sensitization. With this technique, it is possible to study sensitization patterns and investigate whether specific allergen components, such as those from cats, dogs or horses, may be more closely associated with disease development and impaired lung function than previously assumed.
Aim
The aim of this thesis is to contribute to an understanding of how environment, genetics, exposures, and biomarkers in childhood relate to the development and persistence of asthma and allergic rhinitis—from early childhood to adolescence. The projects aim to examine how T2- inflammatory phenotypes manifest in children and how early-life factors and biological markers may help predict disease progression. Furthermore, the importance of sensitization to specific allergen components is investigated, and whether these can be indicators of reduced lung function and a more severe disease course.
Hypotheses
- The type of inflammatory response and the severity of asthma (T2-low and T2-high asthma).
- Early life factors in childhood (ages 0–7) play an important role in the development of atopic disease.
- Sensitization to specific components from furry animals (dog, cat, and horse) influences lung function and thus the severity of potential asthma.
Study Design
The thesis is based on data from the birth cohort, Copenhagen Prospective Studies on Asthma in Childhood2000 (COPSAC2000), which includes 411 children born to mothers with asthma. The children have been closely followed with regular clinical visits from birth through childhood and adolescence, with systematic collection of data on symptoms, environmental exposures, biomarkers, genetics, lung function, and allergic sensitization.
Clinical Relevance
The aim is to contribute new knowledge that can help with a more differentiated approach to risk assessment and treatment. The objective is to investigate the relationships between asthma phenotypes, allergic sensitization, and the disease course of asthma and allergic rhinitis in order to identify children at increased risk of a more severe and persistent disease progression.
Studies
- Type 2‐high airway inflammation in childhood asthma distinguishes a more severe phenotype / Frederikke R Skov, Tamo Sultan, Kasper Fischer‐Rasmussen, Bo L Chawes, Jakob Stokholm, Nilo Vahman, Klaus Bønnelykke, Ann‐Marie M Schoos
- An explainable machine learning approach on early predictors of persistent childhood asthma and allergic rhinitis / Frederikke Rosenvinge Skov*, Mario Lovrić,*, Tamo Sultan, Klaus Bønnelykke, Bo Chawes, Jakob Stokholm, Jonathan Thorsen, Morten Arendt Rasmussen, Ann-Marie Malby Schoos
- Component-Resolved and Whole-Extract Pet Allergen Sensitization Show Similar Associations With Airway Inflammation and Bronchial Hyperresponsiveness at 18 Years / Frederikke Rosenvinge Skov, David Horner, Nilofar Vahman, Bo Chawes, Klaus Bønnelykke, Ann-Marie Malby Schoos
