Atopic Diseases Mechanisms, Exposures, and Diagnostics

Epidemiological data suggest that atopic diseases (asthma, atopic dermatitis, allergic rhinitis, and food allergy) begin in early life and that most cases present clinically during early childhood. The disease incidences increase as communities adopt western lifestyles and the diseases are highly prevalent. Disentangling the pathophysiological mechanisms leading to disease debut is necessary to identify beneficial/harmful exposures so that successful prevention and treatment can be generated. The objective of this thesis is to explore mechanisms of atopic diseases, to investigate the importance of environmental factors in early life, prior to disease development, and finally to explore new diagnostic tools to interpret allergic sensitization more accurately. The thesis is built on nine studies originating from the COPSAC2000 and COPSAC2010 birth cohorts investigating mechanisms of atopic disease and modifiable exposures in the environment that can affect the development of atopic diseases, and finally, examining how component resolved diagnostics can help provide a patient-tailored approach to allergy diagnostics. First, the distribution of sIgE levels in children is investigated, as this is one of the main criteria for the definition of atopy. Thereafter, it is explored how studies of parental atopic status, sensitization patterns, and early debut and severity of atopic dermatitis have substantiated the theory of an early-life window-of-opportunity for intervention that precedes the development of atopic diseases in childhood. Then, it is examined whether early-life exposures such as breastfeeding, dogs, cats, and house dust mites in the home perinatally constitute important influencers in this crucial time of life. Finally, it is explored how component resolved diagnostics may allow patient-tailored recommendations suggesting that some dog allergic patients tolerate female dogs. The utility of molecular diagnostics is also discussed in relation to other allergen sources and future directions are proposed. Last, it is discussed how these findings could be validated in randomized controlled trials, which might prepare the ground for improved diagnostics and prevention strategies to mitigate the current atopic pandemic.