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Background: Eczema in early childhood is associated with developing subsequent allergic diseases, including food allergy, asthma and hay fever. However, eczema has a heterogenous presentation regarding age of onset and persistence, which may lead to different allergic outcomes during childhood/adolescence. Recently, sub-phenotypes of eczema have been suggested as predictor for allergic multimorbidity. Objective: To identify associations of eczema phenotypes with food allergy, asthma and hay fever during childhood/adolescence. Additionally, we aimed to describe the trajectories of eczema, asthma and hay fever, stratifying by food allergy presence. Methods: TRACKER (Trajectories of Allergy in Children in Real Life Databases) is a prospective cross-sectional population-based cohort study of 6,852 children/adolescents from the Lifelines cohort. We investigated associations of seven eczema phenotypes, based on age of onset and persistence, with food allergy, asthma and hay fever using logistic regression, adjusted for appropriate covariates. Disease trajectories were determined by calculating prevalence at different ages. Results: Participants who suffered from eczema throughout childhood showed higher risks of developing food allergy, hay fever and asthma. “Very early onset – persistent” eczema showed the strongest associations with food allergy, asthma and hay fever. The prevalence of eczema, asthma and hay fever at all ages were significantly higher in participants with food allergy, compared to those without. Conclusion: The largest cohort study on this topic to date shows that (very) early onset and persistent eczema increases the risk for allergic multimorbidity. Identification of infants at risk for developing (very) early onset eczema is of utmost importance to prevent allergic multimorbidity.

Chronic obstructive pulmonary disease (COPD) is a complex genetic disorder, strongly associated with smoking. However, 25-45% of the individuals who develop COPD have never been exposed to (environmental) smoking. We hypothesize that these individuals have a strong genetic susceptibility for COPD with rare, pathogenic genetic variants underlying its development. We studied 36 individuals from the prospective Dutch Lifelines cohort with COPD (LLN of FEV1/FVC In total, we found 7,638 unique predicted pathogenic genetic variants in the 36 selected individuals. All 36 individuals carry at least 1 variant (range 1-7) in the top-100 prioritized genes in the COPD network. GeneNetwork pathway analysis revealed that 56 of the prioritized genes were significantly enriched for biological processes involved in cilium functioning. Our results suggest that rare pathogenic variants in ciliary genes underlie non-smoking related COPD and their role in a mono- or oligogenic form of COPD should be further investigated.