Zhebin Yu

The proposed project aims to adopt the exposome approach to investigate the joint impact of urban environment on respiratory health from birth until young adulthood from a longitudinal perspective, alongside elucidating associated molecular mechanisms. Data from the prospective birth cohort BAMSE will be primarily used with validation of key findings through international collaboration. Respiratory outcomes including asthma, lung function and long COVID have been assessed in the cohort. Urban environment exposure including air pollution, noise, built environment, temperature, socioeconomic status has been linked to the residential addresses. Urban expotypes (specific pattern of multiple exposures) will be identified using clustering approach both at single timepoints and longitudinally (trajectories) and further linked to the outcomes. Interactions between urban expotypes with host factors (genetic predisposition, socio-economic status, lifestyle factors) will be assessed. Biological mechanisms will be explored using transcriptome, epigenetics, proteomics and metabolomics data and integrated with multi-omics approaches. Causal mediation analysis will be further applied to link the urban expotypes to respiratory outcomes. This research is vital for enhancing our comprehension of urban environment complexities and advancing respiratory health in urban populations. The project will be conducted over four years, led by the applicant with support from senior researchers at KI.

Research problem and specific questions Identifying the urban environment exposures related to asthma is the key to mitigate the disease burden of asthma in urban areas. Previous studies typically only looked at one urban exposure at one time, which does not reflect the multi-dimensional exposure setting in the real world. The proposed project aims to adopt the exposome-wide approach to address the question: ‘Is there a single urban environment exposure or a combination of several exposures significantly associated with the risk of asthma from childhood to young adulthood?’ and the molecular mechanism behind these associations.Data and method Data from the prospective birth cohort BAMSE (Children, Allergy, Environment, Stockholm, Epidemiology) will be used. Asthma outcomes from childhood to young adult will be assessed based on questionnaire at specific follow-ups. Urban external exposome including ambient air pollution, noise, built environment, temperature, socioeconomic status will be assessed. Internal exposome is represented by untargeted urine and serum metabolomics data. Association between urban external exposome and incident asthma will be investigated using exposome-wide approach as well as cluster-based multi-exposure methods. Meet-in-the-Middle approach will be applied to investigate the metabolites associated with both urban exposome and asthma. Causal mediation analysis will be further applied based on these identified metabolomic features to link the urban exposome to asthma.Societal relevance and utilizationUnderstanding the relationship between urban exposome and asthma will not only provide insights into the asthma etiology, but also help identify disparities in urban environment. The output of the proposed project may offer better understanding to the complex relationships of urban environment exposures and help addressing environmental inequality using a multifaceted approach, eventually improving health outcomes for all individuals living in urban areas.Plan for project realisation The analysis of the proposed project will be conducted by the applicant with the support from senior research colleagues and the BAMSE research group, including equipment and intellectual content. The budget will be mainly used to cover the salary of the applicant.

Identifying the urban environment exposures related to asthma is the key to mitigate the disease burden of asthma in urban areas. We aim to adopt the exposome-wide approach to address the question: ‘Is there a single urban environment exposure or a combination of several exposures significantly associated with the risk of asthma from childhood to young adulthood?’ and the molecular mechanism behind these associations.We will use data from the prospective birth cohort BAMSE (Children, Allergy, Environment, Stockholm, Epidemiology). Asthma outcomes from childhood to young adulthood will be assessed based on questionnaire at specific follow-ups. Time-varying urban external exposome including ambient air pollution, noise, built environment, temperature, socioeconomic status from birth to the latest follow-up will be assessed. The internal exposome is represented by untargeted urine and serum metabolomics data. We will apply exposome-wide approach to investigate the associations of both urban external and internal exposome with the risk of asthma and link the urban exposome to asthma in a causal-inference framework.The output of this project may offer better understanding to the complex relationships of urban environment exposures with asthma and help addressing environmental inequality using a multifaceted approach, eventually improving health outcomes for all individuals living in urban areas.