External exposome and incident asthma across the life course in 14 European cohorts: a prospective analysis within the EXPANSE project

Abstract

Background: The joint impact of exposure to multiple urban environmental factors on asthma remains unclear. Methods: We analysed data from 14 European cohorts to assess the impact of the urban exposome on asthma incidence across the life course. We linked three external exposome domains (air pollution, built environment, ambient temperature) to the participants’ home addresses at baseline. We performed k-means clustering within each domain and assessed associations of clusters with asthma adjusting for potentially relevant covariates in cohort-specific analyses, with subsequent separate meta-analyses for birth and adult cohorts. An environmental risk score using a coefficient-weighted sum approach was used to assess the impact of combining the three domains. Findings: A total of 7428 incident asthma cases were identified among 349,037 participants (from birth up to age 70+). Overall, we observed higher risks of asthma for clusters characterized by high particulate matter and nitrogen dioxide exposure in adults (ORmeta = 1.13, 95%CI:1.01–1.25), and clusters characterized by high built-up area and low levels of greenness in both children and adults (ORmeta = 1.36, 95%CI: 1.14–1.64 for birth cohorts and ORmeta = 1.15, 95%CI: 1.03–1.28 for adult cohorts, respectively). The joint exposure using the environment risk score combining the three domains was consistently associated with higher risks of incident asthma (ORmeta = 1.13, 95%CI: 1.07–1.20 for birth cohorts, ORmeta = 1.15, 95%CI: 1.10–1.20 for adult cohorts per 20% increase). On average 11.6% of the incident asthma cases could be attributed to environmental risk score above cohort-specific median levels. Interpretation: Multiple environmental exposures jointly contribute to incident asthma risk across the life course. Urban planning accounting for these factors may help mitigate asthma development. Funding: This study was funded by the European Union’s Horizon 2020 research and innovation program under agreement No 874627 (EXPANSE).

This study was funded by the European Union’s Horizon 2020 research and innovation program under agreement No 874627 (EXPANSE) and No 857560 (CETOCOEN Excellence). ZY is funded by the Swedish Research Council (VR No. 2024-02345) and Swedish Research Council for Health, Working life and Welfare (Forte No. 2023-01213). AS has received funding from the Swiss National Science Foundation (grant number 210781). MS received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement No. 949906). PD and CT acknowledge support from the grant CEX2023-0001290-S funded by MCIN/AEI/10.13039/501100011033, and support from the Generalitat de Catalunya through the CERCA Program. Cohort-specific fundings are presented in the Supplementary materials. Authors thank the RECETOX Research Infrastructure (No LM2023069) financed by the Ministry of Education, Youth and Sports for supportive background. EM reports grants from Swedish Research Council (2024-03164), The Swedish Heart-Lung Foundation and Region Stockholm (ALF).