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).

Centre for Occupational and Environmental Medicine Region Stockholm Stockholm Sweden

Chair of Epidemiology and Preventive Medicine Jagiellonian University Medical College Kraków Poland

Chair of Epidemiology Institute for Medical Information Processing Biometry and Epidemiology Médical Faculty Ludwig Maximilians Universit at München Munich Germany

CIBER Epidemiología y Salud Pública Spain

Collegium Medicum Jan Kochanowski University of Kielce Poland

Department of Cancer Epidemiology and Primary Prevention Maria Sklodowska Curie National Research Institute of Oncology Warsaw Poland

Department of Cardiology Danderyd Hospital Stockholm Sweden

Department of Clinical Sciences and Education Södersjukhuset Karolinska Institutet Stockholm Sweden

Department of Computer Science and Technology University of Cambridge Cambridge Cambridgeshire United Kingdom

Department of Environment and Health School of Public Health University of Bielefeld Bielefeld Germany

Department of Epidemiology and Data Science Amsterdam UMC Location Vrije Universiteit Amsterdam Amsterdam the Netherlands

Department of Epidemiology University of Groningen University Medical Center Groningen Groningen the Netherlands

Genomes for Life GCAT Lab CORE Program Germans Trias 1 Pujol Research Institute Badalona Spain

German Center for Child and Adolescent Health Munich Germany

German Center for Lung Research Munich Germany

Grup de Recerca en Impacte de Les Malalties Cròniques 1 Les Seves Trajectòries Badalona Spain

Institute for Medical Information Processing Biometry and Epidemiology Medical Faculty Ludwig Maximilians Universität München Munich Germany

Institute for Risk Assessment Sciences Utrecht University Utrecht the Netherlands

Institute of Environmental Medicine Karolinska Institutet Stockholm Sweden

Institute of Epidemiology Helmholtz Zentrum München German Research Center for Environmental Health Neuherberg Germany

Institute of Genomics University of Tartu Estonia

Institute of Mathematics and Statistics University of Tartu Estonia

Institute of Social and Preventive Medicine University of Berne Berne Switzerland

ISGlobal Barcelona Spain

IUF Leibniz Research Institute for Environmental Medicine Düsseldorf Germany

Munich Heart Alliance German Center for Cardiovascular Health Munich Germany

Netherlands Institute of Mental Health and Addiction Utrecht the Netherlands

RECETOX Faculty of Science Masaryk University Brno Czech Republic

Scientific Research Epidemiology and R and D Centre Holycross Cancer Centre Kielce Poland

Swiss Tropical and Public Health Institute Allschwil Switzerland

Universitat Pompeu Fabra Barcelona Spain

University of Basel Basel Switzerland

University of Groningen University Medical Center Groningen Beatrix Children's Hospital Department of Pediatric Pulmonology and Pediatric Allergology Groningen the Netherlands

University of Groningen University Medical Center Groningen Groningen Research Institute for Asthma and COPD Groningen the Netherlands

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