From Data to Action: Identifying Harms and Critical Windows of Combined Environmental Exposures to Air Pollutants and Heat Using Integrated Epidemiological and Toxicological Evidence (360G-Wellcome-334685_Z_25_Z)

Air pollution and climate change represent converging global health crises, with the most vulnerable—especially children—bearing the brunt. This international, interdisciplinary project tackles these challenges by advancing our understanding of how complex and representative exposures to regulated (PM₂.₅, PM₁₀, NO₂, O₃) and unregulated (black carbon, ultrafine particles) air pollutants, combined with heat, shape respiratory health across the life course. Leveraging four long-standing European birth cohorts (N=24,533; follow-up since 1994), spanning Spain to Sweden and birth to age 25, we integrate cutting-edge exposure science, toxicology, epidemiology, risk assessment, and causal inference to quantify health and equity impacts of current exposures, interventions and scenarios, and identify windows of susceptibility. Our focus is on asthma—the most prevalent chronic disease in children—and lung function, a key predictor of adult cardiopulmonary morbidity and mortality. We go beyond single-pollutant approaches to address mixtures and heat interactions using harmonized, high-resolution exposure surfaces, mechanistic biomarkers in standard and novel mouse models, and life-course modeling. Through engaging key stakeholders, we will co-create and evaluate actionable, equitable interventions and feed results back into policy processes. Major advances over our foundational work include addressing more nuanced questions about mixtures, temperature interactions, susceptible windows, and underlying mechanisms as observed in experimental models.