Abstract Rationale Multiple environmental factors, including air pollution, ambient temperature, and low socioeconomic status, have been associated with the risk of chronic obstructive pulmonary disease (COPD). However, the underlying biological mechanisms remain incompletely understood. In this study, we aimed to identify circulating proteomic signatures related to distinct environmental exposures and evaluate their associations with incident COPD in a large population-based cohort. Method We analyzed data from the UK Biobank, comprising 42,445 participants with baseline plasma proteomic profiling and 21 detailed environmental exposure assessments. Protein scores were derived from proteins significantly associated with air pollution, temperature, greenness, traffic indicators, noise levels, distance to coast, and socioeconomic factors. Cox proportional hazards models were applied to evaluate the associations between exposure-related protein scores and incident COPD. In addition, mediation analyses were conducted to assess the potential mediating role of specific proteins in the relationship between environmental exposures and COPD risk. Results Substantial proteomic variation was identified in relation to multiple environmental exposures, and exposure-specific proteomic scores were constructed accordingly. The proteomic signatures were more substantially associated with systemic inflammation and individual’s lung function, as well as the subsequent risk of COPD than the corresponding environmental exposure variables. Enrichment analyses revealed multiple environment-linked proteins are mainly involved in several biological pathways, including cytokine-receptor interactions, pro-inflammatory and pro-fibrotic mediators, and cell-specific immune responses. We further identified multiple proteins significantly associated with risk of COPD, and several proteins such as GDF15, IL-6, and CXCL17 may partially mediate the associations between multiple environmental exposures and COPD, with CXCL17 mediating up to 35.3% of the effect. Conclusion Our findings suggest that specific circulating proteomic profiles capture the biological imprint of environmental exposures and are significantly associated with the risk of COPD. These proteomic signatures may provide insights into the underlying mechanisms linking environmental factors to COPD pathogenesis and serve as potential targets linking environmental exposures and COPD. This abstract is funded by: Hunan Provincial Natural Science Fund for Outstanding Young Scholars (No. 2024JJ4090), Science and Technology Innovation Young Talents of Hunan Province (No. 2024RC3050)
Zhang et al. (Fri,) studied this question.