Exploring the exposome across the life-course; air pollution, metabolomics and lung function

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Background and Aim. Previous studies have explored relationships of air pollution and metabolic profiles with lung function. However, the metabolites linking air pollution and lung function and associated mechanisms have not been reviewed from a life-course perspective. Accordingly, causal inference regarding health effects of single exposures or mixtures remains limited. Methods. We conducted a narrative review summarizing recent evidence on the associations of metabolic profiles with both air pollution exposure and lung function taking different stages of life into consideration (linking metabolites to exposure and outcome). Results. Thirty-two studies were included with 10 studies analyzing air pollution-related metabolic profiles, and 22 analyzing lung function-related metabolic profiles. A wide range of metabolites were identified being associated with short- and long-term exposure, partly overlapping with those linked to lung function in the general population and respiratory diseases such as asthma and COPD, including compounds of amino acid and lipid metabolism. The existing studies show that metabolomics offers potential to identify biomarkers linked to both environmental exposures and respiratory outcomes, which can improve exposure assessment, causal understanding, and identification of individuals at risk. However, many studies suffer from small sample size, cross-sectional designs, preponderance on adult lung function, heterogeneity in exposure assessment, lack of confounding control and omics integration. Conclusions: Studies with prospectively and repeatedly collected biological samples and harmonized exposure assessment are needed to get insights into mechanisms and causality of life-long respiratory effects of air pollution. The ongoing EXposome Powered tools for healthy living in urbAN Settings (EXPANSE) project aims at addressing some of the shortcomings of earlier studies by combining biospecimens from large European cohorts covering different age groups, along with harmonized air pollution exposure and exposome data. Keywords: metabolomics, lung function, spirometry, Chronic obstructive pulmonary disease (COPD), air pollution

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