Background

Exposure to airborne fine particulate matter (PM_2.5) has been associated with a variety of adverse health outcomes including chronic obstructive pulmonary disease (COPD). However, the linkages between PM_2.5 exposure, PM_2.5-related biomarkers, COPD-related biomarkers and COPD remain poorly elucidated.

Objectives

To investigate the linkages between PM_2.5 exposure and COPD outcome by using the meet-in-middle strategy based on urinary metabolic biomarkers.

Methods

A cross-sectional study was designed to illustrate the mentioned quadripartite linkages. Indoor PM_2.5 and its element components were assessed in 41 Chinese elderly participants including COPD patients and their healthy spouses. Metabolic biomarkers involved in PM_2.5 exposure and COPD were identified by using urinary metabolomics. The associations between PM_2.5- and COPD-related biomarkers were investigated by statistics and metabolic pathway analysis.

Results

Seven metabolites were screened and identified with significant correlations to PM_2.5 exposure, which were majorly involved in purine and amino acid metabolism as well as glycolysis. Ten COPD-related metabolic biomarkers were identified, which suggested that amino acid metabolism, lipid and fatty acid metabolism, and glucose metabolism were disturbed in the patients. Also, PM_2.5 and its many elemental components were significantly associated with COPD-related biomarkers. We observed that the two kinds of biomarkers (PM_2.5- and COPD-related) integrated in a locally connected network and the alterations of these metabolic biomarkers can biologically link PM_2.5 exposure to COPD outcome.

Conclusions

Our study indicated the modification of PM_2.5 to COPD via both modes of action of lowering participants' antioxidation capacity and decreasing their lung energy generation; this information would be valuable for the prevention strategy of COPD.

The study hypothesis of meet-in-metabolite and flowchart: an adverse outcome pathway analysis for illustrating PM_2.5 exposure-related COPD modification. PM_2.5- and COPD-related metabolic biomarkers were mined separately, and then their linkages with PM_2.5 and COPD were investigated by taken the urinary metabolism continuum as PM_2.5-COPD communication hub.