Ambient PM Species and Ultrafine Particle Exposure and Their Differential Metabolomic Signatures

Background: The metabolomic signatures of short- and long-term exposure to PM have been reported and linked to inflammation and oxidative stress. However, little is known about the relative contribution of the specific PM species (hence sources) that drive these metabolomic signatures.

Objectives: We aimed to determine the relative contribution of the different species of PM exposure to the perturbed metabolic pathways related to changes in the plasma metabolome.

Methods: We performed mass-spectrometry based metabolomic profiling of plasma samples among men from the Normative Aging Study to identify metabolic pathways associated with PM species. The exposure windows included short-term (one, seven-, and thirty-day moving average) and long-term (one year moving average). We used linear mixed-effect regression with subject-specific intercepts while simultaneously adjusting for PM, NO, O, temperature, relative humidity, and covariates and correcting for multiple testing. We also used independent component analysis (ICA) to examine the relative contribution of patterns of PM species.

Results: Between 2000 and 2016, 456 men provided 648 blood samples, in which 1158 metabolites were quantified. We chose 305 metabolites for the short-term and 288 metabolites for the long-term exposure in this analysis that were significantly associated (p-value < 0.01) with PM to include in our PM species analysis. On average, men were 75.0 years old and their body mass index was 27.7 kg/m. Only 3% were current smokers. In the adjusted models, ultrafine particles (UFPs) were the most significant species of short-term PM exposure followed by nickel, vanadium, potassium, silicon, and aluminum. Black carbon, vanadium, zinc, nickel, iron, copper, and selenium were the significant species of long-term PM exposure. We identified several metabolic pathways perturbed with PM species including glycerophospholipid, sphingolipid, and glutathione. These pathways are involved in inflammation, oxidative stress, immunity, and nucleic acid damage and repair. Results were overlapped with the ICA.

Conclusions: We identified several significant perturbed plasma metabolites and metabolic pathways associated with exposure to PM species. These species are associated with traffic, fuel oil, and wood smoke. This is the largest study to report a metabolomic signature of PM species' exposure and the first to use ICA.