Exhaled Breath Condensate Reveals PM_2.5-Driven Airway Metabolic Signature in Young Adults: A Panel Study

Fine particulate matter (PM_2.5) represents a pervasive global environmental hazard linked to adverse respiratory and systemic health outcomes, yet sensitive and noninvasive early biomarkers for real-world exposure remain poorly defined. In this 35 day panel study conducted in Shijiazhuang, China, we recruited 30 healthy young adult males to characterize proteomic and metabolomic alterations in exhaled breath condensate (EBC) under ambient PM_2.5 exposure. The average personal PM_2.5 concentration was 73.08 μg/m³, with distinct high- and low-exposure periods of 131.33 and 40.46 μg/m³, respectively. High PM_2.5 exposure was associated with mild lung function decline, increased systemic inflammation, and elevated oxidative DNA damage. Proteomic profiling identified consistent downregulation of six key proteins in EBC, including PPIA, ENO1, EEF1A1, HSPA8, GAPDH, and RPSA. Metabolomic analysis further revealed disrupted energy metabolism and lipid homeostasis closely tied to inflammatory and oxidative stress responses. Notably, leucine, ornithine, and phenylalanine displayed consistent dose-response trends across EBC, plasma, and urine, supporting their promise as cross-compartment biomarkers. Our results validate EBC as a minimally invasive matrix to detect both local pulmonary and systemic perturbations induced by ambient PM_2.5 exposure.