A cross-week analysis of urinary extracellular vesicles after respiratory tract exposure intervention in a cohort of isocyanate-exposed workers

Emerging evidence suggests that urinary extracellular vesicles (EVs) may serve as indicators of systemic health; however, the utility of urinary EVs and their cargo for assessing systemic pathophysiology, especially in the context of occupational exposures, has received limited attention. Here, in a small well-characterized group of factory workers with potential inhalational exposure to methylene diphenyl diisocyanate, we determined the utility of different types of urinary EV cargo to monitor the impact of inhalational exposure. EVs were purified from spot urine samples of the same individual collected before and one week after implementation of an organic vapor cartridge respirator intervention (pre-RESP and post-RESP, respectively). Among EV-associated mRNA, non-coding RNA, and protein cargo, EV-mRNA most effectively captured exposure-related biological changes. Differentially enriched EV-mRNAs between the pre-RESP and the post-RESP groups were significantly associated with pathways involved in asthma and lung inflammation. In the Integrated Human Lung Cell Atlas, the pre-RESP-specific EV-mRNA signature was significantly associated with hypersensitivity pneumonitis and chronic obstructive pulmonary disease among the 15 disease phenotypes represented in the atlas, whereas no such association was observed for the post-RESP signature. These findings demonstrate that urinary EVs can be reliably isolated from field samples of occupationally exposed workers and suggest that EV-mRNA cargo may serve as noninvasive biomarker for monitoring systemic responses to respiratory exposures.