Noninvasive systemic biomarkers of e-cigarette or vaping use-associated lung injury: a pilot study

Background Electronic cigarette (e-cigarette) vaping, containing nicotine and/or Delta(8), Delta(9) or Delta(10) or Delta(o) tetrahydrocannabinol (Delta(n)-THC), is associated with an outbreak of e-cigarette, or vaping, product useassociated lung injury (EVALI). Despite thousands being hospitalised with EVALI, much remains unknown about diagnosis, treatment and disease pathogenesis. Biomarkers of inflammation, oxidative stress and lipid mediators may help identify e-cigarette users with EVALI. Methods We collected plasma and urine along with demographic and vaping-related data of EVALI subjects (age 18-35 years) and non-users matched for sex and age in a pilot study. Biomarkers were assessed by ELISA/EIA and Luminex-based assays. Results Elevated levels of THC metabolite (11-nor-9-carboxy-Delta(9)-THC) were found in plasma from EVALI subjects compared to non-users. Levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG), an oxidative DNA damage biomarker, and 8-isoprostane, an oxidative stress marker, were slightly increased in urine samples from EVALI subjects compared to non-users. Conversely, plasma levels of lipid mediators, including resolvin D-1 (RvD(1)) and prostaglandin E-2 (PGE(2)), were significantly lower in EVALI subjects compared to non-users. Both pro-inflammatory biomarkers, such as tumour necrosis factor-alpha, macrophage inflammatory protein-1 beta, RANTES (regulated on activation, normal T-cell expressed and secreted) and granulocyte-macrophage colony-stimulating factor, as well as anti-inflammatory biomarkers, such as interleukin-9 and CC10/16, were decreased in plasma from EVALI subjects compared to non-users, supportive of a possible dysregulated inflammatory response in EVALI subjects. Conclusions Significant elevations in urine and plasma biomarkers of oxidative stress, as well as reductions in lipid mediators, were shown in EVALI subjects. These noninvasive biomarkers (8-OHdG, 8-isoprostane, RvD(1) and CC10/16), either individually or collectively, may serve as tools in diagnosing future EVALI subjects.