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 Δ(8), Δ(9) or Δ(10) or Δ(o) tetrahydrocannabinol (Δ(n)-THC), is associated with an outbreak of e-cigarette, or vaping, product use-associated 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-Δ(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-α, macrophage inflammatory protein-1β, 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.