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

Electronic cigarette (e-cigarette) vaping, containing nicotine and/or Δ⁸, Δ⁹ or Δ¹⁰ or Δ^o tetrahydrocannabinol (Δⁿ-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.

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.

Elevated levels of THC metabolite (11-nor-9-carboxy-Δ⁹-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 D₁ (RvD₁) and prostaglandin E₂ (PGE₂), 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.

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, RvD₁ and CC10/16), either individually or collectively, may serve as tools in diagnosing future EVALI subjects.