Lipid laden macrophages and electronic cigarettes in healthy adults

Background An outbreak of E-cigarette or Vaping Product Use-Associated Lung Injury (EVALI) with significant morbidity and mortality was reported in 2019. While most patients with EVALI report vaping tetrahydrocannabinol (THC) oils contaminated with vitamin E acetate, a subset report only vaping with nicotine-containing electronic cigarettes (e-cigs). Whether or not e-cigs cause EVALI, the outbreak highlights the need for identifying long term health effects of e-cigs. EVALI pathology includes alveolar damage, pneumonitis and/or organizing pneumonia, often with lipid-laden macrophages (LLM). We assessed LLM in the lungs of healthy smokers, e-cig users, and never-smokers as a potential marker of e-cig toxicity and EVALI. Methods A cross-sectional study using bronchoscopy was conducted in healthy smokers, e-cig users, and never-smokers (n = 64). LLM, inflammatory cell counts, and cytokines were determined in bronchial alveolar fluids (BAL). E-cig users included both never-smokers and former light smokers. Findings High LLM was found in the lungs of almost all smokers and half of the e-cig users, but not those of never-smokers. LLM were not related to THC exposure or smoking history. LLM were significantly associated with inflammatory cytokines IL-4 and IL-10 in e-cig users, but not smoking-related cytokines. Interpretation This is the first report of lung LLM comparing apparently healthy smokers, e-cig users, and never-smokers. LLM are not a specific marker for EVALI given the frequent positivity in smokers; whether LLMs are a marker of lung inflammation in some e-cig users requires further study. Funding The National Cancer Institute, the National Heart, Lung, and Blood Institute, the Food and Drug Administration Center for Tobacco Products, the National Center For Advancing Translational Sciences, and Pelotonia Intramural Research Funds