PMID- 35731626 OWN - NLM STAT- MEDLINE DCOM- 20221118 LR - 20231129 IS - 1535-4970 (Electronic) IS - 1073-449X (Print) IS - 1073-449X (Linking) VI - 206 IP - 10 DP - 2022 Nov 15 TI - Biomarkers of Airway Immune Homeostasis Differ Significantly with Generation of E-Cigarettes. PG - 1248-1258 LID - 10.1164/rccm.202202-0373OC [doi] AB - Rationale: Numerous studies have demonstrated that e-cigarettes can impact respiratory immune homeostasis; however, the extent of these effects remains an active area of investigation, and most previous studies were conducted with model systems or subjects exposed to third-generation e-cigarettes, such as vape pens and box mods. Objectives: Given the rise in popularity of nicotine-salt-containing pods and disposable e-cigarettes (fourth generation), we set out to better understand the respiratory effects of these newer e-cigarettes and compare their effects to early-generation devices. Methods: We collected induced sputum samples from a cohort of nonsmokers, smokers, third-generation e-cigarette users, and fourth-generation e-cigarette users (n = 20-30 per group) and evaluated the cellular and fluid-phase composition for markers of inflammation, host defense, and lung injury. Measurements and Main Results: Fourth-generation e-cigarette users had significantly more bronchial epithelial cells in the sputum, suggestive of airway injury. Concentrations of soluble intercellular adhesion molecule 1 (sICAM1) and soluble vascular cell adhesion molecule 1 (sVCAM1) were significantly lower in fourth-generation e-cigarette users in comparison with all other groups, and CRP (C-reactive protein), IFN-gamma, MCP-1 (monocyte chemoattractant protein-1), MMP-2 (matrix metalloproteinase 2), uteroglobin, and VEGF (vascular endothelial growth factor) were significantly lower in fourth- versus third-generation e-cigarette users, suggestive of overall immune suppression in fourth-generation e-cigarette users. Predictive modeling also demonstrated clear separation between exposure groups, indicating that the overall mediator milieu is different between groups, particularly fourth-generation e-cigarette users. Conclusions: Our results indicate disrupted immune homeostasis in fourth-generation e-cigarette users and demonstrate that the biological effects of fourth-generation e-cigarette use are unique compared with those associated with previous-generation e-cigarettes. FAU - Hickman, Elise AU - Hickman E AUID- ORCID: 0000-0001-6152-050X AD - Center for Environmental Medicine, Asthma, and Lung Biology. AD - Curriculum in Toxicology & Environmental Medicine. FAU - Payton, Alexis AU - Payton A AD - Center for Environmental Medicine, Asthma, and Lung Biology. AD - Department of Environmental Sciences and Engineering, and. AD - The Institute for Environmental Health Solutions, Gillings School of Global Public Health, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina. FAU - Duffney, Parker AU - Duffney P AD - Center for Environmental Medicine, Asthma, and Lung Biology. AD - Curriculum in Toxicology & Environmental Medicine. FAU - Wells, Heather AU - Wells H AD - Center for Environmental Medicine, Asthma, and Lung Biology. FAU - Ceppe, Agathe S AU - Ceppe AS AD - Marsico Lung Institute, School of Medicine. FAU - Brocke, Stephanie AU - Brocke S AD - Center for Environmental Medicine, Asthma, and Lung Biology. AD - Curriculum in Toxicology & Environmental Medicine. FAU - Bailey, Aleah AU - Bailey A AD - Center for Environmental Medicine, Asthma, and Lung Biology. AD - Curriculum in Toxicology & Environmental Medicine. FAU - Rebuli, Meghan E AU - Rebuli ME AUID- ORCID: 0000-0003-1918-2257 AD - Center for Environmental Medicine, Asthma, and Lung Biology. AD - Curriculum in Toxicology & Environmental Medicine. FAU - Robinette, Carole AU - Robinette C AD - Center for Environmental Medicine, Asthma, and Lung Biology. FAU - Ring, Brian AU - Ring B AD - Center for Environmental Medicine, Asthma, and Lung Biology. FAU - Rager, Julia E AU - Rager JE AUID- ORCID: 0000-0002-2882-5042 AD - Center for Environmental Medicine, Asthma, and Lung Biology. AD - Curriculum in Toxicology & Environmental Medicine. AD - Department of Environmental Sciences and Engineering, and. AD - The Institute for Environmental Health Solutions, Gillings School of Global Public Health, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina. FAU - Alexis, Neil E AU - Alexis NE AD - Center for Environmental Medicine, Asthma, and Lung Biology. FAU - Jaspers, Ilona AU - Jaspers I AUID- ORCID: 0000-0001-8728-0305 AD - Center for Environmental Medicine, Asthma, and Lung Biology. AD - Curriculum in Toxicology & Environmental Medicine. AD - The Institute for Environmental Health Solutions, Gillings School of Global Public Health, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina. LA - eng GR - T32 ES007126/ES/NIEHS NIH HHS/United States GR - R25 GM089569/GM/NIGMS NIH HHS/United States GR - F31 HL154758/HL/NHLBI NIH HHS/United States GR - R01 HL139369/HL/NHLBI NIH HHS/United States GR - P42 ES031007/ES/NIEHS NIH HHS/United States GR - P50 HL120100/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Am J Respir Crit Care Med JT - American journal of respiratory and critical care medicine JID - 9421642 RN - EC 3.4.24.24 (Matrix Metalloproteinase 2) RN - 0 (Vascular Endothelial Growth Factor A) RN - 0 (Biomarkers) SB - IM CIN - Am J Respir Crit Care Med. 2022 Nov 15;206(10):1195-1197. PMID: 35816433 MH - Humans MH - *Electronic Nicotine Delivery Systems MH - *Vaping/adverse effects MH - Matrix Metalloproteinase 2 MH - Vascular Endothelial Growth Factor A MH - *Tobacco Products MH - Biomarkers MH - Homeostasis PMC - PMC9746848 OTO - NOTNLM OT - immune suppression OT - machine learning OT - pod e-cigarettes EDAT- 2022/06/23 06:00 MHDA- 2022/11/19 06:00 PMCR- 2023/11/15 CRDT- 2022/06/22 12:23 PHST- 2022/06/23 06:00 [pubmed] PHST- 2022/11/19 06:00 [medline] PHST- 2022/06/22 12:23 [entrez] PHST- 2023/11/15 00:00 [pmc-release] AID - 10.1164/rccm.202202-0373OC [doi] PST - ppublish SO - Am J Respir Crit Care Med. 2022 Nov 15;206(10):1248-1258. doi: 10.1164/rccm.202202-0373OC.