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Vaping-induced metabolomic signatures in the circulation of mice are driven by device type, e-liquid, exposure duration and sex

Alexander Moshensky, Mulong Du, John Shin, Ira Advani, Deepti Gunge, Denzil Mathew, Rita Alkolla, Ashley Du, Christian Javier, Lauren Ma, Albert Tran, Nicholas Nguyen, Jarod Olay, Sedtavut Nilaad, Jeffrey Ding, Mahan Najhawan, Jeramie D. Watrous, Christine M. Bojanowksi, Mohit Jain, David C. Christiani, Laura E. Crotty Alexander
ERJ Open Research 2021 7: 00229-2021; DOI: 10.1183/23120541.00229-2021
Alexander Moshensky
1Pulmonary Critical Care Section, VA San Diego Healthcare System, La Jolla, CA, USA
2Division of Pulmonary, Critical Care and Sleep Medicine, Dept of Medicine, University of California San Diego (UCSD), La Jolla, CA, USA
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Mulong Du
3Dept of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA
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John Shin
1Pulmonary Critical Care Section, VA San Diego Healthcare System, La Jolla, CA, USA
2Division of Pulmonary, Critical Care and Sleep Medicine, Dept of Medicine, University of California San Diego (UCSD), La Jolla, CA, USA
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Ira Advani
1Pulmonary Critical Care Section, VA San Diego Healthcare System, La Jolla, CA, USA
2Division of Pulmonary, Critical Care and Sleep Medicine, Dept of Medicine, University of California San Diego (UCSD), La Jolla, CA, USA
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Deepti Gunge
1Pulmonary Critical Care Section, VA San Diego Healthcare System, La Jolla, CA, USA
2Division of Pulmonary, Critical Care and Sleep Medicine, Dept of Medicine, University of California San Diego (UCSD), La Jolla, CA, USA
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Denzil Mathew
1Pulmonary Critical Care Section, VA San Diego Healthcare System, La Jolla, CA, USA
2Division of Pulmonary, Critical Care and Sleep Medicine, Dept of Medicine, University of California San Diego (UCSD), La Jolla, CA, USA
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Rita Alkolla
1Pulmonary Critical Care Section, VA San Diego Healthcare System, La Jolla, CA, USA
2Division of Pulmonary, Critical Care and Sleep Medicine, Dept of Medicine, University of California San Diego (UCSD), La Jolla, CA, USA
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Ashley Du
1Pulmonary Critical Care Section, VA San Diego Healthcare System, La Jolla, CA, USA
2Division of Pulmonary, Critical Care and Sleep Medicine, Dept of Medicine, University of California San Diego (UCSD), La Jolla, CA, USA
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Christian Javier
1Pulmonary Critical Care Section, VA San Diego Healthcare System, La Jolla, CA, USA
2Division of Pulmonary, Critical Care and Sleep Medicine, Dept of Medicine, University of California San Diego (UCSD), La Jolla, CA, USA
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Lauren Ma
1Pulmonary Critical Care Section, VA San Diego Healthcare System, La Jolla, CA, USA
2Division of Pulmonary, Critical Care and Sleep Medicine, Dept of Medicine, University of California San Diego (UCSD), La Jolla, CA, USA
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Albert Tran
1Pulmonary Critical Care Section, VA San Diego Healthcare System, La Jolla, CA, USA
2Division of Pulmonary, Critical Care and Sleep Medicine, Dept of Medicine, University of California San Diego (UCSD), La Jolla, CA, USA
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Nicholas Nguyen
1Pulmonary Critical Care Section, VA San Diego Healthcare System, La Jolla, CA, USA
2Division of Pulmonary, Critical Care and Sleep Medicine, Dept of Medicine, University of California San Diego (UCSD), La Jolla, CA, USA
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Jarod Olay
1Pulmonary Critical Care Section, VA San Diego Healthcare System, La Jolla, CA, USA
2Division of Pulmonary, Critical Care and Sleep Medicine, Dept of Medicine, University of California San Diego (UCSD), La Jolla, CA, USA
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Sedtavut Nilaad
1Pulmonary Critical Care Section, VA San Diego Healthcare System, La Jolla, CA, USA
2Division of Pulmonary, Critical Care and Sleep Medicine, Dept of Medicine, University of California San Diego (UCSD), La Jolla, CA, USA
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Jeffrey Ding
4Depts of Medicine and Pharmacology, UCSD, La Jolla, CA, USA
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Mahan Najhawan
4Depts of Medicine and Pharmacology, UCSD, La Jolla, CA, USA
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  • ORCID record for Mahan Najhawan
Jeramie D. Watrous
4Depts of Medicine and Pharmacology, UCSD, La Jolla, CA, USA
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Christine M. Bojanowksi
1Pulmonary Critical Care Section, VA San Diego Healthcare System, La Jolla, CA, USA
2Division of Pulmonary, Critical Care and Sleep Medicine, Dept of Medicine, University of California San Diego (UCSD), La Jolla, CA, USA
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Mohit Jain
4Depts of Medicine and Pharmacology, UCSD, La Jolla, CA, USA
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David C. Christiani
3Dept of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA
5Division of Pulmonary and Critical Care Medicine, Dept of Medicine, Massachusetts General Hospital, Boston, MA, USA
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  • ORCID record for David C. Christiani
Laura E. Crotty Alexander
1Pulmonary Critical Care Section, VA San Diego Healthcare System, La Jolla, CA, USA
2Division of Pulmonary, Critical Care and Sleep Medicine, Dept of Medicine, University of California San Diego (UCSD), La Jolla, CA, USA
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  • For correspondence: lca@ucsd.edu
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    FIGURE 1

    Changes in circulating metabolites induced by daily, chronic inhalation of aerosols generated from multiple e-devices and e-liquids, and for varying exposure durations. Mice were placed in the inExpose system (Scireq) for 1 h daily. Box Mod, vape pen and pod-based e-devices (JUUL) were activated and negative pressure applied to generate fresh e-cigarette aerosols every 20 s, with puff duration of 4 s across all devices. Plasma isolated on the day of harvest underwent comprehensive nontargeted, liquid chromatography–mass spectrometry-based metabolomics to assay thousands of circulating bioactive molecules. a) Venn diagram of significant metabolites (p<0.05) identified in the plasma of mice that inhaled aerosols generated from box Mod e-cigarette devices. No-nicotine aerosols (vehicle) compared to air controls, nicotine-containing aerosols (EV) versus air controls and vehicle versus EV after 12 weeks of daily 1-h exposures. b) Venn diagram of significant metabolites (p<0.05) identified in comparisons among vehicle versus air, EV versus air and vehicle versus EV after 4 weeks of daily box Mod aerosol exposures. c) Venn diagram of unique and shared metabolites across different time exposures (4 versus 12 weeks) for vehicle versus EV. d) Metabolites detected in JUUL mango versus air, JUUL mint versus air and JUUL mango versus JUUL mint after 4 weeks of exposure. The red circle indicates the sole metabolite shared between JUUL mango and JUUL mint exposures: putative β-hydrocortisone (HC). e) Venn diagram of unique and shared metabolites in the setting of lipopolysaccharide (LPS) challenge across air, JUUL mango and JUUL mint exposures. f) Identification of different metabolites across all device types and exposure durations with no overlapping metabolites across e-cigarette exposures. Inhalation of JUUL aerosols caused the smallest metabolite signatures, relative to box Mod and vape pen aerosols. The reduced metabolite signatures may be due to Mod and JUUL devices applying different temperatures and wattages to e-liquids. g) Sex effects on metabolite changes induced by 4 weeks of e-cigarette aerosol exposure, with males and females only having one shared metabolite induced by e-cigarette exposure. Plots were developed using the VennDiagram package in R.

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Vaping-induced metabolomic signatures in the circulation of mice are driven by device type, e-liquid, exposure duration and sex
Alexander Moshensky, Mulong Du, John Shin, Ira Advani, Deepti Gunge, Denzil Mathew, Rita Alkolla, Ashley Du, Christian Javier, Lauren Ma, Albert Tran, Nicholas Nguyen, Jarod Olay, Sedtavut Nilaad, Jeffrey Ding, Mahan Najhawan, Jeramie D. Watrous, Christine M. Bojanowksi, Mohit Jain, David C. Christiani, Laura E. Crotty Alexander
ERJ Open Research Jul 2021, 7 (3) 00229-2021; DOI: 10.1183/23120541.00229-2021

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Vaping-induced metabolomic signatures in the circulation of mice are driven by device type, e-liquid, exposure duration and sex
Alexander Moshensky, Mulong Du, John Shin, Ira Advani, Deepti Gunge, Denzil Mathew, Rita Alkolla, Ashley Du, Christian Javier, Lauren Ma, Albert Tran, Nicholas Nguyen, Jarod Olay, Sedtavut Nilaad, Jeffrey Ding, Mahan Najhawan, Jeramie D. Watrous, Christine M. Bojanowksi, Mohit Jain, David C. Christiani, Laura E. Crotty Alexander
ERJ Open Research Jul 2021, 7 (3) 00229-2021; DOI: 10.1183/23120541.00229-2021
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