Lung lipids associated with smoking and ECIG use in a cross-sectional study and clinical trial

Abstract Background While electronic cigarettes (ECIG) may have lower toxicant delivery than cigarettes, ECIG-liquids and aerosols still contain toxicants that can potentially disrupt lung lipid homeostasis. Methods Participants from two studies underwent bronchoscopy and bronchoalveolar lavage (BAL...

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Main Authors: Joseph P. McElroy, Min-Ae Song, John R. Barr, Michael S. Gardner, Garret Kinnebrew, Zsuzsanna Kuklenyik, Jennifer D. Kusovschi, Jon C. Rees, Benjamin C. Blount, MuChun Tsai, Mark D Wewers, Sahar Kamel, Sarah A. Reisinger, Amarnath Singh, Daniel Y. Weng, Peter G. Shields
Format: Article
Language:English
Published: BMC 2025-05-01
Series:Respiratory Research
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Online Access:https://doi.org/10.1186/s12931-025-03267-w
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author Joseph P. McElroy
Min-Ae Song
John R. Barr
Michael S. Gardner
Garret Kinnebrew
Zsuzsanna Kuklenyik
Jennifer D. Kusovschi
Jon C. Rees
Benjamin C. Blount
MuChun Tsai
Mark D Wewers
Sahar Kamel
Sarah A. Reisinger
Amarnath Singh
Daniel Y. Weng
Peter G. Shields
author_facet Joseph P. McElroy
Min-Ae Song
John R. Barr
Michael S. Gardner
Garret Kinnebrew
Zsuzsanna Kuklenyik
Jennifer D. Kusovschi
Jon C. Rees
Benjamin C. Blount
MuChun Tsai
Mark D Wewers
Sahar Kamel
Sarah A. Reisinger
Amarnath Singh
Daniel Y. Weng
Peter G. Shields
author_sort Joseph P. McElroy
collection DOAJ
description Abstract Background While electronic cigarettes (ECIG) may have lower toxicant delivery than cigarettes, ECIG-liquids and aerosols still contain toxicants that can potentially disrupt lung lipid homeostasis. Methods Participants from two studies underwent bronchoscopy and bronchoalveolar lavage (BAL). Ninety-eight participants (21-44 years old) were included in a cross-sectional study, with 17 ECIG users, 52 non-smokers, and 29 smokers. In the four-week clinical trial, 30 non-smokers were randomly assigned to use nicotine-free, flavorless ECIG or no use. A panel of 75 quantifiable lipid species and 7 lipid classes were assessed in the BAL using two tandem mass spectrometry (MS/MS) platforms. Ten cytokines and lipid-laden macrophages (LLM) were analyzed using the V-PLEX Plus Proinflam Combo 10 panel and Oil Red O staining, respectively. Results In the cross-sectional study, 43 lipids were associated with smoking status at FDR<0.1, including two between ECIG and non-smokers (PC(14:0/18:1) and PC(18:0/14:0)) in pairwise follow-up analyses (Bonferroni-adjusted p<0.017). Associations between lipid species and cotinine, inflammatory markers, including IL-1β and IL-8, and LLM were also identified, as well as differences in lipid classes between smokers and the other groups. Smokers had higher saturated lipids, including ceramide (CER), sphingomyelin (SM), and diacylglycerol (DAG) than that of non-smokers and ECIG users. No significant associations were identified in the 4-week clinical trial. Conclusions Smoking was associated with altered lipid levels, as compared to both non-smokers and ECIG users; the majority were downregulated and ECIG effects tend to be smaller in magnitude than smoking effects, although some were different than those in the smokers group. This is a novel study of healthy individuals examining lipidomic differences between smokers, ECIG users, and non-smokers, indicating potential roles of smoking and ECIG-related lipid alterations in pulmonary disease. Trial registration The study was approved by The OSU Institutional Review Board (OSU-2015C0088) in accordance with its ethical standards, the Helsinki declaration, and the Belmont Report, and is registered on Clinicaltrials.gov (NCT02596685; 2015-11-04).
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spelling doaj-art-9faa121ae96d43fabde5cf06ef6df0f52025-08-20T02:34:15ZengBMCRespiratory Research1465-993X2025-05-0126111510.1186/s12931-025-03267-wLung lipids associated with smoking and ECIG use in a cross-sectional study and clinical trialJoseph P. McElroy0Min-Ae Song1John R. Barr2Michael S. Gardner3Garret Kinnebrew4Zsuzsanna Kuklenyik5Jennifer D. Kusovschi6Jon C. Rees7Benjamin C. Blount8MuChun Tsai9Mark D Wewers10Sahar Kamel11Sarah A. Reisinger12Amarnath Singh13Daniel Y. Weng14Peter G. Shields15Center for Biostatistics, Department of Biomedical Informatics, College of Medicine, The Ohio State UniversityDivision of Environmental Health Sciences, College of Public Health, The Ohio State UniversityDivision of Laboratory Sciences, Centers for Disease Control and Prevention, National Center for Environmental HealthDivision of Laboratory Sciences, Centers for Disease Control and Prevention, National Center for Environmental HealthDepartment of Biomedical Informatics, College of Medicine, The Ohio State UniversityDivision of Laboratory Sciences, Centers for Disease Control and Prevention, National Center for Environmental HealthDivision of Laboratory Sciences, Centers for Disease Control and Prevention, National Center for Environmental HealthDivision of Laboratory Sciences, Centers for Disease Control and Prevention, National Center for Environmental HealthDivision of Laboratory Sciences, Centers for Disease Control and Prevention, National Center for Environmental HealthComprehensive Cancer Center, The Ohio State University and James Cancer HospitalComprehensive Cancer Center, The Ohio State University and James Cancer HospitalComprehensive Cancer Center, The Ohio State University and James Cancer HospitalComprehensive Cancer Center, The Ohio State University and James Cancer HospitalComprehensive Cancer Center, The Ohio State University and James Cancer HospitalComprehensive Cancer Center, The Ohio State University and James Cancer HospitalComprehensive Cancer Center, The Ohio State University and James Cancer HospitalAbstract Background While electronic cigarettes (ECIG) may have lower toxicant delivery than cigarettes, ECIG-liquids and aerosols still contain toxicants that can potentially disrupt lung lipid homeostasis. Methods Participants from two studies underwent bronchoscopy and bronchoalveolar lavage (BAL). Ninety-eight participants (21-44 years old) were included in a cross-sectional study, with 17 ECIG users, 52 non-smokers, and 29 smokers. In the four-week clinical trial, 30 non-smokers were randomly assigned to use nicotine-free, flavorless ECIG or no use. A panel of 75 quantifiable lipid species and 7 lipid classes were assessed in the BAL using two tandem mass spectrometry (MS/MS) platforms. Ten cytokines and lipid-laden macrophages (LLM) were analyzed using the V-PLEX Plus Proinflam Combo 10 panel and Oil Red O staining, respectively. Results In the cross-sectional study, 43 lipids were associated with smoking status at FDR<0.1, including two between ECIG and non-smokers (PC(14:0/18:1) and PC(18:0/14:0)) in pairwise follow-up analyses (Bonferroni-adjusted p<0.017). Associations between lipid species and cotinine, inflammatory markers, including IL-1β and IL-8, and LLM were also identified, as well as differences in lipid classes between smokers and the other groups. Smokers had higher saturated lipids, including ceramide (CER), sphingomyelin (SM), and diacylglycerol (DAG) than that of non-smokers and ECIG users. No significant associations were identified in the 4-week clinical trial. Conclusions Smoking was associated with altered lipid levels, as compared to both non-smokers and ECIG users; the majority were downregulated and ECIG effects tend to be smaller in magnitude than smoking effects, although some were different than those in the smokers group. This is a novel study of healthy individuals examining lipidomic differences between smokers, ECIG users, and non-smokers, indicating potential roles of smoking and ECIG-related lipid alterations in pulmonary disease. Trial registration The study was approved by The OSU Institutional Review Board (OSU-2015C0088) in accordance with its ethical standards, the Helsinki declaration, and the Belmont Report, and is registered on Clinicaltrials.gov (NCT02596685; 2015-11-04).https://doi.org/10.1186/s12931-025-03267-wSmokingElectronic CigaretteLipidomics
spellingShingle Joseph P. McElroy
Min-Ae Song
John R. Barr
Michael S. Gardner
Garret Kinnebrew
Zsuzsanna Kuklenyik
Jennifer D. Kusovschi
Jon C. Rees
Benjamin C. Blount
MuChun Tsai
Mark D Wewers
Sahar Kamel
Sarah A. Reisinger
Amarnath Singh
Daniel Y. Weng
Peter G. Shields
Lung lipids associated with smoking and ECIG use in a cross-sectional study and clinical trial
Respiratory Research
Smoking
Electronic Cigarette
Lipidomics
title Lung lipids associated with smoking and ECIG use in a cross-sectional study and clinical trial
title_full Lung lipids associated with smoking and ECIG use in a cross-sectional study and clinical trial
title_fullStr Lung lipids associated with smoking and ECIG use in a cross-sectional study and clinical trial
title_full_unstemmed Lung lipids associated with smoking and ECIG use in a cross-sectional study and clinical trial
title_short Lung lipids associated with smoking and ECIG use in a cross-sectional study and clinical trial
title_sort lung lipids associated with smoking and ecig use in a cross sectional study and clinical trial
topic Smoking
Electronic Cigarette
Lipidomics
url https://doi.org/10.1186/s12931-025-03267-w
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