title: Molecular Impact of Electronic Cigarette Aerosol Exposure in Human Bronchial Epithelium.
abstract: Little evidence is available regarding the physiological effects of exposure to electronic cigarette (ECIG) aerosol. We sought to determine the molecular impact of ECIG aerosol exposure in human bronchial epithelial cells (HBECs). Gene-expression profiling was conducted in primary grown at air liquid interface and exposed to 1 of 4 different ECIG aerosols, traditional tobacco cigarette (TCIG) smoke, or clean air. Findings were validated experimentally with quantitative polymerase chain reaction and a reactive oxygen species immunoassay. Using gene set enrichment analysis, signatures of in vitro ECIG exposure were compared with those generated from bronchial epithelial brushings of current TCIG smokers and former TCIG smokers currently using ECIGs. We found 546 genes differentially expressed across the ECIG, TCIG, and air-exposed groups of HBECs (ANOVA; FDR q < .05; fold change > 1.5). A subset of these changes were shared between TCIG- and ECIG-exposed HBECs. ECIG exposure induced genes involved in oxidative and xenobiotic stress pathways and increased a marker of reactive oxygen species production in a dose-dependent manner. ECIG exposure decreased expression of genes involved in cilia assembly and movement. Furthermore, gene-expression differences observed in vitro were concordant with differences observed in airway epithelium collected from ECIG users (q < .01). In summary, our data suggest that ECIG aerosol can induce gene-expression changes in bronchial airway epithelium in vitro, some of which are shared with TCIG smoke. These changes were generally less pronounced than the effects of TCIG exposure and were more pronounced in ECIG products containing nicotine than those without nicotine. Our data further suggest that the gene-expression alterations seen with the in vitro exposure system reflects the physiological effects experienced in vivo by ECIG users.
authors.affiliation: Section of Computational Biomedicine, Department of Medicine Boston University School of Medicine, Boston, Massachusetts 02118.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Moses
authors.affiliation: Section of Computational Biomedicine, Department of Medicine Boston University School of Medicine, Boston, Massachusetts 02118.
authors.forename: Teresa
authors.initials: T
authors.lastname: Wang
authors.affiliation: Section of Computational Biomedicine, Department of Medicine Boston University School of Medicine, Boston, Massachusetts 02118.
authors.forename: Sean
authors.initials: S
authors.lastname: Corbett
authors.affiliation: MatTek Corporation, Ashland, Massachusetts 01721.
authors.forename: George R
authors.initials: GR
authors.lastname: Jackson
authors.affiliation: Section of Computational Biomedicine, Department of Medicine Boston University School of Medicine, Boston, Massachusetts 02118.
authors.forename: Eduard
authors.initials: E
authors.lastname: Drizik
authors.affiliation: Section of Computational Biomedicine, Department of Medicine Boston University School of Medicine, Boston, Massachusetts 02118.
authors.forename: Catalina
authors.initials: C
authors.lastname: Perdomo
authors.affiliation: University of California Los Angeles, Los Angeles, California 90095.
authors.forename: Claudia
authors.initials: C
authors.lastname: Perdomo
authors.affiliation: University of California Los Angeles, Los Angeles, California 90095.
authors.forename: Eric
authors.initials: E
authors.lastname: Kleerup
authors.affiliation: Department of Epidemiology, Boston University School of Public Health, Boston, Massachusetts 02118.
authors.forename: Daniel
authors.initials: D
authors.lastname: Brooks
authors.affiliation: Pulmonary Center, Boston University School of Medicine, Boston, Massachusetts 02118.
authors.forename: George
authors.initials: G
authors.lastname: O'Connor
authors.affiliation: University of California Los Angeles, Los Angeles, California 90095.
authors.forename: Steven
authors.initials: S
authors.lastname: Dubinett
authors.affiliation: MatTek Corporation, Ashland, Massachusetts 01721.
authors.forename: Patrick
authors.initials: P
authors.lastname: Hayden
authors.affiliation: Section of Computational Biomedicine, Department of Medicine Boston University School of Medicine, Boston, Massachusetts 02118; mlenburg@bu.edu.
authors.forename: Marc E
authors.initials: ME
authors.lastname: Lenburg
authors.affiliation: Section of Computational Biomedicine, Department of Medicine Boston University School of Medicine, Boston, Massachusetts 02118.|Pulmonary Center, Boston University School of Medicine, Boston, Massachusetts 02118.
authors.forename: Avrum
authors.initials: A
authors.lastname: Spira
mesh_terms: D000336:Aerosols; D001980:Bronchi / Q000187:drug effects*; D066300:Electronic Nicotine Delivery Systems; D004848:Epithelium / Q000187:drug effects; D006801:Humans; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D000336:Aerosols
keywords: electronic cigarette.; gene expression; smoke; tobacco