Table 1.
Primary Studies on the Effects of E‐Cigarettes on the Upper Aerodigestive Tract and Ear in Cell and Animal Models
| References | Subject of interest | Study design | Exposure time (method) | Outcome(s) |
|---|---|---|---|---|
| Alanazi et al 177 | Primary human gingival fibroblasts | Ex vivo | 1 hour a day for 1, 3, 5, and 7 days (extract in media) | Changes in morphology, decreased viability, increased apoptosis, delayed migration/wound closure |
| Carson et al 197 | Primary human nasal epithelial cell 3D model | Ex vivo | 100 seconds (puffs over air‐liquid interface) | Reduction in ciliary beat frequency, development of fibrillar mesh‐like debris |
| Duggar et al 187 | Oral keratinocytes | In vitro | 24 hours a day for 1, 2, and 3 days (extract in media) | Decreased growth, increase in cytotoxin expression |
| Ganapathy et al 139 | Human oral keratinocyte cell line (POE9n), human oral SCC cell line (UM‐SCC‐1) | In vitro | 1 hour every other day for 2 weeks (extract in media) | Increased oxidative DNA damage |
| Go et al 185 | Human middle ear epithelial cell line (HMEEC) | In vitro | 24 hours (extract in media) | Decreased viability, increased autophagy and apoptosis, increased cytokines, increased mucin production, dysregulation of water channels |
| Ha et al 175 | Murine model (C57BL/6) | In vivo | 31 minutes and 40 seconds a day, 5 days a week, for 16 weeks (whole body chamber) | Differential inflammatory cytotoxin levels |
| Iskandar et al 170 | Human buccal epithelial (EpiOral) 3D model | In vitro | 28 minutes (puffs over culture) | No significant histopathologic changes, significant differential gene expression (especially inflammatory pathways) |
| Ji et al 188 | Human oral epithelial cell line (NHOK) | In vitro | 24 hours (extract in media) | Increased cytotoxicity, increased oxidative stress |
| Ji et al 189 | Human oral epithelial cell line (NHOK) | In vitro | 4 hours (extract in media) | Differential gene expression (especially unfolded protein response) |
| Lungova et al 182 | Human induced pluripotent stem cell (hiPSC)—derived engineered vocal fold mucosae | In vitro | 24 hours a day for 7 days (extract in media) | Changes in mucosal structure, increased mucin clots, dysregulated cytokine production, lipid deposition within cytoplasm and intercellular spaces causing epithelial injury and remodeling |
| Martinez et al 181 | Human vocal fold fibroblast cell line (hVFF) | In vitro | 24 hours (extract in media) | Increased cytotoxicity, no significant differences in gene expression |
| Manyanga et al 198 | Human oral and pharyngeal epithelial cell lines (UM‐SCC‐1, WSU‐HN6, WSU‐HN30) | In vitro | 24 hours a day for 2 and 4 days (extract in media) | Increased viability in setting of cisplatin exposure due to increased cisplatin resistance |
| Pushalkar et al 185 | Human hypopharyngeal SCC (FaDu) and leukoplakia (MSK‐Leuk‐1) cell lines | In vitro | 40 minutes (puffed over culture) | Increased inflammatory cytokines in setting of infection, increased infection efficiency |
| Rouabhia et al 190 | Primary human gingival epithelial cells | Ex vivo | 15 minutes a day for 1, 2, and 3 days (puffs over culture) | Change in morphology, increased apoptosis, increased DNA fragmentation |
| Rouabhia et al 196 | Primary human nasal epithelial cells and 3D model | Ex vivo | 15 minutes twice a day for 1, 2, and 3 days (puffs over culture) | Changes in morphology, decreased viability, changes in mucosal structure, increased inflammatory cytokines |
| Sancilio et al 176 | Primary human gingival fibroblasts | Ex vivo | 6 and 24 hours a day for 1, 2, and 3 days (extract in media) | Changes in morphology, decreased viability, increased apoptosis, increased ROS formation |
| Sancilio et al 179 | Primary human gingival fibroblasts | Ex vivo | 3 and 24 hours a day for 1 and 2 days (extract in media) | Changes in morphology, increased cytotoxicity, changes in collagen release, increase in lysosomes, increased LC3 IIB/LC3 I expression |
| Salturk et al 174 | Murine model (Wistar albino, female) | In vivo | 60 minutes a day for 4 weeks (whole body chamber) | Nonsignificant trend toward increased squamous metaplasia and hyperplasia, no difference in Ki67 expression |
| Song et al 193 | Human middle ear epithelial cell line (HMEEC‐1) | In vitro | 24 hours (extract in media) | Decreased viability |
| Song et al 194 | Human middle ear epithelial cell line (HMEEC‐1) | In vitro | 24 hours (extract in media) | Decreased viability, increased inflammatory cytokines, differential gene expression |
| Sun et al 191 | Human oral leukoplakia cell line (MSK‐Leuk1) | In vitro | 16 hours (extract in media) | Increased metabolism of polycyclic aromatic hydrocarbons to genotoxic products |
| Sundar et al 178 | Human gingival epithelium cell line (HGEPp) and 3D model (EpiGingival) | In vitro | 15 minutes (puffed over culture) | Increased protein carbonylation, increased inflammatory cytokines, increased DNA damage |
| Tellez et al 186 | Human oral epithelial (MOE1A, MOE1B) and leukoplakia (MSK‐Leuk1) cell lines | In vitro | 20 minutes (puffed over culture) | Increased cytotoxicity, increased DNA damage |
| Tsai et al 184 | Human oral SCC cell lines (Ca9‐22, CAL‐27) | In vitro | 24 hours (extract in media) | Altered cell invasion, increased RAGE expression, differential cytokine expression |
| Ureña et al 67 | Human oral SCC (SCC‐25) and gingival fibroblast cell lines (HGF‐1) | In vitro | 3 minutes total—1 minute every 3 hours (puffed over culture) | Decreased viability, increased oxidative stress |
| Vermehren et al 180 | Human gingival fibroblast cell line (HFIB‐G) | In vitro | 15 minutes (puffed over culture) | Decreased proliferation, increased metabolic activity, no significant difference in apoptosis or ROS formation |
| Welz et al 192 | Primary human pharyngeal organoid | Ex vivo | 24 and 2.5 hours per day for 5 days (extract in media) | Increased cytotoxicity, increased DNA fragmentation |
| Yu et al 183 | Human oral SCC cell lines (HN30, UMSCC10B) | In vitro | 24 hours a day for 1 week (extract in media) | Increased DNA strand breaks, increased cell arrest, increased apoptosis and necrosis |