Acute and chronic<i>in vivo</i>effects of exposure to nicotine and propylene glycol from an E-cigarette on mucociliary clearance in a murine model

Laube, Beth L.; Afshar-Mohajer, Nima; Koehler, Kirsten; Chen, Gang; Lazarus, Philip; Collaco, Joseph M.; McGrath‐Morrow, Sharon A.

doi:10.1080/08958378.2017.1336585

Cited by 51 publications

(35 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…TMV reductions after a single dose lasted for ~6 hrs, upon which a repeat dose decreased TMV again. Similar findings of vapor containing nicotine on MCC were reported in a murine model (11). In contrast, that study did not find that e-cig liquid had an immediate effect on murine MCC, suggesting that the large animal is more suited to predict human responses.…”

Section: Discussionsupporting

confidence: 71%

“…Between factors such as wattage settings for the heating element, PG/VG composition, and a user's experience with a device, a single session of inhaled vape can deliver nicotine doses that exceed those in smoke from 1 cigarette (8). Furthermore, recent efforts have partially demonstrated how PG/VG and various e-cig flavorings cause negative outcomes in vitro and in vivo such as cell death, airway inflammation, and impaired airway hydration (9)(10)(11)(12)(13)(14).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Electronic Cigarette Vapor with Nicotine Causes Airway Mucociliary Dysfunction Preferentially via TRPA1 Receptors

Chung

Baumlin

Dennis

et al. 2019

Am J Respir Crit Care Med

View full text Add to dashboard Cite

of Health (NIH) -F32-HL140729 (to S.C.) and R01 HL139365 (to M.S.) RUNNING TITLE: Vaped nicotine impairs mucociliary function preferentially via TRPA1 SUBJECT CATEGORY DESCRIPTOR: 6.17 Smoking Health Effects TOTAL WORD COUNT: 3985 AT A GLANCE COMMENTARY: Scientific Knowledge on the Subject E-cigarettes are marketed as safer alternatives to conventional cigarettes due to their defined composition and noncombustible nature. However, it is unclear how exposure to e-cigarette vapor, colloquially referred to as "vape", affects naïve airway epithelia. It is largely unknown to what extent individual constituents of vape, such as nicotine and flavoring agents, influence pulmonary function, if at all. The transient receptor potential ankyrin 1 (TRPA1) is a molecular target for vape effects due to its expression in airway epithelia and its reported gating by nicotine, reactive oxidants, and flavors, especially cinnamaldehyde. What This Study Adds to the FieldThis study implicates nicotine as a key "vape" constituent that acutely impairs airway mucociliary functions in vitro and in vivo (sheep). A functional, nicotine-sensitive TRPA1 receptor is natively expressed in human and sheep bronchial epithelial cells and mediates the effects of nicotine and e-cigarette vapors. Importantly, its inhibition prevents mucociliary dysfunction in vitro and in vivo. These findings implicate TRPA1 as a driver of mucociliary dysfunction induced by nicotine-containing e-cigarette vapor.ABSTRACT RATIONALE: Electronic cigarette (e-cig) use has been widely adopted under the perception of safety. However, possibly adverse effects of e-cig vapor in never-smokers are not well understood. OBJECTIVES:Effects of nicotine-containing e-cig vapors on airway mucociliary function were tested in differentiated human bronchial epithelial cells (HBECs) isolated from never-smokers and in the airways of a novel, ovine large animal model. METHODS:Mucociliary parameters were measured in HBECs and in sheep. Systemic nicotine delivery to sheep was quantified using plasma cotinine levels, measured by ELISA. MEASUREMENTS AND MAIN RESULTS:In vitro, exposure to e-cig vapor reduced airway surface liquid hydration and increased mucus viscosity of HBECs in a nicotinedependent manner. Acute nicotine exposure increased intracellular calcium levels, an effect primarily dependent on transient receptor potential ankyrin 1 (TRPA1). TRPA1 inhibition with A967079 restored nicotine-mediated impairment of mucociliary parameters including mucus transport in vitro. Sheep tracheal mucus velocity (TMV), an in vivo measure of mucociliary clearance, was also reduced by e-cig vapor. Nebulized e-cig liquid containing nicotine also reduced TMV in a dose-dependent manner and elevated plasma cotinine levels. Importantly, nebulized A967079 reversed the effects of e-cig liquid on sheep TMV. CONCLUSIONS:Our findings show that inhalation of e-cig vapor causes airway mucociliary dysfunction in vitro and in vivo. Furthermore, they suggest that the main Page 4 of 64 2 nicotine effect on mucociliary ...

show abstract

Section: Discussionsupporting

confidence: 71%

Section: Introductionmentioning

confidence: 99%

Electronic Cigarette Vapor with Nicotine Causes Airway Mucociliary Dysfunction Preferentially via TRPA1 Receptors

Chung

Baumlin

Dennis

et al. 2019

Am J Respir Crit Care Med

View full text Add to dashboard Cite

show abstract

“…; Laube et al. ). Although we do not fully understand this phenomenon, it appears consistent across experimental settings that presence of nicotine leads to higher numbers and larger particles and, consequently, a reduced lung deposition.…”

Section: Discussionmentioning

confidence: 98%

Variations in coil temperature/power and e‐liquid constituents change size and lung deposition of particles emitted by an electronic cigarette

Lechasseur

Altmejd²,

Turgeon

et al. 2019

Physiol Rep

View full text Add to dashboard Cite

Electronic cigarette uses propylene glycol and glycerol to deliver nicotine and flavors to the lungs. Given the hundreds of different brands, the thousands of flavors available and the variations in nicotine concentrations, it is likely that electronic cigarette settings and e‐liquid composition affect the size distribution of particles emitted and ultimately pulmonary deposition. We used the inExpose e‐cigarette extension to study two separate modes of operation of electronic cigarettes, namely power‐controlled and the temperature‐controlled. We also assessed several e‐liquids based on propylene glycol and glycerol concentrations, nicotine content, and selected monomolecular flavoring agents (menthol, vanillin, and maltol). Particle size distribution was measured using a Condensation Particle Counter and a Scanning Mobility Particle Sizer spectrometer. Lung deposition was predicted using the International Commission on Radiological Protection model. For all resistance coils, increase in power delivery generated larger particles while maintaining a higher coil temperature generated smaller particles. Increase in glycerol concentration led to the generation of larger particles. With regard to flavors, we showed that despite minor effect of menthol and maltol, vanillin dramatically increased particle size. Presence of nicotine also increased particle size. Finally, particles emitted by the electronic cigarette were predicted to mainly deposit in the alveoli and conditions generating larger particle sizes led to a reduction in predicted lung deposition. This study shows that coil temperature, propylene glycol and glycerol concentrations, presence of nicotine, and flavors affect the size of particles emitted by an electronic cigarette, directly affecting predicted lung deposition of these particles.

show abstract

“…Several recent studies support this finding to varying degrees. Using mice in an in vivo investigation, Laube et al ( 2017 ) determined that chronic exposure, but not acute exposure, to ECIG-generated aerosol in the presence of nicotine slowed mucociliary clearance. Kumral et al ( 2016 ) reported that individuals who use ECIG devices as a means to quit smoking produced a negative impact on sinonasal symptoms and nasal mucociliary clearance as compared to individuals who do not use ECIG devices.…”

Section: Discussionmentioning

confidence: 99%

The Effects of Electronic Cigarette (ECIG)-Generated Aerosol and Conventional Cigarette Smoke on the Mucociliary Transport Velocity (MTV) Using the Bullfrog (R. catesbiana) Palate Paradigm

et al. 2017

View full text Add to dashboard Cite

Background: While ECIGs are under scrutiny concerning safety, particularly in reference to the physiological impact that aerosolized ECIG liquid (E-liquid) may have on respiratory tissues, others believe that ECIGs are a “Harm Reduction” alternative to conventional cigarettes. Previous studies investigating ciliated respiratory epithelium indicate that smoking shortens cilia length, reduces cilia beat frequency and disrupts respiratory epithelium, which most likely contributes to the inhibition of mucocilliary clearance. Monitoring mucous clearance of respiratory tissues exposed to ECIG-generated aerosol or conventional cigarette smoke, as indexed by mucous transport velocity (MTV), is one way to gauge the impact aerosol and smoke have on the respiratory tract. Therefore, we designed an experiment to test the effect of ECIG-generated aerosol and smoke on MTV using the frog palate paradigm.Methods: Peristaltic pumps transport ECIG-generated aerosol and conventional cigarette smoke into custom-made chambers containing excised bullfrog palates. MTVs were determined before exposure, immediately after exposure and approximately 1 day following exposure. MTVs were also determined (at the same time points) for palates exposed to air (control). Surface and cross sectional SEM images of palates from all three groups were obtained to support MTV data.Results: The results indicate that ECIG-generated aerosol has a modest inhibitory effect (p < 0.05) on MTV 1 day post-exposure (0.09 ± 0.01) compared to control MTV (0.16 ± 0.03 mm/s). In contrast, smoke completely inhibits MTV from 0.14 ± 0.03 mm/s immediately before exposure to 0.00 mm/sec immediately after exposure and the MTV is unable to recover 1 day later. SEM images of control palates and palates exposed to ECIG-generated aerosol both show cilia throughout their epithelial surface, while some areas of palates exposed to smoke are completely devoid of cilia. Additionally, the epithelial thickness of aerosol-exposed palates appears thicker than control palates while smoke-exposed palates appear to be thinner due to epithelial disruption.Conclusions: These results indicate that ECIG-generated aerosol has only a modest effect on mucocilary clearance of bullfrog palates and aerosol sedimentation accounts for epithelial thickening. In accordance with the primary literature, conventional cigarette smoke dramatically inhibits mucociliary clearance and is, in part, due to decreased number of cilia and disruption of the smoke-exposed epithelium.

show abstract

Acute and chronicin vivoeffects of exposure to nicotine and propylene glycol from an E-cigarette on mucociliary clearance in a murine model

Cited by 51 publications

References 39 publications

Electronic Cigarette Vapor with Nicotine Causes Airway Mucociliary Dysfunction Preferentially via TRPA1 Receptors

Electronic Cigarette Vapor with Nicotine Causes Airway Mucociliary Dysfunction Preferentially via TRPA1 Receptors

Variations in coil temperature/power and e‐liquid constituents change size and lung deposition of particles emitted by an electronic cigarette

The Effects of Electronic Cigarette (ECIG)-Generated Aerosol and Conventional Cigarette Smoke on the Mucociliary Transport Velocity (MTV) Using the Bullfrog (R. catesbiana) Palate Paradigm

Contact Info

Product

Resources

About