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

Abstract

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.

Nasal Mucociliary Clearance in Smokers: A Systematic Review

“…20,33,34 Other studies also showed that chronic exposure to cigarette smoke stimulates the parasymphatethic nervous system (glandular hypersecretion and vasodilatation), inhibits secretion of Cl À and Kþ conductance in normal respiratory epithelium cells, alters epithelial salts and water transport, alters morphology of the epithelium in the entire of respiratory tract (metaplasia with keratinisation), reduces cells viability, and induces cell apoptosis (opposite mitogenic effect or proapoptotis depending on the concentration of smoke and impairment of cell regeneration in respiratory epithelium), induces matrix metaloproteinases (zinc dependent endopeptidase) that relates to the loss of NMC function and the epithelial disruption exposed to smoke via direct cell-to-cell or cell-to-basement membrane connections, and increases protein kinase-C (PKC) activity related to inhibitory effect on CBF. 7,30,[35][36][37] Proença M (2011) reported that the NMC value in smokers was insignificantly higher immediately after smoking and significantly higher than in non-smokers 8 hours after smoking. The difference between them may be an effect of nicotine on the sympathetic nervous system, which accelerates CBF.…”

“…6,47 Other studies also reported that formaldehyde in ECIG-generated aerosols related to DNA strand breaks and cell death and propylene glycol thicken the respiratory epithelium by increasing the number of goblet cells and increasing the content of mucin within the goblet cell. 6,36 Strength and Limitation of the Study…”

Cell-specific toxicity of short-term JUUL aerosol exposure to human bronchial epithelial cells and murine macrophages exposed at the air–liquid interface

“…In addition to the formation of harmful acetals, humectants, when heated by an ENDS device, have been shown to form toxic carbonyl compounds [40][41][42][43][44][45], some of which, including formaldehyde, are carcinogenic and have been suggested to play a role in several respiratory diseases commonly seen in cigarette smokers [45,46]. Another concern is that base ingredients of e-cig liquids (PG, VG) could be respiratory irritants and be harmful to the lungs, leading to airway obstruction and inflammation [47,48]. While benzoic acid is often used as a food preservative, in inhalable form, it is a well-known respiratory irritant that can cause coughing and sore throat if exposure continues [49].…”

Induction of Metallothionein Expression After Exposure to Conventional Cigarette Smoke but Not Electronic Cigarette (ECIG)-Generated Aerosol in Caenorhabditis elegans

“…Age-synchronized L4 larvae on NGM agar plates containing food were placed into clear cylindrical acrylic exposure chambers uncovered and exposed to 30 puffs air (control), ECIG-generated aerosol, or conventional cigarette smoke. Air, ECIG aerosol, or smoke was pumped into the exposure chambers similar to that previously described ( Palazzolo et al, 2017b ). Briefly, two Cole-Parmer Master Flex L/S peristaltic pumps (Vernon Hills, IL, United States) were used to simulate puffing on Triple 3 (Kennesaw, GA, United States) eGo style ECIG device or conventional Marlboro (84 mm, full strength) cigarettes.…”