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

  title={Electronic Cigarette Vapor with Nicotine Causes Airway Mucociliary Dysfunction Preferentially via TRPA1 Receptors.},
  author={Samuel Chung and Nathalie Baumlin and John S. Dennis and Robert Moore and Sebastian F. Salathe and P L Whitney and Juan R. Sabater and William M. Abraham and Michael D. Kim and Matthias A Salathe},
  journal={American journal of respiratory and critical care medicine},
RATIONALE Electronic cigarette (e-cig) use has been widely adopted under the perception of safety. [] Key MethodMETHODS 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 nicotine-dependent manner. Acute nicotine exposure increased intracellular calcium…

Nicotine-Free e-Cigarette Vapor Exposure Stimulates IL6 and Mucin Production in Human Primary Small Airway Epithelial Cells

The results suggest that human small airway epithelial cells exposed to nicotine-free e-vapor increase the inflammatory response and mucin production, which may contribute to distal lung airflow limitation and airway obstruction.

Vegetable glycerin e-cigarette aerosols cause airway inflammation and ion channel dysfunction

It is found that VG-containing (VG or PG/VG), but not sole PG-containing, e-cigarette aerosols reduced the activity of nasal cystic fibrosis transmembrane conductance regulator (CFTR) in human volunteers who vaped for seven days and in sheep, VG e-cig aerosols can potentially cause harm in the airway by inducing inflammation and ion channel dysfunction with consequent mucus hyperconcentration.

Nebulized Menthol Impairs Mucociliary Clearance via TRPM8 and MUC5AC/MUC5B in Primary Airway Epithelial Cells

Evidence is provided that menthol at the concentrations used in e-cigs could cause harm to the airways and the effects of menthol on MCC and inflammation could be blocked by a specific TRPM8 antagonist.

Effects of Exposure to Tobacco Cigarette, Electronic Cigarette and Heated Tobacco Product on Adipocyte Survival and Differentiation In Vitro

It is demonstrated that CS extract, in contrast to HTP and ECIG extracts, significantly impairs differentiation of pre-adipocytes to beige adipocytes and may therefore impact significantly adipose tissue metabolic function.

Complex Regulatory Role of the TRPA1 Receptor in Acute and Chronic Airway Inflammation Mouse Models

TRPA1 protects against LPS-induced acute pneumonitis and hyperresponsiveness, but is required for CSE-evoked emphysema and respiratory deterioration, and further research is needed to determine TRPA1 as a potential pharmacological target in the lung.

Another Warning Sign: High Nicotine Content in Electronic Cigarettes Disrupts Mucociliary Clearance, the Essential Defense Mechanism of the Lung

  • M. Kesimer
  • Medicine
    American journal of respiratory and critical care medicine
  • 2019
The general misconception by the public that “e-cigarettes are safe,” however, has been challenged or overturned by many recent studies revealing the association between e-cigarettes and adverse cardiovascular, pulmonary, and systemic health effects.

Less burn, more fat: electronic cigarettes and pulmonary lipid homeostasis.

The results of this study identify previously unrecognized adverse effects of ENDS exposure on pulmonary lipid metabolism, although the implication of these effects on long-term respiratory health requires future exploration.

E-cigarette constituents propylene glycol and vegetable glycerin decrease glucose uptake and its metabolism in airway epithelial cells in vitro

Short-term exposure to PG/VG, key components of e-cigarettes, decreased glucose transport and metabolism in airway cells, and it is suggested repeated/chronic exposure to these agents are likely to contribute to airway damage in e-cigarette users.

Evaluation of secondhand smoke effects on CFTR function in vivo

Background Cystic fibrosis transmembrane conductance regulator (CFTR) is an anion channel expressed on the mucosal surface of epithelial cells lining several tissues including airways. Inherited



Chronic electronic cigarette exposure in mice induces features of COPD in a nicotine-dependent manner

The effects of exposure to aerosolised nicotine-free and nicotine-containing e-cigarette fluid on mouse lungs and normal human airway epithelial cells were nicotine-dependent, suggesting that inhaled nicotine contributes to airway and lung disease in addition to its addictive properties.

Cigarette smoke has sensory effects through nicotinic and TRPA1 but not TRPV1 receptors on the isolated mouse trachea and larynx

Nicotinic receptors contribute to the sensory effects of cigarette smoke on the trachea, which are dominated by TRPA1, as well as of typical constituents, such as nicotine and reactive carbonyls.

In vivo versus in vitro airway surface liquid nicotine levels following cigarette smoke exposure.

Results suggest that nicotine is a good dosimetry marker of WCS exposure and provides direct evidence that the use of WCS is more relevant to what is seen in vivo than methods of cigarette smoke application that only use a small fraction of WCS.

Airway epithelial cell exposure to distinct e-cigarette liquid flavorings reveals toxicity thresholds and activation of CFTR by the chocolate flavoring 2,5-dimethypyrazine

Data from high-capacity screening assays demonstrates that individual e-cigarette liquid flavoring chemicals vary in their cytotoxicity profiles and that some constituents evoke a cellular physiological response on their own independent of cell death.

Nicotinic acetylcholine receptor expression in human airway correlates with lung function.

  • D. LamS. Luo J. Minna
  • Biology, Medicine
    American journal of physiology. Lung cellular and molecular physiology
  • 2016
NAChR expression in bronchial epithelium was found to correlate with lung function and insight was given into the potential of targeting nAChRs for therapy in smoking-related inflammation in the airway.

Temporal structure/function variation in cultured differentiated human nasal epithelium associated with acute single exposure to tobacco smoke or E-cigarette vapor

This study demonstrates a similar pattern of epithelial response to acute TS or EV exposure, plausible as NO may contribute to an inflammatory milieu and generation of toxic metabolites, it is plausible that recurrent exposures over time may be contributory to chronic pathologies.

Nicotine activates and up-regulates nicotinic acetylcholine receptors in bronchial epithelial cells.

It is demonstrated that chronic nicotine exposure up-regulates nAChR activity in developing lung, and that nA ChR activity can be further modified by tyrosine phosphorylation.

ATP12A promotes mucus dysfunction during Type 2 airway inflammation

It is proposed that ATP12A promotes airway mucus dysfunction in individuals with T2 inflammatory airway diseases and that ATP 12A may be a novel therapeutic target to improve mucus clearance.

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

In this murine model, a chronic, daily, 20 min-exposure to N/PG, but not an acute exposure, slowed MCC, compared to exposure to PG alone and led to systemic absorption of nicotine.