Electronic Cigarette Liquid Constituents Induce Nasal and Tracheal Sensory Irritation in Mice in Regionally Dependent Fashion

Introduction Electronic cigarettes (e-cigs) are currently used by millions of adults and adolescents worldwide. Major respiratory symptoms, such as coughing reported by e-cig users, including patients with e-cig, or vaping, product use-associated lung injury (EVALI), indicate e-cig constituent-induced sensory irritation. However, e-cig constituent-induced nociceptive activity in nasal and tracheal respiratory epithelia (RE) and neuronal activation in the trigeminal ganglia and brainstem nuclei, which receive airway chemosensory inputs have not been examined and compared. Comparisons of physiological responses between freebase nicotine and nicotine salts are also missing. Aims and Methods Event-related potential (ERP) was recorded electrophysiologically to assess mouse nasal and tracheal RE chemosensory responses to various flavorings, nicotine, including freebase and nicotine salts, e-liquid mixtures, and tussigenic stimuli. Also, mice were subjected to inhalation exposure to aerosol of a vanilla-flavored e-liquid or air (control), and the activated-trigeminal nociceptive neurons and brainstem neurons were examined using immunohistochemistry. Results Individual constituents and mixtures of e-liquids, capsaicin, and citric and acetic acids evoked significantly larger ERP in the nose than in the trachea with the exception of menthol. ERP responses to freebase nicotine were significantly larger than protonated nicotine. Four nicotine salts (benzoate, lactate, levulinate, and salicylate) induced similar responses. Compared with air-exposed mice, e-liquid aerosol-exposed mice showed a significant increase in numbers of activated trigeminal nociceptive neurons and brainstem neurons in the spinal trigeminal nucleus, paratrigeminal nucleus, and nucleus tractus solitarius. Conclusions E-liquid constituents region-dependently stimulate airway nociceptive chemosensory systems, and freebase nicotine is more potent than protonated nicotine. Implications Neural abnormalities have been implicated in the development of nasal and respiratory illnesses. The higher sensitivity of the nasal nociceptive chemosensory system to nicotine and flavorings may indicate a health risk for e-liquid aerosol-induced upper airway illnesses via neurogenic alteration and warrants further investigation.

Vapor Compounds Released from Nicotine-Free Inhalators as a Smoking-Cessation Aid

The health risks of cigarette smoking have been reported to increase continuously, while it is estimated to be responsible for the death toll of more than seven million people globally each year. In an effort to reduce the risk involved in cigarette smoking, nicotine-free inhalators have been developed as smoking-cessation aids. To evaluate the feasibility of nicotine-free inhalators in such respect, we investigated the composition of volatile organic compounds (VOCs) released from the consumption of nicotine-free inhalators of which major components include natural essential oils and traditional Chinese medicinal herbs. Vapor samples from nicotine-free inhalators were generated and collected for analysis using an e-cigarette auto-sampler. The vapor samples were captured onto a multi-bed sorbent tube sampler and a 2,4-dinitrophenylhydrazine (DNPH) cartridge for the quantitative analysis with the aid of thermal desorption-gas chromatography/mass spectrometry and high-performance liquid chromatography, respectively. A total of 29 VOCs were determined in vapor samples at concentrations below 0.2 ppm. Concentrations of (+)-isomenthone and acrolein slightly exceeded the derived no-effect level (DNEL) or sensory irritation level. However, VOCs were below the concentration exposure limit, according to the Occupational Safety and Health Administration (OSHA). According to our study, most of the aroma compounds and VOCs released from nicotine-free inhalator were lower than the DNEL or sensory irritation level. Consequently, it is found that nicotine-free inhalators could be safe to use in reference to toxic guidelines for inhalation exposure. However, if the use of nicotine-free inhalators is over prolonged period, it can also increase the risk of exposure to potentially toxic compounds.