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The rapid proliferation of electronic cigarettes (ECs) has raised significant concerns about their potential health effects on both users and bystanders. This study systematically investigates the impact of EC aerosol exposure on human alveolar epithelial cells (A549), considering variations in device parameters, nicotine concentration, and exposure type. Using a gravity-based air–liquid interface exposure system, we assessed cytotoxicity and epithelial barrier integrity by measuring cell viability and transepithelial electrical resistance (TEER). Our results indicate that EC aerosol exposure significantly reduces cell viability and disrupts monolayer integrity in a dose- and device-dependent manner. Notably, VUSE (pod-type) exposure led to a 16% decrease in viability and a 41% reduction in TEER, while VOOPOO (mod-type) exposure caused a 25% viability loss and a 61% reduction in TEER. Power settings played a critical role: at 60 W, cell viability dropped by 48% at 12 mg/mL nicotine concentration compared to 29% at 0 mg/mL. Moreover, under the same number of puffs (30 puffs), firsthand exposure resulted in a 73% viability decrease, whereas secondhand exposure showed a 47% reduction, indicating substantial bystander risks associated with EC usage. These findings underscore the importance of device specifications and exposure conditions in determining EC aerosol toxicity. The observed epithelial barrier disruption suggests increased vulnerability to respiratory diseases. Given the comparable toxicity of firsthand and secondhand aerosols, regulatory measures should extend beyond direct users to include bystander protection. This study highlights the urgent need for comprehensive toxicity assessments to inform public health policies on EC use. 

This study employed high-time-resolution systems to examine the transient properties of aerosols and gases emitted from electronic cigarette (EC) puffs. Using a fast aerosol sizer, we measured particle size distributions (PSDs) across various EC brands (JUUL, VUSE, VOOPOO), revealing sizes ranging from 5 to 1000 nm at concentrations of 107 to 1010 cm–3. Most aerosols were found to be in the ultrafine range (below 100 nm), with JUUL-, VUSE-, and VOOPOO-producing aerosols with geometric mean sizes of 19.9, 47.3, and 29.4 nm, respectively. Applying the International Commission on Radiological Protection (ICRP) deposition model and assuming no further evolution of aerosols in the respiratory system, we estimated particle deposition in different respiratory regions: 45–60% in the alveolar region, 10–25% in the tracheobronchial region, and 20–35% in the extrathoracic region. The highest single-puff deposition was observed with the VOOPOO device at 60 W, depositing 180.1 ± 7.6 μg in the alveolar region. The gas emissions (CO2, NOx, CO, and total hydrocarbons) were measured at different power settings of the VOOPOO EC. Single-puff NOx and CO levels exceeded the permissible exposure limits of the Occupational Safety and Health Administration, indicating potential acute exposure risks. Higher power settings were correlated with increased gas mixing ratios, suggesting more e-liquid vaporization and possible chemical transformations at higher temperatures. These findings demonstrated significant health risks associated with ultrafine particles from high-power ECs and emphasize the need for advanced measurements to accurately assess their physicochemical properties and potential health implications.