Acute vaping exacerbates microbial pneumonia due to calcium (Ca2+) dysregulation

Abstract

As electronic cigarette (E-cig) use, also known as “vaping”, has rapidly increased in popularity, data regarding potential pathologic effects are recently emerging. Recent associations between vaping and lung pathology have led to an increased need to scrutinize E-cigs for adverse health impacts. Our previous work (and others) has associated vaping with Ca2+-dependent cytotoxicity in cultured human airway epithelial cells. Herein, we develop a vaped e-liquid pulmonary exposure mouse model to evaluate vaping effects in vivo. Using this model, we demonstrate lung pathology through the use of preclinical measures, that is, the lung wet: dry ratio and lung histology/H&E staining. Further, we demonstrate that acute vaping increases macrophage chemotaxis, which was ascertained using flow cytometry-based techniques, and inflammatory cytokine production, via Luminex analysis, through a Ca2+-dependent mechanism. This increase in macrophage activation appears to exacerbate pulmonary pathology resulting from microbial infection. Importantly, modulating Ca2+ signaling may present a therapeutic direction for treatment against vaping-associated pulmonary inflammation.

E-cigarette Flavors, Sensory Perception, and Evoked Responses

“…Studies elucidating multiple aspects of the effects of these products will be necessary and must include animal modeling, especially with younger animal age groups. These types of studies are now being performed, ,, in particular with young mouse cohorts, − to analyze the effects of vaping on overall health. Of note, the possible neurotoxicity associated with e-cigarette use and particularly during neurodevelopment has more recently become a topic being addressed by a small but growing number of researchers through the use of animal studies. − The impact of maternal exposure to vaped aerosols on offspring cognitive function has also been evaluated using animal models and demonstrated short-term memory deficits, reduced anxiety, and hyperactivity in offspring. , These early data are extremely troubling due to the growing popularity of the e-cigarette among vulnerable populations, for example, pregnant women and adolescents (see Ruszkiewicz et al for a thorough review).…”

GC/HRMS Analysis of E-Liquids Complements In Vivo Modeling Methods and can Help to Predict Toxicity

“…At experimental endpoints, broncho-alveolar lavage (BAL) fluid was collected and frozen as has been previously described. − In brief, mice were euthanized, and a catheter attached to a 1 mL syringe was inserted into the trachea. The syringe was then used to deliver 1× PBS, which was gently pipetted up and down 3× to remove the fluid.…”

Vaping-Dependent Pulmonary Inflammation Is Ca2+ Mediated and Potentially Sex Specific

“…E-liquids must be quickly heated to a vaporization temperature (approximately 250-300 • C) and drawn in by the user into the pulmonary tract. Prior exposure models used either vape condensate dropwise intranasal [21,23] or intratracheal exposure or whole body vapor exposure [24], which are riddled with complexities that defray their biological relevance. To establish a more biologically relevant vaping model, we utilized the SCIREQ InExpose compact inhalation system/"vape tower" to simulate airway vaping in a nose-only exposure mouse model (Figure 1B).…”

“…Here, we use the SCIREQ InExpose system to model the vaping of mice through nose-only administration. This system offers a biologically relevant vaping exposure model in mice compared to our and other previously outlined intranasal models [21][22][23]. We aimed to characterize the effect of JUUL Menthol vape exposure on C57-BL/6 mice of both genders through this more biologically relevant means of vaping.…”