E-cigarette exposures, respiratory tract infections, and impaired innate immunity: a narrative review

Abstract

Electronic cigarettes (e-cigarettes) are commonly used devices by adolescents and young adults. Since their introduction, the popularity of e-cigarettes has increased significantly with close to twenty percent of United States high school students reporting current use in 2020. As the number of e-cigarette users has increased, so have reports of vaping related health complications. Overall, respiratory tract infections remain one of the top ten leading causes of death in the US for every age group. Specific to the pediatric population, lower respiratory tract infections are the leading cause for hospitalization. This review highlights the current evidence behind e-cigarette exposure and its association with impaired innate immune function and the risk of lower respiratory tract infections. To date, various preclinical models have evaluated the direct effects of e-cigarette exposure on the innate immune system. More specifically, e-cigarette exposure impairs certain cell types of the innate immune system including the airway epithelium, lung macrophage and neutrophils. Identified effects of e-cigarette exposure common to the lung's innate immunity include abnormal mucus composition, reduced epithelial barrier function, impaired phagocytosis and elevated systemic markers of inflammation. These identified impairments in the lung's innate immunity have been shown to increase adhesion of certain bacteria and fungi as well as to increase virulence of common respiratory pathogens such as influenza virus, Staphylococcus aureus or Streptococcus pneumoniae. Information summarized in this review will provide guidance to healthcare providers, policy advocates and researchers for making informed decisions regarding the associated respiratory health risks of e-cigarette use in pediatric and young adults.

Keywords: Lung; e-cigarette; electronic nicotine delivery system (ENDS); innate immunity.

Figure 1

Electronic nicotine delivery system (ENDS) components and e-liquid constituents. Components include the battery, microprocessor, heating coil, wick, e-liquid and mouthpiece. Common e-liquid humectants include propylene glycol, vegetable glycerin or mixtures of the two (most often, 50:50 ratio). Common e-liquid drugs include nicotine, tetrahydrocannabinol (THC) and cannabidiol (CBD). Common flavorings and additives include cinnamaldehyde, menthol, vanillin and vitamin E acetate (not pictured).

Figure 2

Highlighted components and associated functions of the lung’s innate immune system (left) and identified effects of e-cigarette aerosol exposure on lung innate immunity (right). Specific components of the lung innate immune system include: the airway surface liquid (ASL), the airway epithelium, lung macrophages and neutrophils. The ASL acts as a barrier and allows for clearance for microbes, toxins and debris. The airway epithelium provides barrier function, cilia for mucus clearance, and secretion of soluble factors and cytokines. Lung macrophages contribute to phagocytosis of invading pathogens, efferocytosis of dying cells, increased pro-inflammatory signaling early, and anti-inflammatory signaling in inflammatory resolution as well as lipid and surfactant catabolism. Neutrophils provide neutrophil extracellular trap (NET) formation, phagocytosis, and recruitment of additional inflammatory cells. Summarized effects of e-cigarette exposure on the lung’s innate immune system highlighted above (right). Specific effects include: increased bacterial adhesion and colonization; increased NET activity; increased mucin and reduced PCL thickness; increased epithelial permeability, reduced tight junction (ZO-1) expression, and increased TRPA-1 activation; increased pro-inflammatory cytokine signaling; increased macrophage lipid inclusion; and, reduced macrophage and neutrophil phagocytosis. IFN-γ, interferon gamma; IL-1β, interleukin-1 beta; IL-6, interleukin-6; IL-8, interleukin-8; IL-17, interleukin-17; MCP1, monocyte chemoattractant protein 1; MUC5AC, mucin 5AC; PCL, periciliary fluid layer; TRPA-1, transient receptor potential cation channel 1; TNF-α, tumor necrosis factor-alpha; ZO-1, zonula occludin-1.