Tables
- Box 1: pulmonary effects of propylene glycol and glycerol
In vitro studies suggest vapours of propylene glycol and glycerol could have cytotoxic effects on lung epithelial cells and other cell types; however, animal and clinical studies do not report signs of extensive lung damage or lung function alteration. While minor signs of inflammation have been reported in some in vitro, in animal and clinical studies, the general consensus is that exposure to vapours of propylene glycol and glycerol do not trigger a meaningful inflammatory response. However, alterations of the normal function of immune cells have been reported. While exposure to vapours of propylene glycol and glycerol appears to be well processed by the lungs, more subtle effects such as disruption in lung circadian rhythmicity and mucociliary clearance could impact the response to concomitant exposure to pollutants, allergens and pathogens. - Box 2: pulmonary effects of vaping flavours
Great disproportion towards in vitro studies versus preclinical and clinical research Established potential for flavourings causing cellular cytotoxicity, triggering inflammatory responses, impairing immune function and altering lung functions - Box 3: pulmonary effects of nicotine
Advanced scientific evidence based on decades of research on tobacco smoking In vitro studies show vapours of nicotine have cytotoxic effects on lung epithelial cells and can impair epithelial barrier integrity. While, animal studies do not report signs of extensive lung damage or lung function alteration, early exposure to nicotine may be detrimental to lung development. No significant evidence of significant inflammatory effects but well documented immune-modulatory effects and alterations of the normal antimicrobial function of immune cells - TABLE 1
Methodological characteristics of in vitro studies
Cell culture models [References] Electronic cigarette vapour exposure Air-liquid interface [11, 12, 16, 17, 19, 21, 28, 34, 54, 55, 65, 66, 71, 73, 74, 77, 78, 103] E-liquid mixed with cell medium or electronic cigarette vapour extracts [13–15, 18, 20, 22, 47, 50–53, 56–58, 70, 72, 75, 76, 79, 81, 104] Cell types Lung epithelial cells 16HBE (human) [16, 53f, 64] hTBE (human) [52] A549 cells (human) [12, 13, 18, 50, 58, 64, 73] NHBE (human) [17, 20, 28, 65, 73] Beas-2B (human) [11, 13, 19, 47, 55, 58, 76] H292 (human) [19, 47, 74] Primary bronchial epithelial cells (human) [16, 21, 55] Primary small airway epithelial cells (human) [54] 3-dimensional epithelial cell model (human) [34, 78] Primary tracheal epithelial cells (mouse) [53] RLEC (rat) [76] Nasal epithelial cells HBEpC [58] 3-dimensional epithelial cell model from healthy donors (human) [77] Immune cells White blood cells (human) [18] Blood neutrophils (human) [22, 56, 82] Blood monocyte-derived dendritic cells (human) [104] THP-1 monocytic cells (human) [15] Kupffer cells (rat) [72] Platelets [81] Endothelial cells HUVEC (human) [51, 70] Primary human microvascular cells-lung derived [76] MLEC (mouse) [76] Stem cells Embryonic stem cells (human) [14] Bone marrow-derived mesenchymal stem cells (human) [75] Neural stem cells (mouse) [14] Lung fibroblasts Human pulmonary fibroblasts [14] HFL-1 (human) [19, 47, 103] Skin cells HaCaTs (human) [12, 18] Primary gingival epithelial cells (human) [71, 80] Periodontal ligament fibroblasts (human) [80] Lung surfactant Infasurf (calf) [79] Bacteria Streptococcus pneumoniae [57] Streptococcus gordonii [66] Streptococcus intermedius [66] Streptococcus mitis [66] Streptococcus oralis [66] Nicotine Low nicotine <6 mg·mL−1 [14, 19, 55, 57, 70, 76] Medium nicotine 6–18 mg·mL−1 [11, 14, 15, 19, 21, 47, 52, 75, 77, 81, 103–105] High nicotine >18 mg·mL−1 [13, 14, 17, 19, 20, 22, 28, 47, 50, 54, 58, 66, 71–74, 78–80, 82, 104, 106] No nicotine [13, 14, 16, 17, 19–21, 28, 47, 53, 54, 56–58, 66, 72, 73, 79–82] Unspecified concentration [12] Flavours Tobacco flavours [11, 14, 19, 52, 54, 58, 70–74, 76–78, 80–82, 103, 105] Menthol [11, 14, 74, 78–80] Cinnamon [55] Coffee [47] Fruit flavours [14, 15, 19, 50, 53, 57, 74, 75, 79] Dessert and sweet drink flavours [14, 19, 53, 74, 76] Other [12] Targeted aromatic molecules [19, 47, 51, 53, 56] Unflavoured [11, 13, 14, 16, 19–22, 28, 55, 66, 76, 79, 104, 106] HBE: human bronchial epithelial; NHBE: normal and diseased bronchial epithelial.
- TABLE 2
Methodological characteristics of animal studies
Animals models [References] Electronic cigarette vapour exposure Nose only [18, 50, 64, 65] Whole body [19, 23–35, 59–61, 67–69, 83–86, 107–109, 110] Electronic cigarette vapour extract [58] Electronic cigarette vapour exposure period Up to 4 days [19, 26, 27, 34, 35, 50, 58, 64] Between a week and a month [18, 22–25, 31, 68, 69, 83, 84, 86, 107, 109] Over a month [27–30, 32, 33, 59–61, 65, 67, 83, 85, 108, 110] Nicotine Low nicotine <6 mg·mL−1 [69, 76] Medium nicotine 6–18 mg·mL−1 [15, 18, 19, 23, 24, 27, 28, 50, 59, 60, 67, 85, 86, 107, 110] High nicotine >18 mg·mL−1 [22, 25, 26, 31, 33–35, 58, 61, 65, 68, 83, 84, 108, 109] No nicotine [15, 23, 24, 26, 27, 29, 30, 32–35, 61, 69, 108] Flavours Tobacco flavours [18, 19, 27, 58, 60, 61, 76, 83, 107] Menthol [86] Fruit flavours [15, 18, 23, 50] Dessert and sweet beverage flavours [18, 23, 30, 76, 108] Cinnamon [23, 84] Coffee [18, 85] Unflavoured [18, 22, 24–35, 59, 65, 67–69, 109, 110] Animals Mice BALB/c [23, 29, 32, 59–61, 67, 84] C57BL/6 [19, 22, 25–27, 30, 31, 33–35, 50, 57, 65, 68, 85, 86, 107, 109] CD-1 [18, 24, 58, 64, 65, 69] A/J [28] FVBN [110] ApoE -/- (C57BL/6 background) [83, 108] Rats [64] Sprague-Dawley Sex (all species) Male only [27, 31, 50, 67, 83, 86, 107, 110] Female only [18, 22, 24, 25, 29, 30, 32, 33, 58–60, 65, 85, 108] Both [23, 26, 34, 35, 61, 68, 84, 109] Unspecified [19, 28, 57] - TABLE 3
Methodological characteristics of clinical studies
Clinical studies [References] Electronic cigarette use status Never users [39–43, 58, 88, 89] Active users [58, 90, 91] Tobacco cigarette smoking status Never smokers [39, 41–43, 62, 87, 91] Active smokers [40, 62, 87–90] Former smokers [58, 90] Health status Healthy [39–43, 58, 62, 87, 88, 90, 91] Asthmatic [39, 40] Period of electronic cigarette use in the study Up to 1 h inclusively [39, 40, 42, 43, 62, 87] 1 h to 1 day inclusively 1 day to 1 week inclusively [88] 1 week to 1 month inclusively [41, 90] 1–6 months inclusively [89] 6 months to 1 year inclusively >1 year Undisclosed or self-reported [58, 91] Number of study participants <50 [39–43, 58, 62, 87] 51–100 [91] >100 [88, 89] Flavour used Tobacco [87, 89] Menthol [89] Dessert flavours [62] Unflavoured [39–43] User's choice (multiple flavours) [58, 90, 91] Nicotine concentration used Low nicotine <6 mg·mL−1 [40, 89] Medium nicotine 6–18 mg·mL−1 [87] High nicotine >18 mg·mL−1 [88] No nicotine [39–41, 43, 62] User's choice (multiple nicotine concentration) [58, 90, 91] Unknown [42] Tissue collected or analysis performed Bronchoalveolar lavage [41, 42] Nasal epithelial cells [58] Sputum [90] Bronchial brushings [41, 42, 91] Lung function assessment [39, 40, 42, 62, 87–89] Cardiac function assessment [88] Blood analysis [40, 43, 87, 89] Urine analysis [41, 42] - Box 4: pulmonary effects of vaping that cannot specifically be attributable to a given e-liquid component
Clear detrimental effects of flavoured e-liquids with nicotine on lung epithelial cell viability and cell function in vitro, with most of the studies using tobacco flavours Adverse effects on airway resistance and lung development The nature of the inflammatory response triggered by flavoured e-liquids with nicotine is not clear, with mixed results from animal models Impaired response to bacterial and viral lung infections with worse outcomes
Vol 29 Issue 157
Table of Contents
The fog, the attractive and the addictive: pulmonary effects of vaping with a focus on the contribution of each major vaping liquid constituent
