High-Wattage E-Cigarettes Induce Tissue Hypoxia and Lower Airway Injury: A Randomized Clinical Trial

Acute exposure to high-wattage e-cigarettes: 1) induced a 60-minute skin tissue hypoxia (assessed by the PeriFlow system 5000, PF 5040 with combined transcutaneous oxygen [O2] and carbon dioxide [CO2] E5280 electrode; Perimed), with the nadir reached during the first 30 minutes after exposure (mean 6 SEM) (84 6 2 mm Hg to 70 6 4 mm Hg; P < 0.001 vs. baseline; Figure 1); 2) did not modify transcutaneous CO2 tension (analysis of covariance group X period interaction; P > 0.5); 3) injured the lower airway, as reflected by serum CC16 (club cell protein 16) rise within the vaping session (median [interquartile range], mg L-1: 4.6 [3.6-6.75] to 5.65 [4.5-7.4]; P = 0.012 vs. baseline; Table 1) and when comparing the changes between vaping and sham vaping (P = 0.015); 4) increased small airway resistances, as suggested by decrease of forced expiratory flow at 50% (L s-1, 4.8 [4-6.1] to 4.2 [3.7-5.5]; P = 0.002 vs. baseline), forced expiratory flow at 25% (L s-1, 2.5 [1.7-2.6] to 2 [1.4-2.3]; P = 0.005 vs. baseline), and forced midexpiratory flow rate (L s-1, 4.2 [3.5-5.4] to 3.7 [3.1-4.9]; P = 0.005 vs. baseline), and the same changes were found when comparing between the sessions (all P < 0.004; results not shown); 5) did not modify baseline skin continuous microcirculatory flow (PeriFlow system 5000, PF 5010/5020 with the thermostatic probe 457; Perimed; ANOVA session X time interaction; P > 0.1), skin vasodilator responses to acetylcholine (P > 0.1 vs. sham vaping), and sodium nitroprusside (P > 0.8 vs. sham vaping) iontophoresis or heat test in the control condition (pretreatment with normal saline) nor after pretreatment with L-N-arginine-methyl-ester (all P > 0.6 vs. sham vaping; MOORLDI2-IR, Moor Instruments); and finally, 6) did not increase plasma oxidative stress biomarkers nor superoxide anion production in human umbilical vein endothelial cells incubated with participants' sera (Table 1).The CC16 increase and small airway constriction we observed could be a result of lung irritative aldehydes (8, 9) produced by the e-cigarette tested in this study (3) and/or the deposition, deep in the lungs, of large amounts of a hot and moist nanoparticular propylene glycol/glycerol aerosol (10), resulting in surfactant and mucus adsorption/desorption kinetics disturbances, interface rheology, and surface tension perturbations with small bronchioles and alveoli collapses (11), and the subsequent decrease of V/Q ratio and lung gas exchange perturbations, ensuing arter