Fourth generation e-cigarette vaping induces transient lung inflammation and gas exchange disturbances: results from two randomized clinical trials

Abstract

When heated by an electronic cigarette, propylene glycol and glycerol produce a nicotine-carrying-aerosol. This hygroscopic/hyperosmolar aerosol can deposit deep within the lung. Whether these deposits trigger local inflammation and disturb pulmonary gas exchanges is not known. The aim of this study was to assess the acute effects of high-wattage electronic cigarette vaping with or without nicotine on lung inflammation biomarkers, transcutaneous gas tensions, and pulmonary function tests in young and healthy tobacco smokers. Acute effects of vaping without nicotine on arterial blood gas tensions were also assessed in heavy smokers suspected of coronary artery disease. Using a single-blind within-subjects study design, 25 young tobacco smokers underwent three experimental sessions in random order: sham-vaping and vaping with and without nicotine at 60 W. Twenty heavy smokers were also exposed to sham-vaping (n = 10) or vaping without nicotine (n = 10) in an open-label, randomized parallel study. In the young tobacco smokers, compared with sham-vaping: 1) serum club cell protein-16 increased after vaping without nicotine (mean ± SE, -0.5 ± 0.2 vs. +1.1 ± 0.3 µg/l, P = 0.013) and vaping with nicotine (+1.2 ± 0.3 µg/l, P = 0.009); 2) transcutaneous oxygen tension decreased for 60 min after vaping without nicotine (nadir, -0.3 ± 1 vs. -15.3 ± 2.3 mmHg, P < 0.001) and for 80-min after vaping with nicotine (nadir, -19.6 ± 2.8 mmHg, P < 0.001). Compared with sham vaping, vaping without nicotine decreased arterial oxygen tension for 5 min in heavy-smoking patients (+5.4 ± 3.3 vs. -5.4 ± 1.9 mmHg, P = 0.012). Acute vaping of propylene glycol/glycerol aerosol at high wattage with or without nicotine induces airway epithelial injury and sustained decrement in transcutaneous oxygen tension in young tobacco smokers. Intense vaping conditions also transiently impair arterial oxygen tension in heavy smokers.

Keywords: arterial oxygen tension; club cell protein-16; e-cigarette; transcutaneous oxygen tension.

Fig. 1.

Individual changes in and overall mean value (horizontal lines) of serum club cell protein-16 (CC16) at baseline (BSL) and 30 min (T30) after sham vaping (n = 21), vaping without (w/o) nicotine (n = 24), and vaping with nicotine (n = 18) in the first study (healthy occasional smokers). Serum concentration of CC16 levels increased after vaping w/o and with nicotine. Horizontal brackets represent P values for comparison between BSL inside each experimental session (short bracket) and for comparison between sessions (long bracket). A mixed-effects linear model analysis was performed with experimental sessions and time points as fixed effects and subject baselines as random effect (random intercept model).

Fig. 2.

A: electronic cigarette liquid (e-liquid) quantity (ml) consumed after acute sham vaping (○), vaping without (w/o) nicotine (■), and vaping with nicotine (▲) in the first study (healthy occasional smokers) (means ± SE). B: Δ-serum nicotine 30 min and 150 min after acute vaping with nicotine (means ± SE). C and D: Δ-serum propylene glycol (PG) 30 min (median [min-max]; C) and 150 min (means ± SE; D) after sham vaping, vaping w/o nicotine, and vaping with nicotine. Horizontal brackets represent P values for comparison of Δ values between sessions (A, C, and D). Horizontal brackets represent P values for comparison between baseline inside the vaping-with-nicotine session (B). A mixed-effects linear model analysis was performed with experimental sessions and time points as fixed effects and subject baselines as random effect (random intercept model).

Fig. 3.

Absolute changes in transcutaneous oxygen tension (Tcpo₂; A) and transcutaneous carbon dioxide tension (Tcpco₂; B) over time in sham-vaping (n = 22, blue circles), vaping-without-nicotine (n = 20, black squares), and vaping-with-nicotine (n = 19, red triangles) sessions in the first study (healthy occasional smokers). Compared with sham vaping, vaping with or without nicotine was associated with significant decreases in Tcpo₂ for 80 and 60 min postexposure, respectively. Compared with vaping without nicotine, vaping with nicotine decreased Tcpo₂ for 30 min postexposure. Compared with sham vaping, vaping with nicotine was associated with significant decreases in Tcpco₂ that persisted for 20 min postexposure. Black and red asterisks denote P values for comparisons with sham vaping; gold asterisks denote P values for comparisons between vaping without nicotine and vaping with nicotine (*P < 0.05, **P < 0.01, ***P < 0.001). Data presented are means ± SE. A mixed-effects linear model analysis was performed with experimental sessions and time points as fixed effects and subject baselines as random effect (random intercept model).

Fig. 4.

Correlation of Δ-serum club cell protein-16 (CC16) 150 min after acute vaping without nicotine (A), vaping with nicotine (B), and nadir of Δ-transcutaneous oxygen tension (Tcpo₂) in the first study (healthy occasional smokers). Positive correlation of electronic cigarette liquid (e-liquid) quantity consumed and Δ-serum propylene glycol (PG) 30 and 150 min after vaping without nicotine (C and E, respectively) and vaping with nicotine (D and F, respectively). Correlation analyses used the Spearman nonparametric correlation coefficient.

Fig. 5.

Positive correlation of Δ-serum propylene glycol (PG) and Δ-serum nicotine 30 min (A) and 150 min (B) after acute vaping with nicotine exposure in the first study (healthy occasional smokers). Positive correlation of electronic cigarette liquid (e-liquid) quantity (ml) consumed and Δ-serum nicotine 30 min (C) and 150 min (D) after acute vaping with nicotine exposure. Correlation analyses used the Spearman nonparametric correlation coefficient.

Fig. 6.

Individual changes in and overall mean values (horizontal lines) of arterial O₂ and CO₂ tensions at baseline and 5 min after sham vaping (n = 10; A and D, respectively) and vaping without nicotine (n = 10; B and E, respectively) in the second study (heavy smokers). Results of statistical tests are also provided (horizontal brackets). Absolute change in arterial O₂ and CO₂ tensions at baseline, 5 min, and 20 min after sham vaping (dashed line, ○; C and F), and vaping without nicotine (solid line, ■; C and F). Results of statistical tests comparing sham vaping and vaping without nicotine are also provided. A mixed-effects linear model analysis was performed with experimental sessions and time points as fixed effects and subject baselines as random effect (random intercept model). Data are means ± SE.

Fig. 7.

Absolute changes in transcutaneous oxygen tension (Tcpco₂, dashed line) and arterial CO₂ partial pressure (Pco₂, solid line) at baseline and 5 and 20 min after acute sham vaping (blue line, n = 5) and vaping without (w/o) nicotine (black line, n = 7). A mixed-effects linear model analysis was performed with experimental sessions and time points as fixed effects and subject baselines as random effect (random intercept model). Data presented are means ± SE.