Differential effects of heat-not-burn, electronic cigarettes and conventional cigarettes on endothelial glycocalyx

Abstract Background Heat-not-burn cigarette (HNBC) and electronic cigarette (Ecig) constitute non-combustible smoke products. Their effect on endothelial glycocalyx has not been investigated so far. Patients and Methods: Out of 100 subjects attending smoking cessation clinic: α) 50 smokers were randomized to usage of HNBC (n=25) or Ecig (n=25) and β) 50 smokers were used as control group. Participants randomized to the newer tobacco products had similar clinical and demographic characteristics to the control group. Smoking status was verified by measuring the concentration of exhaled carbon monoxide [(e CO) (ppm), Bedfont Scientific, Maidstone, Kent UK]. Perfused Boundary Region (PBR), which is inversely related to endothelial glycocalyx thickness in sublingual arterioles (range 5–25 μm) and blood levels of cotinine, a stable metabolite of nicotine, was assessed in all participants. Exhaled CO, endothelial glycocalyx, and blood cotinine were assessed at baseline and after 1 month. Results Conventional cigarette smokers were aged: 48 ± 5 years, 53% female and used 27 ± 9 cigarettes/day, 29 ± 9 pack-years. HNBC users were aged: 46 ± 14 years, 55% female and used 26 ± 8 cigarettes/day, 30 ± 8 pack-years. Ecig users were aged: 45 ± 8 years, 51% female and used 27 ± 10 cigarettes/day, 28 ± 10 pack-years. Compared to baseline, switching to HNBC for 1 month improved only PBR20-25 (2.55±0.49 vs 2.34±0.34 μm, p=0.002). Ecig use did not alter endothelial glycocalyx in any range of microvessels throughout the study (p>0.05). In contrast, Tcig smoking for one month further worsened endothelial glycocalyx in all microvessels ranges compared to baseline (p<0.05). Blood cotinine levels were similar at baseline and after 1 month using HNBC (p=0.432), Ecig (p=0.535) or conventional cigarette (p=0.489). Compared to baseline, exhaled CO decreased in HNBC or Ecig users (mean percent change: -55% and -58% respectively p<0.001), while remained unchanged in Tcig smokers (p=0.312) at 1 month. Thus, Tcig smokers had higher CO than those who switched to HNBC or E-cig after one month (p<0.01). Conclusion Conventional cigarette users further worsened endothelial glycocalyx after continuing to smoke for one month. In contrast, smokers who switched to Ecig maintained glycocalyx integrity, while those who switched to HNBC showed modest improvement in glycocalyx integrity in microvessels ranging from 20 to 25 μm. Cotinine levels, which reflect nicotine exposure, were similar between the Tcig, HNBC and Ecig groups. Thus, endothelial glycocalyx impairment in the conventional cigarette group was independent of nicotine consumption and possibly related to greater exposure to toxic emissions, such as CO, after Tcig use than after switching to HNBC or Ecig.