Systematic review of biomarker findings from clinical studies of electronic cigarettes and heated tobacco products

Toxicology Reports

Volumn 8, Issue , 2021, Pages 282-294

  Akiyama, Yukio ^a   Sherwood, Neil ^b  

^a UNIVERSITY OF OCCUPATIONAL AND ENVIRONMENTAL HEALTH   (Japan)

^b Neil Sherwood Consulting   (Switzerland)

Author keywords

Biomarkers of biological effect (BOBE); Biomarkers of tobacco smoke exposure (BOE); Clinical study; Electronic cigarette; Heated tobacco products

Indexed keywords

2 CYANOETHYLMERCAPTURIC ACID; 3 HYDROXY 1 METHYLPROPYLMERCAPTURIC ACID; 3 HYDROXYPROPYLMERCAPTURIC ACID; BIOLOGICAL MARKER; CARBON MONOXIDE; GROWTH FACTOR; HIGH DENSITY LIPOPROTEIN CHOLESTEROL; LOW DENSITY LIPOPROTEIN CHOLESTEROL; MONOHYDROXYBUTENYL AND DIHYDROXYBUTYL MERCAPTURIC ACID; NICOTINE; S PHENYLMERCAPTURIC ACID; THROMBOXANE; TOBACCO SMOKE; TRIACYLGLYCEROL; UNCLASSIFIED DRUG;

ASCERTAINMENT BIAS; BIOLOGICAL ACTIVITY; DATA EXTRACTION; DEMOGRAPHY; EXPOSURE; FOLLOW UP; HUMAN; INFLAMMATION; NEUTROPHIL COUNT; OUTCOME ASSESSMENT; OXIDATIVE STRESS; QUALITATIVE ANALYSIS; QUALITY CONTROL; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; SYSTEMATIC REVIEW; TOBACCO;

EID: 85100315232     PISSN: 22147500     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.toxrep.2021.01.014     Document Type: Review

References (71)

1. Rom, O., Pecorelli, A., Valacchi, G., Reznick, A.Z., Are e-cigarettes a safe and good alternative to cigarette smoking?. Ann. N. Y. Acad. Sci. 2015:1340 (2015), 65–74, 10.1111/nyas.12609.
2. Gotts, J.E., Jordt, S.E., McConnell, R., Tarran, R., What are the respiratory effects of e-cigarettes?. BMJ., 2019(366), 2019, l5275, 10.1136/bmj.l5275.
3. Unger, M., Unger, D.W., E-cigarettes/electronic nicotine delivery systems: a word of caution on health and new product development. J. Thorac. Dis. 10:Suppl 22 (2018), S2588–S2592, 10.21037/jtd.2018.07.99 2018.
4. WHO Regional Office for Europe, Electronic Nicotine and Non-nicotine Delivery Systems: a Brief. 2020 https://www.euro.who.int/__data/assets/pdf_file/0009/443673/Electronic-nicotine-and-non-nicotine-delivery-systems-brief-eng.pdf.
5. WHO Regional Office for Europe, Heated Tobacco Products: a Brief. 2020 https://www.euro.who.int/__data/assets/pdf_file/0008/443663/Heated-tobacco-products-brief-eng.pdf.
6. Simonavicius, E., McNeill, A., Shahab, L., Brose, L.S., Heat-not-burn tobacco products: a systematic literature review. Tob. Control 28:5 (2019), 582–594, 10.1136/tobaccocontrol-2018-054419 2019.
7. Jankowski, M., Brożek, G.M., Lawson, J., Skoczyński, S., Majek, P., Zejda, J.E., New ideas, old problems? Heated tobacco products - a systematic review. Int. J. Occup. Med. Environ. Health 32:5 (2019), 595–634, 10.13075/ijomeh.1896.01433 2019.
8. Drovandi, A., Salem, S., Barker, D., Booth, D., Kairuz, T., Human biomarker exposure from cigarettes versus novel heat-not-Burn devices: a systematic review and meta-analysis. Nicotine Tob. Res. 22:7 (2020), 1077–1085, 10.1093/ntr/ntz200 2019.
9. Liberati, A., Altman, D.G., Tetzlaff, J., Mulrow, C., Gøtzsche, P.C., Ioannidis, J.P., Clarke, M., Devereaux, P.J., Kleijnen, J., Moher, D., The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration. BMJ, 21(July339), 2009, 10.1136/bmj.b2700 b27002009.
10. Higgins, J.P., Altman, D.G., Gøtzsche, P.C., Jüni, P., Moher, D., Oxman, A.D., Savovic, J., Schulz, K.F., Weeks, L., Sterne, J.A., Cochrane Bias Methods Group, Cochrane Statistical Methods Group, The Cochrane Collaboration's tool for assessing risk of bias in randomised trials. BMJ, 2011(343), 2011, d5928, 10.1136/bmj.d5928.
11. Peterson, J., Welch, V., Losos, M., Tugwell, P., The Newcastle-ottawa Scale (NOS) for Assessing the Quality of Nonrandomised Studies in Meta-analyses. 2011, Ottawa Hospital Research Institute, Ottawa http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp.
12. Lüdicke, F., Haziza, C., Weitkunat, R., Magnette, J., Evaluation of biomarkers of exposure in smokers switching to a carbon-heated tobacco product: a controlled, randomized, open-label 5-Day exposure study. Nicotine Tob. Res. 18:7 (2016), 1606–1613, 10.1093/ntr/ntw022 2016.
13. Haziza, C., de La Bourdonnaye, G., Merlet, S., Benzimra, M., Ancerewicz, J., Donelli, A., Baker, G., Picavet, P., Lüdicke, F., Assessment of the reduction in levels of exposure to harmful and potentially harmful constituents in Japanese subjects using a novel tobacco heating system compared with conventional cigarettes and smoking abstinence: A randomized controlled study in confinement. Regul. Toxicol. Pharmacol. 2016:81 (2016), 489–499, 10.1016/j.yrtph.2016.09.014.
14. Haziza, C., de La Bourdonnaye, G., Skiada, D., Ancerewicz, J., Baker, G., Picavet, P., Lüdicke, F., Biomarker of exposure level data set in smokers switching from conventional cigarettes to Tobacco Heating System 2.2, continuing smoking or abstaining from smoking for 5 days. Data Brief 2017:10 (2017), 283–293, 10.1016/j.dib.2016.11.047.
15. Lüdicke, F., Baker, G., Magnette, J., Picavet, P., Weitkunat, R., Reduced exposure to harmful and potentially harmful smoke constituents with the tobacco heating system 2.1. Nicotine Tob. Res. 19:2 (2017), 168–175, 10.1093/ntr/ntw164 2017.
16. Lüdicke, F., Picavet, P., Baker, G., Haziza, C., Poux, V., Lama, N., Weitkunat, R., Effects of switching to the tobacco heating system 2.2 menthol, smoking abstinence, or continued cigarette smoking on biomarkers of exposure: a randomized, controlled, open-label, multicenter study in sequential confinement and ambulatory settings (Part 1). Nicotine Tob. Res. 20:2 (2018), 161–172, 10.1093/ntr/ntw287 2018.
17. Haziza, C., de La Bourdonnaye, G., Donelli, A., Poux, V., Skiada, D., Weitkunat, R., Baker, G., Picavet, P., Lüdicke, F., Reduction in exposure to selected harmful and potentially harmful constituents approaching those observed upon smoking abstinence in smokers switching to the menthol tobacco heating system 2.2 for 3 months (Part 1). Nicotine Tob. Res. 22:4 (2020), 539–548, 10.1093/ntr/ntz013 2020.
18. Yuki, D., Takeshige, Y., Nakaya, K., Futamura, Y., Assessment of the exposure to harmful and potentially harmful constituents in healthy Japanese smokers using a novel tobacco vapor product compared with conventional cigarettes and smoking abstinence. Regul. Toxicol. Pharmacol. 2018:96 (2018), 127–134, 10.1016/j.yrtph.2018.05.001.
19. Tricker, A.R., Kanada, S., Takada, K., Martin Leroy, C., Lindner, D., Schorp, M.K., Dempsey, R., Reduced exposure evaluation of an Electrically Heated Cigarette Smoking System. Part 6: 6-Day randomized clinical trial of a menthol cigarette in Japan. Regul. Toxicol. Pharmacol. 2018:96 (2012), 127–134, 10.1016/j.yrtph.2012.08.007.
20. Gale, N., McEwan, M., Eldridge, A.C., Fearon, I.M., Sherwood, N., Bowen, E., McDermott, S., Holmes, E., Hedge, A., Hossack, S., Wakenshaw, L., Glew, J., Camacho, O.M., Errington, G., McAughey, J., Murphy, J., Liu, C., Proctor, C.J., Changes in biomarkers of exposure on switching from a conventional cigarette to tobacco heating products: a randomized, controlled study in healthy japanese subjects. Nicotine Tob. Res. 21:9 (2019), 1220–1227, 10.1093/ntr/nty104 2019.
21. Roethig, H.J., Kinser, R.D., Lau, R.W., Walk, R.A., Wang, N., Short-term exposure evaluation of adult smokers switching from conventional to first-generation electrically heated cigarettes during controlled smoking. J. Clin. Pharmacol. 45:2 (2005), 133–145, 10.1177/0091270004271253 2005.
22. Tricker, A.R., Kanada, S., Takada, K., Leroy, C.M., Lindner, D., Schorp, M.K., Dempsey, R., Reduced exposure evaluation of an Electrically Heated Cigarette Smoking System. Part 5: 8-Day randomized clinical trial in Japan. Regul. Toxicol. Pharmacol. 64:2 Suppl (2012), 54–63, 10.1016/j.yrtph.2012.08.003 2012.
23. Martin Leroy, C., Jarus-Dziedzic, K., Ancerewicz, J., Lindner, D., Kulesza, A., Magnette, J., Reduced exposure evaluation of an Electrically Heated Cigarette Smoking System. Part 7: A one-month, randomized, ambulatory, controlled clinical study in Poland. Regul. Toxicol. Pharmacol. 64:2 Suppl (2012), 74–84, 10.1016/j.yrtph.2012.08.006 2012.
24. Tricker, A.R., Stewart, A.J., Leroy, C.M., Lindner, D., Schorp, M.K., Dempsey, R., Reduced exposure evaluation of an Electrically Heated Cigarette Smoking System. Part 3: eight-day randomized clinical trial in the UK. Regul. Toxicol. Pharmacol. 64:2 Suppl (2012), 35–44, 10.1016/j.yrtph.2012.08.010 2012.
25. Tricker, A.R., Jang, I.J., Martin Leroy, C., Lindner, D., Dempsey, R., Reduced exposure evaluation of an Electrically Heated Cigarette Smoking System. Part 4: Eight-day randomized clinical trial in Korea. Regul. Toxicol. Pharmacol. 64:2 Suppl (2012), 45–53, 10.1016/j.yrtph.2012.08.013 2012.
26. Sakaguchi, C., Kakehi, A., Minami, N., Kikuchi, A., Futamura, Y., Exposure evaluation of adult male Japanese smokers switched to a heated cigarette in a controlled clinical setting. Regul. Toxicol. Pharmacol. 69:3 (2014), 338–347, 10.1016/j.yrtph.2014.04.016 2014.
27. Lüdicke, F., Ansari, S.M., Lama, N., Blanc, N., Bosilkovska, M., Donelli, A., Picavet, P., Baker, G., Haziza, C., Peitsch, M., Weitkunat, R., Effects of switching to a heat-not-Burn tobacco product on biologically relevant biomarkers to assess a candidate modified risk tobacco product: a randomized trial. Cancer Epidemiol. Biomarkers Prev. 28:11 (2019), 1934–1943, 10.1158/1055-9965.EPI-18-0915 2019.
28. Shepperd, C.J., Newland, N., Eldridge, A., Haswell, L., Lowe, F., Papadopoulou, E., Camacho, O., Proctor, C.J., Graff, D., Meyer, I., Changes in levels of biomarkers of exposure and biological effect in a controlled study of smokers switched from conventional cigarettes to reduced-toxicant-prototype cigarettes. Regul. Toxicol. Pharmacol. 72:2 (2015), 273–291, 10.1016/j.yrtph.2015.04.016 2015.
29. Ogden, M.W., Marano, K.M., Jones, B.A., Morgan, W.T., Stiles, M.F., Switching from usual brand cigarettes to a tobacco-heating cigarette or snus: part 2. Biomarkers of exposure. Biomarkers 20:6-7 (2015), 391–403, 10.3109/1354750X.2015.1094134 2015.
30. O'Connell, G., Graff, D.W., D'Ruiz, C.D., Reductions in biomarkers of exposure (BoE) to harmful or potentially harmful constituents (HPHCs) following partial or complete substitution of cigarettes with electronic cigarettes in adult smokers. Toxicol. Mech. Methods 26:6 (2016), 443–454, 10.1080/15376516.2016.1196282 2016.
31. Round, E.K., Chen, P., Taylor, A.K., Schmidt, E., Biomarkers of tobacco exposure decrease after smokers switch to an E-Cigarette or nicotine gum. Nicotine Tob. Res. 21:9 (2019), 1239–1247, 10.1093/ntr/nty140 2019.
32. Jay, J., Pfaunmiller, E.L., Huang, N.J., Cohen, G., Graff, D.W., Five-day changes in biomarkers of exposure among adult smokers after completely switching from combustible cigarettes to a nicotine-salt pod system. Nicotine Tob. Res. 22:8 (2020), 1285–1293, 10.1093/ntr/ntz206 2020.
33. Goniewicz, M.L., Gawron, M., Smith, D.M., Peng, M., Jacob, P. 3rd, Benowitz, N.L., Exposure to nicotine and selected toxicants in cigarette smokers who switched to electronic cigarettes: a longitudinal within-subjects observational study. Nicotine Tob. Res. 19:2 (2017), 160–167, 10.1093/ntr/ntw160 2017.
34. McRobbie, H., Phillips, A., Goniewicz, M.L., Smith, K.M., Knight-West, O., Przulj, D., Hajek, P., Effects of switching to electronic cigarettes with and without concurrent smoking on exposure to nicotine, carbon monoxide, and acrolein. Cancer Prev. Res. Phila. (Phila) 8:9 (2015), 873–878, 10.1158/1940-6207.CAPR-15-0058 2015.
35. Pulvers, K., Emami, A.S., Nollen, N.L., Romero, D.R., Strong, D.R., Benowitz, N.L., Ahluwalia, J.S., Tobacco consumption and toxicant exposure of cigarette smokers using electronic cigarettes. Nicotine Tob. Res. 20:2 (2018), 206–214, 10.1093/ntr/ntw333 2018.
36. Hatsukami, D.K., Meier, E., Lindgren, B.R., Anderson, A., Reisinger, S.A., Norton, K.J., Strayer, L., Jensen, J.A., Dick, L., Murphy, S.E., Carmella, S.G., Tang, M.K., Chen, M., Hecht, S.S., O'connor, R.J., Shields, P.G., A randomized clinical trial examining the effects of instructions for electronic cigarette use on smoking-related behaviors and biomarkers of exposure. Nicotine Tob. Res. 22:9 (2020), 1524–1532, 10.1093/ntr/ntz233 2020.
37. Cravo, A.S., Bush, J., Sharma, G., Savioz, R., Martin, C., Craige, S., Walele, T., A randomised, parallel group study to evaluate the safety profile of an electronic vapour product over 12 weeks. Regul. Toxicol. Pharmacol. 81:Suppl 1 (2016), S1–S14, 10.1016/j.yrtph.2016.10.003 2016.
38. Walele, T., Bush, J., Koch, A., Savioz, R., Martin, C., O'Connell, G., Evaluation of the safety profile of an electronic vapour product used for two years by smokers in a real-life setting. Regul. Toxicol. Pharmacol. 2018:92 (2018), 226–238, 10.1016/j.yrtph.2017.12.010.
39. Shahab, L., Goniewicz, M.L., Blount, B.C., Brown, J., McNeill, A., Alwis, K.U., Feng, J., Wang, L., West, R., Nicotine, carcinogen, and toxin exposure in long-term E-Cigarette and nicotine replacement therapy users: a cross-sectional study. Ann. Intern. Med. 166:6 (2017), 390–400, 10.7326/M16-1107 2017.
40. Goniewicz, M.L., Smith, D.M., Edwards, K.C., Blount, B.C., Caldwell, K.L., Feng, J., Wang, L., Christensen, C., Ambrose, B., Borek, N., van Bemmel, D., Konkel, K., Erives, G., Stanton, C.A., Lambert, E., Kimmel, H.L., Hatsukami, D., Hecht, S.S., Niaura, R.S., Travers, M., et al. Comparison of nicotine and toxicant exposure in users of electronic cigarettes and combustible cigarettes. JAMA Netw Open., 1(8), 2018, e185937, 10.1001/jamanetworkopen.2018.5937 2018.
41. Oliveri, D., Liang, Q., Sarkar, M., Real-world evidence of differences in biomarkers of exposure to select harmful and potentially harmful constituents and biomarkers of potential harm between adult e-vapor users and adult cigarette smokers. Nicotine Tob. Res. 22:7 (2020), 1114–1122, 10.1093/ntr/ntz185 2020.
42. Ye, D., Gajendra, S., Lawyer, G., Jadeja, N., Pishey, D., Pathagunti, S., Lyons, J., Veazie, P., Watson, G., McIntosh, S., Rahman, I., Inflammatory biomarkers and growth factors in saliva and gingival crevicular fluid of e-cigarette users, cigarette smokers, and dual smokers: A pilot study. [published online ahead of print, 2020 Feb 12]. J. Periodontol., 2020, 10.1002/JPER.19-0457 2020;10.1002/JPER.19-0457.
43. Lorkiewicz, P., Riggs, D.W., Keith, R.J., Conklin, D.J., Xie, Z., Sutaria, S., Lynch, B., Srivastava, S., Bhatnagar, A., Comparison of urinary biomarkers of exposure in humans using electronic cigarettes, combustible cigarettes, and smokeless tobacco. Nicotine Tob. Res. 21:9 (2019), 1228–1238, 10.1093/ntr/nty089 2019.
44. Bustamante, G., Ma, B., Yakovlev, G., Yershova, K., Le, C., Jensen, J., Hatsukami, D.K., Stepanov, I., Presence of the carcinogen N’-Nitrosonornicotine in saliva of E-cigarette users. Chem. Res. Toxicol. 31:8 (2018), 731–738, 10.1021/acs.chemrestox.8b00089 2018.
45. Ghosh, A., Coakley, R.D., Ghio, A.J., Muhlebach, M.S., Esther, C.R. Jr, Alexis, N.E., Tarran, R., Chronic E-Cigarette use increases neutrophil elastase and matrix metalloprotease levels in the lung. Am. J. Respir. Crit. Care Med. 200:11 (2019), 1392–1401, 10.1164/rccm.201903-0615OC 2019.
46. Lüdicke, F., Picavet, P., Baker, G., Haziza, C., Poux, V., Lama, N., Weitkunat, R., Effects of switching to the menthol tobacco heating system 2.2, smoking abstinence, or continued cigarette smoking on clinically relevant risk markers: a randomized, controlled, open-label, multicenter study in sequential confinement and ambulatory settings (part 2). Nicotine Tob. Res. 20:2 (2018), 173–182, 10.1093/ntr/ntx028 2018.
47. Haziza, C., de La Bourdonnaye, G., Donelli, A., Skiada, D., Poux, V., Weitkunat, R., Baker, G., Picavet, P., Lüdicke, F., Favorable changes in biomarkers of potential harm to reduce the adverse health effects of smoking in smokers switching to the menthol tobacco heating system 2.2 for 3 months (Part 2). Nicotine Tob. Res. 22:4 (2020), 549–559, 10.1093/ntr/ntz084 2020.
48. Ogden, M.W., Marano, K.M., Jones, B.A., Morgan, W.T., Stiles, M.F., Switching from usual brand cigarettes to a tobacco-heating cigarette or snus: part 3. Biomarkers of biological effect. Biomarkers. 20:6-7 (2015), 404–410, 10.3109/1354750X.2015.1094135 2015.
49. D'Ruiz, C.D., O'Connell, G., Graff, D.W., Yan, X.S., Measurement of cardiovascular and pulmonary function endpoints and other physiological effects following partial or complete substitution of cigarettes with electronic cigarettes in adult smokers. Regul. Toxicol. Pharmacol. 2017:87 (2017), 36–53, 10.1016/j.yrtph.2017.05.002.
50. S Song, M.A., Freudenheim, J.L., Brasky, T.M., Mathe, E.A., McElroy, J.P., Nickerson, Q.A., Reisinger, S.A., Smiraglia, D.J., Weng, D.Y., Ying, K.L., Wewers, M.D., Shields, P.G., Biomarkers of exposure and effect in the lungs of smokers, nonsmokers, and electronic cigarette users. Cancer Epidemiol. Biomarkers Prev. 29:2 (2020), 443–451, 10.1158/1055-9965.EPI-19-1245 2020.
51. Tsai, M., Song, M.A., McAndrew, C., Brasky, T.M., Freudenheim, J.L., Mathé, E., McElroy, J., Reisinger, S.A., Shields, P.G., Wewers, M.D., Electronic versus combustible cigarette effects on inflammasome component release into human lung. Am. J. Respir. Crit. Care Med. 199:7 (2019), 922–925, 10.1164/rccm.201808-1467LE 2019.
52. Scherer, G., Biomonitoring of inhaled complex mixtures–ambient air, diesel exhaust and cigarette smoke. Exp. Toxicol. Pathol. 57:Suppl 1 (2005), 75–110, 10.1016/j.etp.2005.05.007 2005.
53. Gregg, E.O., Minet, E., McEwan, M., Urinary biomarkers of smokers’ exposure to tobacco smoke constituents in tobacco products assessment: a fit for purpose approach. Biomarkers. 18:6 (2013), 467–486, 10.3109/1354750X.2013.821523 2013.
54. Scherer, G., Suitability of biomarkers of biological effects (BOBEs) for assessing the likelihood of reducing the tobacco related disease risk by new and innovative tobacco products: a literature review. Regul. Toxicol. Pharmacol. 94 (2018), 203–233, 10.1016/j.yrtph.2018.02.002.
55. Varella, S.D., Rampazo, R.A., Varanda, E.A., Urinary mutagenicity in chemical laboratory workers exposed to solvents. J. Occup. Health 50:5 (2008), 415–422, 10.1539/joh.l7151 2008.
56. U.S. Environmental Protection Agency. 1,3-Butadiene. https://www.epa.gov/sites/production/files/2016-08/documents/13-butadiene.pdf.
57. Arnett, D.K., Blumenthal, R.S., Albert, M.A., Buroker, A.B., Goldberger, Z.D., Hahn, E.J., Himmelfarb, C.D., Khera, A., Lloyd-Jones, D., McEvoy, J.W., Michos, E.D., Miedema, M.D., Muñoz, D., Smith, S.C. Jr, Virani, S.S., Williams, K.A. Sr, Yeboah, J., Ziaeian, B., 2019 ACC/AHA guideline on the primary prevention of cardiovascular disease: executive summary: a report of the american college of Cardiology/American heart association task force on clinical practice guidelines. J. Am. Coll. Cardiol. 74:10 (2019), 1376–1414, 10.1016/j.jacc.2019.03.009 2019.
58. Gordon, D.J., Probstfield, J.L., Garrison, R.J., Neaton, J.D., Castelli, W.P., Knoke, J.D., Jacobs, D.R. Jr., Bangdiwala, S., Tyroler, H.A., High-density lipoprotein cholesterol and cardiovascular disease. Four prospective American studies. Circulation. 79:1 (1989), 8–15, 10.1161/01.cir.79.1.8 1989.
59. Ridker, P.M., Hennekens, C.H., Roitman-Johnson, B., Stampfer, M.J., Allen, J., Plasma concentration of soluble intercellular adhesion molecule 1 and risks of future myocardial infarction in apparently healthy men. Lancet. 351:9096 (1998), 88–92, 10.1016/S0140-6736(97)09032-6 1998.
60. Malik, I., Danesh, J., Whincup, P., Bhatia, V., Papacosta, O., Walker, M., Lennon, L., Thomson, A., Haskard, D., Soluble adhesion molecules and prediction of coronary heart disease: a prospective study and meta-analysis. Lancet. 358:9286 (2001), 971–976, 10.1016/S0140-6736(01)06104-9 2001.
61. Madjid, M., Awan, I., Willerson, J.T., Casscells, S.W., Leukocyte count and coronary heart disease: implications for risk assessment. J. Am. Coll. Cardiol. 44:10 (2004), 1945–1956, 10.1016/j.jacc.2004.07.056 2004.
62. Nowak, J., Murray, J.J., Oates, J.A., FitzGerald, G.A., Biochemical evidence of a chronic abnormality in platelet and vascular function in healthy individuals who smoke cigarettes. Circulation. 76:1 (1987), 6–14, 10.1161/01.cir.76.1.6 1987.
63. Schwedhelm, E., Bartling, A., Lenzen, H., Tsikas, D., Maas, R., Brümmer, J., Gutzki, F.M., Berger, J., Frölich, J.C., Böger, R.H., Urinary 8-iso-prostaglandin F2alpha as a risk marker in patients with coronary heart disease: a matched case-control study. Circulation. 109:7 (2004), 843–848, 10.1161/01.CIR.0000116761.93647.30 2004.
64. Murthy, V.H., E-cigarette use among youth and young adults: a major public health concern. JAMA Pediatr. 171:3 (2017), 209–210, 10.1001/jamapediatrics.2016.4662 2017.
65. Roethig, H.J., Zedler, B.K., Kinser, R.D., Feng, S., Nelson, B.L., Liang, Q., Short-term clinical exposure evaluation of a second-generation electrically heated cigarette smoking system. J. Clin. Pharmacol. 47:4 (2007), 518–530, 10.1177/0091270006297686 2007.
66. Frost-Pineda, K., Zedler, B.K., Oliveri, D., Feng, S., Liang, Q., Roethig, H.J., Short-term clinical exposure evaluation of a third-generation electrically heated cigarette smoking system (EHCSS) in adult smokers. Regul. Toxicol. Pharmacol. 52:2 (2008), 104–110, 10.1016/j.yrtph.2008.05.016 2008.
67. Frost-Pineda, K., Zedler, B.K., Oliveri, D., Liang, Q., Feng, S., Roethig, H.J., 12-week clinical exposure evaluation of a third-generation electrically heated cigarette smoking system (EHCSS) in adult smokers. Regul. Toxicol. Pharmacol. 52:2 (2008), 111–117, 10.1016/j.yrtph.2008.05.015 2008.
68. Roethig, H.J., Feng, S., Liang, Q., Liu, J., Rees, W.A., Zedler, B.K., A 12-month, randomized, controlled study to evaluate exposure and cardiovascular risk factors in adult smokers switching from conventional cigarettes to a second-generation electrically heated cigarette smoking system. J. Clin. Pharmacol. 48:5 (2008), 580–591, 10.1177/0091270008315316 2008.
69. National Center for Chronic Disease Prevention and Health Promotion (US) Office on Smoking and Health, The Health Consequences of Smoking—50 Years of Progress: A Report of the Surgeon General. Centers for Disease Control and Prevention (US)., 2014 https://www.ncbi.nlm.nih.gov/books/NBK179276/.
70. Hirn, C., Kanemaru, Y., Stedeford, T., Paschke, T., Baskerville-Abraham, I., Comparative and cumulative quantitative risk assessments on a novel heated tobacco product versus the 3R4F reference cigarette. Toxicol. Rep. 7 (2020), 1502–1513, 10.1016/j.toxrep.2020.10.019.
71. Thorne, D., Whitwell, J., Clements, J., Walker, P., Breheny, D., Gaca, M., The genotoxicological assessment of a tobacco heating product relative to cigarette smoke using the in vitro micronucleus assay. Toxicol. Rep. 7 (2020), 1010–1019, 10.1016/j.toxrep.2020.08.013.