Table 2.
Cross-sectional studies investigating potential harm of DUs compared to ESCC.
| First Author, Year of Publication, Country, Conflict 0f Interest | Method | Participants | Risk of Selection Bias/Weighted Data/Adjusted Analyses/Adjusted for Former Tobacco Consumption | Major Outcomes | Overall Findings Significantly (Higher Risk/Prevalence/Level in ESCC = ## Higher Risk/Prevalence/Level in ESCC, Significance Level Not Tested or Not Significant = # Same Risk/Prevalence/Level in ESCC and DUs = ¤ Higher Risk/Prevalence/Level in DUs, Significance Level Not Tested or Not Significant = * Significantly Higher Risk/Prevalence/Level in DUs = ** |
|
|---|---|---|---|---|---|---|
| Harmful substances | Carroll D.M. [53] 2018, USA None |
Cross-sectional study | 94 volunteer adults of American Indian descent |
High/-/(no)/no | Carcinogen metabolite (NNAL) in urine | DUs same level of carcinogen biomarker as ESCC ¤ |
| Goniewicz M. [15] 2018, USA  Yes |
Cross-sectional analyses of nationally representative cohort study | 5105 adults | Low/yes/yes/no | 50 biomarkers of toxicity (TSNAs, metals, PAHs, and VOCs) in urine |
DUs: significantly higher concentration of most biomarkers of toxicity/carcinogenicity than ESCC ** | |
| Jain R. [54] 2019, USA None |
Cross-sectional analyses of population-based survey | 1139 adults | Low/yes/yes/no | Harmful metals (cadmium, lead, and mercury) in blood | DUs same levels of harmful metals in blood as ESCC ¤ | |
| Keith R. [55] 2020, USA None |
Cross-sectional analysis of cohort study | 371 volunteer adults | Low/no/yes/no | Volatile organic compound (VOC) metabolites in urine | DUs and ESCC had similar levels of most VOC metabolites, except four, which were significantly higher in ESCC than in DU ¤ ## | |
| Piper M [34] 2018, USA None |
Cross-sectional analysis of cohort study | 422 volunteer adults | Low/no/yes/no | Carcinogen metabolite (NNAL) in urine | DUs had significantly lower levels of NNAL than ESCC ## | |
| Prokopowicz A. [52] 2019, Poland  Yes |
Cross-sectional study | 156 young volunteer adults | High/-/yes/no | Harmful metals cadmium and lead in blood | DUs: levels of harmful metals not significantly different than ESCC ¤ | |
| Prokopowicz A. [56] 2020, Poland Yes |
Cross-sectional study | 88 young volunteer adults | High/-/yes/no | 11 toxic metals in urine | Significance level between ESCC and DUs not tested, but DUs had higher values for 8 out of 11 metals in urine * | |
| Rostron B. L. [57] 2019, USA None |
Cross-sectional analysis of a nationally representative cohort | 2710 adults | Low/yes/yes/no | Carcinogen and toxin exposure, biomarkers (VOCs, PAHs and TSNAs) in urine and blood | DUs: significantly higher levels of some toxic and carcinogenic biomarkers (NNAL, 1-HOP, HPMA and MHB3) compared to ESCC ** ¤ | |
| Shahab L. [58] 2017, UK Yes |
Cross-sectional study | 181 volunteer adults with long-term use | High/-/yes/yes | Carcinogen and toxin exposure, biomarkers (VOCs and TSNAs) in urine and saliva | DUs and ESCC had similar levels of toxic and carcinogenic substances, but DU had significantly higher level of one carcinogenic substance, benzene than ESCC ¤ ** | |
| Smith D. ^ [59] 2020, Poland, UK and USA Yes |
Cross-sectional study | 456 volunteer adults with long-term use | High/-/yes/no | Carcinogen and toxin exposure biomarkers (VOCs, TSNAs and minor alkaloids) in urine and saliva | DUs and ESCC had similar levels of toxic and carcinogenic substances, but ESCC had significantly higher level of three TSNAs and acrylonitrile than DUs ¤ ## | |
| Cho J. H. [60] 2016, South Korea None |
Nationally representative survey | 35,904 adolescents | Low/no?/yes/no | Self-reported diagnosed with asthma | DUs higher odds of reporting asthma than ESCC but not significant in adjusted analyses * | |
| Chung S. J. [61] 2019, South Korea None |
Nationally representative survey | 60,040 adolescents | Low/yes/yes/no | Self-reported diagnosed with asthma or/and allergic rhinitis | DUs had higher odds for current allergic rhinitis but lower odds of current asthma than ESCC, but significance level not tested * # | |
| Hedman L. [12] 2018, Sweden Yes |
2 population-based surveys | 30,272 adults | Low/no/yes/no | Self-reported respiratory symptoms: long-standing cough, sputum production, wheeze | DUs had higher odds of self-reported respiratory symptoms than than ESCC but significance level not tested * |
|
| Lee A. [62] 2019, South Korea None |
Population-based survey | 58,336 adolescents | Low/yes/yes/no | Self-reported asthma, allergic rhinitis and atopic dermatitis | DUs har lower odds of asthma than ESCC, but comparable odds of allergic rhinitis and atopic dermatitis. Significance level not tested # ¤ | |
| Li D. [63] § 2020, USA Yes |
Nationally representative survey | 28,171 adults | Low/yes/yes/no | Self-reported respiratory symptoms and physical health | DUs same odds of respiratory symptoms as ESCC ¤ DUs: same prevalence of poor physical health as ESCC ¤ |
|
| Osei A. [64] 2020, USA Yes |
Nationally representative survey | 705,159 adults | Low/yes/yes/no | Self-reported diagnosed with COPD/emphysema/chronic bronchitis | DUs had significantly higher odds of COPD/emphysema/chronic bronchitis than ESCC ** | |
| Parekh T. [65] 2020, USA None |
Nationally representative survey | 161,965 young adult women | Low/yes/yes/no | Self-reported diagnosed with COPD/emphysema/chronic bronchitis and asthma | DUs had higher odds of asthma and COPD compared than ESCC, but significance level not tested * | |
| Wang J. B. [66] § 2018, USA Yes |
Internet population -based survey | 39,747 adults | Low/no/yes/no | Self-reported cardiopulmonary symptoms in the last months General health in the last month (SF-12) |
DUs had significantly higher/worse breathing difficulty score than ESCC ** DUs: significantly worse median general health scores than ESCC** DUs: significantly higher prevalence of history of an arrhythmia than ESCC ** |
|
| Wills T. A. [67] 2019, USA None |
Population-based survey | 8087 adults | Low/yes/yes/no | Self-reported diagnosed with asthma, COPD | DUs and ESCC same odds of asthma ¤ DUs higher odds of COPD than ESCC but not significant * |
|
| Wills T.A. [68] 2020, USA None |
Nationally representative youth survey | 14,765 adolescents | Low/yes/yes/no | Self-reported asthma diagnosis | DUs had higher odds of asthma than ESCC but not sign. ¤ Significantly higher in a sensitivity analysis tested in a sample with complete data ** |
|
| Xie Z. [24] 2020, USA None | Nationally representative youth survey | 887,182 adults | Low/yes/yes/no | Self-reported COPD diagnosis told by doctor | DUs had significantly higher risk of self-reported COPD diagnosis told by doctor than ESCC ** | |
|
Cardiovascular and metabolic outcomes
|
Choi D-W [69] 2018, South Korea None |
Nationally representative survey | 8809 adults | Low/yes/yes/yes | Diabetes (HbA1c) | DUs had higher HbA1c levels than ESCC but significance level not tested * |
| Fetterman J. [70] 2020, USA None |
Human clinical study with noninvasive vascular function testing | 467 younger adults | High/-/yes/no | Cardiovascular health (augmentation index) | DUs had similar arterial stiffness as ESCC ¤ | |
| Kim C. [21] 2020, South Korea None |
Population-based survey | 7505 adult men | Low/yes/yes/no | Cardiovascular risk factors (waist circumference, blood pressure, triglycerides, fasting glucose, HDL-cholesterol, diagnosis of metabolic syndrome) |
DUs had significantly higher prevalence odds ratio of cardiovascular risk factors (waist circumference, triglycerides, HDL-cholesterol, blood pressure) and diagnosis of metabolic syndrome than ESCC DUs had similar fasting glucose as ESCC ¤ ** |
|
| Kim T. [22] 2020, South Korea None |
Nationally representative survey | 14,738 adults | Low/yes/yes/no | Cardiovascular risk factors (waist circumference, blood pressure, triglycerides, fasting glucose, HDL-cholesterol, diagnosis of metabolic syndrome) |
DUs had significantly higher odds of abdominal obesity than ESCC ** Other outcomes: no s significant difference but tendency to higher odds in DUs (except blood pressure) # * |
|
| Mainous A. [71] 2020, USA None |
Nationally representative survey | 4659 adults | Low/yes/yes/no | Biomarker of inflammation and predictor of cardiovascular disease (CRP) | DUs had significantly higher odds of elevated CRP than ESCC ** | |
| Miller C. R. [27] 2021, USA Yes |
Population-based survey | 19,147 adults | Low/yes/yes/no | Self-reported diagnosis of hypertension in the last 12 months | DUs had higher odds for hypertension than ESCC, but significance not reached (0.99 for lower 95%CI) * | |
| Orimoloye O. [72] 2019, USA None |
Population-based survey | 3415 adults | Low/yes/yes/no | Insulin resistance (measured by HOMA-IR and GTT levels) | DUs had same risk of insulin resistance as ESCC ¤ | |
| Osei A. [26] 2019, USA None |
Nationally representative survey | 449,092 adults | Low/yes/yes/no | Self-reported diagnosed with cardiovascular disease (stroke, myocardial infarction or coronary heart disease) |
DUs had significantly higher odds of CVD than ESCC ** DUs had significantly higher odds of premature CVD than ESCC ** |
|
| Parekh T. [73] 2019, USA None |
Nationally representative survey | 161,529 young adults | Low/yes/yes/no | Self-reported stroke | DUs had significantly higher risk of stroke than ESCC ** | |
| Vindhyal M. [74] 2020, USA None |
Nationally representative survey | 16,855 adults | Low/yes/yes/no | Self-reported diagnosed with cardiovascular disease | DUs had higher odds of myocardial infarction and stroke than ESCC, but significantly level not tested * | |
| Other | Akinkugbe A. A. [75] 2019, USA None |
Population-based survey | 13,650 adolescents | Low/yes/yes/no | Self-reported past-year diagnosis with dental problems | DUs: higher odds of dental problems than ESCC, but significance level not tested * |
| Chen D. TH. [25] 2021, United Kingdom None | 4 population-based surveys | 13,077 adults | Low/yes/yes/no | Self-reported experience of COVID-19 symptoms and diagnosis | DUs had higher odds of covid-19 symptoms and higher odds of confirmed/suspected covid-19 diagnosis than ESCC but significance level not tested * | |
| Dinkeloo E. [76] 2019, USA None |
Online survey |
2854 men, soldiers | Low/no/yes/no | Physical activity | DUs: significantly worse fitness than ESCC ** | |
| Gaiha S. M. [77] 2020, USA None |
National online survey |
4351 young adults | Low/yes/yes/no | Self-reported COVID-19 symptoms, testing and diagnosis | DUs higher risk of COVID-19 symptoms and diagnosis than ESCC but significance level not tested * | |
| Kim T. [23] 2021, South Korea None |
Nationally representative population-based survey | 10,692 adults | Low/yes/yes/no | Levels of serum uric acid and hyperuricemia | DUs significantly higher levels of uric acid and prevalence of hyperuricemia than ESCC ** | |
| Leavens E. [78] 2020, USA None |
Interview-survey | 4148 homeless adults | High/no/no/no | Self-reported chronic health conditions | DUs significantly higher rates of asthma ** and cancer compared to ESCC ** | |
| Merianos A. [79] 2021, USA None |
School based nationally representative survey | 11,296 high school students | Low/yes/yes/no | Self-reported duration of sleep | DUs were significantly more likely to report insufficient sleep compared with ESCC ** | |
| Ye D. [80] 2020, USA None |
Human clinical study | 48 adults | High/-/no/no | Systemic inflammation, oxidative stress, angiogenesis and tissue injury/repair in saliva and gingival crevicular fluid (GCF) | DUs: higher levels of most biomarkers of systemic inflammation than ESCC, but no significant difference * |
^ Participants from UK, Shahab 2017, also included in this study. § Also other health outcome than respiratory. Conflict of interest: pharmaceutical industry. Conflict of interest with the tobacco or e-cigarette industry.