Shauna Goldberg Scott and her colleagues recently published the first longitudinal evidence (where people are followed forward in time, the strongest kind of epidemiological study) showing that e-cigarette use was associated with increased risk of death.
Their paper, Demographic, Clinical, and Behavioral Factors Associated With Electronic Nicotine Delivery Systems Use in a Large Cohort in the United States, used the large Kaiser Permanente Research Bank, a biorepository that includes longitudinal electronic health record information, lifestyle surveys, and biospecimens (saliva or blood) from Kaiser Permanente adult health plan members in Colorado, Georgia, Hawaii, Mid-Atlantic States (District of Columbia, Maryland, Virginia), Northern California, Southern California, Northwest Oregon and Washington state to determine longitudinal and cross-sectional associations between e-cigarette use and a wide range of outcomes.
In particular, controlling for a wide range of demographic variables as well as cigarette and marijuana use, they found longitudinal associations (in people the followed forward in time for a median of 504 days) between e-cigarette use and significantly increased risk of emergency room visits (hazard rate [HR] = 1.17; CI: 1.05-1.30) and death (HR = 1.84; CI:1.02-3.32).
Longitudinal studies are considered the strongest kind of epidemiological studies because they follow people without the disease forward in time to see if people who used e-cigarettes at the beginning (baseline) were more likely to have an event (in this case an emergency room visit or death) than people who did not use e-cigarettes. The problem with longitudinal studies is that they only capture events that occurred during the study, in this case a median of just 504 days. Fully capturing the diseases caused by e-cigarettes would require much longer times for people to age and diseases to appear.
Another difficulty is that the sensitivity of the study (what statisticians call power) depends on the number of events that occur. It takes time to accumulate events.
The fact that Goldberg Scott and colleagues found such major effects in such a short time is impressive.
Cross-sectional studies, which represent a snapshot in time, usually have an advantage in terms of the number of events. Because cross-sectional studies examine the association between the presence of disease at the time of the study, there are often many more events and so higher sensitivity (power) to detect an association between e-cigarettes and disease. The disadvantage of cross-sectional studies is that you do not know for sure the timing of e-cigarette use and disease developing, so you can only talk about associations not causal relations.
Goldberg Scott also reports results of cross-sectional analysis for several outcomes and found statistically significant associations between e-cigarette use and history of lung cancer (odds ratio [OR] = 2.64; CI:1.42-4.92), non-stroke cerebral vascular disease (OR = 1.55; CI:1.21-1.99), and chronic obstructive pulmonary disease (OR = 2.16; CI:1.77-2.63).
This paper adds to the rapidly growing evidence base on actual disease risks of e-cigarettes. FDA and other regulators and decision makers need to shift their focus away from biomarkers (which are indirect measures of disease) and use these direct measures instead when assessing the health risks of e-cigarettes.
Here is the abstract:
Introduction: Our primary purpose is to understand comorbidities and health outcomes associated with electronic nicotine delivery systems (ENDS) use.
Methods: Study participants were Kaiser Permanente (KP) members from eight US regions who joined the Kaiser Permanente Research Bank (KPRB) from September 2015 through December 2019 and completed a questionnaire assessing demographic and behavioral factors, including ENDS and traditional cigarette use. Medical history and health outcomes were obtained from electronic health records. We used multinomial logistic regression to estimate odd ratios (ORs) and 95% confidence intervals (CIs) of current and former ENDS use according to member characteristics, behavioral factors, and clinical history. We used Cox regression to estimate hazard ratios (HRs) and 95% CIs comparing risk of health outcomes according to ENDS use.
Results: Of 119 593 participants, 1594 (1%) reported current ENDS use and 5603 (5%) reported past ENDS use. ENDS users were more likely to be younger, male, gay or lesbian, and American Indian / Alaskan Native or Asian. After adjustment for confounding, current ENDS use was associated with current traditional cigarette use (OR = 39.55; CI:33.44-46.77), current marijuana use (OR = 6.72; CI:5.61-8.05), history of lung cancer (OR = 2.64; CI:1.42-4.92), non-stroke cerebral vascular disease (OR = 1.55; CI:1.21-1.99), and chronic obstructive pulmonary disease (OR = 2.16; CI:1.77-2.63). Current ENDS use was also associated with increased risk of emergency room (ER) visits (HR = 1.17; CI: 1.05-1.30) and death (HR = 1.84; CI:1.02-3.32).
Conclusions: Concurrent traditional cigarette use, marijuana use, and comorbidities were prevalent among those who used ENDS, and current ENDS use was associated with an increased risk of ER visits and death. Additional research focused on health risks associated with concurrent ENDS and traditional cigarette use in those with underlying comorbidities is needed.
Goldberg Scott S, Feigelson HS, Powers JD, Clennin MN, Lyons JA, Gray MT, Vachani A, Burnett-Hartman AN. Demographic, Clinical, and Behavioral Factors Associated With Electronic Nicotine Delivery Systems Use in a Large Cohort in the United States. Tob Use Insights. 2023 Jan 5;16:1179173X221134855. doi: 10.1177/1179173X221134855. PMID: 36636234; PMCID: PMC9829996. It is available here.
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