Diseases That Studies Linked to E-Cigarettes Generally Were Diagnosed Before Subjects Began Vaping

The failure to consider the timing of diagnoses makes it impossible to draw causal inferences.

In recent years, a bunch of studies have reported correlations between nicotine vaping and various smoking-related diseases, seemingly undermining the case for e-cigarettes as a harm-reducing alternative to combusted tobacco. But as a new analysis in the journal Internal and Emergency Medicine notes, those studies paid no attention to the question of whether the diseases were diagnosed before or after the subjects began vaping—a glaring omission when you are trying to figure out whether the associations indicate cause-and-effect relationships.

Sometimes information on the timing of diagnoses was not included in the survey data on which researchers relied. But the Population Assessment of Tobacco and Health (PATH) Survey, which was the basis for some of the studies, does include such information, which the authors conspicuously ignored. In the Internal and Emergency Medicine article, University of Louisville researchers Brad Rodu and Nantaporn Plurphanswat consider those overlooked data and find that the diseases reported by subjects generally predated their first use of vaping products, making a causal interpretation logically impossible.

Rodu and Plurphanswat considered four conditions "strongly associated with smoking" that previous research had suggested are also associated with vaping: chronic obstructive pulmonary disease (COPD), emphysema, myocardial infarction (MI), and stroke. Although the PATH data available to researchers do not specify the precise ages at which the survey respondents began smoking regularly, began vaping, and received their diagnoses, the data do include age ranges that can be used to test the hypothesis that e-cigarette use causes these diseases.

Rodu and Plurphanswat found that diagnoses among subjects that "definitely occurred" after they started smoking regularly accounted for 97 percent of COPD cases, 96 percent of emphysema cases, 98 percent of MIs, and 93 percent of strokes. Subjects who "reported the same age group for first e-cigarette use and first diagnosis" typically "were smoking cigarettes regularly prior to using e-cigarettes," in most cases "decades earlier." That was true for 97 percent of COPD cases, 96 percent of emphysema cases, 99 percent of MIs, and 89 percent of strokes.

"Only 4% of COPD and emphysema cases, 6% of MIs and 11% of stroke had occurred in PATH participants who had used e-cigarettes prior to the diagnoses," Rodu and Plurphanswat report. "In contrast, over 94% of all cases occurred after smoking cigarettes fairly regularly."

Among survey participants who were in the same age range when they were diagnosed and when they first used e-cigarettes, Rodu and Plurphanswat note, "large majorities had smoked cigarettes regularly prior to e-cigarette initiation and only a few never smokers used e-cigarettes," which "indicates a potential reverse association between e-cigarette use and these diseases." In other words, it could be that "having a diagnosis for respiratory and cardiovascular diseases leads smokers to use e-cigarettes."

These findings underline the folly of inferring a causal connection between vaping and disease based on the associations found in cross-sectional studies. "Although the authors of those studies did not make causal claims in the reports," Rodu and Plurphanswat note, "university media releases and subsequent media articles invariably misled the public to believe that e-cigarette use increases risk for diseases."

A University of California, San Francisco, press release about a 2018 study based on the National Health Interview Survey, for example, warned that "use of e-cigarettes every day can nearly double the odds of a heart attack." A 2020 Johns Hopkins press release about two studies based on data from the Behavioral Risk Factor Surveillance System claimed that vaping "increases [the] odds of asthma and COPD."

Those glosses generated predictably alarming press coverage. "Vapers who use e-cigarettes every day are almost TWICE as likely to suffer a heart attack," the Daily Mail said in its story about the 2018 study, which was published by the American Journal of Preventive Medicine. "Vaping Increases Chances for Asthma and COPD," warned the headline above an Everyday Health report on the Johns Hopkins studies, which were published in the same journal and in BMC Pulmonary Medicine.

Those conclusions were quite a leap, since the studies were based on surveys that did not provide data on when respondents were diagnosed or when they started vaping. Peer reviewers evidently did not think that lack of basic information was an important flaw.

For an even more striking example of such incuriosity, consider a study that the Journal of the American Heart Association published in 2019. That study was based on PATH data that did include information about the timing of diagnoses, but the researchers did not make use of it. They nevertheless claimed the results, which indicated that vapers were twice as likely to report heart attacks as subjects who had never smoked or vaped, showed that "e-cigarette use is an independent risk factor for having had a myocardial infarction." A co-author of the study went further in a blog post, saying it provided "more evidence that e-cigs cause heart attacks."

Soon after the study appeared, Rodu and Plurphanswat noted an obvious problem with that conclusion: The heart attacks generally occurred before the subjects started vaping, a point that the study conveniently obscured. The journal eventually conceded the validity of that objection, retracting the study eight months after publishing it.

"During peer review," the American Heart Association reported after looking into what had happened, "the reviewers identified the important question of whether the myocardial infarctions occurred before or after the respondents initiated e‐cigarette use, and requested that the authors use additional data in the PATH codebook (age of first MI and age of first e‐cigarettes use) to address this concern. While the authors did provide some additional analysis, the reviewers and editors did not confirm that the authors had both understood and complied with the request prior to acceptance of the article for publication."

As the study's retraction shows, that was a pretty big oversight. How does this sort of thing happen?

In a commentary that accompanies Rodu and Plurphanswat's Internal and Emergency Medicine article, Italian respiratory specialist Riccardo Polosa and Greek smoking researcher Konstantinos Farsalinos say the failure to consider the temporal relationship between vaping and disease is a "fatal" flaw that should be obvious to reviewers. "The unopposed acceptance of these (low-quality) papers by prestigious journals is symptomatic of a significant dysfunction in scientific publishing, which is distorting the practice of science," they write. "In the context of highly polarized scientific debates (as in e-cigarette research) the peer review process becomes strongly biased for or against a certain narrative."

The bias against e-cigarettes, in turn, shapes public perceptions. Although authoritative sources such as the Food and Drug Administration, the Royal College of Physicians, and the National Academies of Sciences, Engineering, and Medicine acknowledge that vaping is far less hazardous than smoking, surveys find that most Americans believe otherwise.

The controversy about vaping is "sustained by research" that is "often poorly designed, conducted, and interpreted," Polosa and Farsalinos note. "Dissemination of inaccurate information on smoke-free alternatives in the media contributes to public skepticism and uncertainty, particularly among smokers, who as a result are discouraged from adopting reduced-risk lifestyles."