Deficient and Unreliable Studies of Vaping and Disease

 

At least a dozen medical studies over the past few years have found that vaping is associated with heart attack, stroke, hypertension, emphysema and other lung disease, as well as diabetes (see the list at the end of this entry).  The studies are cross-sectional; they are drawn from population samples at one point in time.  They only produce associations, but those are then inflated to imply or outright claim that vaping causes those disease conditions.  The studies appeared in respected medical journals and, together, form a powerful disincentive for smokers to switch to vaping.  They also add fuel to the regulatory fire to suppress vape products, which are actually vastly safer than cigarettes. 

My research group has published a new analysis entitled, “Cross‑sectional e‑cigarette studies are unreliable without timing of exposure and disease diagnosis,” in the journal Internal and Emergency Medicine.

Our analysis shows that the dozen are irrevocably deficient and unreliable.  Some used data from National Health Interview Surveys (NHIS), the Behavioral Risk Factor Surveillance System (BRFSS), or the FDA’s Population Assessment of Tobacco and Health (PATH) surveys, all of which profile participants who smoked and/or vaped and who had ever been diagnosed with numerous diseases.  However, there is absolutely no information in the NHIS or BRFSS about when participants started to smoke or vape, or when they were first diagnosed with a disease. Absent this critical data, it is impossible to demonstrate that smoking or vaping preceded the disease, and therefore had any role in causing it.

While authors of some of the studies tried to use a statistical sleight of hand by claiming that their results were “adjusted” for smoking, that is not a legitimate work-around for the missing cause-and-effect information.

Some studies used PATH data, which does contain all of the information needed to analyze whether smoking and vaping preceded the diseases and therefore might have caused them.  Readers of my blog know that my research group in 2019 used PATH data to demonstrate that a heart attack study published in the flagship journal of the American Heart Association was pure fiction, resulting in its retraction by journal editors.  Now we have analyzed PATH data to demonstrate that none of the vaping-caused-disease claims in the recent studies are valid.

Our design was simple: We started by determining at what age participants were diagnosed with smoking-attributable diseases – chronic obstructive pulmonary disease (COPD), emphysema, myocardial infarction (MI, or heart attack) and stroke.  We then noted when participants started smoking or vaping.  The results were crystal clear.  As we reported in our study, “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. In contrast, over 94% of all cases occurred after smoking cigarettes fairly regularly.” 

In summary, the cited studies’ claims that vaping is related to or causes airway and circulatory diseases are not valid, as the authors lacked or ignored causative pathway information.  As for those few cases in which vaping preceded the disease, we note in our article, this may indicate “a potential reverse association between e-cigarette use and these diseases. In other words, having a diagnosis for respiratory and cardiovascular diseases leads smokers to use e-cigarettes.”

 

   Deficient and Unreliable Studies of Vaping and Disease

   Alzahrani T, Pena I, Temesgen N, Glantz SA (2018).  Association between electronic cigarette use and myocardial infarction.  Am J Prev Med 55(4):455-461. https://pubmed.ncbi.nlm.nih.gov/30166079/   

Vindhyal MR, Okut H, Ablah E, Ndunda PM, Kallail KJ, Choi WS (2020).  Cardiovascular outcomes associated with adult electronic cigarette use.  Cureus 12(8): e9618.  https://pubmed.ncbi.nlm.nih.gov/32923219/ 

Wills TA, Pagano I, Williams RJ, Tam EK (2019).  E-cigarette use and respiratory disorder in an adult sample.  Drug Alc Depend 194:363-370.  https://doi.org/10.1016/j.drugalcdep.2018.10.004 

Osei AD, Mirbolouk M, Orimoloye OA, et al (2019).  Association between e-cigarette use and cardiovascular disease among never and current combustible-cigarette smokers.  Am J Med 132:949-954.  https://doi.org/10.1016/j.amjmed.2019.02.016 

Parekh T, Pemmasani S, Desai R (2020).  Risk of stroke with e-cigarette and combustible cigarette use in young adults.  Am J Prev Med 58(3):446-452.

   Bircan E, Bezirhan U, Porter A, Fagan P, Orloff MS (2021).  Electronic cigarette use and its association with asthma, chronic obstructive pulmonary disease (COPD) and asthma-COPD overlap syndrome among never cigarette smokers.  Tob Ind Dis 19:23. https://doi.org/10.18332/tid/132833 

   Wills TA, Choi K, Pokhrel P, Pagano I (2022).  Tests for confounding with cigarette smoking in the association of e-cigarette use with respiratory disorder: 2020 national-sample data. Prev Med  https://doi.org/10.1016/j.ypmed.2022.107137

Perez MF, Atuegwu N, Mead E, Oncken C, Mortensen EM (2018).  E-cigarette use is associated with emphysema, chronic bronchitis and COPD.  Am J Respir Crit Care Med 197:A6245.  

Zhang Z, Jiao Z, Blaha MJ, et al (2022).  The association between e-cigarette use and prediabetes: results from the Behavioral Risk Factor Surveillance System, 2016-2018.  Am J Prev Med 62(6):872-877.  https://doi.org/10.1016/j.amepre.2021.12.009 

Atuegwu NC, Perez MF, Oncken C, Mead EL, Maheshwari N, Mortensen EM (2019).  E-cigarette use is associated with a self-reported diagnosis of prediabetes in never cigarette smokers: results from the Behavioral Risk Factor Surveillance System Survey.  Drug Alc Depend 205: 107692. doi:10.1016/j.drugalcdep.2019.10769

Miller CR, Shi H, Li D, Goniewicz ML (2021).  Cross-sectional associations of smoking and e-cigarette use with self-reported diagnosed hypertension: findings from Wave 3 of the Population Assessment of Tobacco and Health Study.  Toxics 9:52 https://doi.org/10.3390/toxics9030052 

Osei AD, Mirbolouk M, Orimoloye OA et al. Association between e-cigarette use and chronic obstructive pulmonary disease by smoking status: Behavioral Risk Factor Surveillance System 2016 and 2017.  Am J Prev Med 58, ISSUE 3, P336-342, March 01, 2020.  https://doi.org/10.1016/j.amepre.2019.10.014  

Osei AD, Mirbolouk M, Orimoloye, OA et al. The association between e-cigarette use and asthma among never combustible cigarette smokers: Behavioral Risk Factor Surveillance System (BRFSS) 2016 & 2017. BMC Pulm Med 19, 180 (2019). https://doi.org/10.1186/s12890-019-0950-3

Federal Funds Misspent on Anti-Vaping Research

The Journal of the American Heart Association on February 18 retracted an article by Dharma Bhatta and Stanton Glantz.  As I documented earlier, Bhatta and Glantz published demonstrably false findings.  Details of the retraction were reported by USA Today’s Jayne O’Donnell, Ivan Oransky at Retraction Watch and Alex Norcia of Vice, among others.

The Bhatta-Glantz article states that “This work was supported by grants R01DA043950 from the National Institute on Drug Abuse, P50CA180890 from the National Cancer Institute and the Food and Drug Administration Center for Tobacco Products, U54HL147127 from the National Heart, Lung, and Blood Institute and the Food and Drug Administration Center for Tobacco Products.”  Those grants, itemized below (Source, NIH RePORTER), probably funded additional research beyond the flawed vape heart attack study.

Federal Support of Retracted JAHA Article By Dharma Bhatta and Stanton Glantz
Federal Grant Number	2017	2018	2019	All Years
R01DA043950	$511,397	$526,209	$541,346	$1,578,952
P50CA180890	$3,829,020	$155,362	---	$3,984,382
U54HL147127	---	$4,000,000	$4,000,000	$8,000,000
All	$4,340,417	$4,681,571	$4,541,346	$13,563,334

The $13.6 million are termed “direct costs,” the amount of money Dr. Glantz was awarded to conduct his research.  Each university negotiates an additional payment from NIH for facility and administrative (F&A) costs.  The rate for UCSF during the period was about 59%.  That means the federal government paid UCSF as much as $8 million more, a significant sum.

Still, that $13.6 million was only a fraction of the $51 million funneled from the National Institutes of Health to Glantz since 2005.  That funding supported 292 Glantz articles recorded in PubMed.

The next chart, courtesy of Clive Bates, illustrates Glantz's annual NIH funding since 1985.  Note the significant increase in 2013, which reflects the start of massive transfers from FDA to NIH of hundreds of millions in tobacco company user fees.

This body of taxpayer-supported work, universally anti-tobacco, anti-harm-reduction, is in keeping with the government’s stated objective “to create a world free of tobacco use.”  This prohibitionist mission supports thousands of NIH-funded researchers, and cows countless more into silence when they could be producing life-saving harm reduction data and analyses.

A true public health agenda would include federal support for honest research aimed at prolonging healthy lives, regardless of lifestyle.

Swedish Study: After a Heart Attack, Quitting Tobacco Better Than No Tobacco

A recent study by Gabriel Arefalk and colleagues at the University of Uppsala in Sweden, published in the American Heart Association flagship journal Circulation (abstract here), was purported by the authors, the AHA (here) and the media (here) to show that continuing snus use or smoking after a heart attack (myocardial infarction, MI) is twice as harmful as quitting.   

These conclusions are questionable.  Using the Arefalk numbers, Carl Phillips and I found that snus users, and perhaps even some smokers, are better off than non-users. 

We have submitted a letter to the editor of Circulation, and Carl has the full text of our letter in his CASAA blog post (here).    

The bottom line is that the authors tried to spin the results as suggesting that continuing snus use is dangerous after an MI.  In fact, continuing snus users actually had a lower death rate than people who used neither snus nor cigarettes. 

Whatever is happening in this population, it clearly does not support the simplistic “snus is bad” mantra.  There is a glaringly obvious explanation for why people who quit snus (or smoking) after an MI fare better than those who do not:  Those who are healthy (except for the recent MI, of course) and hope to recover are more likely to take steps to minimize their risks.  After being advised to give up snus, many also get physical therapy, exercise and maintain a healthier diet.  Meanwhile, those who are less healthy may not make changes in an attempt to regain long-term health.  The Arefalk analysis may not have adequately controlled for these confounding factors.

Of course, this would only partially explain the better outcomes of quitters compared to continuing users; it does nothing to explain why all of them (except those who continued to smoke) apparently fared better than non-users.  There are possible explanations for this in the form of statistical artifacts or real effects.  The key observation is that these unreported results do not support the authors’ main interpretation that snus use is dangerous after an MI.

With the publication of this article, peer review appears to have been woefully inadequate.   The prime statistical error we discovered is the key number reported in the first paragraph of the article’s results section.  Reviewers of this study failed to detect the glaring error.

Even without correcting that error or calculating the mortality rate for non-users, the (incorrect) number for the population as a whole the authors reported can still be compared to rates for people who used snus or cigarettes at the time of their MI.  This is enough to raise red flags about the analysis and conclusions, since it is still higher than the rate for those who kept using snus, and far higher than the rates for those who stopped using either product. 

In 2011 Arefalk was lead author on a study making dubious claims about snus use and heart failure.  I described that effort as “neither legitimate nor persuasive until the authors resolve the fundamental questions about the analysis.” (here).

The current article in Circulation is a classic example of anti-tobacco propaganda.  Credible epidemiologic studies do not report risks in exposed groups without reporting the comparable baseline risk among the unexposed.  The authors, and the journal editors and reviewers who enabled them, omitted this critical information.  Our letter to the editor gives them a chance to correct these deficiencies.