- Italian researchers argue that a recent meta-analysis overstated the evidence linking vaping to COPD.
- They say most studies failed to adjust properly for smoking history – the main cause of COPD.
- The critics highlight “reverse causation,” where people with COPD may take up vaping after diagnosis.
- They call for future research to rely on longitudinal data and avoid misleading cross-sectional designs.
A meta-analysis that claimed vape users face a higher risk of chronic obstructive pulmonary disease (COPD) is under fire from respiratory researchers who say the study’s methods are flawed and its conclusions misleading.
The original review by Shabil et al. pooled 17 observational studies and concluded that both current and former vape use were associated with increased COPD risk.
But in a sharply worded response, three Italian academics argue that the findings are based on “critical methodological and conceptual flaws” that risk confusing harm reduction with harm creation.
In their letter, Lucia Spicuzza, Francesco Pennisi and Giulio Geraci, from the University of Catania, say the analysis failed to properly control for cigarette smoking, which is “the predominant cause of COPD.”
They argue that most vape users are current or former smokers, making it “highly likely” that any association between vaping and COPD “reflects the effects of combustible cigarette use rather than e-cigarette use per se.”
Smoking confounding and missing comparisons
The authors note that few of the included studies adjusted for key smoking variables such as pack-years (a measure combining how much and how long someone has smoked), age of smoking initiation or years since quitting. These are all critical factors in COPD risk. They also criticise the lack of a direct comparison between vape users and cigarette smokers.
“Without benchmarking the risk of e-cigarette use against that of cigarette smoking, the analysis cannot inform in a meaningful or balanced way,” they write.
Reverse causation and study design problems
Another major flaw, the authors argue, is a lack of data on when participants developed COPD relative to when they began vaping. They cite previous research showing that cross-sectional studies, which measure exposure and disease at the same time, can create false associations if people with pre-existing COPD switch to vapes after diagnosis.
“This reverse causation produces a spurious association in which e-cigarette use appears linked to COPD, when in fact COPD preceded the exposure,” they note, citing work by Rodu and Plurphanswat.
Crucially, the Italian team highlights that the meta-analysis itself reported a smaller, statistically insignificant association in longitudinal cohort studies compared to cross-sectional ones. “This is a crucial finding,” they write, because cohort studies better establish cause and effect.
Implausible results and inconsistent definitions
The authors also flag what they call “biologically implausible” results. The meta-analysis reported a higher odds ratio for former vape users than for current users. This is the opposite of what would be expected if vaping caused COPD.
“This pattern is entirely consistent with residual confounding by cigarette smoking,” they argue, since many former vapers may have returned to smoking or never quit cigarettes completely.
Further issues include overlapping datasets, which can lead to double-counting participants, and inconsistent definitions of what constitutes current, former, or ever use. Many studies relied on self-reported COPD diagnoses, introducing recall bias and potential misclassification.
“The review also omits a detailed risk-of-bias assessment,” the authors write, calling such an omission “a serious weakness given the well-documented shortcomings in this field.”
No evidence of risk among never-smokers
Spicuzza and colleagues point out that among people who have never smoked, there is no evidence that vape use increases COPD risk. They cite a 2025 systematic review by Caci et al., which found no significant respiratory effects in never-smokers who vape.
They also note that an “umbrella review” – considered the highest level of evidence – found no short- or medium-term changes in respiratory function for any pattern of vape use.
‘Misleading’ causal claims
In their conclusion, the authors warn against drawing strong conclusions from such flawed evidence. “Residual confounding, reverse causation, biologically implausible patterns, and data overlap substantially weaken the reported associations,” they write.
“At most, it shows that many COPD patients have used e-cigarettes – a finding more plausibly explained by smoking history and switching behaviour than by e-cigarette harms.” Drawing causal conclusions from such data, they add, “is akin to claiming nicotine replacement therapy causes COPD because many patients have used it.”
The authors call for greater methodological integrity in future research and more cautious interpretation of results. They urge researchers to focus on longitudinal data, explicitly control for confounding factors, and avoid over-interpreting associations.
The correspondence, “Reassessing the link between e-cigarette use and COPD: addressing critical methodological and conceptual flaws,” is published open access in npj Primary Care Respiratory Medicine.
