The diacetyl-to-popcorn-lung link is real, but it comes from factory workers, not vapers. Bronchiolitis obliterans became known as "popcorn lung" after cases in microwave popcorn manufacturing plants, and the CDC subsequently identified seven additional cases in workers at a flavoring manufacturing company.

Around the year 2000 a group of popcorn factory workers in the USA developed the condition after breathing in diacetyl used as a popcorn flavouring, and this was not related to e-cigarette use.

Diacetyl has been measured in e-liquids. In a sample of 51 flavours, diacetyl was detected above the laboratory limit of detection in 39 products, ranging up to 239 μg per e-cigarette, while 2,3-pentanedione and acetoin were detected in 23 and 46 flavours respectively. The authors' own conclusion was a call for further evaluation, not a finding of disease: "urgent action is recommended to further evaluate this potentially widespread exposure via flavored e-cigarettes." The accompanying journal commentary noted the finding was preliminary in health terms: new findings suggested diacetyl could be widespread in e-juice, but it was too soon to say how that might translate into human health effects.

No confirmed case of popcorn lung has been attributed to e-cigarettes by UK health authorities. Cancer Research UK states there have been no confirmed cases of popcorn lung linked to e-cigarettes, and that some e-cigarette liquids used to contain diacetyl.

It further notes that in the UK diacetyl was banned in e-cigarettes and e-liquids under the EU Tobacco Products Directive in 2016, so legal UK e-liquids are not allowed to contain it.

A UK parliamentary document records that the NHS website states vaping does not cause "popcorn lung," describing the disease as one found in factory workers exposed to diacetyl, and cites Cancer Research UK's conclusion that there have been no confirmed cases.

Health Canada, the New Zealand Ministry of Health and the UK Health Security Agency have similarly clarified that no evidence exists for such a link.

There are, however, a small number of published case reports of bronchiolitis-type injury in vapers. The CMAJ 2019 report described a 17-year-old male who presented with intractable cough, progressive dyspnea and malaise after intensively vaping flavoured e-liquids and tetrahydrocannabinol. Commentary on that case was explicitly cautious: the clinical features indicated a form of bronchiolitis, "possibly bronchiolitis obliterans," a pathology not previously described with e-cigarette use but long considered a likely consequence, and the case "may represent" the first direct evidence of that disease resulting from e-cigarette use. A 2022 case series found structural small airway damage: imaging in two patients showed small airway-centered fibrosis with bronchiolar narrowing and lumen irregularities, and the predominant histopathologic feature on surgical lung biopsy was small airway-centered fibrosis including constrictive bronchiolitis , in four patients with chronic lung disease associated with e-cigarette use .

Exposure dose is contested. A published comment noted that diacetyl and 2,3-pentanedione occur in mainstream cigarette smoke at levels hundreds of thousands of times higher than occupational exposure limits, yet cigarette smoking is not associated with "popcorn lung," and that diketone exposures from traditional cigarettes are higher than those from e-cigarettes.

Farsalinos similarly stated that cigarette smoke contains diacetyl and acetyl propionyl at levels on average 100 and 10 times higher than in the e-liquid samples tested.