Vaping induced severe respiratory disease outbreak: What went wrong?

Vaping products, also commonly called e-cigarettes (EC), were originally developed as alternative tobacco products to deliver nicotine without tobacco smoke. Vaping (EC use) is perceived by some as a substitute for smoking, and thus has potential benefits. However, emerging data show continued increases in vaping among tobacco naïve youth, particularly in the U.S. Vaping has soared in popularity to such an extent that the U.S. Surgeon General has declared [Margin link to Surgeon General’s advisory] it an “epidemic”. Per preliminary statistics from the National Youth Tobacco Survey [margin link to survey] recently released by the CDC, one in four high-school students in the U.S. are current EC users.

Vaping products are engineered to heat a liquid solution so that the aerosol generated (colloquially called “vapor”) can be inhaled by the user. Early vaping products (first generation) were referred to as ‘cig-a-likes’ because they generally resembled a conventional cigarette in size and shape (Figure 1). Second generation devices resemble pens and use more powerful batteries with cartridges (‘tanks’) that can be refilled with liquid. Third generation devices (‘mods’) are larger, refillable, and allow the user to control many features (e.g., device power, heating temperature). The most recent iteration of vaping-products, pod-based devices (like Juul) are smaller, and use disposable or refillable ‘pods’ that contain highly-concentrated nicotine salts.

Figure 1.

Different generations of vaping products.

While ECs have become highly effective in delivering nicotine through inhalation, these devices have also been used to vaporize other psychoactive substances, particularly cannabinoids (e.g. THC and CBD). This raises numerous challenges in interpreting research findings, as many surveys do not specifically assess which substances respondents are currently vaping, whether nicotine-containing solutions or cannabis oils. Further, similar terms are used to refer to nicotine and cannabis vaping products (e.g., “vape pen”, “vaporizer”). Ignoring such crucial details could result in inaccurate estimates, and may result in misattribution of related health outcomes. Additionally, a significant proportion of nicotine-containing EC users, also vape cannabis oils. This raises an important concern as potential respiratory effects associated with co-use of nicotine and cannabinoids are not known.

Although vaping products are likely to be substantially less harmful than combustible products, they are not without harm. The respiratory hazards result from both the physical properties of inhaled aerosols and the chemical effects created by the way in which specific chemicals affect the lung. EC aerosols contain potentially harmful chemicals [margin link to public health consequences of e-cigs], such as acrolein and formaldehyde, cytotoxic flavor chemicals, such as diacetyl and cinnamaldehyde, and ultrafine particles. Nicotine and cannabinoids are pharmacologically active drugs with a wide range of health effects. The inhalation risks of two commonly used nicotine solvents, propylene glycol and vegetable glycerin, are not well characterized, despite their approved use for other purposes. Aerosolized droplets of lipophilic solvents used in cannabis oils (e.g., Vitamin E acetate) can irritate the lung mucosa, the bronchi, and lead to chronic hypoxia. Additionally, concerns have been raised about potential contamination of liquid by phthalates, organophosphate flame retardants, and pesticides for which respiratory safety has not been routinely evaluated.

A literature search identified a very limited number of isolated case reports or abstracts (earliest from 2012[margin link to CHEST paper – ref 4] that proposed a link between EC usage with hospitalization of the subject due to respiratory failure, with a diagnosis of lipoid pneumonia in 3 cases, hypersensitivity and ARDS in 2 instances and 1 individual diagnosed with eosinophilic pneumonia. Fast forward to October, 2019, when a wave of 1080 cases across 48 states and one US territory, with 18 deaths causally linked to vaping, according to the CDC. While it is known that subjects vaped various substances, all other characteristics of products remain to be identified and are likely quite diverse. At this point in the investigation it is not clear if there was consistency in the device, the liquid composition or the range of flavorings in the products used, making it difficult to identify the common denominator.

Overall, some patients initially presented with gastrointestinal symptoms that resolved quickly and preceded the respiratory symptoms which were more sustained and severe or fatal. Other symptoms encompassed a broad spectrum and included fever, tachycardia, tachypnea, hypoxia, serum leukocytosis with neutrophil predominance, elevated serum markers of inflammation, lipid laden macrophages and a diagnosis of a range of pneumonitis. CT scans revealed diffuse infiltrates and ground glass opacity. This symptom profile brings up the unanswered question: are we dealing with a new syndrome or a newly diagnosed syndrome? It is pertinent to note that no concurrent outbreaks have been reported in other countries than the U.S., raising the question: is the true spectrum of the disease yet unrecognized and are we just looking at the tip of the iceberg?

The extreme variability of products used including nicotine, cannabinoids, solvents, potential contaminants, the duration and frequency of vaping all contribute to the uncertainty as to the cause of the recent cluster of cases. It is therefore incumbent on the medical profession going forward, that patients are asked about their history of vaping, and in the event of a hospitalization obtain, if possible for analysis, a sample of the vaping product used. It is also critically important to report all cases to the CDC and state health authorities so that the true extent of the problem can be accurately appreciated. If a single common causative agent can be identified, this would then justify a ban of that ingredient at the state or federal level. As the term ‘vaping’ applies to many substances, often used concurrently, it is important for the health practitioner to ask their patients relevant questions using appropriate terminology. There is also a need for evidence-based guidelines from government and medical societies to assist the clinicians in the event of a patient presenting with potential vaping-associated pulmonary disease. The establishment of a data base that records the true extent of the diversity of vaping products would also facilitate an epidemiological assessment of the magnitude of the problem. Finally, there needs to be a concerted public campaign to educate youth, highlighting the potential dangers associated with vaping.