Lung Injury From Vaping: What We Know

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History

The term “vaping” refers to the use of various devices and techniques to produce an inhaled vapor from a liquid (usually oil) which serves as the delivery vehicle for a large variety of substances, commonly nicotine, tetrahydrocannabinol (THC), or other herbs and flavors that can be vaporized. This activity is mentioned by the Roman statesman Cicero in reference to Herodotus, a Greek writer who used the technique circa 450 B.C. Egyptian hieroglyphics describe the use of hot rocks to vaporize herbs as early as the fifth century B.C., and devices such as shishas and hookahs have been in use in Afghanistan, India, and the Middle East for centuries.

The modern use of vaporizing devices was heralded by Joseph Robinson in 1927, who envisioned a “smokeless tobacco cigarette”, but he never capitalized on his design. In 1965, Herbert Gilbert patented an e-cigarette prototype, similar to those in use today. A Chinese pharmaceutical company began manufacturing such a device in 2005, and began marketing it in the United States in 2007.

Use

Generally, currently used devices consist of a battery which heats a liquid-filled cartridge and aerosolizes any of large variety of solubilized agents, including nicotine, tetrahydrocannabinol (THC), and cherry, cinnamon, mint and menthol flavors. Few analyses of these vapors have been undertaken (the FDA does not regulate these agents), but propylene glycol, liquid glycerin, acrolein, formaldehyde and diacetyl  (2,3 butanedione) have been found in commercial brands; this last agent is of particular concern, as it has been identified as the causative agent in the development of “popcorn lung”, a particularly aggressive form of bronchiolitis obliterans observed in factory workers exposed to high concentrations of diacetyl used as a flavoring  in production of microwave popcorn.

Potential Benefits

There is ongoing controversy regarding the use of e-cigarettes, with proponents arguing that their use is likely to be an important harm-reduction technique in tobacco cessation programs, especially when the vapor includes nicotine. This concept is particularly in favor in Canada, New Zealand, and Great Britain, where hospitalized smokers are allowed to use e-cigarettes in hospital. A study published in the New England Journal of Medicine (NEJM) in February of this year described a randomized trial of 886 adults assigned to a smoking cessation program which included nicotine replacement by means of nicotine-based e-cigarettes, versus other means of nicotine replacement. The 1-year abstinence rate was validated biochemically at the last visit; 18% of the e-cigarette group were abstinent, versus 9.9% of those using other nicotine products. Public Health England, an executive agency of Public Health and Social Care of the United Kingdom has posited in the British Medical Journal that “e-cigarettes are 95% safer than smoking”.

E-cigarrete/Vaping Associated Lung Injury (EVALI)

In mid-summer of 2019, the Illinois and Wisconsin health authorities initiated a coordinated investigation into an apparent cluster of cases of severe lung injury in young healthy persons who reported recent e-cigarette use, and who presented with dyspnea, cough, pulmonary infiltrates, and for which there was no evidence of infection or other cause for the findings. In collaboration with CDC, these observations were published in the September 6 issue of the NEJM, which described 53 cases: median age was 19, 83% were male, and all presented with bilateral pulmonary infiltrates, respiratory complaints, and constitutional symptoms. Of these, 94% were hospitalized, 32% required intubation, and one died. A total of 84% reported recent use of THC via vaping. CDC has since been receiving new case reports from 49 states and the District of Columbia, totaling 1,604 as of October 22, 2019 with 34 deaths, some of whom had used THC products exclusively.

Clinical Features

Symptoms at presentation have included dyspnea, chest pain, cough, nausea and vomiting, hemoptysis, subjective fever, and fatigue. Vital signs demonstrated tachycardia, tachypnea, and hypoxemia.  Median duration of symptoms prior to admission was 6 days. Laboratory findings included leukocytosis, elevated erythrocyte sedimentation rate, and normal procalcitonin levels. All have had bilateral infiltrates, either on chest radiographs or CT scans. Glucocorticoid therapy was administered in 92%; 65% were thought to have improved with glucocorticoid therapy. Lung biopsies were available in 17; findings included acute fibrinous pneumonitis, diffuse alveolar damage, and organizing pneumonia, usually with bronchiolitis. Foamy macrophages and pneumocyte vacuolization were present in all. None of the biopsies demonstrated findings of lipoid pneumonia, which previously had been raised as a possibility.

CDC Recommendations for Case Identification

Confirmed case:

  1. Use of vaping within 90 days before symptoms
  2. Bilateral pulmonary infiltrates
  3. Absence of pulmonary infection (negative viral panel, urine antigen for S. pneumonia and Legionella, negative PCR for influenza, and negative sputum culture or broncholalveolar lavage if done).
  4. No underlying condition which is plausible as an etiology (cardiac, rheumatologic, neoplastic).

Probable case:

  1. Use of vaping within 90 days before symptoms
  2. Bilateral pulmonary infiltrates
  3. Clinical team finds no plausible alternative diagnosis     

Potential Causative Agents:

THC is the most common exposure identified in the available reports when a single agent was used (80 %), but many cases involved the use of 2 or more agents, such as nicotine and THC together. Since the makeup of many of the commercial liquids is unknown, there may be products in the carrier liquids that need further study. Declared components in nicotine-based vaping agents include propylene glycol and glycerin as well as nicotine. When commercial vaping products have been analyzed, contaminants identified have included nitrosamines, toxic metals, and aromatic hydrocarbons. The flavoring compounds  2,3 pentanedione and diacetyl are of particular interest (as noted above, diacetyl has been identified as the cause of “popcorn lung”, in which the pathologic findings of bronchiolitis obliterens have been similar to those in the few available biopsies in EVALI patients).

Current CDC Recommendations:

  1. As products containing THC, especially when obtained off the street or from family and friends are linked to a majority of reported EVALI cases, persons should not use e-cigarettes obtained in that manner.
  2. Persons should not add any substances to a commercially-purchased e-cigarette.
  3. Although only a small percentage of patients with EVALI reported use of only nicotine in their vaping, CDC recommends not using nicotine-containing e-cigarettes.
  4. CDC recommends that youths, young adults, and pregnant women not vape.
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