Physicians Committee Urges CDC To Use Human-Relevant Models in Study of Lung Injuries Associated With Vaping and E-cigarettes
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FROM Physicians Committee
February 2020

Physical differences between human and nonhuman lungs do not allow for a clear line of equivalence to be drawn in these studies, so no direct benefit to human health will be gained.


On Nov. 8, 2019, a telebriefing from the Centers for Disease Control and Prevention (CDC) identified vitamin E acetate as a “potential toxin of concern” in the recent outbreak of lung injuries associated with the use of e-cigarette and vaping products.

During the briefing, Anne Schuchat, MD, Principal Deputy Director of the CDC, expressed that further animal studies should be conducted to determine what other lung injuries may be caused by vitamin E acetate. The Physicians Committee wrote a letter, included below, to Dr. Schuchat to express disappointment in the call for further animal studies to be conducted, as the negative effects of vitamin E acetate inhaled into human lungs are already well documented.

Additionally, the physical differences between human and nonhuman lungs do not allow for a clear line of equivalence to be drawn in these studies, so no direct benefit to human health will be gained. The Physicians Committee encourages the CDC to instead support technologically advanced human-based research methods, such as 3D models of human lungs, to yield relevant information faster.

Instead of testing e-cigarette products on animals, we encourage regulatory agencies to keep dangerous additives or contaminants out of the hands of consumers. The FDA is moving in this direction, thankfully, announcing on Jan. 2, 2020 that it will take action against flavored e-cigarette products that appeal to children, effectively banning all flavors from cartridge-based e-cigarettes other than tobacco or menthol.

December 2, 2019

Anne Schuchat, MD
Principal Deputy Director
Centers for Disease Control and Prevention (CDC)
1600 Clifton Road, Atlanta, GA 30329

Dear Dr. Schuchat: The Physicians Committee for Responsible Medicine (PCRM) is a nationwide nonprofit organization comprised of over 175,000 supporters advocating for efficient, effective and ethical medical practice, nutrition, and research. In CDC's November 8 telebriefing on lung injury associated with vaping, we were disappointed by your recommendations for animal studies of vitamin E acetate and other suspected toxicants. While animal studies are unlikely to yield information that will better protect public health, studies using in vitro and ex vivo methods based on human tissue are especially well-suited to the study of emerging health threats, as they provide more relevant information and require less time to conduct than animal studies.

Differences in respiratory physiology among species present difficulties for extrapolating the results of respiratory toxicology studies in animals to humans. Whether an animal is an obligate nose breather, the structure of the nasal turbinates, respiration rate, etc. influence the size and number of particles reaching the alveoli. For example, rodents are obligate nose breathers with more convoluted nasal passages than humans, potentially resulting in test substances being deposited in the nasal passages before they can cause lung injury.

Fortunately, human tissue-based methods for studying inhalation toxicity are available. Human airway epithelium can be reconstructed from primary cells obtained from donor tissue of healthy or diseased origin which are cultured on porous membranes at the air-liquid interface. Commercially available reconstructed human airway epithelium models contain multiple cell types, including ciliated columnar cells, mucus-producing Goblet cells, and basal cells, and recapitulate key physiological functions. These cultures can extend to weeks and months allowing the observation of both short term events, such as changes in ciliary beat frequency, and long term events, such as Goblet cell hyperplasia. Tissues modeling the small airways and alveolar regions of the lung tissues generate inflammatory cytokine responses.

Other methods are based on precision-cut lung slices from donor tissue obtained in a clinical setting. These cultures contain all lung cell types present in the tissue at the time of slicing while retaining the native architecture of the lung including small airways and respiratory parenchyma. Precision-cut lung slices have been maintained for many weeks and demonstrate both acute changes, including robust cytokine responses and loss of viability, and chronic changes, including activated macrophage staining, collagen deposition, and tissue remodeling. They have also been used to show no effect level and to identify test substance concentration-specific reversibility of inflammatory marker expression – a key element in understanding whether an insult to respiratory tissue may persist or resolve after test article removal.

We urge CDC to support and conduct studies using human-based tissue to study the effects of vitamin E acetate and other inhaled toxicants.


Joseph Manuppello
Senior Research Analyst
Physicians Committee for Responsible Medicine
5100 Wisconsin Ave., NW, Suite 400, Washington, DC 20016

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