CDC Responds to Suspected E-cigarette-Related Death, Offering Three Key Recommendations

On September 4, news emerged that the Centers for Disease Control and Prevention (CDC) in the United States recently released a statement regarding a case in Illinois involving a suspected e-cigarette product that led to a respiratory disease death. Below is the full statement:
 
The CDC provides: 1) background information on e-cigarette product forms, 2) characteristics of patients with severe lung disease related to e-cigarette product use (devices, liquids, refill containers, and cartridges), and 3) clinical features of patients with severe lung disease. This health advisory also offers recommendations for clinicians, public health officials, and the public based on currently available information.

General Background

E-cigarettes typically contain nicotine, most also contain flavorings and other chemicals, and some may contain cannabis or other substances. They are known by many different names and come in many shapes, sizes, and types of devices. Devices can be referred to as "e-cigarettes," "vapes," "e-hookahs," "vape pens," "mods," or electronic nicotine delivery systems (ENDS). Some e-cigarette devices resemble other tobacco products, such as cigarettes; some resemble ordinary household items, such as USB flash drives, pens, and flashlights; and others have unique shapes. The use of e-cigarettes is sometimes referred to as "vaping" or "juuling."

E-cigarettes may contain harmful or potentially harmful substances, including nicotine, heavy metals (such as lead), volatile organic compounds, and carcinogenic chemicals. Additionally, some e-cigarette products are used to deliver illegal substances; they can be obtained from unknown or unauthorized (i.e., "street") sources; and they can be modified for potential uses that may increase harm to users. For example, some disposable e-cigarette cartridges or pods can be refilled with illegal or unknown substances. Additionally, some e-cigarette products are used for "dripping" or "dabbing." Dripping involves placing e-liquid directly onto the heating coil of the e-cigarette, which can lead to high concentrations of compounds (e.g., tetrahydrocannabinol [THC] and cannabinoid compounds).

Adolescents, young adults, pregnant women, and adults who currently do not use tobacco products should not use e-cigarettes. E-cigarettes containing nicotine have the potential to help some adult smokers reduce their use of combustible cigarettes and transition. However, e-cigarettes have not yet been approved by the U.S. Food and Drug Administration (FDA) as smoking cessation aids, and existing science has not determined whether e-cigarettes are effective for quitting smoking.

Outbreak Background

As of August 27, 2019, 215 possible cases have been reported across 25 states, with additional reports of lung disease under investigation. One patient (from Illinois) had a recent history of e-cigarette use, was hospitalized for severe lung disease, and subsequently died. Although the cause of e-cigarette-related lung disease has not been determined, epidemiological investigations in affected states are ongoing to better describe patients' exposures, demographics, clinical and laboratory characteristics, and behaviors. All patients reported using e-cigarette products. The exact number is currently unclear, but many patients reported using e-cigarettes containing cannabinoid products (such as THC or CBD).

According to reports from several states, patients presented with respiratory symptoms (cough, shortness of breath, or chest pain), with some also experiencing gastrointestinal symptoms (nausea, vomiting, or diarrhea) or nonspecific systemic symptoms (fatigue, fever, or weight loss). Symptoms typically developed within days but can sometimes last for weeks. Gastrointestinal symptoms may sometimes occur alongside respiratory symptoms. Fever, tachycardia, and elevated white blood cell counts have been reported in the absence of identifiable infectious diseases. Many patients had sought initial care in outpatient settings before hospitalization, with some patients having multiple visits.

Radiological findings varied and were not present in all patients at initial presentation. Bilateral pulmonary infiltrates and diffuse ground-glass opacities have been reported. Many patients required supplemental oxygen, some required assisted ventilation and oxygenation, and some required intubation. Some patients have received corticosteroid treatment and have shown improvement. Standalone antimicrobial treatment has not always been associated with clinical improvement. Many patients have completed evaluations for infectious etiologies, but no definitive infectious cause has been identified.

Several patients from one state were diagnosed with lipoid pneumonia based on clinical presentation, and specific staining for lipids was detected in bronchoalveolar lavage samples.

All patients reported using e-cigarette products, with the onset of symptoms ranging from days to weeks after e-cigarette use. In two states, many patients had recently inhaled cannabinoid products, THC or CBD. So far, no single substance or e-cigarette product has consistently been associated with the illness. The CDC is working closely with state health departments to facilitate the collection of product samples for testing at the FDA's forensic chemistry center in the U.S.

Recommendations for Clinicians

Report cases of severe lung disease with unknown causes and a history of e-cigarette product use to your state or local health department within the past 90 days. Reporting cases may assist the CDC and state health departments in determining the causes of these lung diseases.

Ask all patients who reported e-cigarette product use in the past 90 days about signs and symptoms of lung disease.

If you suspect that the use of e-cigarette products may be the cause of a patient's severe lung disease, inquire about the following:

Substances used: nicotine, cannabinoids (e.g., cannabis, THC, THC concentrates, CBD, CBD oil, synthetic cannabinoids [e.g., K2 or spice], hash oil, Dank vapes), flavorings, or other substances

Source of substances: commercially available liquids (i.e., bottles, cartridges, or pods), homemade liquids, and reuse of old cartridges or pods with homemade or commercially purchased liquids

Devices used: manufacturer; brand; product name; model; serial number of the product, device, or e-liquid; whether the device can be customized by the user; and any modifications made by the user (e.g., exposure of the atomizer or heating coil)

Methods of product use

Methods of substance use: vaping, dripping, or dabbing

Other potential cases: sharing e-cigarette products (devices, liquids, refill containers, or cartridges) with others

Determine if any remaining products (including devices and liquids) are available for testing. Coordination with local or state health departments for testing may be possible.

Consider reporting all possible causes of illness for patients with respiratory and gastrointestinal symptoms and a history of e-cigarette product use. Assess and treat other possible causes of illness (e.g., infectious diseases, rheumatological conditions, tumors) based on clinical indications. Consider consulting specialists (pulmonology, infectious diseases, critical care, medical toxicology) as appropriate.

Clinical improvement has been reported in patients with severe lung disease related to e-cigarette use who have been treated with corticosteroids. The decision to use corticosteroids should be made on a case-by-case basis, weighing risks and benefits and the likelihood of other etiologies.

Testing for lipid-laden alveolar macrophages obtained through bronchoalveolar lavage (BAL) has been reported in association with lipoid pneumonia related to the inhalation of lipids from e-cigarette aerosol. The decision to perform BAL should be based on individual clinical circumstances.

Some patients have undergone lung biopsies. If lung biopsies are obtained, lipid staining should be considered during pathological examination, preferably on fresh tissue. Routine pathological processing (including formalin fixation and paraffin embedding) can remove lipids. Routine tissue processing and histopathological evaluation remain important. Consider consulting pulmonary medicine and pathology experts to assist in any evaluation plans.

Patients who have received treatment for severe lung disease related to e-cigarette use should undergo follow-up evaluations as clinically indicated to monitor lung function.

Recommendations for Public Health Officials

State public health officials should promptly notify the CDC of possible cases via VapingAssocIllness@cdc.gov.

For case classification criteria, reporting guidelines, case investigation forms, and questions regarding this outbreak, please contact the CDC via VapingAssocIllness@cdc.gov.

Consider using existing data sources for case discovery activities (e.g., local poison control centers, medical examiner and coroner offices, and other applicable monitoring systems, including syndrome monitoring). The CDC has developed two effective syndrome monitoring definitions (one with specific symptoms and another focusing on e-cigarette product use). The CDC will program these definitions into the BioSense / ESSENCE platform of the CDC's national syndrome monitoring program for case discovery within the platform.

Consider encouraging medical examiners or coroner offices and other pathologists to report possible cases, especially those with no other possible diagnoses. If individuals exhibit signs of severe lung disease as described above after death or autopsy, medical examiners and coroners are encouraged to report cases to local or state health departments. Thorough sampling of the trachea, bronchi, and lung parenchyma is recommended, collecting fresh lung tissue for lipid staining (e.g., oil red O), and providing formalin-fixed, paraffin-embedded tissue for routine histopathological examination. For further consultation, public health officials can contact the CDC's Infectious Disease Pathology Division via pathology@cdc.gov.

State health department officials seeking epidemiological investigation technical assistance can contact the CDC via VapingAssocIllness@cdc.gov. State health department officials seeking laboratory testing technical assistance can discuss with state health department laboratories or contact the CDC via VapingAssocIllness@cdc.gov.

Recommendations for the Public

Although this investigation is ongoing, if you are concerned about these specific health risks, consider avoiding the use of e-cigarette products.

Regardless of the ongoing investigation, anyone using e-cigarette products should not purchase these products on the street (e.g., e-cigarette products containing THC or other cannabinoids), should not modify e-cigarette products, or add any substances to these products that are not intended by the manufacturer.

Regardless of the ongoing investigation, adolescents, young adults, pregnant women, and adults who currently do not use tobacco products should not use e-cigarette products. If you use e-cigarette products, monitor your symptoms (such as cough, shortness of breath, chest pain), and if you have health concerns, seek medical attention immediately. As more information becomes available, the CDC and FDA will continue to provide advice and warnings to the public.

Adult smokers trying to quit should use evidence-based treatments, including counseling and FDA-approved medications. If you need help quitting tobacco products, including e-cigarettes, please contact your doctor.

If you are concerned about the harmful effects of e-cigarette products, please call your local poison control center: 1-800-222-1222.

We encourage the public to submit detailed reports of any unexpected tobacco or e-cigarette-related health or product issues through the FDA's online safety reporting portal.