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CDC: 5 deaths, more than 450 cases of pulmonary disease possibly linked to vaping

CDC has announced that more than 450 possible cases of pulmonary disease associated with e-cigarette use, including five confirmed deaths, have been reported in 33 states and one U.S. territory.

During a telebriefing on Sept. 6, CDC also provided further information about the investigation as well as details of an outbreak of lipoid pneumonia associated with vaping in North Carolina.

As Healio Pulmonology previously reported, CDC, FDA and state and local health departments are conducting a joint investigation of these cases. Currently, all possible and confirmed cases presented with similar symptoms, such as shortness of breath, fatigue, fever and nausea or vomiting, and all reported use of e-cigarette products, or vaping, in the 90 days before presentation. Many also reported use of tetrayhydrocannabinol (THC)-containing products; however, no specific substance or product has been linked to the disease and it remains unclear whether the rash of respiratory illnesses are the same disease or different diseases with similar presentations.

On Sept. 5, the New York State Department of Health shared findings from recent testing of samples of products used by some patients in these cases. In a press release, the agency stated that very high levels of vitamin E acetate were found in nearly all cannabis-containing samples analyzed by the Wadsworth Center as part of its investigation into the state’s cases of pulmonary disease possibly linked to vaping, noting that at least one vitamin E acetate-containing vape product has been linked to each patient who submitted a product for testing. The agency also stated that vitamin E acetate is not an approved additive for vape products authorized by the New York State Medical Marijuana Program and that vitamin E acetate was not present in the nicotine-based products that were tested.

During the CDC telebriefing, however, Dana Meaney-Delman, MD, MPH, incident manager for CDC 2019 Lung Injury Response, emphasized that CDC and the FDA have not yet confirmed that any one exposure is responsible for all cases.

“Based on clinical and laboratory evidence to date, we believe a chemical exposure is likely associated with these illnesses. However — and I want to really stress this — more information is needed to determine which specific product or substances are involved. We’re aware that some labs have identified vitamin E acetate in product samples and we’ve connected those laboratories with the FDA forensic laboratories to compare results. At this time, no one device, product or substance has been linked to all cases and continued investigation is needed to better understand if a true relationship exists between any specific product or substance and the illnesses we’re observing in patients. And to find the answer, we need to combine the information about e-cigarette use, the product sample testing and the clinical information from patients,” she said.

Report from Illinois, Wisconsin

In a preliminary report published in The New England Journal of Medicine (NEJM), Jennifer E. Layden, MD, PhD, CMO and state epidemiologist at the Illinois Department of Public Health, Jonathan Meiman, MD, CMO at the Wisconsin Department of Health Services, and colleagues provided details on 53 probable or confirmed cases in Illinois and Wisconsin — the two states that currently have the largest cohort of patients.

Using an interim case definition, the researchers considered patients to have a respiratory illness associated with vaping if they reported use of e-cigarette devices and related products in the 90 days before symptom onset, if their illnesses were not attributable to other causes and if pulmonary infiltrates were present on imaging.

Of the 53 patients included in the case series, 83% were boys or men and the median age was 19 years. All patients presented with constitutional symptoms, such as fever, fatigue or weight loss, 98% had respiratory symptoms, including shortness of breath, and 81% reported gastrointestinal symptoms, such as nausea or vomiting. In keeping with the case definition, all patients had bilateral infiltrates on chest imaging. Patients reported use of a wide variety of products and devices, but a majority (84%) reported use of THC products in e-cigarettes.

Of these patients, 94% were hospitalized and 32% underwent intubation and mechanical ventilation. Ninety-two percent of patients received IV or oral systemic glucocorticoids during admission, all of whom were treated for at least 7 days, and 65% had improvement in respiratory symptoms documented in their medical records.

“As far as treatments received, the vast majority did get antibiotics at some point, either during the hospitalization or sometimes before hospitalization, and the vast majority also received steroids...Although clinical improvement was observed on steroids, we can’t say with certainty that this was an effective treatment in this case,” Meiman said during the CDC telebriefing.

He also noted that many patients who were started on steroids continued to receive them as an outpatient after discharge, but whether the respiratory illness will have long term effects requires further investigation.

A major question that has been raised throughout the investigation is whether this outbreak of cases represents a true increase in vaping-associated pulmonary disease or whether it is a hallmark of increased recognition among physicians. This question may be, in part, answered by syndromic surveillance data from Illinois in the NEJM report showing that the mean monthly rate of visits related to severe pulmonary disease in June through August this year was twice that observed during the same time period in 2018, according to Layden. However, she noted that the findings are still preliminary.

Outbreak of lipoid pneumonia

In addition to the information on the Illinois and Wisconsin cases published in NEJM, a report published in MMWR provided details on an outbreak of acute lipoid pneumonia associated with e-cigarette use in North Carolina.

During July and August, clinicians identified five patients aged 18 to 35 years who experienced several days of worsening dyspnea, nausea, vomiting, abdominal discomfort and fever. Patients also demonstrated tachypnea, hypoxemia and bilateral lung infiltrates on chest X-ray. Use of e-cigarettes with refillable chambers or interchangeable cartridges with THC vaping concentrates or oils — all purchased on the street — was reported by all patients. Three patients also reported use of nicotine-containing e-cigarettes and two reported smoking marijuana or conventional cigarettes. All patients required hospitalization for hypoxemic respiratory failure, three required intensive care and one required intubation and mechanical ventilation. All survived, according to the MMWR report.

Tests suggested the disease did not have an infectious cause, and a diagnosis of acute exogenous lipoid pneumonia was made based on clinical history, radiography and lab and bronchoscopic diagnostics. Patients were then treated with IV methylprednisone and discharged on a taper of oral prednisone.

“One potential explanation for acute lipoid pneumonia among these patients is that aerosolized oils inhaled from e-cigarettes deposited within their distal airways and alveoli, inciting a local inflammatory response that impaired vital gas exchange,” the researchers wrote. “Lipoid pneumonia has long been described from aspiration of oil into the lungs and has been associated with e-cigarette use in some case reports.”

During the telebriefing, Daniel Fox, MD, from the department of pulmonary and critical care medicine at WakeMed Health and Hospitals in North Carolina, also noted that lipoid pneumonia is a rare diagnosis that is probably underrecognized across all populations.

Moving forward

Until its joint investigation with the FDA and state and local health departments has concluded, CDC recommends that people consider not using e-cigarettes and strongly advises against using products or substances bought on the street or modifying their e-cigarette to use products or substances not intended for use by the device’s manufacturer, Meaney-Delman said.

The CDC also issued a Health Alert Network Health Advisory last week with recommendations for clinicians, public health officials and patients.

Mitch Zeller, JD, director of Center for Tobacco Products at the FDA, stated that more than 120 samples of products submitted by state health departments to the FDA are being analyzed for the presence of a broad range of chemicals, including nicotine, THC, other cannabinoids, cutting agents, dilutants, additives, pesticides, poisons and toxins.

He noted that officials are at a “critical fact-gathering stage” and encouraged the public to submit detailed reports of any unexpected tobacco or e-cigarette-related health or product issues to FDA through their online safety reporting portal: www.safetyreporting.hhs.gov.

“The FDA is going to leave no stone unturned in following any potential leads regarding any particular constituent or compound that may be at issue and we’re committed to taking appropriate actions as the facts emerge,” Zeller said during the telebriefing.

Healio Pulmonology is closely monitoring this story and will update the article as new information becomes available. – by Melissa Foster

Reference:

Christiani DC. N Engl J Med. 2019;doi:10.1056/NEJMe1912032.

Davidson K, et al. MMWR Morbid Mortal Wkly Rep. 2019;doi:10.15585/mmwr.mm6836e1.

Layden JE, et al. N Engl J Med. 2019;doi:10.1056/NEJMoa1911614.

Schier JG, et al. MMWR Morbid Mortal Wkly Rep. 2019;doi:10.15585/mmwr.mm6836e2.

Disclosures: Authors for the NEJM and MMWR publications report no relevant financial disclosures.

Editor's note: This story was updated on Sept. 11 to include new information from CDC on the number of confirmed deaths possibly related to e-cigarette use.

CDC has announced that more than 450 possible cases of pulmonary disease associated with e-cigarette use, including five confirmed deaths, have been reported in 33 states and one U.S. territory.

During a telebriefing on Sept. 6, CDC also provided further information about the investigation as well as details of an outbreak of lipoid pneumonia associated with vaping in North Carolina.

As Healio Pulmonology previously reported, CDC, FDA and state and local health departments are conducting a joint investigation of these cases. Currently, all possible and confirmed cases presented with similar symptoms, such as shortness of breath, fatigue, fever and nausea or vomiting, and all reported use of e-cigarette products, or vaping, in the 90 days before presentation. Many also reported use of tetrayhydrocannabinol (THC)-containing products; however, no specific substance or product has been linked to the disease and it remains unclear whether the rash of respiratory illnesses are the same disease or different diseases with similar presentations.

On Sept. 5, the New York State Department of Health shared findings from recent testing of samples of products used by some patients in these cases. In a press release, the agency stated that very high levels of vitamin E acetate were found in nearly all cannabis-containing samples analyzed by the Wadsworth Center as part of its investigation into the state’s cases of pulmonary disease possibly linked to vaping, noting that at least one vitamin E acetate-containing vape product has been linked to each patient who submitted a product for testing. The agency also stated that vitamin E acetate is not an approved additive for vape products authorized by the New York State Medical Marijuana Program and that vitamin E acetate was not present in the nicotine-based products that were tested.

During the CDC telebriefing, however, Dana Meaney-Delman, MD, MPH, incident manager for CDC 2019 Lung Injury Response, emphasized that CDC and the FDA have not yet confirmed that any one exposure is responsible for all cases.

“Based on clinical and laboratory evidence to date, we believe a chemical exposure is likely associated with these illnesses. However — and I want to really stress this — more information is needed to determine which specific product or substances are involved. We’re aware that some labs have identified vitamin E acetate in product samples and we’ve connected those laboratories with the FDA forensic laboratories to compare results. At this time, no one device, product or substance has been linked to all cases and continued investigation is needed to better understand if a true relationship exists between any specific product or substance and the illnesses we’re observing in patients. And to find the answer, we need to combine the information about e-cigarette use, the product sample testing and the clinical information from patients,” she said.

PAGE BREAK

Report from Illinois, Wisconsin

In a preliminary report published in The New England Journal of Medicine (NEJM), Jennifer E. Layden, MD, PhD, CMO and state epidemiologist at the Illinois Department of Public Health, Jonathan Meiman, MD, CMO at the Wisconsin Department of Health Services, and colleagues provided details on 53 probable or confirmed cases in Illinois and Wisconsin — the two states that currently have the largest cohort of patients.

Using an interim case definition, the researchers considered patients to have a respiratory illness associated with vaping if they reported use of e-cigarette devices and related products in the 90 days before symptom onset, if their illnesses were not attributable to other causes and if pulmonary infiltrates were present on imaging.

Of the 53 patients included in the case series, 83% were boys or men and the median age was 19 years. All patients presented with constitutional symptoms, such as fever, fatigue or weight loss, 98% had respiratory symptoms, including shortness of breath, and 81% reported gastrointestinal symptoms, such as nausea or vomiting. In keeping with the case definition, all patients had bilateral infiltrates on chest imaging. Patients reported use of a wide variety of products and devices, but a majority (84%) reported use of THC products in e-cigarettes.

Of these patients, 94% were hospitalized and 32% underwent intubation and mechanical ventilation. Ninety-two percent of patients received IV or oral systemic glucocorticoids during admission, all of whom were treated for at least 7 days, and 65% had improvement in respiratory symptoms documented in their medical records.

“As far as treatments received, the vast majority did get antibiotics at some point, either during the hospitalization or sometimes before hospitalization, and the vast majority also received steroids...Although clinical improvement was observed on steroids, we can’t say with certainty that this was an effective treatment in this case,” Meiman said during the CDC telebriefing.

He also noted that many patients who were started on steroids continued to receive them as an outpatient after discharge, but whether the respiratory illness will have long term effects requires further investigation.

A major question that has been raised throughout the investigation is whether this outbreak of cases represents a true increase in vaping-associated pulmonary disease or whether it is a hallmark of increased recognition among physicians. This question may be, in part, answered by syndromic surveillance data from Illinois in the NEJM report showing that the mean monthly rate of visits related to severe pulmonary disease in June through August this year was twice that observed during the same time period in 2018, according to Layden. However, she noted that the findings are still preliminary.

PAGE BREAK

Outbreak of lipoid pneumonia

In addition to the information on the Illinois and Wisconsin cases published in NEJM, a report published in MMWR provided details on an outbreak of acute lipoid pneumonia associated with e-cigarette use in North Carolina.

During July and August, clinicians identified five patients aged 18 to 35 years who experienced several days of worsening dyspnea, nausea, vomiting, abdominal discomfort and fever. Patients also demonstrated tachypnea, hypoxemia and bilateral lung infiltrates on chest X-ray. Use of e-cigarettes with refillable chambers or interchangeable cartridges with THC vaping concentrates or oils — all purchased on the street — was reported by all patients. Three patients also reported use of nicotine-containing e-cigarettes and two reported smoking marijuana or conventional cigarettes. All patients required hospitalization for hypoxemic respiratory failure, three required intensive care and one required intubation and mechanical ventilation. All survived, according to the MMWR report.

Tests suggested the disease did not have an infectious cause, and a diagnosis of acute exogenous lipoid pneumonia was made based on clinical history, radiography and lab and bronchoscopic diagnostics. Patients were then treated with IV methylprednisone and discharged on a taper of oral prednisone.

“One potential explanation for acute lipoid pneumonia among these patients is that aerosolized oils inhaled from e-cigarettes deposited within their distal airways and alveoli, inciting a local inflammatory response that impaired vital gas exchange,” the researchers wrote. “Lipoid pneumonia has long been described from aspiration of oil into the lungs and has been associated with e-cigarette use in some case reports.”

During the telebriefing, Daniel Fox, MD, from the department of pulmonary and critical care medicine at WakeMed Health and Hospitals in North Carolina, also noted that lipoid pneumonia is a rare diagnosis that is probably underrecognized across all populations.

Moving forward

Until its joint investigation with the FDA and state and local health departments has concluded, CDC recommends that people consider not using e-cigarettes and strongly advises against using products or substances bought on the street or modifying their e-cigarette to use products or substances not intended for use by the device’s manufacturer, Meaney-Delman said.

The CDC also issued a Health Alert Network Health Advisory last week with recommendations for clinicians, public health officials and patients.

Mitch Zeller, JD, director of Center for Tobacco Products at the FDA, stated that more than 120 samples of products submitted by state health departments to the FDA are being analyzed for the presence of a broad range of chemicals, including nicotine, THC, other cannabinoids, cutting agents, dilutants, additives, pesticides, poisons and toxins.

PAGE BREAK

He noted that officials are at a “critical fact-gathering stage” and encouraged the public to submit detailed reports of any unexpected tobacco or e-cigarette-related health or product issues to FDA through their online safety reporting portal: www.safetyreporting.hhs.gov.

“The FDA is going to leave no stone unturned in following any potential leads regarding any particular constituent or compound that may be at issue and we’re committed to taking appropriate actions as the facts emerge,” Zeller said during the telebriefing.

Healio Pulmonology is closely monitoring this story and will update the article as new information becomes available. – by Melissa Foster

Reference:

Christiani DC. N Engl J Med. 2019;doi:10.1056/NEJMe1912032.

Davidson K, et al. MMWR Morbid Mortal Wkly Rep. 2019;doi:10.15585/mmwr.mm6836e1.

Layden JE, et al. N Engl J Med. 2019;doi:10.1056/NEJMoa1911614.

Schier JG, et al. MMWR Morbid Mortal Wkly Rep. 2019;doi:10.15585/mmwr.mm6836e2.

Disclosures: Authors for the NEJM and MMWR publications report no relevant financial disclosures.

Editor's note: This story was updated on Sept. 11 to include new information from CDC on the number of confirmed deaths possibly related to e-cigarette use.