Pulmonology

Adolescents’ past 30-day use of e-cigarettes more than doubled from 2017 to 2019, and in 2019 almost 12% of high school seniors reported that they were vaping every day, according to data from the Monitoring the Future surveys.

Daily use – defined as vaping on 20 or more of the previous 30 days – was reported by 6.9% of 10th-grade and 1.9% of 8th-grade respondents in the 2019 survey, which was the first time use in these age groups was assessed. “The substantial levels of daily vaping suggest the development of nicotine addiction,” Richard Miech, PhD, and associates said Sept. 18 in the New England Journal of Medicine.

From 2017 to 2019, e-cigarette use over the previous 30 days increased from 11.0% to 25.4% among 12th graders, from 8.2% to 20.2% in 10th graders, and from 3.5% to 9.0% of 8th graders, suggesting that “current efforts by the vaping industry, government agencies, and schools have thus far proved insufficient to stop the rapid spread of nicotine vaping among adolescents,” the investigators wrote.

By 2019, over 40% of 12th-grade students reported ever using e-cigarettes, along with more than 36% of 10th graders and almost 21% of 8th graders. Corresponding figures for past 12-month use were 35.1%, 31.1%, and 16.1%, they reported.

“New efforts are needed to protect youth from using nicotine during adolescence, when the developing brain is particularly susceptible to permanent changes from nicotine use and when almost all nicotine addiction is established,” the investigators wrote.

The analysis was funded by a grant from the National Institute on Drug Abuse to Dr. Miech.

[email protected]

SOURCE: Miech R et al. N Engl J Med. 2019 Sep 18. doi: 10.1056/NEJMc1910739.

Adolescents’ past 30-day use of e-cigarettes more than doubled from 2017 to 2019, and in 2019 almost 12% of high school seniors reported that they were vaping every day, according to data from the Monitoring the Future surveys.

Daily use – defined as vaping on 20 or more of the previous 30 days – was reported by 6.9% of 10th-grade and 1.9% of 8th-grade respondents in the 2019 survey, which was the first time use in these age groups was assessed. “The substantial levels of daily vaping suggest the development of nicotine addiction,” Richard Miech, PhD, and associates said Sept. 18 in the New England Journal of Medicine.

From 2017 to 2019, e-cigarette use over the previous 30 days increased from 11.0% to 25.4% among 12th graders, from 8.2% to 20.2% in 10th graders, and from 3.5% to 9.0% of 8th graders, suggesting that “current efforts by the vaping industry, government agencies, and schools have thus far proved insufficient to stop the rapid spread of nicotine vaping among adolescents,” the investigators wrote.

By 2019, over 40% of 12th-grade students reported ever using e-cigarettes, along with more than 36% of 10th graders and almost 21% of 8th graders. Corresponding figures for past 12-month use were 35.1%, 31.1%, and 16.1%, they reported.

“New efforts are needed to protect youth from using nicotine during adolescence, when the developing brain is particularly susceptible to permanent changes from nicotine use and when almost all nicotine addiction is established,” the investigators wrote.

The analysis was funded by a grant from the National Institute on Drug Abuse to Dr. Miech.

[email protected]

SOURCE: Miech R et al. N Engl J Med. 2019 Sep 18. doi: 10.1056/NEJMc1910739.

Adolescents’ past 30-day use of e-cigarettes more than doubled from 2017 to 2019, and in 2019 almost 12% of high school seniors reported that they were vaping every day, according to data from the Monitoring the Future surveys.

Daily use – defined as vaping on 20 or more of the previous 30 days – was reported by 6.9% of 10th-grade and 1.9% of 8th-grade respondents in the 2019 survey, which was the first time use in these age groups was assessed. “The substantial levels of daily vaping suggest the development of nicotine addiction,” Richard Miech, PhD, and associates said Sept. 18 in the New England Journal of Medicine.

From 2017 to 2019, e-cigarette use over the previous 30 days increased from 11.0% to 25.4% among 12th graders, from 8.2% to 20.2% in 10th graders, and from 3.5% to 9.0% of 8th graders, suggesting that “current efforts by the vaping industry, government agencies, and schools have thus far proved insufficient to stop the rapid spread of nicotine vaping among adolescents,” the investigators wrote.

By 2019, over 40% of 12th-grade students reported ever using e-cigarettes, along with more than 36% of 10th graders and almost 21% of 8th graders. Corresponding figures for past 12-month use were 35.1%, 31.1%, and 16.1%, they reported.

“New efforts are needed to protect youth from using nicotine during adolescence, when the developing brain is particularly susceptible to permanent changes from nicotine use and when almost all nicotine addiction is established,” the investigators wrote.

The analysis was funded by a grant from the National Institute on Drug Abuse to Dr. Miech.

[email protected]

SOURCE: Miech R et al. N Engl J Med. 2019 Sep 18. doi: 10.1056/NEJMc1910739.

The 2019 wildfire season is underway in many locales across the United States, exposing millions of individuals to smoky conditions that will have health consequences ranging from stinging eyes to scratchy throats to a trip to the ED for asthma or chronic obstructive pulmonary disease (COPD) exacerbation. Questions about long-term health impacts are on the minds of many, including physicians and their patients who live with cardiorespiratory conditions.

US Forest Service photo courtesy of Peter Buschmann.

John R. Balmes, MD, a pulmonologist at the University of California, San Francisco, and an expert on the respiratory and cardiovascular effects of air pollutants, suggested that the best available published literature points to “pretty strong evidence for acute effects of wildfire smoke on respiratory health, meaning people with preexisting asthma and COPD are at risk for exacerbations, and probably for respiratory tract infections as well.” He said, “It’s a little less clear, but there’s good biological plausibility for increased risk of respiratory tract infections because when your alveolar macrophages are overloaded with carbon particles that are toxic to those cells, they don’t function as well as a first line of defense against bacterial infection, for example.”

The new normal of wildfires

Warmer, drier summers in recent years in the western United States and many other regions, attributed by climate experts to global climate change, have produced catastrophic wildfires (PNAS;2016 Oct 18;113[42]11770-5; Science 2006 Aug 18;313:940-3). The Camp Fire in Northern California broke out in November 2018, took the lives of at least 85 people, and cost more than $16 billion in damage. Smoke from that blaze reached hazardous levels in San Francisco, Sacramento, Fresno, and many other smaller towns. Other forest fires in that year caused heavy smoke conditions in Portland, Seattle, Vancouver, and Anchorage. Such events are expected to be repeated often in the coming years (Int J Environ Res Public Health. 2019 Jul 6;16[13]).

Courtesy Dr. Wayne Cascio

Wildfire smoke can contain a wide range of substances, chemicals, and gases with known and unknown cardiorespiratory implications. “Smoke is composed primarily of carbon dioxide, water vapor, carbon monoxide, particulate matter, hydrocarbons and other organic chemicals, nitrogen oxides, trace minerals and several thousand other compounds,” according to the U.S. Environmental Protection Agency (Wildfire smoke: A guide for public health officials 2019. Washington, D.C.: EPA, 2019). The EPA report noted, “Particles with diameters less than 10 mcm (particulate matter, or PM₁₀) can be inhaled into the lungs and affect the lungs, heart, and blood vessels. The smallest particles, those less than 2.5 mcm in diameter (PM_2.5), are the greatest risk to public health because they can reach deep into the lungs and may even make it into the bloodstream.”

Research on health impact

In early June of 2008, Wayne Cascio, MD, awoke in his Greenville, N.C., home to the stench of smoke emanating from a large peat fire burning some 65 miles away. By the time he reached the parking lot at East Carolina University in Greenville to begin his workday as chief of cardiology, the haze of smoke had thickened to the point where he could only see a few feet in front of him.

Over the next several weeks, the fire scorched 41,000 acres and produced haze and air pollution that far exceeded National Ambient Air Quality Standards for particulate matter and blanketed rural communities in the state’s eastern region. The price tag for management of the blaze reached $20 million. Because of his interest in the health effects of wildfire smoke and because of his relationship with investigators at the EPA, Dr. Cascio initiated an epidemiology study to investigate the effects of exposure on cardiorespiratory outcomes in the population affected by the fire (Environ Health Perspect. 2011 Oct;119[10]:1415-20).

By combining satellite data with syndromic surveillance drawn from hospital records in 41 counties contained in the North Carolina Disease Event Tracking and Epidemiologic Collection Tool, he and his colleagues found that exposure to the peat wildfire smoke led to increases in the cumulative risk ratio for asthma (relative risk, 1.65), chronic obstructive pulmonary disease (RR, 1.73), and pneumonia and acute bronchitis (RR, 1.59). ED visits related to cardiopulmonary symptoms and heart failure also were significantly increased (RR, 1.23 and 1.37, respectively). “That was really the first study to strongly identify a cardiac endpoint related to wildfire smoke exposure,” said Dr. Cascio, who now directs the EPA’s National Health and Environmental Effects Research Laboratory. “It really pointed out how little we knew about the health effects of wildfire up until that time.”

Those early findings have been replicated in subsequent research about the acute health effects of exposure to wildfire smoke, which contains PM_2.5 and other toxic substances from structures, electronic devices, and automobiles destroyed in the path of flames, including heavy metals and asbestos. Most of the work has focused on smoke-related cardiovascular and respiratory ED visits and hospitalizations.

A study of the 2008 California wildfire impact on ED visits accounted for ozone levels in addition to PM_2.5 in the smoke. During the active fire periods, PM_2.5 was significantly associated with exacerbations of asthma and COPD and these effects remained after controlling for ozone levels. PM_2.5 inhalation during the wildfires was associated with increased risk of an ED visit for asthma (RR, 1.112; 95% confidence interval, 1.087-1.138) for a 10 mcg/m³ increase in PM_2.5 and COPD (RR, 1.05; 95% CI, 1.019-1.0825), as well as for combined respiratory visits (RR, 1.035; 95% CI, 1.023-1.046) (Environ Int. 2109 Aug;129:291-8).

Researchers who evaluated the health impacts of wildfires in California during the 2015 fire season found an increase in all-cause cardiovascular and respiratory ED visits, especially among those aged 65 years and older during smoke days. The population-based study included 1,196,233 ED visits during May 1–Sept. 30 that year. PM_2.5 concentrations were categorized as light, medium, or dense. Relative risk rose with the amount of smoke in the air. Rates of all-cause cardiovascular ED visits were elevated across levels of smoke density, with the greatest increase on dense smoke days and among those aged 65 years or older (RR,1.15; 95% CI, 1.09-1.22). All-cause cerebrovascular visits were associated with dense smoke days, especially among those aged 65 years and older (RR, 1.22; 95% CI, 1.00-1.49). Respiratory conditions also were increased on dense smoke days (RR, 1.18; 95% CI, 1.08-1.28) (J Am Heart Assoc. 2018 Apr 11;7:e007492. doi: 10.1161/JAHA.117.007492).

Long-term effects unknown

When it comes to the long-term effects of wildfire smoke on human health outcomes, much less is known. In a recent literature review, Colleen E. Reid, PhD, and Melissa May Maestas, PhD, found only one study that investigated long-term respiratory health impacts of wildfire smoke, and only a few studies that have estimated future health impacts of wildfires under likely climate change scenarios (Curr Opin Pulm Med. 2019 Mar;25:179-87).

“We know that there are immediate respiratory health effects from wildfire smoke,” said Dr. Reid of the department of geography at the University of Colorado Boulder. “What’s less known is everything else. That’s challenging, because people want to know about the long-term health effects.”

Evidence from the scientific literature suggests that exposure to air pollution adversely affects cardiovascular health, but whether exposure to wildfire smoke confers a similar risk is less clear. “Until just a few years ago we haven’t been able to study wildfire exposure measures on a large scale,” said EPA scientist Ana G. Rappold, PhD, a statistician there in the environmental public health division of the National Health and Environmental Effects Research Laboratory. “It’s also hard to predict wildfires, so it’s hard to plan for an epidemiologic study if you don’t know where they’re going to occur.”

Dr. Rappold and colleagues examined cardiopulmonary hospitalizations among adults aged 65 years and older in 692 U.S. counties within 200 km of 123 large wildfires during 2008-2010 (Environ Health Perspect. 2019;127[3]:37006. doi: 10.1289/EHP3860). They observed that an increased risk of PM_2.5-related cardiopulmonary hospitalizations was similar on smoke and nonsmoke days across multiple lags and exposure metrics, while risk for asthma-related hospitalizations was higher during smoke days. “One hypothesis is that this was an older study population, so naturally if you’re inhaling smoke, the first organ that’s impacted in an older population is the lungs,” Dr. Rappold said. “If you go to the hospital for asthma, wheezing, or bronchitis, you are taken out of the risk pool for cardiovascular and other diseases. That could explain why in other studies we don’t see a clear cardiovascular signal as we have for air pollution studies in general. Another aspect to this study is, the exposure metric was PM_2.5, but smoke contains many other components, particularly gases, which are respiratory irritants. It could be that this triggers a higher risk for respiratory [effects] than regular episodes of high PM_2.5 exposure, just because of the additional gases that people are exposed to.”

Another complicating factor is the paucity of data about solutions to long-term exposure to wildfire smoke. “If you’re impacted by high-exposure levels for 60 days, that is not something we have experienced before,” Dr. Rappold noted. “What are the solutions for that community? What works? Can we show that by implementing community-level resilience plans with HEPA [high-efficiency particulate air] filters or other interventions, do the overall outcomes improve? Doctors are the first ones to talk with their patients about their symptoms and about how to take care of their conditions. They can clearly make a difference in emphasizing reducing exposures in a way that fits their patients individually, either reducing the amount of time spent outside, the duration of exposure, and the level of exposure. Maybe change activities based on the intensity of exposure. Don’t go for a run outside when it’s smoky, because your ventilation rate is higher and you will breathe in more smoke. Become aware of those things.”

Advising vulnerable patients

While research in this field advances, the unforgiving wildfire season looms, assuring more destruction of property and threats to cardiorespiratory health. “There are a lot of questions that research will have an opportunity to address as we go forward, including the utility and the benefit of N95 masks, the utility of HEPA filters used in the house, and even with HVAC [heating, ventilation, and air conditioning] systems,” Dr. Cascio said. “Can we really clean up the indoor air well enough to protect us from wildfire smoke?”

The way he sees it, the time is ripe for clinicians and officials in public and private practice settings to refine how they distribute information to people living in areas affected by wildfire smoke. “We can’t force people do anything, but at least if they’re informed, then they understand they can make an informed decision about how they might want to affect what they do that would limit their exposure,” he said. “As a patient, my health care system sends text and email messages to me. So, why couldn’t the hospital send out a text message or an email to all of the patients with COPD, coronary disease, and heart failure when an area is impacted by smoke, saying, ‘Check your air quality and take action if air quality is poor?’ Physicians don’t have time to do this kind of education in the office for all of their patients. I know that from experience. But if one were to only focus on those at highest risk, and encourage them to follow our guidelines, which might include doing HEPA filter treatment in the home, we probably would reduce the number of clinical events in a cost-effective way.”

[email protected]

The 2019 wildfire season is underway in many locales across the United States, exposing millions of individuals to smoky conditions that will have health consequences ranging from stinging eyes to scratchy throats to a trip to the ED for asthma or chronic obstructive pulmonary disease (COPD) exacerbation. Questions about long-term health impacts are on the minds of many, including physicians and their patients who live with cardiorespiratory conditions.

US Forest Service photo courtesy of Peter Buschmann.

John R. Balmes, MD, a pulmonologist at the University of California, San Francisco, and an expert on the respiratory and cardiovascular effects of air pollutants, suggested that the best available published literature points to “pretty strong evidence for acute effects of wildfire smoke on respiratory health, meaning people with preexisting asthma and COPD are at risk for exacerbations, and probably for respiratory tract infections as well.” He said, “It’s a little less clear, but there’s good biological plausibility for increased risk of respiratory tract infections because when your alveolar macrophages are overloaded with carbon particles that are toxic to those cells, they don’t function as well as a first line of defense against bacterial infection, for example.”

The new normal of wildfires

Warmer, drier summers in recent years in the western United States and many other regions, attributed by climate experts to global climate change, have produced catastrophic wildfires (PNAS;2016 Oct 18;113[42]11770-5; Science 2006 Aug 18;313:940-3). The Camp Fire in Northern California broke out in November 2018, took the lives of at least 85 people, and cost more than $16 billion in damage. Smoke from that blaze reached hazardous levels in San Francisco, Sacramento, Fresno, and many other smaller towns. Other forest fires in that year caused heavy smoke conditions in Portland, Seattle, Vancouver, and Anchorage. Such events are expected to be repeated often in the coming years (Int J Environ Res Public Health. 2019 Jul 6;16[13]).

Courtesy Dr. Wayne Cascio

Wildfire smoke can contain a wide range of substances, chemicals, and gases with known and unknown cardiorespiratory implications. “Smoke is composed primarily of carbon dioxide, water vapor, carbon monoxide, particulate matter, hydrocarbons and other organic chemicals, nitrogen oxides, trace minerals and several thousand other compounds,” according to the U.S. Environmental Protection Agency (Wildfire smoke: A guide for public health officials 2019. Washington, D.C.: EPA, 2019). The EPA report noted, “Particles with diameters less than 10 mcm (particulate matter, or PM₁₀) can be inhaled into the lungs and affect the lungs, heart, and blood vessels. The smallest particles, those less than 2.5 mcm in diameter (PM_2.5), are the greatest risk to public health because they can reach deep into the lungs and may even make it into the bloodstream.”

Research on health impact

In early June of 2008, Wayne Cascio, MD, awoke in his Greenville, N.C., home to the stench of smoke emanating from a large peat fire burning some 65 miles away. By the time he reached the parking lot at East Carolina University in Greenville to begin his workday as chief of cardiology, the haze of smoke had thickened to the point where he could only see a few feet in front of him.

Over the next several weeks, the fire scorched 41,000 acres and produced haze and air pollution that far exceeded National Ambient Air Quality Standards for particulate matter and blanketed rural communities in the state’s eastern region. The price tag for management of the blaze reached $20 million. Because of his interest in the health effects of wildfire smoke and because of his relationship with investigators at the EPA, Dr. Cascio initiated an epidemiology study to investigate the effects of exposure on cardiorespiratory outcomes in the population affected by the fire (Environ Health Perspect. 2011 Oct;119[10]:1415-20).

By combining satellite data with syndromic surveillance drawn from hospital records in 41 counties contained in the North Carolina Disease Event Tracking and Epidemiologic Collection Tool, he and his colleagues found that exposure to the peat wildfire smoke led to increases in the cumulative risk ratio for asthma (relative risk, 1.65), chronic obstructive pulmonary disease (RR, 1.73), and pneumonia and acute bronchitis (RR, 1.59). ED visits related to cardiopulmonary symptoms and heart failure also were significantly increased (RR, 1.23 and 1.37, respectively). “That was really the first study to strongly identify a cardiac endpoint related to wildfire smoke exposure,” said Dr. Cascio, who now directs the EPA’s National Health and Environmental Effects Research Laboratory. “It really pointed out how little we knew about the health effects of wildfire up until that time.”

Those early findings have been replicated in subsequent research about the acute health effects of exposure to wildfire smoke, which contains PM_2.5 and other toxic substances from structures, electronic devices, and automobiles destroyed in the path of flames, including heavy metals and asbestos. Most of the work has focused on smoke-related cardiovascular and respiratory ED visits and hospitalizations.

A study of the 2008 California wildfire impact on ED visits accounted for ozone levels in addition to PM_2.5 in the smoke. During the active fire periods, PM_2.5 was significantly associated with exacerbations of asthma and COPD and these effects remained after controlling for ozone levels. PM_2.5 inhalation during the wildfires was associated with increased risk of an ED visit for asthma (RR, 1.112; 95% confidence interval, 1.087-1.138) for a 10 mcg/m³ increase in PM_2.5 and COPD (RR, 1.05; 95% CI, 1.019-1.0825), as well as for combined respiratory visits (RR, 1.035; 95% CI, 1.023-1.046) (Environ Int. 2109 Aug;129:291-8).

Researchers who evaluated the health impacts of wildfires in California during the 2015 fire season found an increase in all-cause cardiovascular and respiratory ED visits, especially among those aged 65 years and older during smoke days. The population-based study included 1,196,233 ED visits during May 1–Sept. 30 that year. PM_2.5 concentrations were categorized as light, medium, or dense. Relative risk rose with the amount of smoke in the air. Rates of all-cause cardiovascular ED visits were elevated across levels of smoke density, with the greatest increase on dense smoke days and among those aged 65 years or older (RR,1.15; 95% CI, 1.09-1.22). All-cause cerebrovascular visits were associated with dense smoke days, especially among those aged 65 years and older (RR, 1.22; 95% CI, 1.00-1.49). Respiratory conditions also were increased on dense smoke days (RR, 1.18; 95% CI, 1.08-1.28) (J Am Heart Assoc. 2018 Apr 11;7:e007492. doi: 10.1161/JAHA.117.007492).

Long-term effects unknown

When it comes to the long-term effects of wildfire smoke on human health outcomes, much less is known. In a recent literature review, Colleen E. Reid, PhD, and Melissa May Maestas, PhD, found only one study that investigated long-term respiratory health impacts of wildfire smoke, and only a few studies that have estimated future health impacts of wildfires under likely climate change scenarios (Curr Opin Pulm Med. 2019 Mar;25:179-87).

“We know that there are immediate respiratory health effects from wildfire smoke,” said Dr. Reid of the department of geography at the University of Colorado Boulder. “What’s less known is everything else. That’s challenging, because people want to know about the long-term health effects.”

Evidence from the scientific literature suggests that exposure to air pollution adversely affects cardiovascular health, but whether exposure to wildfire smoke confers a similar risk is less clear. “Until just a few years ago we haven’t been able to study wildfire exposure measures on a large scale,” said EPA scientist Ana G. Rappold, PhD, a statistician there in the environmental public health division of the National Health and Environmental Effects Research Laboratory. “It’s also hard to predict wildfires, so it’s hard to plan for an epidemiologic study if you don’t know where they’re going to occur.”

Dr. Rappold and colleagues examined cardiopulmonary hospitalizations among adults aged 65 years and older in 692 U.S. counties within 200 km of 123 large wildfires during 2008-2010 (Environ Health Perspect. 2019;127[3]:37006. doi: 10.1289/EHP3860). They observed that an increased risk of PM_2.5-related cardiopulmonary hospitalizations was similar on smoke and nonsmoke days across multiple lags and exposure metrics, while risk for asthma-related hospitalizations was higher during smoke days. “One hypothesis is that this was an older study population, so naturally if you’re inhaling smoke, the first organ that’s impacted in an older population is the lungs,” Dr. Rappold said. “If you go to the hospital for asthma, wheezing, or bronchitis, you are taken out of the risk pool for cardiovascular and other diseases. That could explain why in other studies we don’t see a clear cardiovascular signal as we have for air pollution studies in general. Another aspect to this study is, the exposure metric was PM_2.5, but smoke contains many other components, particularly gases, which are respiratory irritants. It could be that this triggers a higher risk for respiratory [effects] than regular episodes of high PM_2.5 exposure, just because of the additional gases that people are exposed to.”

Another complicating factor is the paucity of data about solutions to long-term exposure to wildfire smoke. “If you’re impacted by high-exposure levels for 60 days, that is not something we have experienced before,” Dr. Rappold noted. “What are the solutions for that community? What works? Can we show that by implementing community-level resilience plans with HEPA [high-efficiency particulate air] filters or other interventions, do the overall outcomes improve? Doctors are the first ones to talk with their patients about their symptoms and about how to take care of their conditions. They can clearly make a difference in emphasizing reducing exposures in a way that fits their patients individually, either reducing the amount of time spent outside, the duration of exposure, and the level of exposure. Maybe change activities based on the intensity of exposure. Don’t go for a run outside when it’s smoky, because your ventilation rate is higher and you will breathe in more smoke. Become aware of those things.”

Advising vulnerable patients

While research in this field advances, the unforgiving wildfire season looms, assuring more destruction of property and threats to cardiorespiratory health. “There are a lot of questions that research will have an opportunity to address as we go forward, including the utility and the benefit of N95 masks, the utility of HEPA filters used in the house, and even with HVAC [heating, ventilation, and air conditioning] systems,” Dr. Cascio said. “Can we really clean up the indoor air well enough to protect us from wildfire smoke?”

The way he sees it, the time is ripe for clinicians and officials in public and private practice settings to refine how they distribute information to people living in areas affected by wildfire smoke. “We can’t force people do anything, but at least if they’re informed, then they understand they can make an informed decision about how they might want to affect what they do that would limit their exposure,” he said. “As a patient, my health care system sends text and email messages to me. So, why couldn’t the hospital send out a text message or an email to all of the patients with COPD, coronary disease, and heart failure when an area is impacted by smoke, saying, ‘Check your air quality and take action if air quality is poor?’ Physicians don’t have time to do this kind of education in the office for all of their patients. I know that from experience. But if one were to only focus on those at highest risk, and encourage them to follow our guidelines, which might include doing HEPA filter treatment in the home, we probably would reduce the number of clinical events in a cost-effective way.”

[email protected]

The 2019 wildfire season is underway in many locales across the United States, exposing millions of individuals to smoky conditions that will have health consequences ranging from stinging eyes to scratchy throats to a trip to the ED for asthma or chronic obstructive pulmonary disease (COPD) exacerbation. Questions about long-term health impacts are on the minds of many, including physicians and their patients who live with cardiorespiratory conditions.

US Forest Service photo courtesy of Peter Buschmann.

John R. Balmes, MD, a pulmonologist at the University of California, San Francisco, and an expert on the respiratory and cardiovascular effects of air pollutants, suggested that the best available published literature points to “pretty strong evidence for acute effects of wildfire smoke on respiratory health, meaning people with preexisting asthma and COPD are at risk for exacerbations, and probably for respiratory tract infections as well.” He said, “It’s a little less clear, but there’s good biological plausibility for increased risk of respiratory tract infections because when your alveolar macrophages are overloaded with carbon particles that are toxic to those cells, they don’t function as well as a first line of defense against bacterial infection, for example.”

The new normal of wildfires

Warmer, drier summers in recent years in the western United States and many other regions, attributed by climate experts to global climate change, have produced catastrophic wildfires (PNAS;2016 Oct 18;113[42]11770-5; Science 2006 Aug 18;313:940-3). The Camp Fire in Northern California broke out in November 2018, took the lives of at least 85 people, and cost more than $16 billion in damage. Smoke from that blaze reached hazardous levels in San Francisco, Sacramento, Fresno, and many other smaller towns. Other forest fires in that year caused heavy smoke conditions in Portland, Seattle, Vancouver, and Anchorage. Such events are expected to be repeated often in the coming years (Int J Environ Res Public Health. 2019 Jul 6;16[13]).

Courtesy Dr. Wayne Cascio

Wildfire smoke can contain a wide range of substances, chemicals, and gases with known and unknown cardiorespiratory implications. “Smoke is composed primarily of carbon dioxide, water vapor, carbon monoxide, particulate matter, hydrocarbons and other organic chemicals, nitrogen oxides, trace minerals and several thousand other compounds,” according to the U.S. Environmental Protection Agency (Wildfire smoke: A guide for public health officials 2019. Washington, D.C.: EPA, 2019). The EPA report noted, “Particles with diameters less than 10 mcm (particulate matter, or PM₁₀) can be inhaled into the lungs and affect the lungs, heart, and blood vessels. The smallest particles, those less than 2.5 mcm in diameter (PM_2.5), are the greatest risk to public health because they can reach deep into the lungs and may even make it into the bloodstream.”

Research on health impact

In early June of 2008, Wayne Cascio, MD, awoke in his Greenville, N.C., home to the stench of smoke emanating from a large peat fire burning some 65 miles away. By the time he reached the parking lot at East Carolina University in Greenville to begin his workday as chief of cardiology, the haze of smoke had thickened to the point where he could only see a few feet in front of him.

Over the next several weeks, the fire scorched 41,000 acres and produced haze and air pollution that far exceeded National Ambient Air Quality Standards for particulate matter and blanketed rural communities in the state’s eastern region. The price tag for management of the blaze reached $20 million. Because of his interest in the health effects of wildfire smoke and because of his relationship with investigators at the EPA, Dr. Cascio initiated an epidemiology study to investigate the effects of exposure on cardiorespiratory outcomes in the population affected by the fire (Environ Health Perspect. 2011 Oct;119[10]:1415-20).

By combining satellite data with syndromic surveillance drawn from hospital records in 41 counties contained in the North Carolina Disease Event Tracking and Epidemiologic Collection Tool, he and his colleagues found that exposure to the peat wildfire smoke led to increases in the cumulative risk ratio for asthma (relative risk, 1.65), chronic obstructive pulmonary disease (RR, 1.73), and pneumonia and acute bronchitis (RR, 1.59). ED visits related to cardiopulmonary symptoms and heart failure also were significantly increased (RR, 1.23 and 1.37, respectively). “That was really the first study to strongly identify a cardiac endpoint related to wildfire smoke exposure,” said Dr. Cascio, who now directs the EPA’s National Health and Environmental Effects Research Laboratory. “It really pointed out how little we knew about the health effects of wildfire up until that time.”

Those early findings have been replicated in subsequent research about the acute health effects of exposure to wildfire smoke, which contains PM_2.5 and other toxic substances from structures, electronic devices, and automobiles destroyed in the path of flames, including heavy metals and asbestos. Most of the work has focused on smoke-related cardiovascular and respiratory ED visits and hospitalizations.

A study of the 2008 California wildfire impact on ED visits accounted for ozone levels in addition to PM_2.5 in the smoke. During the active fire periods, PM_2.5 was significantly associated with exacerbations of asthma and COPD and these effects remained after controlling for ozone levels. PM_2.5 inhalation during the wildfires was associated with increased risk of an ED visit for asthma (RR, 1.112; 95% confidence interval, 1.087-1.138) for a 10 mcg/m³ increase in PM_2.5 and COPD (RR, 1.05; 95% CI, 1.019-1.0825), as well as for combined respiratory visits (RR, 1.035; 95% CI, 1.023-1.046) (Environ Int. 2109 Aug;129:291-8).

Researchers who evaluated the health impacts of wildfires in California during the 2015 fire season found an increase in all-cause cardiovascular and respiratory ED visits, especially among those aged 65 years and older during smoke days. The population-based study included 1,196,233 ED visits during May 1–Sept. 30 that year. PM_2.5 concentrations were categorized as light, medium, or dense. Relative risk rose with the amount of smoke in the air. Rates of all-cause cardiovascular ED visits were elevated across levels of smoke density, with the greatest increase on dense smoke days and among those aged 65 years or older (RR,1.15; 95% CI, 1.09-1.22). All-cause cerebrovascular visits were associated with dense smoke days, especially among those aged 65 years and older (RR, 1.22; 95% CI, 1.00-1.49). Respiratory conditions also were increased on dense smoke days (RR, 1.18; 95% CI, 1.08-1.28) (J Am Heart Assoc. 2018 Apr 11;7:e007492. doi: 10.1161/JAHA.117.007492).

Long-term effects unknown

When it comes to the long-term effects of wildfire smoke on human health outcomes, much less is known. In a recent literature review, Colleen E. Reid, PhD, and Melissa May Maestas, PhD, found only one study that investigated long-term respiratory health impacts of wildfire smoke, and only a few studies that have estimated future health impacts of wildfires under likely climate change scenarios (Curr Opin Pulm Med. 2019 Mar;25:179-87).

“We know that there are immediate respiratory health effects from wildfire smoke,” said Dr. Reid of the department of geography at the University of Colorado Boulder. “What’s less known is everything else. That’s challenging, because people want to know about the long-term health effects.”

Evidence from the scientific literature suggests that exposure to air pollution adversely affects cardiovascular health, but whether exposure to wildfire smoke confers a similar risk is less clear. “Until just a few years ago we haven’t been able to study wildfire exposure measures on a large scale,” said EPA scientist Ana G. Rappold, PhD, a statistician there in the environmental public health division of the National Health and Environmental Effects Research Laboratory. “It’s also hard to predict wildfires, so it’s hard to plan for an epidemiologic study if you don’t know where they’re going to occur.”

Dr. Rappold and colleagues examined cardiopulmonary hospitalizations among adults aged 65 years and older in 692 U.S. counties within 200 km of 123 large wildfires during 2008-2010 (Environ Health Perspect. 2019;127[3]:37006. doi: 10.1289/EHP3860). They observed that an increased risk of PM_2.5-related cardiopulmonary hospitalizations was similar on smoke and nonsmoke days across multiple lags and exposure metrics, while risk for asthma-related hospitalizations was higher during smoke days. “One hypothesis is that this was an older study population, so naturally if you’re inhaling smoke, the first organ that’s impacted in an older population is the lungs,” Dr. Rappold said. “If you go to the hospital for asthma, wheezing, or bronchitis, you are taken out of the risk pool for cardiovascular and other diseases. That could explain why in other studies we don’t see a clear cardiovascular signal as we have for air pollution studies in general. Another aspect to this study is, the exposure metric was PM_2.5, but smoke contains many other components, particularly gases, which are respiratory irritants. It could be that this triggers a higher risk for respiratory [effects] than regular episodes of high PM_2.5 exposure, just because of the additional gases that people are exposed to.”

Another complicating factor is the paucity of data about solutions to long-term exposure to wildfire smoke. “If you’re impacted by high-exposure levels for 60 days, that is not something we have experienced before,” Dr. Rappold noted. “What are the solutions for that community? What works? Can we show that by implementing community-level resilience plans with HEPA [high-efficiency particulate air] filters or other interventions, do the overall outcomes improve? Doctors are the first ones to talk with their patients about their symptoms and about how to take care of their conditions. They can clearly make a difference in emphasizing reducing exposures in a way that fits their patients individually, either reducing the amount of time spent outside, the duration of exposure, and the level of exposure. Maybe change activities based on the intensity of exposure. Don’t go for a run outside when it’s smoky, because your ventilation rate is higher and you will breathe in more smoke. Become aware of those things.”

Advising vulnerable patients

While research in this field advances, the unforgiving wildfire season looms, assuring more destruction of property and threats to cardiorespiratory health. “There are a lot of questions that research will have an opportunity to address as we go forward, including the utility and the benefit of N95 masks, the utility of HEPA filters used in the house, and even with HVAC [heating, ventilation, and air conditioning] systems,” Dr. Cascio said. “Can we really clean up the indoor air well enough to protect us from wildfire smoke?”

The way he sees it, the time is ripe for clinicians and officials in public and private practice settings to refine how they distribute information to people living in areas affected by wildfire smoke. “We can’t force people do anything, but at least if they’re informed, then they understand they can make an informed decision about how they might want to affect what they do that would limit their exposure,” he said. “As a patient, my health care system sends text and email messages to me. So, why couldn’t the hospital send out a text message or an email to all of the patients with COPD, coronary disease, and heart failure when an area is impacted by smoke, saying, ‘Check your air quality and take action if air quality is poor?’ Physicians don’t have time to do this kind of education in the office for all of their patients. I know that from experience. But if one were to only focus on those at highest risk, and encourage them to follow our guidelines, which might include doing HEPA filter treatment in the home, we probably would reduce the number of clinical events in a cost-effective way.”

[email protected]

About a third of peanut-allergic patients given oral immunotherapy (OIT) passed a peanut challenge when the therapy was reduced, based on data from a phase 2 randomized trial of individuals with confirmed peanut allergies.

yktr/ThinkStock

Previous studies have shown that desensitization to peanuts can be successful, but sustained response to oral immunotherapy after treatment reduction or discontinuation has not been well studied, wrote R. Sharon Chinthrajah, MD, of Stanford (Calif.)University, and colleagues.

“We found that OIT with peanut was able to desensitise people with peanut allergy to 4,000 mg of peanut protein, but that discontinuation of peanut, or even a reduction to 300 mg daily, increased the likelihood of regaining clinical reactivity to peanut,” they wrote. “With peanut allergy therapies in varying stages of clinical development, and some nearing [Food and Drug Administration] approval, vital questions remain regarding the durability of treatment effects and the appropriate maintenance doses.”

In the Peanut Oral Immunotherapy Study: Safety Efficacy and Discovery (POISED), published in The Lancet, the researchers randomized 120 participants to three groups:

• 60 patients built up to a maintenance dose of 4,000 mg of peanut protein for 104 weeks followed by total discontinuation (peanut-0).

• 35 patients built up to a maintenance dose of 4,000 mg of peanut protein for 104 weeks followed by a 300-mg maintenance dose of peanut protein in the form of peanut flour (peanut-300).

• 25 patients to an oat flour placebo.

All participants were trained on how and when to use epinephrine autoinjector devices to treat allergic symptoms such as respiratory problems (cough, shortness of breath, or change in voice), widespread hives or erythema, repetitive vomiting, persistent abdominal pain, angioedema of the face, or feeling faint.

The primary outcome was passing a double-blind, placebo-controlled, food challenge (DBPCFC) to 4,000 mg of peanut protein, which was measured at baseline and at weeks 104, 117, 130, 143, and 156.

SOURCE: Chinthrajah RS et al. Lancet. 2019 Sep 12. doi: 10.1016/S0140-6736(19)31793-3.

About a third of peanut-allergic patients given oral immunotherapy (OIT) passed a peanut challenge when the therapy was reduced, based on data from a phase 2 randomized trial of individuals with confirmed peanut allergies.

yktr/ThinkStock

Previous studies have shown that desensitization to peanuts can be successful, but sustained response to oral immunotherapy after treatment reduction or discontinuation has not been well studied, wrote R. Sharon Chinthrajah, MD, of Stanford (Calif.)University, and colleagues.

“We found that OIT with peanut was able to desensitise people with peanut allergy to 4,000 mg of peanut protein, but that discontinuation of peanut, or even a reduction to 300 mg daily, increased the likelihood of regaining clinical reactivity to peanut,” they wrote. “With peanut allergy therapies in varying stages of clinical development, and some nearing [Food and Drug Administration] approval, vital questions remain regarding the durability of treatment effects and the appropriate maintenance doses.”

In the Peanut Oral Immunotherapy Study: Safety Efficacy and Discovery (POISED), published in The Lancet, the researchers randomized 120 participants to three groups:

• 60 patients built up to a maintenance dose of 4,000 mg of peanut protein for 104 weeks followed by total discontinuation (peanut-0).

• 35 patients built up to a maintenance dose of 4,000 mg of peanut protein for 104 weeks followed by a 300-mg maintenance dose of peanut protein in the form of peanut flour (peanut-300).

• 25 patients to an oat flour placebo.

All participants were trained on how and when to use epinephrine autoinjector devices to treat allergic symptoms such as respiratory problems (cough, shortness of breath, or change in voice), widespread hives or erythema, repetitive vomiting, persistent abdominal pain, angioedema of the face, or feeling faint.

The primary outcome was passing a double-blind, placebo-controlled, food challenge (DBPCFC) to 4,000 mg of peanut protein, which was measured at baseline and at weeks 104, 117, 130, 143, and 156.

SOURCE: Chinthrajah RS et al. Lancet. 2019 Sep 12. doi: 10.1016/S0140-6736(19)31793-3.

About a third of peanut-allergic patients given oral immunotherapy (OIT) passed a peanut challenge when the therapy was reduced, based on data from a phase 2 randomized trial of individuals with confirmed peanut allergies.

yktr/ThinkStock

Previous studies have shown that desensitization to peanuts can be successful, but sustained response to oral immunotherapy after treatment reduction or discontinuation has not been well studied, wrote R. Sharon Chinthrajah, MD, of Stanford (Calif.)University, and colleagues.

“We found that OIT with peanut was able to desensitise people with peanut allergy to 4,000 mg of peanut protein, but that discontinuation of peanut, or even a reduction to 300 mg daily, increased the likelihood of regaining clinical reactivity to peanut,” they wrote. “With peanut allergy therapies in varying stages of clinical development, and some nearing [Food and Drug Administration] approval, vital questions remain regarding the durability of treatment effects and the appropriate maintenance doses.”

In the Peanut Oral Immunotherapy Study: Safety Efficacy and Discovery (POISED), published in The Lancet, the researchers randomized 120 participants to three groups:

• 60 patients built up to a maintenance dose of 4,000 mg of peanut protein for 104 weeks followed by total discontinuation (peanut-0).

• 35 patients built up to a maintenance dose of 4,000 mg of peanut protein for 104 weeks followed by a 300-mg maintenance dose of peanut protein in the form of peanut flour (peanut-300).

• 25 patients to an oat flour placebo.

All participants were trained on how and when to use epinephrine autoinjector devices to treat allergic symptoms such as respiratory problems (cough, shortness of breath, or change in voice), widespread hives or erythema, repetitive vomiting, persistent abdominal pain, angioedema of the face, or feeling faint.

The primary outcome was passing a double-blind, placebo-controlled, food challenge (DBPCFC) to 4,000 mg of peanut protein, which was measured at baseline and at weeks 104, 117, 130, 143, and 156.

SOURCE: Chinthrajah RS et al. Lancet. 2019 Sep 12. doi: 10.1016/S0140-6736(19)31793-3.

The Centers for Disease Control and Prevention has activated its Emergency Operations Center for the purpose of improving multiple agencies’ responses to the current investigation into two cases of lung injury associated with vaping.

This move allows the CDC “to provide increased operational support” to CDC staff to meet the evolving challenges of the outbreak of vaping-related injuries and deaths, says a statement from the CDC.

“CDC has made it a priority to find out what is causing this outbreak,” noted CDC Director Robert Redfield, MD, in the statement.

The agency “continues to work closely with the U.S. Food and Drug Administration to collect information about recent e-cigarette product use, or vaping, among patients and to test the substances or chemicals within e-cigarette products used by case patients,” according to the statement.

The CDC provided email addresses and site addresses for gathering information and communicating about e-cigarettes.

Information about the collection of e-cigarettes for possible testing by FDA can be obtained through contacting [email protected].

To communicate with CDC about this public health response, clinicians and health officials can contact [email protected].

More information on the current outbreak related to e-cigarettes is available at https://www.cdc.gov/tobacco/basic_information/e-cigarettes/severe-lung-disease.html.

General information on electronic cigarette products, can be found at www.cdc.gov/e-cigarettes.

Individuals concerned about health risks of vaping should consider refraining from e-cigarette use while the cases of lung injury are being investigated, the CDC said.

[email protected]

The Centers for Disease Control and Prevention has activated its Emergency Operations Center for the purpose of improving multiple agencies’ responses to the current investigation into two cases of lung injury associated with vaping.

This move allows the CDC “to provide increased operational support” to CDC staff to meet the evolving challenges of the outbreak of vaping-related injuries and deaths, says a statement from the CDC.

“CDC has made it a priority to find out what is causing this outbreak,” noted CDC Director Robert Redfield, MD, in the statement.

The agency “continues to work closely with the U.S. Food and Drug Administration to collect information about recent e-cigarette product use, or vaping, among patients and to test the substances or chemicals within e-cigarette products used by case patients,” according to the statement.

The CDC provided email addresses and site addresses for gathering information and communicating about e-cigarettes.

Information about the collection of e-cigarettes for possible testing by FDA can be obtained through contacting [email protected].

To communicate with CDC about this public health response, clinicians and health officials can contact [email protected].

More information on the current outbreak related to e-cigarettes is available at https://www.cdc.gov/tobacco/basic_information/e-cigarettes/severe-lung-disease.html.

General information on electronic cigarette products, can be found at www.cdc.gov/e-cigarettes.

Individuals concerned about health risks of vaping should consider refraining from e-cigarette use while the cases of lung injury are being investigated, the CDC said.

[email protected]

The Centers for Disease Control and Prevention has activated its Emergency Operations Center for the purpose of improving multiple agencies’ responses to the current investigation into two cases of lung injury associated with vaping.

This move allows the CDC “to provide increased operational support” to CDC staff to meet the evolving challenges of the outbreak of vaping-related injuries and deaths, says a statement from the CDC.

“CDC has made it a priority to find out what is causing this outbreak,” noted CDC Director Robert Redfield, MD, in the statement.

The agency “continues to work closely with the U.S. Food and Drug Administration to collect information about recent e-cigarette product use, or vaping, among patients and to test the substances or chemicals within e-cigarette products used by case patients,” according to the statement.

The CDC provided email addresses and site addresses for gathering information and communicating about e-cigarettes.

Information about the collection of e-cigarettes for possible testing by FDA can be obtained through contacting [email protected].

To communicate with CDC about this public health response, clinicians and health officials can contact [email protected].

More information on the current outbreak related to e-cigarettes is available at https://www.cdc.gov/tobacco/basic_information/e-cigarettes/severe-lung-disease.html.

General information on electronic cigarette products, can be found at www.cdc.gov/e-cigarettes.

Individuals concerned about health risks of vaping should consider refraining from e-cigarette use while the cases of lung injury are being investigated, the CDC said.

[email protected]

A group of mint- and menthol-flavored e-liquids and smokeless tobacco products contained significantly more pulegone – a known carcinogen that causes hepatic carcinomas, pulmonary metaplasia, and other neoplasms – than the Food and Drug Administration considers acceptable, according to new findings.

Pulegone, an oil extract from mint plants such as peppermint, spearmint, and pennyroyal, was banned as a food additive by the agency in 2018, and the tobacco industry has taken steps to minimize pulegone levels in cigarettes because of the toxicity concerns.

Studies from the Centers for Disease Control and Prevention, however, have indicated that mint- and menthol-flavored e-cigarette liquids and smokeless tobacco products marketed in the United States contain substantial amounts of the substance, Sairam V. Jabba, DVM, PhD, and Sven-Eric Jordt, PhD, said in a research letter published in JAMA Internal Medicine.

Dr. Jabba and Dr. Jordt, both with the department of anesthesiology at Duke University, Durham, N.C., calculated the margin of exposure in five e-liquids (V2 Menthol, V2 Peppermint, Premium Menthol, South Beach Smoke Menthol, and South Beach Smoke Peppermint) and one smokeless tobacco product (Skoal Xtra Mint snuff) by dividing the no–observed adverse event level (13.39 mg/kg of bodyweight per day) by the mean human exposure to e-liquids or smokeless tobacco. The FDA considers margin-of-exposure values of 10,000 or less to require mitigation strategies.

The six products included in the analysis had pulegone concentration levels ranging from 25.7 to 119.0 mcg/g (a menthol cigarette has a pulegone concentration of 0.037-0.290 mcg/g). Based on those levels, light daily use (5 mL e-liquid, 10 g smokeless tobacco, half a pack of cigarettes) exposed e-cigarette users to 44-198 times more pulegone, compared with menthol cigarettes, and exposed smokeless tobacco users to 168-1,319 times as much pulegone. The margin of exposure ranged from 1,298 to 6,012, all below 10,000 threshhold the FDA deems acceptable.

For heavy daily use (20 mL e-liquid, 30 g smokeless tobacco, two packs of cigarettes), e-cigarette users were exposed to 282-1,608 times more pulegone, compared with menthol cigarettes; smokeless tobacco users were exposed to 126-990 times more pulegone. The margin of exposure ranged from 325 to 1,503.

The study findings “appear to establish health risks associated with pulegone intake and concerns that the FDA should address before suggesting mint- and menthol-flavored e-cigarettes and smokeless tobacco products as alternatives for people who use combustible tobacco products,” Dr. Jabba and Dr. Jordt concluded.

The study was funded by a grant from the National Institute of Environmental Health Sciences. Dr. Jordt reported receiving grants from the NIEHS and the National Institute on Drug Abuse, personal fees from Hydra Biosciences and Sanofi, and nonfinancial support from GlaxoSmithKline. Dr. Jabba reported no disclosures.

[email protected]

SOURCE: Jabba SV, Jordt S-E. JAMA Intern Med. 2019 Sep 16. doi: 10.1001/jamainternmed.2019.3649.

A group of mint- and menthol-flavored e-liquids and smokeless tobacco products contained significantly more pulegone – a known carcinogen that causes hepatic carcinomas, pulmonary metaplasia, and other neoplasms – than the Food and Drug Administration considers acceptable, according to new findings.

Pulegone, an oil extract from mint plants such as peppermint, spearmint, and pennyroyal, was banned as a food additive by the agency in 2018, and the tobacco industry has taken steps to minimize pulegone levels in cigarettes because of the toxicity concerns.

Studies from the Centers for Disease Control and Prevention, however, have indicated that mint- and menthol-flavored e-cigarette liquids and smokeless tobacco products marketed in the United States contain substantial amounts of the substance, Sairam V. Jabba, DVM, PhD, and Sven-Eric Jordt, PhD, said in a research letter published in JAMA Internal Medicine.

Dr. Jabba and Dr. Jordt, both with the department of anesthesiology at Duke University, Durham, N.C., calculated the margin of exposure in five e-liquids (V2 Menthol, V2 Peppermint, Premium Menthol, South Beach Smoke Menthol, and South Beach Smoke Peppermint) and one smokeless tobacco product (Skoal Xtra Mint snuff) by dividing the no–observed adverse event level (13.39 mg/kg of bodyweight per day) by the mean human exposure to e-liquids or smokeless tobacco. The FDA considers margin-of-exposure values of 10,000 or less to require mitigation strategies.

The six products included in the analysis had pulegone concentration levels ranging from 25.7 to 119.0 mcg/g (a menthol cigarette has a pulegone concentration of 0.037-0.290 mcg/g). Based on those levels, light daily use (5 mL e-liquid, 10 g smokeless tobacco, half a pack of cigarettes) exposed e-cigarette users to 44-198 times more pulegone, compared with menthol cigarettes, and exposed smokeless tobacco users to 168-1,319 times as much pulegone. The margin of exposure ranged from 1,298 to 6,012, all below 10,000 threshhold the FDA deems acceptable.

For heavy daily use (20 mL e-liquid, 30 g smokeless tobacco, two packs of cigarettes), e-cigarette users were exposed to 282-1,608 times more pulegone, compared with menthol cigarettes; smokeless tobacco users were exposed to 126-990 times more pulegone. The margin of exposure ranged from 325 to 1,503.

The study findings “appear to establish health risks associated with pulegone intake and concerns that the FDA should address before suggesting mint- and menthol-flavored e-cigarettes and smokeless tobacco products as alternatives for people who use combustible tobacco products,” Dr. Jabba and Dr. Jordt concluded.

The study was funded by a grant from the National Institute of Environmental Health Sciences. Dr. Jordt reported receiving grants from the NIEHS and the National Institute on Drug Abuse, personal fees from Hydra Biosciences and Sanofi, and nonfinancial support from GlaxoSmithKline. Dr. Jabba reported no disclosures.

[email protected]

SOURCE: Jabba SV, Jordt S-E. JAMA Intern Med. 2019 Sep 16. doi: 10.1001/jamainternmed.2019.3649.

A group of mint- and menthol-flavored e-liquids and smokeless tobacco products contained significantly more pulegone – a known carcinogen that causes hepatic carcinomas, pulmonary metaplasia, and other neoplasms – than the Food and Drug Administration considers acceptable, according to new findings.

Pulegone, an oil extract from mint plants such as peppermint, spearmint, and pennyroyal, was banned as a food additive by the agency in 2018, and the tobacco industry has taken steps to minimize pulegone levels in cigarettes because of the toxicity concerns.

Studies from the Centers for Disease Control and Prevention, however, have indicated that mint- and menthol-flavored e-cigarette liquids and smokeless tobacco products marketed in the United States contain substantial amounts of the substance, Sairam V. Jabba, DVM, PhD, and Sven-Eric Jordt, PhD, said in a research letter published in JAMA Internal Medicine.

Dr. Jabba and Dr. Jordt, both with the department of anesthesiology at Duke University, Durham, N.C., calculated the margin of exposure in five e-liquids (V2 Menthol, V2 Peppermint, Premium Menthol, South Beach Smoke Menthol, and South Beach Smoke Peppermint) and one smokeless tobacco product (Skoal Xtra Mint snuff) by dividing the no–observed adverse event level (13.39 mg/kg of bodyweight per day) by the mean human exposure to e-liquids or smokeless tobacco. The FDA considers margin-of-exposure values of 10,000 or less to require mitigation strategies.

The six products included in the analysis had pulegone concentration levels ranging from 25.7 to 119.0 mcg/g (a menthol cigarette has a pulegone concentration of 0.037-0.290 mcg/g). Based on those levels, light daily use (5 mL e-liquid, 10 g smokeless tobacco, half a pack of cigarettes) exposed e-cigarette users to 44-198 times more pulegone, compared with menthol cigarettes, and exposed smokeless tobacco users to 168-1,319 times as much pulegone. The margin of exposure ranged from 1,298 to 6,012, all below 10,000 threshhold the FDA deems acceptable.

For heavy daily use (20 mL e-liquid, 30 g smokeless tobacco, two packs of cigarettes), e-cigarette users were exposed to 282-1,608 times more pulegone, compared with menthol cigarettes; smokeless tobacco users were exposed to 126-990 times more pulegone. The margin of exposure ranged from 325 to 1,503.

The study findings “appear to establish health risks associated with pulegone intake and concerns that the FDA should address before suggesting mint- and menthol-flavored e-cigarettes and smokeless tobacco products as alternatives for people who use combustible tobacco products,” Dr. Jabba and Dr. Jordt concluded.

The study was funded by a grant from the National Institute of Environmental Health Sciences. Dr. Jordt reported receiving grants from the NIEHS and the National Institute on Drug Abuse, personal fees from Hydra Biosciences and Sanofi, and nonfinancial support from GlaxoSmithKline. Dr. Jabba reported no disclosures.

[email protected]

SOURCE: Jabba SV, Jordt S-E. JAMA Intern Med. 2019 Sep 16. doi: 10.1001/jamainternmed.2019.3649.

A pill designed to desensitize peanut-allergic children and teenagers may be on the way.

The Food and Drug Administration’s Allergenic Products Advisory Committee has voted to recommend approval of the AR101 peanut protein capsules (Palforzia) for use in oral immunotherapy in those aged 4-17 years old with a confirmed peanut allergy. Conditions for approval include stipulations that a black-box warning and medication use guide are included in the packaging, the panel said. The FDA usually follows the recommendations of its advisory panels. 

bankrx/Getty Images

The committee members voted 7-2 that the drug was effective and 8-1 that it was safe. 

John Kelso, MD, the sole dissenter on safety, voiced concerns about the dearth of long-term follow-up in Aimmune Therapeutic’s body of research and the finding that children who received the treatment during the dose-escalation and maintenance periods had twice the number of allergic reactions requiring epinephrine, compared with those who received placebo. There are no long-term safety data to rely on yet, he added.

“Efficacy has not been demonstrated, except on the day the peanut challenge is administered,” said Dr. Kelso, an allergist at the Scripps Clinic, San Diego, adding that only long-term follow-up data would fully convince him that the drug’s benefits outweigh the risks.

In the discussion, however, other committee members pointed out that new drugs are often approved without long-term efficacy and safety data. Those data are extrapolated from clinical trials, and only real-world experience will confirm the data, they noted.

Company representatives did not explicitly address the potential cost of the therapy, but a recent review by the Institute for Clinical and Economic Review estimated the cost to be $4,200 a year. Palforzia would have to be taken every day, for an unknown amount of time, to maintain peanut tolerance.

“Using prices from analysts for AR101 ($4,200 a year), we estimated that only 41% of eligible patients could be treated in a given year without exceeding ICER’s budget impact threshold,” the institute concluded in a publicly released analysis.

Palforzia comes in individual packs of capsules filled with peanut protein, not flour. The capsules come in doses of 0.5, 1, 10, 20, and 100, and 300 mg. A single-dose sachet contains 300 mg. Treatment begins with 0.5-6 mg over 1 day and escalates every 2 weeks until 300 mg is reached or there is a reaction requiring epinephrine. Passing at least a 300-mg dose was the requirement for exiting the escalation phase and moving on to the daily, year-long maintenance phase.

The four efficacy studies presented showed that 96% of patients tolerated 300 mg, 84% tolerated 600 mg, and 63% 1,000 mg – about 10 times the reactive dose observed in the placebo controls.

“Only 125 mg of peanut protein – the amount in about half a peanut kernel – can be enough to provoke a reaction,” said Daniel Adelman, MD, chief medical officer of Aimmune. If patients can tolerate 600 mg of protein – the equivalent of two kernels, accidental ingestion will result in a “predictable, manageable” reaction.

“This is truly a clinically significant result for patients and families who report lives dictated by the allergy,” Dr. Adelman said.

Consistent manufacturing processes and positive safety data should reassure clinicians and patients that they are receiving a safe, effective, and well-regulated treatment, he added.

The capsule, however, is not a panacea. The company advises that families continue with the peanut avoidance diet. “It’s important to remember that reactive episodes can occur with dosing, and accidental exposures can occur at unpredictable times, away from home, and despite the best efforts at avoidance,” Dr. Adelman said. “This is not a drug for everyone, but it is an effective desensitization tool and would clearly be the first therapy to treat a food allergy, providing statistically significant and clinically important improvement. Outcomes align with patients’ goals.”

Safety was assessed in 709 treated patients who received the medication and 292 who received placebo. Treatment-related adverse events were most common in initial dosing: 89% of the treatment group and 58% of the placebo group experienced at least one adverse event during that time. Adverse events were mostly mild to moderate and decreased in severity over the study period. They included abdominal pain (45% active vs. 18% placebo), throat irritation (40% vs. 17%), pruritus (33% vs. 20%), vomiting (37% vs. 16%), cough (32% vs. 24%), nausea (32% vs. 14%), urticaria (28% vs. 19%), and upper abdominal pain (30% vs. 14%).

Discontinuations caused by these adverse events were infrequent, with only 1.8% of participants who were taking the active capsule and 1% of those taking placebo discontinuing the study product during initial dose escalation. Only the severe systemic allergic reactions were considered to be anaphylaxis, and they had to affect at least two body systems.

Respiratory events were more common in those in the active group, especially in children with asthma. These events included cough, wheezing, dyspnea, dysphonia, throat irritation and tightness, and exercise-induced asthma. There was, however, no “concerning change” in asthma control.

Systemic allergic reactions and anaphylaxis were more common in the active-dose group. Systemic reactions during dose escalation occurred in 9.4% of active patients and 3.8% those taking placebo. During the maintenance phase, they occurred in 8.7% and 1.7% of patients, respectively. Three patients in the active group had a serious systemic reaction – two during up-dosing and one during maintenance.

• The first dose of each progressive dose must be administered in a facility that is equipped to treat systemic allergic reactions.
• Families must have a valid prescription for injectable epinephrine before treatment starts and must demonstrate that they know how to use it.
• There must be distribution controls in every pharmacy that dispenses the product.
• Packaging will be dose specific to ensure proper at-home administration.
• Pharmacologic questionnaires will be used as data collection instruments.
• Professional and patient-focused labeling will include a medication guide and educational material.

Palforzia is not the only peanut desensitization product in the works. DBC Technology has resubmitted its biologics license application to the FDA in the hope of getting approval for its peanut allergy treatment, the Viaskin Peanut patch.

The patch is designed to desensitize allergic children aged 4-11 years through a skin-patch method known as epicutaneous immunotherapy. Results from two controlled clinical trials were included in the submission. The company is also investigating the potential of this form of skin-patch therapy for milk and egg allergies.

Correction, 9/15/19: An earlier version of this article did not clearly state that the panel recommended approval rather than granted approval for the drug.

[email protected]

A pill designed to desensitize peanut-allergic children and teenagers may be on the way.

The Food and Drug Administration’s Allergenic Products Advisory Committee has voted to recommend approval of the AR101 peanut protein capsules (Palforzia) for use in oral immunotherapy in those aged 4-17 years old with a confirmed peanut allergy. Conditions for approval include stipulations that a black-box warning and medication use guide are included in the packaging, the panel said. The FDA usually follows the recommendations of its advisory panels. 

bankrx/Getty Images

The committee members voted 7-2 that the drug was effective and 8-1 that it was safe. 

John Kelso, MD, the sole dissenter on safety, voiced concerns about the dearth of long-term follow-up in Aimmune Therapeutic’s body of research and the finding that children who received the treatment during the dose-escalation and maintenance periods had twice the number of allergic reactions requiring epinephrine, compared with those who received placebo. There are no long-term safety data to rely on yet, he added.

“Efficacy has not been demonstrated, except on the day the peanut challenge is administered,” said Dr. Kelso, an allergist at the Scripps Clinic, San Diego, adding that only long-term follow-up data would fully convince him that the drug’s benefits outweigh the risks.

In the discussion, however, other committee members pointed out that new drugs are often approved without long-term efficacy and safety data. Those data are extrapolated from clinical trials, and only real-world experience will confirm the data, they noted.

Company representatives did not explicitly address the potential cost of the therapy, but a recent review by the Institute for Clinical and Economic Review estimated the cost to be $4,200 a year. Palforzia would have to be taken every day, for an unknown amount of time, to maintain peanut tolerance.

“Using prices from analysts for AR101 ($4,200 a year), we estimated that only 41% of eligible patients could be treated in a given year without exceeding ICER’s budget impact threshold,” the institute concluded in a publicly released analysis.

Palforzia comes in individual packs of capsules filled with peanut protein, not flour. The capsules come in doses of 0.5, 1, 10, 20, and 100, and 300 mg. A single-dose sachet contains 300 mg. Treatment begins with 0.5-6 mg over 1 day and escalates every 2 weeks until 300 mg is reached or there is a reaction requiring epinephrine. Passing at least a 300-mg dose was the requirement for exiting the escalation phase and moving on to the daily, year-long maintenance phase.

The four efficacy studies presented showed that 96% of patients tolerated 300 mg, 84% tolerated 600 mg, and 63% 1,000 mg – about 10 times the reactive dose observed in the placebo controls.

“Only 125 mg of peanut protein – the amount in about half a peanut kernel – can be enough to provoke a reaction,” said Daniel Adelman, MD, chief medical officer of Aimmune. If patients can tolerate 600 mg of protein – the equivalent of two kernels, accidental ingestion will result in a “predictable, manageable” reaction.

“This is truly a clinically significant result for patients and families who report lives dictated by the allergy,” Dr. Adelman said.

Consistent manufacturing processes and positive safety data should reassure clinicians and patients that they are receiving a safe, effective, and well-regulated treatment, he added.

The capsule, however, is not a panacea. The company advises that families continue with the peanut avoidance diet. “It’s important to remember that reactive episodes can occur with dosing, and accidental exposures can occur at unpredictable times, away from home, and despite the best efforts at avoidance,” Dr. Adelman said. “This is not a drug for everyone, but it is an effective desensitization tool and would clearly be the first therapy to treat a food allergy, providing statistically significant and clinically important improvement. Outcomes align with patients’ goals.”

Safety was assessed in 709 treated patients who received the medication and 292 who received placebo. Treatment-related adverse events were most common in initial dosing: 89% of the treatment group and 58% of the placebo group experienced at least one adverse event during that time. Adverse events were mostly mild to moderate and decreased in severity over the study period. They included abdominal pain (45% active vs. 18% placebo), throat irritation (40% vs. 17%), pruritus (33% vs. 20%), vomiting (37% vs. 16%), cough (32% vs. 24%), nausea (32% vs. 14%), urticaria (28% vs. 19%), and upper abdominal pain (30% vs. 14%).

Discontinuations caused by these adverse events were infrequent, with only 1.8% of participants who were taking the active capsule and 1% of those taking placebo discontinuing the study product during initial dose escalation. Only the severe systemic allergic reactions were considered to be anaphylaxis, and they had to affect at least two body systems.

Respiratory events were more common in those in the active group, especially in children with asthma. These events included cough, wheezing, dyspnea, dysphonia, throat irritation and tightness, and exercise-induced asthma. There was, however, no “concerning change” in asthma control.

Systemic allergic reactions and anaphylaxis were more common in the active-dose group. Systemic reactions during dose escalation occurred in 9.4% of active patients and 3.8% those taking placebo. During the maintenance phase, they occurred in 8.7% and 1.7% of patients, respectively. Three patients in the active group had a serious systemic reaction – two during up-dosing and one during maintenance.

• The first dose of each progressive dose must be administered in a facility that is equipped to treat systemic allergic reactions.
• Families must have a valid prescription for injectable epinephrine before treatment starts and must demonstrate that they know how to use it.
• There must be distribution controls in every pharmacy that dispenses the product.
• Packaging will be dose specific to ensure proper at-home administration.
• Pharmacologic questionnaires will be used as data collection instruments.
• Professional and patient-focused labeling will include a medication guide and educational material.

Palforzia is not the only peanut desensitization product in the works. DBC Technology has resubmitted its biologics license application to the FDA in the hope of getting approval for its peanut allergy treatment, the Viaskin Peanut patch.

The patch is designed to desensitize allergic children aged 4-11 years through a skin-patch method known as epicutaneous immunotherapy. Results from two controlled clinical trials were included in the submission. The company is also investigating the potential of this form of skin-patch therapy for milk and egg allergies.

Correction, 9/15/19: An earlier version of this article did not clearly state that the panel recommended approval rather than granted approval for the drug.

[email protected]

A pill designed to desensitize peanut-allergic children and teenagers may be on the way.

The Food and Drug Administration’s Allergenic Products Advisory Committee has voted to recommend approval of the AR101 peanut protein capsules (Palforzia) for use in oral immunotherapy in those aged 4-17 years old with a confirmed peanut allergy. Conditions for approval include stipulations that a black-box warning and medication use guide are included in the packaging, the panel said. The FDA usually follows the recommendations of its advisory panels. 

bankrx/Getty Images

The committee members voted 7-2 that the drug was effective and 8-1 that it was safe. 

John Kelso, MD, the sole dissenter on safety, voiced concerns about the dearth of long-term follow-up in Aimmune Therapeutic’s body of research and the finding that children who received the treatment during the dose-escalation and maintenance periods had twice the number of allergic reactions requiring epinephrine, compared with those who received placebo. There are no long-term safety data to rely on yet, he added.

“Efficacy has not been demonstrated, except on the day the peanut challenge is administered,” said Dr. Kelso, an allergist at the Scripps Clinic, San Diego, adding that only long-term follow-up data would fully convince him that the drug’s benefits outweigh the risks.

In the discussion, however, other committee members pointed out that new drugs are often approved without long-term efficacy and safety data. Those data are extrapolated from clinical trials, and only real-world experience will confirm the data, they noted.

Company representatives did not explicitly address the potential cost of the therapy, but a recent review by the Institute for Clinical and Economic Review estimated the cost to be $4,200 a year. Palforzia would have to be taken every day, for an unknown amount of time, to maintain peanut tolerance.

“Using prices from analysts for AR101 ($4,200 a year), we estimated that only 41% of eligible patients could be treated in a given year without exceeding ICER’s budget impact threshold,” the institute concluded in a publicly released analysis.

Palforzia comes in individual packs of capsules filled with peanut protein, not flour. The capsules come in doses of 0.5, 1, 10, 20, and 100, and 300 mg. A single-dose sachet contains 300 mg. Treatment begins with 0.5-6 mg over 1 day and escalates every 2 weeks until 300 mg is reached or there is a reaction requiring epinephrine. Passing at least a 300-mg dose was the requirement for exiting the escalation phase and moving on to the daily, year-long maintenance phase.

The four efficacy studies presented showed that 96% of patients tolerated 300 mg, 84% tolerated 600 mg, and 63% 1,000 mg – about 10 times the reactive dose observed in the placebo controls.

“Only 125 mg of peanut protein – the amount in about half a peanut kernel – can be enough to provoke a reaction,” said Daniel Adelman, MD, chief medical officer of Aimmune. If patients can tolerate 600 mg of protein – the equivalent of two kernels, accidental ingestion will result in a “predictable, manageable” reaction.

“This is truly a clinically significant result for patients and families who report lives dictated by the allergy,” Dr. Adelman said.

Consistent manufacturing processes and positive safety data should reassure clinicians and patients that they are receiving a safe, effective, and well-regulated treatment, he added.

The capsule, however, is not a panacea. The company advises that families continue with the peanut avoidance diet. “It’s important to remember that reactive episodes can occur with dosing, and accidental exposures can occur at unpredictable times, away from home, and despite the best efforts at avoidance,” Dr. Adelman said. “This is not a drug for everyone, but it is an effective desensitization tool and would clearly be the first therapy to treat a food allergy, providing statistically significant and clinically important improvement. Outcomes align with patients’ goals.”

Safety was assessed in 709 treated patients who received the medication and 292 who received placebo. Treatment-related adverse events were most common in initial dosing: 89% of the treatment group and 58% of the placebo group experienced at least one adverse event during that time. Adverse events were mostly mild to moderate and decreased in severity over the study period. They included abdominal pain (45% active vs. 18% placebo), throat irritation (40% vs. 17%), pruritus (33% vs. 20%), vomiting (37% vs. 16%), cough (32% vs. 24%), nausea (32% vs. 14%), urticaria (28% vs. 19%), and upper abdominal pain (30% vs. 14%).

Discontinuations caused by these adverse events were infrequent, with only 1.8% of participants who were taking the active capsule and 1% of those taking placebo discontinuing the study product during initial dose escalation. Only the severe systemic allergic reactions were considered to be anaphylaxis, and they had to affect at least two body systems.

Respiratory events were more common in those in the active group, especially in children with asthma. These events included cough, wheezing, dyspnea, dysphonia, throat irritation and tightness, and exercise-induced asthma. There was, however, no “concerning change” in asthma control.

Systemic allergic reactions and anaphylaxis were more common in the active-dose group. Systemic reactions during dose escalation occurred in 9.4% of active patients and 3.8% those taking placebo. During the maintenance phase, they occurred in 8.7% and 1.7% of patients, respectively. Three patients in the active group had a serious systemic reaction – two during up-dosing and one during maintenance.

• The first dose of each progressive dose must be administered in a facility that is equipped to treat systemic allergic reactions.
• Families must have a valid prescription for injectable epinephrine before treatment starts and must demonstrate that they know how to use it.
• There must be distribution controls in every pharmacy that dispenses the product.
• Packaging will be dose specific to ensure proper at-home administration.
• Pharmacologic questionnaires will be used as data collection instruments.
• Professional and patient-focused labeling will include a medication guide and educational material.

Palforzia is not the only peanut desensitization product in the works. DBC Technology has resubmitted its biologics license application to the FDA in the hope of getting approval for its peanut allergy treatment, the Viaskin Peanut patch.

The patch is designed to desensitize allergic children aged 4-11 years through a skin-patch method known as epicutaneous immunotherapy. Results from two controlled clinical trials were included in the submission. The company is also investigating the potential of this form of skin-patch therapy for milk and egg allergies.

Correction, 9/15/19: An earlier version of this article did not clearly state that the panel recommended approval rather than granted approval for the drug.

[email protected]

The Food and Drug Administration is warning that the entire class of the cyclin-dependent kinase 4/6 (CDK 4/6) inhibitors used to treat advanced breast cancer may cause rare but severe inflammation of the lungs.

“We reviewed CDK 4/6 inhibitors cases from completed and ongoing clinical trials undertaken by manufacturers and their postmarket safety databases that described specific types of inflammation of the lungs, called interstitial lung disease and pneumonitis. Across the entire drug class, there were reports of serious cases, including fatalities,” the FDA said in a press statement.

The overall benefit of CDK 4/6 inhibitors, however, is still greater than the risks when used as prescribed, the agency said.

CDK 4/6 inhibitors are used in combination with hormone therapies to treat adults with hormone receptor–positive, human epidermal growth factor 2–negative advanced or metastatic breast cancer that has spread to other parts of the body. The FDA approved the CDK 4/6 inhibitors palbociclib (Ibrance) in 2015 and ribociclib (Kisqali) and abemaciclib (Verzenio) in 2017, based on improvements in progression-free survival.

Health care professionals should monitor patients regularly for pulmonary symptoms indicative of interstitial lung disease and/or pneumonitis. Signs and symptoms may include hypoxia, cough, dyspnea, or interstitial infiltrates on radiologic exams in patients in whom infectious, neoplastic, and other causes have been excluded. Interrupt CDK 4/6 inhibitor treatment in patients who have new or worsening respiratory symptoms, and permanently discontinue treatment in patients with severe interstitial lung disease and/or pneumonitis, the FDA said.






 

The Food and Drug Administration is warning that the entire class of the cyclin-dependent kinase 4/6 (CDK 4/6) inhibitors used to treat advanced breast cancer may cause rare but severe inflammation of the lungs.

“We reviewed CDK 4/6 inhibitors cases from completed and ongoing clinical trials undertaken by manufacturers and their postmarket safety databases that described specific types of inflammation of the lungs, called interstitial lung disease and pneumonitis. Across the entire drug class, there were reports of serious cases, including fatalities,” the FDA said in a press statement.

The overall benefit of CDK 4/6 inhibitors, however, is still greater than the risks when used as prescribed, the agency said.

CDK 4/6 inhibitors are used in combination with hormone therapies to treat adults with hormone receptor–positive, human epidermal growth factor 2–negative advanced or metastatic breast cancer that has spread to other parts of the body. The FDA approved the CDK 4/6 inhibitors palbociclib (Ibrance) in 2015 and ribociclib (Kisqali) and abemaciclib (Verzenio) in 2017, based on improvements in progression-free survival.

Health care professionals should monitor patients regularly for pulmonary symptoms indicative of interstitial lung disease and/or pneumonitis. Signs and symptoms may include hypoxia, cough, dyspnea, or interstitial infiltrates on radiologic exams in patients in whom infectious, neoplastic, and other causes have been excluded. Interrupt CDK 4/6 inhibitor treatment in patients who have new or worsening respiratory symptoms, and permanently discontinue treatment in patients with severe interstitial lung disease and/or pneumonitis, the FDA said.






 

The Food and Drug Administration is warning that the entire class of the cyclin-dependent kinase 4/6 (CDK 4/6) inhibitors used to treat advanced breast cancer may cause rare but severe inflammation of the lungs.

“We reviewed CDK 4/6 inhibitors cases from completed and ongoing clinical trials undertaken by manufacturers and their postmarket safety databases that described specific types of inflammation of the lungs, called interstitial lung disease and pneumonitis. Across the entire drug class, there were reports of serious cases, including fatalities,” the FDA said in a press statement.

The overall benefit of CDK 4/6 inhibitors, however, is still greater than the risks when used as prescribed, the agency said.

CDK 4/6 inhibitors are used in combination with hormone therapies to treat adults with hormone receptor–positive, human epidermal growth factor 2–negative advanced or metastatic breast cancer that has spread to other parts of the body. The FDA approved the CDK 4/6 inhibitors palbociclib (Ibrance) in 2015 and ribociclib (Kisqali) and abemaciclib (Verzenio) in 2017, based on improvements in progression-free survival.

Health care professionals should monitor patients regularly for pulmonary symptoms indicative of interstitial lung disease and/or pneumonitis. Signs and symptoms may include hypoxia, cough, dyspnea, or interstitial infiltrates on radiologic exams in patients in whom infectious, neoplastic, and other causes have been excluded. Interrupt CDK 4/6 inhibitor treatment in patients who have new or worsening respiratory symptoms, and permanently discontinue treatment in patients with severe interstitial lung disease and/or pneumonitis, the FDA said.






 

Add-on benralizumab is not associated with a significantly lower annualized rate of exacerbations in patients with moderate to severe chronic obstructive pulmonary disease (COPD) and eosinophilic inflammation, according to results from two phase 3 trials. The data were published in the New England Journal of Medicine.

Benralizumab, an interleukin-5 receptor alpha–directed cytolytic monoclonal antibody, is approved for the treatment of patients with severe eosinophilic asthma. To assess whether the treatment may prevent COPD exacerbations, Gerard J. Criner, MD, chair and professor of thoracic medicine and surgery at Temple University in Philadelphia and colleagues conducted two randomized, double-blind, parallel-group studies: GALATHEA and TERRANOVA. Researchers enrolled patients with frequent moderate or severe COPD exacerbations and blood eosinophil counts of at least 220 per mm³.

A 56-week treatment period

“An eosinophil threshold of 220 per mm³ was selected on the basis of the phase 2 trial of benralizumab in patients with COPD, in which modeling of annual exacerbations according to baseline blood eosinophil count indicated that patients with eosinophil counts above a similar threshold were more likely to have a response to benralizumab,” the authors wrote. “The doses selected were 30 mg, the approved dose for asthma treatment; 100 mg, to inform the safety margin; and 10 mg (in TERRANOVA), to evaluate the dose-efficacy relationship.”

Patients received placebo or benralizumab via subcutaneous injection every 4 weeks for the first three doses, then every 8 weeks for the rest of the 56-week treatment period. The primary end point was the annualized COPD exacerbation rate ratio (benralizumab vs. placebo) at week 56.

The primary analysis populations included 1,120 patients in GALATHEA and 1,545 patients in TERRANOVA. Most patients were white men, and the average age was 65 years. The percentages of patients with current asthma (5.4% in GALATHEA and 3.3% in TERRANOVA) or past asthma (8.3% in GALATHEA and 6.1% in TERRANOVA) were low.

In GALATHEA, the estimated annualized exacerbation rates were 1.19 per year in the 30-mg benralizumab group, 1.03 per year in the 100-mg benralizumab group, and 1.24 per year in the placebo group. Compared with placebo, the rate ratio was 0.96 for 30 mg of benralizumab and 0.83 for 100 mg of benralizumab.

In TERRANOVA, the estimated annualized exacerbation rates for 10 mg, 30 mg, and 100 mg of benralizumab and for placebo were 0.99 per year, 1.21 per year, 1.09 per year, and 1.17 per year, respectively. The corresponding rate ratios were 0.85, 1.04, and 0.93. “At 56 weeks, none of the annualized COPD exacerbation rate ratios for any dose of benralizumab as compared with placebo reached significance in either trial,” the researchers said. “Types and frequencies of adverse events were similar with benralizumab and placebo.”

Depletion of eosinophils in blood and sputum

By week 4, benralizumab substantially depleted blood eosinophils. In addition, treatment substantially depleted sputum eosinophils by week 24. “However, in contrast to the results in benralizumab-treated patients with severe eosinophilic asthma, this eosinophil depletion did not correspond to a significant difference in the rate of exacerbations. This finding, together with the effect on eosinophils – with minimal effect on the COPD exacerbation rate – that was observed in the mepolizumab trials, suggests that eosinophil depletion is unlikely to ameliorate exacerbation outcomes for the majority of patients with COPD,” Dr. Criner and his coauthors concluded. “Future investigation is required to identify additional clinical factors or biomarkers that may characterize the patients with COPD who are most likely to benefit from anti–interleukin-5 receptor antibody therapy.”

The trials were sponsored by AstraZeneca, which manufactures benralizumab (Fasenra), and by Kyowa Hakko Kirin. One author is supported by the National Institute for Health Research Manchester Biomedical Research Centre. The authors’ disclosures included grants and personal fees from AstraZeneca and other pharmaceutical companies.

[email protected]

SOURCE: Criner GJ et al. N Engl J Med. 2019;382(11):1023-34. doi: 10.1056/NEJMoa1905248.

Add-on benralizumab is not associated with a significantly lower annualized rate of exacerbations in patients with moderate to severe chronic obstructive pulmonary disease (COPD) and eosinophilic inflammation, according to results from two phase 3 trials. The data were published in the New England Journal of Medicine.

Benralizumab, an interleukin-5 receptor alpha–directed cytolytic monoclonal antibody, is approved for the treatment of patients with severe eosinophilic asthma. To assess whether the treatment may prevent COPD exacerbations, Gerard J. Criner, MD, chair and professor of thoracic medicine and surgery at Temple University in Philadelphia and colleagues conducted two randomized, double-blind, parallel-group studies: GALATHEA and TERRANOVA. Researchers enrolled patients with frequent moderate or severe COPD exacerbations and blood eosinophil counts of at least 220 per mm³.

A 56-week treatment period

“An eosinophil threshold of 220 per mm³ was selected on the basis of the phase 2 trial of benralizumab in patients with COPD, in which modeling of annual exacerbations according to baseline blood eosinophil count indicated that patients with eosinophil counts above a similar threshold were more likely to have a response to benralizumab,” the authors wrote. “The doses selected were 30 mg, the approved dose for asthma treatment; 100 mg, to inform the safety margin; and 10 mg (in TERRANOVA), to evaluate the dose-efficacy relationship.”

Patients received placebo or benralizumab via subcutaneous injection every 4 weeks for the first three doses, then every 8 weeks for the rest of the 56-week treatment period. The primary end point was the annualized COPD exacerbation rate ratio (benralizumab vs. placebo) at week 56.

The primary analysis populations included 1,120 patients in GALATHEA and 1,545 patients in TERRANOVA. Most patients were white men, and the average age was 65 years. The percentages of patients with current asthma (5.4% in GALATHEA and 3.3% in TERRANOVA) or past asthma (8.3% in GALATHEA and 6.1% in TERRANOVA) were low.

In GALATHEA, the estimated annualized exacerbation rates were 1.19 per year in the 30-mg benralizumab group, 1.03 per year in the 100-mg benralizumab group, and 1.24 per year in the placebo group. Compared with placebo, the rate ratio was 0.96 for 30 mg of benralizumab and 0.83 for 100 mg of benralizumab.

In TERRANOVA, the estimated annualized exacerbation rates for 10 mg, 30 mg, and 100 mg of benralizumab and for placebo were 0.99 per year, 1.21 per year, 1.09 per year, and 1.17 per year, respectively. The corresponding rate ratios were 0.85, 1.04, and 0.93. “At 56 weeks, none of the annualized COPD exacerbation rate ratios for any dose of benralizumab as compared with placebo reached significance in either trial,” the researchers said. “Types and frequencies of adverse events were similar with benralizumab and placebo.”

Depletion of eosinophils in blood and sputum

By week 4, benralizumab substantially depleted blood eosinophils. In addition, treatment substantially depleted sputum eosinophils by week 24. “However, in contrast to the results in benralizumab-treated patients with severe eosinophilic asthma, this eosinophil depletion did not correspond to a significant difference in the rate of exacerbations. This finding, together with the effect on eosinophils – with minimal effect on the COPD exacerbation rate – that was observed in the mepolizumab trials, suggests that eosinophil depletion is unlikely to ameliorate exacerbation outcomes for the majority of patients with COPD,” Dr. Criner and his coauthors concluded. “Future investigation is required to identify additional clinical factors or biomarkers that may characterize the patients with COPD who are most likely to benefit from anti–interleukin-5 receptor antibody therapy.”

The trials were sponsored by AstraZeneca, which manufactures benralizumab (Fasenra), and by Kyowa Hakko Kirin. One author is supported by the National Institute for Health Research Manchester Biomedical Research Centre. The authors’ disclosures included grants and personal fees from AstraZeneca and other pharmaceutical companies.

[email protected]

SOURCE: Criner GJ et al. N Engl J Med. 2019;382(11):1023-34. doi: 10.1056/NEJMoa1905248.

Add-on benralizumab is not associated with a significantly lower annualized rate of exacerbations in patients with moderate to severe chronic obstructive pulmonary disease (COPD) and eosinophilic inflammation, according to results from two phase 3 trials. The data were published in the New England Journal of Medicine.

Benralizumab, an interleukin-5 receptor alpha–directed cytolytic monoclonal antibody, is approved for the treatment of patients with severe eosinophilic asthma. To assess whether the treatment may prevent COPD exacerbations, Gerard J. Criner, MD, chair and professor of thoracic medicine and surgery at Temple University in Philadelphia and colleagues conducted two randomized, double-blind, parallel-group studies: GALATHEA and TERRANOVA. Researchers enrolled patients with frequent moderate or severe COPD exacerbations and blood eosinophil counts of at least 220 per mm³.

A 56-week treatment period

“An eosinophil threshold of 220 per mm³ was selected on the basis of the phase 2 trial of benralizumab in patients with COPD, in which modeling of annual exacerbations according to baseline blood eosinophil count indicated that patients with eosinophil counts above a similar threshold were more likely to have a response to benralizumab,” the authors wrote. “The doses selected were 30 mg, the approved dose for asthma treatment; 100 mg, to inform the safety margin; and 10 mg (in TERRANOVA), to evaluate the dose-efficacy relationship.”

Patients received placebo or benralizumab via subcutaneous injection every 4 weeks for the first three doses, then every 8 weeks for the rest of the 56-week treatment period. The primary end point was the annualized COPD exacerbation rate ratio (benralizumab vs. placebo) at week 56.

The primary analysis populations included 1,120 patients in GALATHEA and 1,545 patients in TERRANOVA. Most patients were white men, and the average age was 65 years. The percentages of patients with current asthma (5.4% in GALATHEA and 3.3% in TERRANOVA) or past asthma (8.3% in GALATHEA and 6.1% in TERRANOVA) were low.

In GALATHEA, the estimated annualized exacerbation rates were 1.19 per year in the 30-mg benralizumab group, 1.03 per year in the 100-mg benralizumab group, and 1.24 per year in the placebo group. Compared with placebo, the rate ratio was 0.96 for 30 mg of benralizumab and 0.83 for 100 mg of benralizumab.

In TERRANOVA, the estimated annualized exacerbation rates for 10 mg, 30 mg, and 100 mg of benralizumab and for placebo were 0.99 per year, 1.21 per year, 1.09 per year, and 1.17 per year, respectively. The corresponding rate ratios were 0.85, 1.04, and 0.93. “At 56 weeks, none of the annualized COPD exacerbation rate ratios for any dose of benralizumab as compared with placebo reached significance in either trial,” the researchers said. “Types and frequencies of adverse events were similar with benralizumab and placebo.”

Depletion of eosinophils in blood and sputum

By week 4, benralizumab substantially depleted blood eosinophils. In addition, treatment substantially depleted sputum eosinophils by week 24. “However, in contrast to the results in benralizumab-treated patients with severe eosinophilic asthma, this eosinophil depletion did not correspond to a significant difference in the rate of exacerbations. This finding, together with the effect on eosinophils – with minimal effect on the COPD exacerbation rate – that was observed in the mepolizumab trials, suggests that eosinophil depletion is unlikely to ameliorate exacerbation outcomes for the majority of patients with COPD,” Dr. Criner and his coauthors concluded. “Future investigation is required to identify additional clinical factors or biomarkers that may characterize the patients with COPD who are most likely to benefit from anti–interleukin-5 receptor antibody therapy.”

The trials were sponsored by AstraZeneca, which manufactures benralizumab (Fasenra), and by Kyowa Hakko Kirin. One author is supported by the National Institute for Health Research Manchester Biomedical Research Centre. The authors’ disclosures included grants and personal fees from AstraZeneca and other pharmaceutical companies.

[email protected]

SOURCE: Criner GJ et al. N Engl J Med. 2019;382(11):1023-34. doi: 10.1056/NEJMoa1905248.

Pharmacist-led intervention reduced inappropriate medication prescriptions

An outpatient pharmacy-led intervention of notifying prescribing physicians to discontinue inappropriate Beers Criteria medications resulted in a greater discontinuation of inappropriate medications for older adults at 6 months, compared with the control group (43% vs. 12% discontinuation).

Citation: Martin P et al. Effect of a pharmacist-led educational intervention on inappropriate medication prescriptions in older adults: The D-PRESCRIBE randomized clinical trial. JAMA. 2018;320(18):1889-98.

Omadacycline noninferior for community-acquired pneumonia and acute bacterial soft tissue skin infections

Randomized, double-blind, double-dummy trials showed omadacycline is a noninferior alternative to moxifloxacin for the treatment of community-acquired pneumonia and to linezolid for acute bacterial soft-tissue skin infections.

Citation: Nuzyra (omadacycline) [package insert]. Boston, MA: Paratek Pharmaceuticals. 2018.

Lack of evidence to support low-salt diet in adult heart failure patients

Systematic review of multiple databases demonstrated there is limited high-quality evidence to support current guidelines that recommend a low-salt diet to heart failure patients.

Citation: Mahtani KR et al. Reduced salt intake for heart failure: A systematic review. JAMA Int Med. 2018;178(12):1693-700.

Magnesium for rate control in rapid atrial fibrillation

Randomized, controlled trial demonstrated that intravenous magnesium sulfate in combination with atrioventricular (AV) nodal blocking agents resulted in better rate control for atrial fibrillation with rapid ventricular response than did placebo given in combination with AV nodal blocking agents.

Citation: Bouida W et al. Low-dose magnesium sulfate versus high-dose in the early management of rapid atrial fibrillation: Randomized controlled double-blind study (LOMAGHI Study). Acad Emerg Med. 2019 Feb;26(2):183-91.

Low versus intermediate tidal volume strategy on ventilator-free days in ICU patients without ARDS

Randomized, clinical trial of low tidal volume versus intermediate tidal volume strategies in invasively ventilated patients without accute respiratory distress syndrome (ARDS) demonstrated no difference in number of ventilator-free days, ICU length of stay, hospital length of stay, incidence of ventilator-associated adverse events (ARDS, pneumonia, severe atelectasis, pneumothorax), or 28-day mortality.

Citation: Writing Group for the PReVENT Investigators, Simonis FD, Serpa Neto A. Effect of a low vs intermediate tidal volume strategy on ventilator-free days in intensive care unit patients without ARDS: A randomized clinical trial. JAMA. 2018;320(18):1872-80.

Pharmacist-led intervention reduced inappropriate medication prescriptions

An outpatient pharmacy-led intervention of notifying prescribing physicians to discontinue inappropriate Beers Criteria medications resulted in a greater discontinuation of inappropriate medications for older adults at 6 months, compared with the control group (43% vs. 12% discontinuation).

Citation: Martin P et al. Effect of a pharmacist-led educational intervention on inappropriate medication prescriptions in older adults: The D-PRESCRIBE randomized clinical trial. JAMA. 2018;320(18):1889-98.

Omadacycline noninferior for community-acquired pneumonia and acute bacterial soft tissue skin infections

Randomized, double-blind, double-dummy trials showed omadacycline is a noninferior alternative to moxifloxacin for the treatment of community-acquired pneumonia and to linezolid for acute bacterial soft-tissue skin infections.

Citation: Nuzyra (omadacycline) [package insert]. Boston, MA: Paratek Pharmaceuticals. 2018.

Lack of evidence to support low-salt diet in adult heart failure patients

Systematic review of multiple databases demonstrated there is limited high-quality evidence to support current guidelines that recommend a low-salt diet to heart failure patients.

Citation: Mahtani KR et al. Reduced salt intake for heart failure: A systematic review. JAMA Int Med. 2018;178(12):1693-700.

Magnesium for rate control in rapid atrial fibrillation

Randomized, controlled trial demonstrated that intravenous magnesium sulfate in combination with atrioventricular (AV) nodal blocking agents resulted in better rate control for atrial fibrillation with rapid ventricular response than did placebo given in combination with AV nodal blocking agents.

Citation: Bouida W et al. Low-dose magnesium sulfate versus high-dose in the early management of rapid atrial fibrillation: Randomized controlled double-blind study (LOMAGHI Study). Acad Emerg Med. 2019 Feb;26(2):183-91.

Low versus intermediate tidal volume strategy on ventilator-free days in ICU patients without ARDS

Randomized, clinical trial of low tidal volume versus intermediate tidal volume strategies in invasively ventilated patients without accute respiratory distress syndrome (ARDS) demonstrated no difference in number of ventilator-free days, ICU length of stay, hospital length of stay, incidence of ventilator-associated adverse events (ARDS, pneumonia, severe atelectasis, pneumothorax), or 28-day mortality.

Citation: Writing Group for the PReVENT Investigators, Simonis FD, Serpa Neto A. Effect of a low vs intermediate tidal volume strategy on ventilator-free days in intensive care unit patients without ARDS: A randomized clinical trial. JAMA. 2018;320(18):1872-80.

Pharmacist-led intervention reduced inappropriate medication prescriptions

An outpatient pharmacy-led intervention of notifying prescribing physicians to discontinue inappropriate Beers Criteria medications resulted in a greater discontinuation of inappropriate medications for older adults at 6 months, compared with the control group (43% vs. 12% discontinuation).

Citation: Martin P et al. Effect of a pharmacist-led educational intervention on inappropriate medication prescriptions in older adults: The D-PRESCRIBE randomized clinical trial. JAMA. 2018;320(18):1889-98.

Omadacycline noninferior for community-acquired pneumonia and acute bacterial soft tissue skin infections

Randomized, double-blind, double-dummy trials showed omadacycline is a noninferior alternative to moxifloxacin for the treatment of community-acquired pneumonia and to linezolid for acute bacterial soft-tissue skin infections.

Citation: Nuzyra (omadacycline) [package insert]. Boston, MA: Paratek Pharmaceuticals. 2018.

Lack of evidence to support low-salt diet in adult heart failure patients

Systematic review of multiple databases demonstrated there is limited high-quality evidence to support current guidelines that recommend a low-salt diet to heart failure patients.

Citation: Mahtani KR et al. Reduced salt intake for heart failure: A systematic review. JAMA Int Med. 2018;178(12):1693-700.

Magnesium for rate control in rapid atrial fibrillation

Randomized, controlled trial demonstrated that intravenous magnesium sulfate in combination with atrioventricular (AV) nodal blocking agents resulted in better rate control for atrial fibrillation with rapid ventricular response than did placebo given in combination with AV nodal blocking agents.

Citation: Bouida W et al. Low-dose magnesium sulfate versus high-dose in the early management of rapid atrial fibrillation: Randomized controlled double-blind study (LOMAGHI Study). Acad Emerg Med. 2019 Feb;26(2):183-91.

Low versus intermediate tidal volume strategy on ventilator-free days in ICU patients without ARDS

Randomized, clinical trial of low tidal volume versus intermediate tidal volume strategies in invasively ventilated patients without accute respiratory distress syndrome (ARDS) demonstrated no difference in number of ventilator-free days, ICU length of stay, hospital length of stay, incidence of ventilator-associated adverse events (ARDS, pneumonia, severe atelectasis, pneumothorax), or 28-day mortality.

Citation: Writing Group for the PReVENT Investigators, Simonis FD, Serpa Neto A. Effect of a low vs intermediate tidal volume strategy on ventilator-free days in intensive care unit patients without ARDS: A randomized clinical trial. JAMA. 2018;320(18):1872-80.

Physicians have been alarmed about the vaping craze for quite some time. This alarm has grown louder in the wake of news that electronic cigarettes have been associated with a mysterious lung disease.

LiudmylaSupynska/Thinkstock

Public health officials have reported that there have been 530 cases of vaping-related respiratory disease,¹ and as of press time at least seven deaths had been attributed to vaping*. On Sept. 6, 2019, the Food and Drug Administration, Centers for Disease Control and Prevention, and other health officials issued an investigation notice on vaping and e-cigarettes,² cautioning teenagers, young adults, and pregnant women to avoid e-cigarettes completely and cautioning all users to never buy e-cigarettes off the street or from social sources.

A few days later, on Sept. 9, the FDA’s Center for Tobacco Products issued a warning letter to JUUL Labs, makers of a popular e-cigarette, for illegal marketing of modified-risk tobacco products.³ Then on Sept. 10, health officials in Kansas reported that a sixth person has died of a lung illness related to vaping.⁴

Researchers have found that 80% of those diagnosed with the vaping illness used products that contained THC, the psychoactive ingredient in marijuana, 61% had used nicotine products, and 7% used cannabidiol (CBD) products. Vitamin E acetate is another substance identified in press reports as tied to the severe lung disease.

Most of the patients affected are adolescents and young adults, with the average age of 19 years.⁵ This comes as vaping among high school students rose 78% between 2017 and 2018.6 According the U.S. surgeon general, one in five teens vapes. Other data show that teen use of e-cigarettes comes with most users having never smoked a traditional cigarette.⁷ Teens and young adults frequently borrow buy* e-cigarette “pods” from gas stations but borrow and purchase from friends or peers. In addition, young people are known to alter the pods to insert other liquids, such as CBD and other marijuana products.

Teens and young adults are at higher risk for vaping complications. Their respiratory and immune systems are still developing. In addition to concerns about the recent surge of respiratory illnesses, nicotine is known to also suppress the immune system, which makes people who use it more susceptible to viral and bacterial infections – and also making it harder for them to recover.

In addition nicotine hyperactivates the reward centers of the brain, which can trigger addictive behaviors. Because the brains of young adults are not yet fully developed until at or after age 26, nicotine use before this can “prime the pump” of a still-developing brain, thereby increasing the likelihood for addiction to harder drugs. Nicotine has been shown to disrupt sleep patterns, which are critical for mental and physical health. Lastly, research shows that smoking increases the risks of various psychiatric disorders, such as depression and anxiety. My teen and young adult patients have endlessly debated with me the idea that smoking – either nicotine or marijuana – eases their anxiety or helps them get to sleep. I tell them that, in the long run, the data show that smoking makes those problems worse.^8-11

Nationally, we are seeing an explosion of multistate legislation pushing marijuana as a health food. E-cigarettes have followed as the “healthy” alternative to traditional tobacco. Unfortunately for our patients, the market has found a new way to promote e-cigarettes as the “cleaner, harmless” substitute to smoking. As clinicians, we must counter those messages.

Finally, our world is now filled with smartphones, sexting, and social media overuse. An entire peer group exists that knows life only with constant electronic stimulation. It is not without irony that our national nicotine obsessions have morphed from paper cigarettes to electronic versions. This raises questions: Are teens and young adults using e-cigarettes because of boredom? Are we witnessing a generational ADHD borne from restlessness that stems from lives with fewer meaningful face-to-face human interactions?

In addition to educating our teens and young adults about the physical risks tied to vaping, we need to teach them to build meaning into their lives that exists outside of this digital age.

Dr. Jorandby is chief medical officer of Lakeview Health in Jacksonville, Fla. She trained in addiction psychiatry at Yale University, New Haven, Conn.
 

References

1. CDC. Outbreak of lung injury associated with e-cigarette use, or vaping. 2019 Sep 19. 

2. CDC. Outbreak of lung illness associated with using e-cigarette products. Investigation notice. 2019 Sep 6.

3. FDA. Warning letter, JUUL Labs. 2019 Sep 9.

4. Sixth person dies of vaping-related illness. The Hill. 2019 Sep 10.

5. Layden JE. Pulmonary illness related to cigarette use in Illinois and Wisconsin – preliminary report. N Engl J Med. 2019 Sep 6. doi: 10.1056/NEJMoa1911614.

6. Cullen KA et al. CDC. MMWR. 2018 Nov 16;67(45):1276-7.

7. National Academies of Sciences, Engineering, and Medicine. Public health consequences of e-cigarettes. 2018.

8. Patton GC et al. Am J Public Health. 1996 Feb;86(2):225-30.

9. Leventhal AM et al. J Psychiatr Res. 2016 Feb;73:71-8.

10. Levine A et al. J Am Acad Child Adolesc Psychiatry. 2017 Mar;56(3):214-2.

11. Leadbeater BJ et al. Addiction. 2019 Feb;114(2):278-93.

* This column was updated 9/24/2019.

Physicians have been alarmed about the vaping craze for quite some time. This alarm has grown louder in the wake of news that electronic cigarettes have been associated with a mysterious lung disease.

LiudmylaSupynska/Thinkstock

Public health officials have reported that there have been 530 cases of vaping-related respiratory disease,¹ and as of press time at least seven deaths had been attributed to vaping*. On Sept. 6, 2019, the Food and Drug Administration, Centers for Disease Control and Prevention, and other health officials issued an investigation notice on vaping and e-cigarettes,² cautioning teenagers, young adults, and pregnant women to avoid e-cigarettes completely and cautioning all users to never buy e-cigarettes off the street or from social sources.

A few days later, on Sept. 9, the FDA’s Center for Tobacco Products issued a warning letter to JUUL Labs, makers of a popular e-cigarette, for illegal marketing of modified-risk tobacco products.³ Then on Sept. 10, health officials in Kansas reported that a sixth person has died of a lung illness related to vaping.⁴

Researchers have found that 80% of those diagnosed with the vaping illness used products that contained THC, the psychoactive ingredient in marijuana, 61% had used nicotine products, and 7% used cannabidiol (CBD) products. Vitamin E acetate is another substance identified in press reports as tied to the severe lung disease.

Most of the patients affected are adolescents and young adults, with the average age of 19 years.⁵ This comes as vaping among high school students rose 78% between 2017 and 2018.6 According the U.S. surgeon general, one in five teens vapes. Other data show that teen use of e-cigarettes comes with most users having never smoked a traditional cigarette.⁷ Teens and young adults frequently borrow buy* e-cigarette “pods” from gas stations but borrow and purchase from friends or peers. In addition, young people are known to alter the pods to insert other liquids, such as CBD and other marijuana products.

Teens and young adults are at higher risk for vaping complications. Their respiratory and immune systems are still developing. In addition to concerns about the recent surge of respiratory illnesses, nicotine is known to also suppress the immune system, which makes people who use it more susceptible to viral and bacterial infections – and also making it harder for them to recover.

In addition nicotine hyperactivates the reward centers of the brain, which can trigger addictive behaviors. Because the brains of young adults are not yet fully developed until at or after age 26, nicotine use before this can “prime the pump” of a still-developing brain, thereby increasing the likelihood for addiction to harder drugs. Nicotine has been shown to disrupt sleep patterns, which are critical for mental and physical health. Lastly, research shows that smoking increases the risks of various psychiatric disorders, such as depression and anxiety. My teen and young adult patients have endlessly debated with me the idea that smoking – either nicotine or marijuana – eases their anxiety or helps them get to sleep. I tell them that, in the long run, the data show that smoking makes those problems worse.^8-11

Nationally, we are seeing an explosion of multistate legislation pushing marijuana as a health food. E-cigarettes have followed as the “healthy” alternative to traditional tobacco. Unfortunately for our patients, the market has found a new way to promote e-cigarettes as the “cleaner, harmless” substitute to smoking. As clinicians, we must counter those messages.

Finally, our world is now filled with smartphones, sexting, and social media overuse. An entire peer group exists that knows life only with constant electronic stimulation. It is not without irony that our national nicotine obsessions have morphed from paper cigarettes to electronic versions. This raises questions: Are teens and young adults using e-cigarettes because of boredom? Are we witnessing a generational ADHD borne from restlessness that stems from lives with fewer meaningful face-to-face human interactions?

In addition to educating our teens and young adults about the physical risks tied to vaping, we need to teach them to build meaning into their lives that exists outside of this digital age.

Dr. Jorandby is chief medical officer of Lakeview Health in Jacksonville, Fla. She trained in addiction psychiatry at Yale University, New Haven, Conn.
 

References

1. CDC. Outbreak of lung injury associated with e-cigarette use, or vaping. 2019 Sep 19. 

2. CDC. Outbreak of lung illness associated with using e-cigarette products. Investigation notice. 2019 Sep 6.

3. FDA. Warning letter, JUUL Labs. 2019 Sep 9.

4. Sixth person dies of vaping-related illness. The Hill. 2019 Sep 10.

5. Layden JE. Pulmonary illness related to cigarette use in Illinois and Wisconsin – preliminary report. N Engl J Med. 2019 Sep 6. doi: 10.1056/NEJMoa1911614.

6. Cullen KA et al. CDC. MMWR. 2018 Nov 16;67(45):1276-7.

7. National Academies of Sciences, Engineering, and Medicine. Public health consequences of e-cigarettes. 2018.

8. Patton GC et al. Am J Public Health. 1996 Feb;86(2):225-30.

9. Leventhal AM et al. J Psychiatr Res. 2016 Feb;73:71-8.

10. Levine A et al. J Am Acad Child Adolesc Psychiatry. 2017 Mar;56(3):214-2.

11. Leadbeater BJ et al. Addiction. 2019 Feb;114(2):278-93.

* This column was updated 9/24/2019.

Physicians have been alarmed about the vaping craze for quite some time. This alarm has grown louder in the wake of news that electronic cigarettes have been associated with a mysterious lung disease.

LiudmylaSupynska/Thinkstock

Public health officials have reported that there have been 530 cases of vaping-related respiratory disease,¹ and as of press time at least seven deaths had been attributed to vaping*. On Sept. 6, 2019, the Food and Drug Administration, Centers for Disease Control and Prevention, and other health officials issued an investigation notice on vaping and e-cigarettes,² cautioning teenagers, young adults, and pregnant women to avoid e-cigarettes completely and cautioning all users to never buy e-cigarettes off the street or from social sources.

A few days later, on Sept. 9, the FDA’s Center for Tobacco Products issued a warning letter to JUUL Labs, makers of a popular e-cigarette, for illegal marketing of modified-risk tobacco products.³ Then on Sept. 10, health officials in Kansas reported that a sixth person has died of a lung illness related to vaping.⁴

Researchers have found that 80% of those diagnosed with the vaping illness used products that contained THC, the psychoactive ingredient in marijuana, 61% had used nicotine products, and 7% used cannabidiol (CBD) products. Vitamin E acetate is another substance identified in press reports as tied to the severe lung disease.

Most of the patients affected are adolescents and young adults, with the average age of 19 years.⁵ This comes as vaping among high school students rose 78% between 2017 and 2018.6 According the U.S. surgeon general, one in five teens vapes. Other data show that teen use of e-cigarettes comes with most users having never smoked a traditional cigarette.⁷ Teens and young adults frequently borrow buy* e-cigarette “pods” from gas stations but borrow and purchase from friends or peers. In addition, young people are known to alter the pods to insert other liquids, such as CBD and other marijuana products.

Teens and young adults are at higher risk for vaping complications. Their respiratory and immune systems are still developing. In addition to concerns about the recent surge of respiratory illnesses, nicotine is known to also suppress the immune system, which makes people who use it more susceptible to viral and bacterial infections – and also making it harder for them to recover.

In addition nicotine hyperactivates the reward centers of the brain, which can trigger addictive behaviors. Because the brains of young adults are not yet fully developed until at or after age 26, nicotine use before this can “prime the pump” of a still-developing brain, thereby increasing the likelihood for addiction to harder drugs. Nicotine has been shown to disrupt sleep patterns, which are critical for mental and physical health. Lastly, research shows that smoking increases the risks of various psychiatric disorders, such as depression and anxiety. My teen and young adult patients have endlessly debated with me the idea that smoking – either nicotine or marijuana – eases their anxiety or helps them get to sleep. I tell them that, in the long run, the data show that smoking makes those problems worse.^8-11

Nationally, we are seeing an explosion of multistate legislation pushing marijuana as a health food. E-cigarettes have followed as the “healthy” alternative to traditional tobacco. Unfortunately for our patients, the market has found a new way to promote e-cigarettes as the “cleaner, harmless” substitute to smoking. As clinicians, we must counter those messages.

Finally, our world is now filled with smartphones, sexting, and social media overuse. An entire peer group exists that knows life only with constant electronic stimulation. It is not without irony that our national nicotine obsessions have morphed from paper cigarettes to electronic versions. This raises questions: Are teens and young adults using e-cigarettes because of boredom? Are we witnessing a generational ADHD borne from restlessness that stems from lives with fewer meaningful face-to-face human interactions?

In addition to educating our teens and young adults about the physical risks tied to vaping, we need to teach them to build meaning into their lives that exists outside of this digital age.

Dr. Jorandby is chief medical officer of Lakeview Health in Jacksonville, Fla. She trained in addiction psychiatry at Yale University, New Haven, Conn.
 

References

1. CDC. Outbreak of lung injury associated with e-cigarette use, or vaping. 2019 Sep 19. 

2. CDC. Outbreak of lung illness associated with using e-cigarette products. Investigation notice. 2019 Sep 6.

3. FDA. Warning letter, JUUL Labs. 2019 Sep 9.

4. Sixth person dies of vaping-related illness. The Hill. 2019 Sep 10.

5. Layden JE. Pulmonary illness related to cigarette use in Illinois and Wisconsin – preliminary report. N Engl J Med. 2019 Sep 6. doi: 10.1056/NEJMoa1911614.

6. Cullen KA et al. CDC. MMWR. 2018 Nov 16;67(45):1276-7.

7. National Academies of Sciences, Engineering, and Medicine. Public health consequences of e-cigarettes. 2018.

8. Patton GC et al. Am J Public Health. 1996 Feb;86(2):225-30.

9. Leventhal AM et al. J Psychiatr Res. 2016 Feb;73:71-8.

10. Levine A et al. J Am Acad Child Adolesc Psychiatry. 2017 Mar;56(3):214-2.

11. Leadbeater BJ et al. Addiction. 2019 Feb;114(2):278-93.

* This column was updated 9/24/2019.