Pulmonology

An important measure of U.S. flu activity for the 2019-2020 season has already surpassed last season’s high, and more than half the states are experiencing high levels of activity, according to the Centers for Disease Control and Prevention.

Nationwide, visits for influenza-like illness represented 5.1% of all outpatient visits to health care providers for the week ending Dec. 21, up from 4.0% the week before and higher than at any point during the 2018-2019 season, the CDC influenza division reported Dec. 27.

The last time the outpatient visit rate was higher than that was in February of the 2017-2018 season, when it peaked at 7.5%. The peak month of flu activity occurs most often – about once every 3 years – in February, and the odds of a December peak are about one in five, the CDC has said.

Outpatient illness activity also increased at the state level during the week ending Dec. 21. There were 20 jurisdictions – 18 states, the District of Columbia, and Puerto Rico – at level 10 on the CDC’s 1-10 scale of activity, compared with 13 the previous week, and the number of jurisdictions in the “high” range (levels 8-10) jumped from 21 to 28, the CDC data show.

The influenza division estimated that there have been 4.6 million flu illnesses so far this season, nearly a million more than the total after last week, along with 39,000 hospitalizations. The overall hospitalization rate for the season is up to 6.6 per 100,000 population, which is about average at this point. The proportion of deaths attributed to pneumonia and influenza increased to 5.7%, which is below the epidemic threshold, the CDC said.

Three pediatric deaths related to influenza-like illness were reported during the week ending Dec. 21, two of which occurred in an earlier week. For the 2019-2020 season so far, a total of 22 pediatric deaths have been reported to the CDC.

[email protected]

An important measure of U.S. flu activity for the 2019-2020 season has already surpassed last season’s high, and more than half the states are experiencing high levels of activity, according to the Centers for Disease Control and Prevention.

Nationwide, visits for influenza-like illness represented 5.1% of all outpatient visits to health care providers for the week ending Dec. 21, up from 4.0% the week before and higher than at any point during the 2018-2019 season, the CDC influenza division reported Dec. 27.

The last time the outpatient visit rate was higher than that was in February of the 2017-2018 season, when it peaked at 7.5%. The peak month of flu activity occurs most often – about once every 3 years – in February, and the odds of a December peak are about one in five, the CDC has said.

Outpatient illness activity also increased at the state level during the week ending Dec. 21. There were 20 jurisdictions – 18 states, the District of Columbia, and Puerto Rico – at level 10 on the CDC’s 1-10 scale of activity, compared with 13 the previous week, and the number of jurisdictions in the “high” range (levels 8-10) jumped from 21 to 28, the CDC data show.

The influenza division estimated that there have been 4.6 million flu illnesses so far this season, nearly a million more than the total after last week, along with 39,000 hospitalizations. The overall hospitalization rate for the season is up to 6.6 per 100,000 population, which is about average at this point. The proportion of deaths attributed to pneumonia and influenza increased to 5.7%, which is below the epidemic threshold, the CDC said.

Three pediatric deaths related to influenza-like illness were reported during the week ending Dec. 21, two of which occurred in an earlier week. For the 2019-2020 season so far, a total of 22 pediatric deaths have been reported to the CDC.

[email protected]

An important measure of U.S. flu activity for the 2019-2020 season has already surpassed last season’s high, and more than half the states are experiencing high levels of activity, according to the Centers for Disease Control and Prevention.

Nationwide, visits for influenza-like illness represented 5.1% of all outpatient visits to health care providers for the week ending Dec. 21, up from 4.0% the week before and higher than at any point during the 2018-2019 season, the CDC influenza division reported Dec. 27.

The last time the outpatient visit rate was higher than that was in February of the 2017-2018 season, when it peaked at 7.5%. The peak month of flu activity occurs most often – about once every 3 years – in February, and the odds of a December peak are about one in five, the CDC has said.

Outpatient illness activity also increased at the state level during the week ending Dec. 21. There were 20 jurisdictions – 18 states, the District of Columbia, and Puerto Rico – at level 10 on the CDC’s 1-10 scale of activity, compared with 13 the previous week, and the number of jurisdictions in the “high” range (levels 8-10) jumped from 21 to 28, the CDC data show.

The influenza division estimated that there have been 4.6 million flu illnesses so far this season, nearly a million more than the total after last week, along with 39,000 hospitalizations. The overall hospitalization rate for the season is up to 6.6 per 100,000 population, which is about average at this point. The proportion of deaths attributed to pneumonia and influenza increased to 5.7%, which is below the epidemic threshold, the CDC said.

Three pediatric deaths related to influenza-like illness were reported during the week ending Dec. 21, two of which occurred in an earlier week. For the 2019-2020 season so far, a total of 22 pediatric deaths have been reported to the CDC.

[email protected]

A newly approved triple-combination modulator to treat cystic fibrosis (CF) has raised expectations of a treatment turning point among patients and specialists. If the early results are sustained, elexacaftor/ivacaftor/tezacaftor (Trikafta) could prove to be the rare case of a much-touted new medicine that meets high expectations.

Courtesy Susan Millard, MD

“CF even in infants causes inflammation, so we know that lung damage can start early and progress,” said Susan Millard, MD, FCCP, of Helen DeVos Children’s Hospital in Grand Rapids, Mich., and the local clinical research director for the pediatric pulmonary and sleep medicine section. “This oral drug therapy is actually treating the underlying problem, as opposed to many of the therapies we have that take hours to nebulize and only work locally in the airways.”

Dr. Millard is the recent past pediatric editor for Chest Physician and has been a local principal investigator at Helen DeVos Children’s Hospital for many Vertex-sponsored clinical studies.

The pivotal studies

The Food and Drug Administration approval of Trikafta rested on two pivotal phase 3, placebo-controlled studies, one in patients with two copies of the most common CF mutations, F508del, and the second in patients with one copy of F508del and a second mutation that was called a “minimal-function” mutation. The findings have ignited the hopes of many people with CF and their physicians. The drug was approved in October 2019 for patients aged 12 years and older who have at least one F508del mutation of the cystic fibrosis transmembrane conductance regulator gene. About 90% of patients in the United States have at least one copy of F508del. In the study looking at patients with one copy of F508del, the mean predicted forced expiratory volume in 1 second increased 13.8% in patients taking the drug versus placebo (N Engl J Med. 2019 Oct 31. doi: 10.1056/NEJMoa1908639). The number of pulmonary exacerbations decreased by 63% in the Trikafta group, compared with placebo. Pulmonary exacerbations were described as a change in specific symptoms that required treatment with a new oral, intravenous, or inhaled antibiotic. Serious adverse drug reactions that occurred more frequently in patients receiving Trikafta, compared with placebo, were rash and influenza events.

In the study that included patients with two copies of F508del, on average, the lung function increased 10% versus patients on ivacaftor/tezacaftor at 4 weeks. In addition, there was a 45.1 mmol/L on average decrease in the sweat chloride level in the Trikafta group, compared with ivacaftor/tezacaftor.
 

A hopeful start

Robert Giusti, MD, a pediatric pulmonologist at New York University Langone Health, is also hopeful. “This could be the kind of treatment that will make a revolution in terms of [cystic fibrosis] care if it can be started very early in life shortly after diagnosis. We anticipate that patients will be disease free for a longer period of time.”

The Cystic Fibrosis Foundation’s (CFF) “venture philanthropy” initiative played an important role in the development of the drug by Vertex Pharmaceuticals. The CFF has invested many millions of dollars in research by drug companies since the 1980s and was an early backer of Vertex. According to a statement on the CFF website, the Foundation sold its royalty rights for treatments developed by Vertex for $3.3 billion in 2014. The drug has a list price of about $311,000 a year. Payment issues may arise in the future, but for now, Vertex has stated that insurers and some Medicaid programs have begun paying claims for Trikafta

Specialists who treat CF now are watching to see how well patients tolerate this highly anticipated drug – and how well it meets expectations. The Therapeutic Development Network, the clinical research division of the CFF, is enrolling patients taking Trikafta in an observational study to follow for long-term follow-up.
 

Meeting expectations

“[Long-term efficacy is] something that we’re always concerned about. When the drug comes to market, is it going to be as effective as we thought it might be?” said Ryan Thomas, MD, director of the Cystic Fibrosis Center at Michigan State University, East Lansing. The MSU Cystic Fibrosis Center receives funding from the Cystic Fibrosis Foundation.

A different disease

Trikafta is the latest in a series of improvements of CF treatment in recent decades, recalled Dr. Giusti, who has been in this field for about 3 decades. “It used to be that I attended many funerals for children with CF. Now with patients living longer and healthier lives I am invited to attend their weddings and even their children’s baptisms and bris ceremonies. It is a very different disease than it used to be.”

The promise of Trikafta leaves behind the minority of patients for whom the drug won’t work. This is for the 10% of patients that have rare mutations. That can lead to difficult conversations with parents about why this new option is not a choice for their child, Dr. Millard said. “It just crushes you, but the Cystic Fibrosis Foundation is committing a lot of new research in that direction. Their mantra is ‘until it is done.’ ”
 

Realistic expectations

William (Randy) Hunt, MD, FAAP, FACP, assistant professor of medicine in the Division of Pulmonary, Allergy, Critical Care and Sleep, Emory University School of Medicine, Atlanta, agrees that Trikafta is an exciting development in CF treatment. He noted,  “Starting this medication early in life may very well significantly attenuate the disease, but it is not a cure. For individuals who already have significant disease, we may not see the same level of improvements in lung function as what we saw in the studies. The studies generally excluded individuals with ppFEV1 < 40%.  Nevertheless, I remain optimistic and have been prescribing it to nearly everyone that qualifies after a discussion.” 

Dr. Hunt added, “Patients are asking if they can stop their current chronic CF therapies once they start Trikafta. The answer is “no, at least not right now.” While all the relatively short-term data around Trikafta are very promising, we do not yet know how sustained the long-term benefits will be.  Still, safely removing therapeutic burden from our patient population is a real interest. There are plans underway by the CFF and other institutions to systematically research whether discontinuing chronic CF therapies is safe in the setting of Trikafta.”

He concluded that 10% of individuals with CF mutations still do not respond to the modulators currently available. “We will not leave that population behind, but treating these remaining mutations is going to take continued efforts and likely modulators that are therapeutically differently from the mechanism of actions of those that are currently available,” he said.
 

Therese Borden contributed to this article.

1/2/2020 - This story was updated.

A newly approved triple-combination modulator to treat cystic fibrosis (CF) has raised expectations of a treatment turning point among patients and specialists. If the early results are sustained, elexacaftor/ivacaftor/tezacaftor (Trikafta) could prove to be the rare case of a much-touted new medicine that meets high expectations.

Courtesy Susan Millard, MD

“CF even in infants causes inflammation, so we know that lung damage can start early and progress,” said Susan Millard, MD, FCCP, of Helen DeVos Children’s Hospital in Grand Rapids, Mich., and the local clinical research director for the pediatric pulmonary and sleep medicine section. “This oral drug therapy is actually treating the underlying problem, as opposed to many of the therapies we have that take hours to nebulize and only work locally in the airways.”

Dr. Millard is the recent past pediatric editor for Chest Physician and has been a local principal investigator at Helen DeVos Children’s Hospital for many Vertex-sponsored clinical studies.

The pivotal studies

The Food and Drug Administration approval of Trikafta rested on two pivotal phase 3, placebo-controlled studies, one in patients with two copies of the most common CF mutations, F508del, and the second in patients with one copy of F508del and a second mutation that was called a “minimal-function” mutation. The findings have ignited the hopes of many people with CF and their physicians. The drug was approved in October 2019 for patients aged 12 years and older who have at least one F508del mutation of the cystic fibrosis transmembrane conductance regulator gene. About 90% of patients in the United States have at least one copy of F508del. In the study looking at patients with one copy of F508del, the mean predicted forced expiratory volume in 1 second increased 13.8% in patients taking the drug versus placebo (N Engl J Med. 2019 Oct 31. doi: 10.1056/NEJMoa1908639). The number of pulmonary exacerbations decreased by 63% in the Trikafta group, compared with placebo. Pulmonary exacerbations were described as a change in specific symptoms that required treatment with a new oral, intravenous, or inhaled antibiotic. Serious adverse drug reactions that occurred more frequently in patients receiving Trikafta, compared with placebo, were rash and influenza events.

In the study that included patients with two copies of F508del, on average, the lung function increased 10% versus patients on ivacaftor/tezacaftor at 4 weeks. In addition, there was a 45.1 mmol/L on average decrease in the sweat chloride level in the Trikafta group, compared with ivacaftor/tezacaftor.
 

A hopeful start

Robert Giusti, MD, a pediatric pulmonologist at New York University Langone Health, is also hopeful. “This could be the kind of treatment that will make a revolution in terms of [cystic fibrosis] care if it can be started very early in life shortly after diagnosis. We anticipate that patients will be disease free for a longer period of time.”

The Cystic Fibrosis Foundation’s (CFF) “venture philanthropy” initiative played an important role in the development of the drug by Vertex Pharmaceuticals. The CFF has invested many millions of dollars in research by drug companies since the 1980s and was an early backer of Vertex. According to a statement on the CFF website, the Foundation sold its royalty rights for treatments developed by Vertex for $3.3 billion in 2014. The drug has a list price of about $311,000 a year. Payment issues may arise in the future, but for now, Vertex has stated that insurers and some Medicaid programs have begun paying claims for Trikafta

Specialists who treat CF now are watching to see how well patients tolerate this highly anticipated drug – and how well it meets expectations. The Therapeutic Development Network, the clinical research division of the CFF, is enrolling patients taking Trikafta in an observational study to follow for long-term follow-up.
 

Meeting expectations

“[Long-term efficacy is] something that we’re always concerned about. When the drug comes to market, is it going to be as effective as we thought it might be?” said Ryan Thomas, MD, director of the Cystic Fibrosis Center at Michigan State University, East Lansing. The MSU Cystic Fibrosis Center receives funding from the Cystic Fibrosis Foundation.

A different disease

Trikafta is the latest in a series of improvements of CF treatment in recent decades, recalled Dr. Giusti, who has been in this field for about 3 decades. “It used to be that I attended many funerals for children with CF. Now with patients living longer and healthier lives I am invited to attend their weddings and even their children’s baptisms and bris ceremonies. It is a very different disease than it used to be.”

The promise of Trikafta leaves behind the minority of patients for whom the drug won’t work. This is for the 10% of patients that have rare mutations. That can lead to difficult conversations with parents about why this new option is not a choice for their child, Dr. Millard said. “It just crushes you, but the Cystic Fibrosis Foundation is committing a lot of new research in that direction. Their mantra is ‘until it is done.’ ”
 

Realistic expectations

William (Randy) Hunt, MD, FAAP, FACP, assistant professor of medicine in the Division of Pulmonary, Allergy, Critical Care and Sleep, Emory University School of Medicine, Atlanta, agrees that Trikafta is an exciting development in CF treatment. He noted,  “Starting this medication early in life may very well significantly attenuate the disease, but it is not a cure. For individuals who already have significant disease, we may not see the same level of improvements in lung function as what we saw in the studies. The studies generally excluded individuals with ppFEV1 < 40%.  Nevertheless, I remain optimistic and have been prescribing it to nearly everyone that qualifies after a discussion.” 

Dr. Hunt added, “Patients are asking if they can stop their current chronic CF therapies once they start Trikafta. The answer is “no, at least not right now.” While all the relatively short-term data around Trikafta are very promising, we do not yet know how sustained the long-term benefits will be.  Still, safely removing therapeutic burden from our patient population is a real interest. There are plans underway by the CFF and other institutions to systematically research whether discontinuing chronic CF therapies is safe in the setting of Trikafta.”

He concluded that 10% of individuals with CF mutations still do not respond to the modulators currently available. “We will not leave that population behind, but treating these remaining mutations is going to take continued efforts and likely modulators that are therapeutically differently from the mechanism of actions of those that are currently available,” he said.
 

Therese Borden contributed to this article.

1/2/2020 - This story was updated.

A newly approved triple-combination modulator to treat cystic fibrosis (CF) has raised expectations of a treatment turning point among patients and specialists. If the early results are sustained, elexacaftor/ivacaftor/tezacaftor (Trikafta) could prove to be the rare case of a much-touted new medicine that meets high expectations.

Courtesy Susan Millard, MD

“CF even in infants causes inflammation, so we know that lung damage can start early and progress,” said Susan Millard, MD, FCCP, of Helen DeVos Children’s Hospital in Grand Rapids, Mich., and the local clinical research director for the pediatric pulmonary and sleep medicine section. “This oral drug therapy is actually treating the underlying problem, as opposed to many of the therapies we have that take hours to nebulize and only work locally in the airways.”

Dr. Millard is the recent past pediatric editor for Chest Physician and has been a local principal investigator at Helen DeVos Children’s Hospital for many Vertex-sponsored clinical studies.

The pivotal studies

The Food and Drug Administration approval of Trikafta rested on two pivotal phase 3, placebo-controlled studies, one in patients with two copies of the most common CF mutations, F508del, and the second in patients with one copy of F508del and a second mutation that was called a “minimal-function” mutation. The findings have ignited the hopes of many people with CF and their physicians. The drug was approved in October 2019 for patients aged 12 years and older who have at least one F508del mutation of the cystic fibrosis transmembrane conductance regulator gene. About 90% of patients in the United States have at least one copy of F508del. In the study looking at patients with one copy of F508del, the mean predicted forced expiratory volume in 1 second increased 13.8% in patients taking the drug versus placebo (N Engl J Med. 2019 Oct 31. doi: 10.1056/NEJMoa1908639). The number of pulmonary exacerbations decreased by 63% in the Trikafta group, compared with placebo. Pulmonary exacerbations were described as a change in specific symptoms that required treatment with a new oral, intravenous, or inhaled antibiotic. Serious adverse drug reactions that occurred more frequently in patients receiving Trikafta, compared with placebo, were rash and influenza events.

In the study that included patients with two copies of F508del, on average, the lung function increased 10% versus patients on ivacaftor/tezacaftor at 4 weeks. In addition, there was a 45.1 mmol/L on average decrease in the sweat chloride level in the Trikafta group, compared with ivacaftor/tezacaftor.
 

A hopeful start

Robert Giusti, MD, a pediatric pulmonologist at New York University Langone Health, is also hopeful. “This could be the kind of treatment that will make a revolution in terms of [cystic fibrosis] care if it can be started very early in life shortly after diagnosis. We anticipate that patients will be disease free for a longer period of time.”

The Cystic Fibrosis Foundation’s (CFF) “venture philanthropy” initiative played an important role in the development of the drug by Vertex Pharmaceuticals. The CFF has invested many millions of dollars in research by drug companies since the 1980s and was an early backer of Vertex. According to a statement on the CFF website, the Foundation sold its royalty rights for treatments developed by Vertex for $3.3 billion in 2014. The drug has a list price of about $311,000 a year. Payment issues may arise in the future, but for now, Vertex has stated that insurers and some Medicaid programs have begun paying claims for Trikafta

Specialists who treat CF now are watching to see how well patients tolerate this highly anticipated drug – and how well it meets expectations. The Therapeutic Development Network, the clinical research division of the CFF, is enrolling patients taking Trikafta in an observational study to follow for long-term follow-up.
 

Meeting expectations

“[Long-term efficacy is] something that we’re always concerned about. When the drug comes to market, is it going to be as effective as we thought it might be?” said Ryan Thomas, MD, director of the Cystic Fibrosis Center at Michigan State University, East Lansing. The MSU Cystic Fibrosis Center receives funding from the Cystic Fibrosis Foundation.

A different disease

Trikafta is the latest in a series of improvements of CF treatment in recent decades, recalled Dr. Giusti, who has been in this field for about 3 decades. “It used to be that I attended many funerals for children with CF. Now with patients living longer and healthier lives I am invited to attend their weddings and even their children’s baptisms and bris ceremonies. It is a very different disease than it used to be.”

The promise of Trikafta leaves behind the minority of patients for whom the drug won’t work. This is for the 10% of patients that have rare mutations. That can lead to difficult conversations with parents about why this new option is not a choice for their child, Dr. Millard said. “It just crushes you, but the Cystic Fibrosis Foundation is committing a lot of new research in that direction. Their mantra is ‘until it is done.’ ”
 

Realistic expectations

William (Randy) Hunt, MD, FAAP, FACP, assistant professor of medicine in the Division of Pulmonary, Allergy, Critical Care and Sleep, Emory University School of Medicine, Atlanta, agrees that Trikafta is an exciting development in CF treatment. He noted,  “Starting this medication early in life may very well significantly attenuate the disease, but it is not a cure. For individuals who already have significant disease, we may not see the same level of improvements in lung function as what we saw in the studies. The studies generally excluded individuals with ppFEV1 < 40%.  Nevertheless, I remain optimistic and have been prescribing it to nearly everyone that qualifies after a discussion.” 

Dr. Hunt added, “Patients are asking if they can stop their current chronic CF therapies once they start Trikafta. The answer is “no, at least not right now.” While all the relatively short-term data around Trikafta are very promising, we do not yet know how sustained the long-term benefits will be.  Still, safely removing therapeutic burden from our patient population is a real interest. There are plans underway by the CFF and other institutions to systematically research whether discontinuing chronic CF therapies is safe in the setting of Trikafta.”

He concluded that 10% of individuals with CF mutations still do not respond to the modulators currently available. “We will not leave that population behind, but treating these remaining mutations is going to take continued efforts and likely modulators that are therapeutically differently from the mechanism of actions of those that are currently available,” he said.
 

Therese Borden contributed to this article.

1/2/2020 - This story was updated.

Measles made a comeback in 2019.

The Centers for Disease Control and Prevention reported that, as of Dec. 5, 2019, 1,276 individual cases of measles of measles were confirmed in 31 states, the largest number since 1992. This number is a major uptick in cases, compared with previous years since 2000 when the CDC declared measles eliminated from the United States. No deaths have been reported for 2019.

Three-quarters of these cases in 2019 were linked to recent outbreaks in New York and occurred in primarily in underimmunized, close-knit communities and in patients with links to international travel. A total of 124 of the people who got measles this year were hospitalized, and 61 reported having complications, including pneumonia and encephalitis. The overall median patient age was 6 years (31% aged 1-4 years, 27% aged 5-17 years, and 29% aged at least 18 years).

The good news is that most of these cases occurred in unvaccinated patients. The national vaccination rate for the almost 4 million kindergartners reported as enrolled in 2018-2019 was 94.7% for two doses of the MMR vaccine, falling just short of the CDC recommended 95% vaccination rate threshold. The CDC reported an approximate 2.5% rate of vaccination exemptions among school-age children.

The bad news is that, despite the high rate of MMR vaccination rates among U.S. children, there are gaps in measles protection in the U.S. population because of factors leaving patients immunocompromised and antivaccination sentiment that has led some parents to defer or refuse the MMR.

In addition, adults who were vaccinated prior to 1968 with either inactivated measles vaccine or measles vaccine of unknown type may have limited immunity. The inactivated measles vaccine, which was available in 1963-1967, did not achieve effective measles protection.
 

A global measles surge

While antivaccination sentiment contributed to the 2019 measles cases, a more significant factor may be the global surge of measles. More than 140,000 people worldwide died from measles in 2018, according to the World Health Organization and the CDC.

“[Recent data on measles] indicates that during the first 6 months of the year there have been more measles cases reported worldwide than in any year since 2006. From Jan. 1 to July 31, 2019, 182 countries reported 364,808 measles cases to the WHO. This surpasses the 129,239 reported during the same time period in 2018. WHO regions with the biggest increases in cases include the African region (900%), the Western Pacific region (230%), and the European region (150%),” according to a CDC report.

Studies on hospitalization and complications linked to measles in the United States are scarce, but two outbreaks in Minnesota (2011 and 2017) provided some data on what to expect if the measles surge continues into 2020. The investigators found that poor feeding was a primary reason for admission (97%); additional complications included otitis media (42%), pneumonia (30%), and tracheitis (6%). Three-quarters received antibiotics, 30% required oxygen, and 21% received vitamin A. Median length of stay was 3.7 days (range, 1.1-26.2 days) (Pediatr Infect Dis J. 2019 Jun;38[6]:547-52. doi: 10.1097/INF.0000000000002221).
 

‘Immunological amnesia’

Infection with the measles virus appears to reduce immunity to other pathogens, according to a paper published in Science (2019 Nov 1;366[6465]599-606).

CDC/Dr. Edwin P. Ewing, Jr.

The hypothesis that the measles virus could cause “immunological amnesia” by impairing immune memory is supported by early research showing children with measles had negative cutaneous tuberculin reactions after having previously tested positive.

“Subsequent studies have shown decreased interferon signaling, skewed cytokine responses, lymphopenia, and suppression of lymphocyte proliferation shortly after infection,” wrote Michael Mina, MD, from Brigham and Women’s Hospital in Boston, and coauthors.

“Given the variation in the degree of immune repertoire modulation we observed, we anticipate that future risk of morbidity and mortality after measles would not be homogeneous but would be skewed toward individuals with the most severe elimination of immunological memory,” they wrote. “These findings underscore the crucial need for continued widespread vaccination.”

In this study, researchers compared the levels of around 400 pathogen-specific antibodies in blood samples from 77 unvaccinated children, taken before and 2 months after natural measles infection, with 5 unvaccinated children who did not contract measles. A total of 34 children experienced mild measles, and 43 had severe measles.

They found that the samples taken after measles infection showed “substantial” reductions in the number of pathogen epitopes, compared with the samples from children who did not get infected with measles.

This amounted to approximately a 20% mean reduction in overall diversity or size of the antibody repertoire. However, in children who experienced severe measles, there was a median loss of 40% (range, 11%-62%) of antibody repertoire, compared with a median of 33% (range, 12%-73%) range in children who experienced mild infection. Meanwhile, the control subjects retained approximately 90% of their antibody repertoire over a similar or longer time period. Some children lost up to 70% of antibodies for specific pathogens.
 

Maternal-acquired immunity fades

In another study of measles immunity, maternal antibodies were found to be insufficient to provide immunity to infants after 6 months.

The study of 196 infants showed that maternal measles antibodies had dropped below the protective threshold by 3 months of age – well before the recommended age of 12-15 months for the first dose of MMR vaccine.

The odds of inadequate protection doubled for each additional month of age, Michelle Science, MD, of the University of Toronto and associates reported in Pediatrics (2019 Dec 1. doi 10.1542/peds.2019-0630).

“The widening gap between loss of maternal antibodies and measles vaccination described in our study leaves infants vulnerable to measles for much of their infancy and highlights the need for further research to support public health policy,” Dr. Science and colleagues wrote.

The researchers randomly selected 25 samples for each of eight different age groups: up to 30 days old; 1 month (31-60 days), 2 months (61-89 days), 3 months (90-119 days), 4 months, 5 months, 6-9 months, and 9-11 months.

Just over half the babies (56%) were male, and 35% had an underlying condition, but none had conditions that might affect antibody levels. The conditions were primarily a developmental delay or otherwise affecting the central nervous system, liver, or gastrointestinal function. Mean maternal age was 32 years.

To ensure high test sensitivity, the researchers used the plaque-reduction neutralization test to test for measles-neutralizing antibodies instead of using enzyme-linked immunosorbent assay, because “ELISA sensitivity decreases as antibody titers decrease,” Dr. Science and colleagues wrote. They used a neutralization titer of less than 192 mIU/mL as the threshold for protection against measles.

When the researchers calculated the predicted standardized mean antibody titer for infants with a mother aged 32 years, they determined their mean to be 541 mIU/mL at 1 month, 142 mIU/mL at 3 months (below the measles threshold of susceptibility of 192 mIU/mL), and 64 mIU/mL at 6 months. None of the infants had measles antibodies above the protective threshold at 6 months old, the authors noted.

Children’s odds of susceptibility to measles doubled for each additional month of age, after adjustment for infant sex and maternal age (odds ratio, 2.13). Children’s likelihood of susceptibility to measles modestly increased as maternal age increased in 5-year increments from 25 to 40 years.

Children with an underlying conditions had greater susceptibility to measles (83%), compared with those without a comorbidity (68%, P = .03). No difference in susceptibility existed between males and females or based on gestational age at birth (ranging from 37 to 41 weeks).

The Advisory Committee on Immunization Practices permits measles vaccination “as early as 6 months for infants who plan to travel internationally, infants with ongoing risk for exposure during measles outbreaks and as postexposure prophylaxis,” Huong Q. McLean, PhD, of Marshfield (Wisc.) Clinic Research Institute, and Walter A. Orenstein, MD, of Emory University, Atlanta, noted in an editorial.

The research was funded by the Public Health Ontario Project Initiation Fund. The authors had no relevant financial disclosures.

[email protected]

Bianca Nogrady and Tara Haelle contributed to this story.

Measles made a comeback in 2019.

The Centers for Disease Control and Prevention reported that, as of Dec. 5, 2019, 1,276 individual cases of measles of measles were confirmed in 31 states, the largest number since 1992. This number is a major uptick in cases, compared with previous years since 2000 when the CDC declared measles eliminated from the United States. No deaths have been reported for 2019.

Three-quarters of these cases in 2019 were linked to recent outbreaks in New York and occurred in primarily in underimmunized, close-knit communities and in patients with links to international travel. A total of 124 of the people who got measles this year were hospitalized, and 61 reported having complications, including pneumonia and encephalitis. The overall median patient age was 6 years (31% aged 1-4 years, 27% aged 5-17 years, and 29% aged at least 18 years).

The good news is that most of these cases occurred in unvaccinated patients. The national vaccination rate for the almost 4 million kindergartners reported as enrolled in 2018-2019 was 94.7% for two doses of the MMR vaccine, falling just short of the CDC recommended 95% vaccination rate threshold. The CDC reported an approximate 2.5% rate of vaccination exemptions among school-age children.

The bad news is that, despite the high rate of MMR vaccination rates among U.S. children, there are gaps in measles protection in the U.S. population because of factors leaving patients immunocompromised and antivaccination sentiment that has led some parents to defer or refuse the MMR.

In addition, adults who were vaccinated prior to 1968 with either inactivated measles vaccine or measles vaccine of unknown type may have limited immunity. The inactivated measles vaccine, which was available in 1963-1967, did not achieve effective measles protection.
 

A global measles surge

While antivaccination sentiment contributed to the 2019 measles cases, a more significant factor may be the global surge of measles. More than 140,000 people worldwide died from measles in 2018, according to the World Health Organization and the CDC.

“[Recent data on measles] indicates that during the first 6 months of the year there have been more measles cases reported worldwide than in any year since 2006. From Jan. 1 to July 31, 2019, 182 countries reported 364,808 measles cases to the WHO. This surpasses the 129,239 reported during the same time period in 2018. WHO regions with the biggest increases in cases include the African region (900%), the Western Pacific region (230%), and the European region (150%),” according to a CDC report.

Studies on hospitalization and complications linked to measles in the United States are scarce, but two outbreaks in Minnesota (2011 and 2017) provided some data on what to expect if the measles surge continues into 2020. The investigators found that poor feeding was a primary reason for admission (97%); additional complications included otitis media (42%), pneumonia (30%), and tracheitis (6%). Three-quarters received antibiotics, 30% required oxygen, and 21% received vitamin A. Median length of stay was 3.7 days (range, 1.1-26.2 days) (Pediatr Infect Dis J. 2019 Jun;38[6]:547-52. doi: 10.1097/INF.0000000000002221).
 

‘Immunological amnesia’

Infection with the measles virus appears to reduce immunity to other pathogens, according to a paper published in Science (2019 Nov 1;366[6465]599-606).

CDC/Dr. Edwin P. Ewing, Jr.

The hypothesis that the measles virus could cause “immunological amnesia” by impairing immune memory is supported by early research showing children with measles had negative cutaneous tuberculin reactions after having previously tested positive.

“Subsequent studies have shown decreased interferon signaling, skewed cytokine responses, lymphopenia, and suppression of lymphocyte proliferation shortly after infection,” wrote Michael Mina, MD, from Brigham and Women’s Hospital in Boston, and coauthors.

“Given the variation in the degree of immune repertoire modulation we observed, we anticipate that future risk of morbidity and mortality after measles would not be homogeneous but would be skewed toward individuals with the most severe elimination of immunological memory,” they wrote. “These findings underscore the crucial need for continued widespread vaccination.”

In this study, researchers compared the levels of around 400 pathogen-specific antibodies in blood samples from 77 unvaccinated children, taken before and 2 months after natural measles infection, with 5 unvaccinated children who did not contract measles. A total of 34 children experienced mild measles, and 43 had severe measles.

They found that the samples taken after measles infection showed “substantial” reductions in the number of pathogen epitopes, compared with the samples from children who did not get infected with measles.

This amounted to approximately a 20% mean reduction in overall diversity or size of the antibody repertoire. However, in children who experienced severe measles, there was a median loss of 40% (range, 11%-62%) of antibody repertoire, compared with a median of 33% (range, 12%-73%) range in children who experienced mild infection. Meanwhile, the control subjects retained approximately 90% of their antibody repertoire over a similar or longer time period. Some children lost up to 70% of antibodies for specific pathogens.
 

Maternal-acquired immunity fades

In another study of measles immunity, maternal antibodies were found to be insufficient to provide immunity to infants after 6 months.

The study of 196 infants showed that maternal measles antibodies had dropped below the protective threshold by 3 months of age – well before the recommended age of 12-15 months for the first dose of MMR vaccine.

The odds of inadequate protection doubled for each additional month of age, Michelle Science, MD, of the University of Toronto and associates reported in Pediatrics (2019 Dec 1. doi 10.1542/peds.2019-0630).

“The widening gap between loss of maternal antibodies and measles vaccination described in our study leaves infants vulnerable to measles for much of their infancy and highlights the need for further research to support public health policy,” Dr. Science and colleagues wrote.

The researchers randomly selected 25 samples for each of eight different age groups: up to 30 days old; 1 month (31-60 days), 2 months (61-89 days), 3 months (90-119 days), 4 months, 5 months, 6-9 months, and 9-11 months.

Just over half the babies (56%) were male, and 35% had an underlying condition, but none had conditions that might affect antibody levels. The conditions were primarily a developmental delay or otherwise affecting the central nervous system, liver, or gastrointestinal function. Mean maternal age was 32 years.

To ensure high test sensitivity, the researchers used the plaque-reduction neutralization test to test for measles-neutralizing antibodies instead of using enzyme-linked immunosorbent assay, because “ELISA sensitivity decreases as antibody titers decrease,” Dr. Science and colleagues wrote. They used a neutralization titer of less than 192 mIU/mL as the threshold for protection against measles.

When the researchers calculated the predicted standardized mean antibody titer for infants with a mother aged 32 years, they determined their mean to be 541 mIU/mL at 1 month, 142 mIU/mL at 3 months (below the measles threshold of susceptibility of 192 mIU/mL), and 64 mIU/mL at 6 months. None of the infants had measles antibodies above the protective threshold at 6 months old, the authors noted.

Children’s odds of susceptibility to measles doubled for each additional month of age, after adjustment for infant sex and maternal age (odds ratio, 2.13). Children’s likelihood of susceptibility to measles modestly increased as maternal age increased in 5-year increments from 25 to 40 years.

Children with an underlying conditions had greater susceptibility to measles (83%), compared with those without a comorbidity (68%, P = .03). No difference in susceptibility existed between males and females or based on gestational age at birth (ranging from 37 to 41 weeks).

The Advisory Committee on Immunization Practices permits measles vaccination “as early as 6 months for infants who plan to travel internationally, infants with ongoing risk for exposure during measles outbreaks and as postexposure prophylaxis,” Huong Q. McLean, PhD, of Marshfield (Wisc.) Clinic Research Institute, and Walter A. Orenstein, MD, of Emory University, Atlanta, noted in an editorial.

The research was funded by the Public Health Ontario Project Initiation Fund. The authors had no relevant financial disclosures.

[email protected]

Bianca Nogrady and Tara Haelle contributed to this story.

Measles made a comeback in 2019.

The Centers for Disease Control and Prevention reported that, as of Dec. 5, 2019, 1,276 individual cases of measles of measles were confirmed in 31 states, the largest number since 1992. This number is a major uptick in cases, compared with previous years since 2000 when the CDC declared measles eliminated from the United States. No deaths have been reported for 2019.

Three-quarters of these cases in 2019 were linked to recent outbreaks in New York and occurred in primarily in underimmunized, close-knit communities and in patients with links to international travel. A total of 124 of the people who got measles this year were hospitalized, and 61 reported having complications, including pneumonia and encephalitis. The overall median patient age was 6 years (31% aged 1-4 years, 27% aged 5-17 years, and 29% aged at least 18 years).

The good news is that most of these cases occurred in unvaccinated patients. The national vaccination rate for the almost 4 million kindergartners reported as enrolled in 2018-2019 was 94.7% for two doses of the MMR vaccine, falling just short of the CDC recommended 95% vaccination rate threshold. The CDC reported an approximate 2.5% rate of vaccination exemptions among school-age children.

The bad news is that, despite the high rate of MMR vaccination rates among U.S. children, there are gaps in measles protection in the U.S. population because of factors leaving patients immunocompromised and antivaccination sentiment that has led some parents to defer or refuse the MMR.

In addition, adults who were vaccinated prior to 1968 with either inactivated measles vaccine or measles vaccine of unknown type may have limited immunity. The inactivated measles vaccine, which was available in 1963-1967, did not achieve effective measles protection.
 

A global measles surge

While antivaccination sentiment contributed to the 2019 measles cases, a more significant factor may be the global surge of measles. More than 140,000 people worldwide died from measles in 2018, according to the World Health Organization and the CDC.

“[Recent data on measles] indicates that during the first 6 months of the year there have been more measles cases reported worldwide than in any year since 2006. From Jan. 1 to July 31, 2019, 182 countries reported 364,808 measles cases to the WHO. This surpasses the 129,239 reported during the same time period in 2018. WHO regions with the biggest increases in cases include the African region (900%), the Western Pacific region (230%), and the European region (150%),” according to a CDC report.

Studies on hospitalization and complications linked to measles in the United States are scarce, but two outbreaks in Minnesota (2011 and 2017) provided some data on what to expect if the measles surge continues into 2020. The investigators found that poor feeding was a primary reason for admission (97%); additional complications included otitis media (42%), pneumonia (30%), and tracheitis (6%). Three-quarters received antibiotics, 30% required oxygen, and 21% received vitamin A. Median length of stay was 3.7 days (range, 1.1-26.2 days) (Pediatr Infect Dis J. 2019 Jun;38[6]:547-52. doi: 10.1097/INF.0000000000002221).
 

‘Immunological amnesia’

Infection with the measles virus appears to reduce immunity to other pathogens, according to a paper published in Science (2019 Nov 1;366[6465]599-606).

CDC/Dr. Edwin P. Ewing, Jr.

The hypothesis that the measles virus could cause “immunological amnesia” by impairing immune memory is supported by early research showing children with measles had negative cutaneous tuberculin reactions after having previously tested positive.

“Subsequent studies have shown decreased interferon signaling, skewed cytokine responses, lymphopenia, and suppression of lymphocyte proliferation shortly after infection,” wrote Michael Mina, MD, from Brigham and Women’s Hospital in Boston, and coauthors.

“Given the variation in the degree of immune repertoire modulation we observed, we anticipate that future risk of morbidity and mortality after measles would not be homogeneous but would be skewed toward individuals with the most severe elimination of immunological memory,” they wrote. “These findings underscore the crucial need for continued widespread vaccination.”

In this study, researchers compared the levels of around 400 pathogen-specific antibodies in blood samples from 77 unvaccinated children, taken before and 2 months after natural measles infection, with 5 unvaccinated children who did not contract measles. A total of 34 children experienced mild measles, and 43 had severe measles.

They found that the samples taken after measles infection showed “substantial” reductions in the number of pathogen epitopes, compared with the samples from children who did not get infected with measles.

This amounted to approximately a 20% mean reduction in overall diversity or size of the antibody repertoire. However, in children who experienced severe measles, there was a median loss of 40% (range, 11%-62%) of antibody repertoire, compared with a median of 33% (range, 12%-73%) range in children who experienced mild infection. Meanwhile, the control subjects retained approximately 90% of their antibody repertoire over a similar or longer time period. Some children lost up to 70% of antibodies for specific pathogens.
 

Maternal-acquired immunity fades

In another study of measles immunity, maternal antibodies were found to be insufficient to provide immunity to infants after 6 months.

The study of 196 infants showed that maternal measles antibodies had dropped below the protective threshold by 3 months of age – well before the recommended age of 12-15 months for the first dose of MMR vaccine.

The odds of inadequate protection doubled for each additional month of age, Michelle Science, MD, of the University of Toronto and associates reported in Pediatrics (2019 Dec 1. doi 10.1542/peds.2019-0630).

“The widening gap between loss of maternal antibodies and measles vaccination described in our study leaves infants vulnerable to measles for much of their infancy and highlights the need for further research to support public health policy,” Dr. Science and colleagues wrote.

The researchers randomly selected 25 samples for each of eight different age groups: up to 30 days old; 1 month (31-60 days), 2 months (61-89 days), 3 months (90-119 days), 4 months, 5 months, 6-9 months, and 9-11 months.

Just over half the babies (56%) were male, and 35% had an underlying condition, but none had conditions that might affect antibody levels. The conditions were primarily a developmental delay or otherwise affecting the central nervous system, liver, or gastrointestinal function. Mean maternal age was 32 years.

To ensure high test sensitivity, the researchers used the plaque-reduction neutralization test to test for measles-neutralizing antibodies instead of using enzyme-linked immunosorbent assay, because “ELISA sensitivity decreases as antibody titers decrease,” Dr. Science and colleagues wrote. They used a neutralization titer of less than 192 mIU/mL as the threshold for protection against measles.

When the researchers calculated the predicted standardized mean antibody titer for infants with a mother aged 32 years, they determined their mean to be 541 mIU/mL at 1 month, 142 mIU/mL at 3 months (below the measles threshold of susceptibility of 192 mIU/mL), and 64 mIU/mL at 6 months. None of the infants had measles antibodies above the protective threshold at 6 months old, the authors noted.

Children’s odds of susceptibility to measles doubled for each additional month of age, after adjustment for infant sex and maternal age (odds ratio, 2.13). Children’s likelihood of susceptibility to measles modestly increased as maternal age increased in 5-year increments from 25 to 40 years.

Children with an underlying conditions had greater susceptibility to measles (83%), compared with those without a comorbidity (68%, P = .03). No difference in susceptibility existed between males and females or based on gestational age at birth (ranging from 37 to 41 weeks).

The Advisory Committee on Immunization Practices permits measles vaccination “as early as 6 months for infants who plan to travel internationally, infants with ongoing risk for exposure during measles outbreaks and as postexposure prophylaxis,” Huong Q. McLean, PhD, of Marshfield (Wisc.) Clinic Research Institute, and Walter A. Orenstein, MD, of Emory University, Atlanta, noted in an editorial.

The research was funded by the Public Health Ontario Project Initiation Fund. The authors had no relevant financial disclosures.

[email protected]

Bianca Nogrady and Tara Haelle contributed to this story.

At least a quarter of rehospitalizations for vaping-related lung injuries occurred within 2 days of initial discharge, and 13.5% of all deaths have occurred after patients left the hospital, according to the U.S. Centers for Disease Control and Prevention.

Those who required rehospitalization for e-cigarette or vaping product use–associated lung injury (EVALI) and those who died after discharge were more likely to have one or more chronic conditions than were other EVALI patients, and those “who died also were more likely to have been admitted to an intensive care unit, experienced respiratory failure necessitating intubation and mechanical ventilation, and were significantly older,” Christina A. Mikosz, MD, and associates wrote in the Morbidity and Mortality Weekly Report.

Their analysis included the 1,139 EVALI patients who were discharged on or after Oct. 31, 2019. Of that group, 31 (2.7%) patients were rehospitalized and subsequently discharged and another 7 died after the initial discharge. The median age was 54 years for those who died, 27 years for those who were rehospitalized, and 23 for those who survived without rehospitalization, said Dr. Mikosz of the CDC National Center for Injury Prevention and Control, Atlanta, and associates.

Those findings, along with the rates of one or more comorbidities – 83% for those who died, 71% for those who were rehospitalized, and 26% for those who did not die or get readmitted – prompted the CDC to update its guidance for postdischarge follow-up of EVALI patients.

That update involves six specific recommendations to determine readiness for discharge, which include “confirming no clinically significant fluctuations in vital signs for at least 24-48 hours before discharge [and] preparation for hospital discharge and postdischarge care coordination to reduce risk of rehospitalization and death,” Mary E. Evans, MD, and associates said in a separate CDC communication (MMWR. 2019 Dec. 20. 68[early release]:1-6).

As of Dec. 17, the CDC reports that 2,506 patients have been hospitalized with EVALI since March 31, 2019, and 54 deaths have been confirmed in 27 states and the District of Columbia. The outbreak appears to have peaked in September, but cases are still being reported: 13 during the week of Dec. 1-7 and one case for the week of Dec. 8-14.

[email protected]

SOURCE: Mikosz CA et al. MMWR. 2019 Dec. 20. 68[early release]:1-7.

At least a quarter of rehospitalizations for vaping-related lung injuries occurred within 2 days of initial discharge, and 13.5% of all deaths have occurred after patients left the hospital, according to the U.S. Centers for Disease Control and Prevention.

Those who required rehospitalization for e-cigarette or vaping product use–associated lung injury (EVALI) and those who died after discharge were more likely to have one or more chronic conditions than were other EVALI patients, and those “who died also were more likely to have been admitted to an intensive care unit, experienced respiratory failure necessitating intubation and mechanical ventilation, and were significantly older,” Christina A. Mikosz, MD, and associates wrote in the Morbidity and Mortality Weekly Report.

Their analysis included the 1,139 EVALI patients who were discharged on or after Oct. 31, 2019. Of that group, 31 (2.7%) patients were rehospitalized and subsequently discharged and another 7 died after the initial discharge. The median age was 54 years for those who died, 27 years for those who were rehospitalized, and 23 for those who survived without rehospitalization, said Dr. Mikosz of the CDC National Center for Injury Prevention and Control, Atlanta, and associates.

Those findings, along with the rates of one or more comorbidities – 83% for those who died, 71% for those who were rehospitalized, and 26% for those who did not die or get readmitted – prompted the CDC to update its guidance for postdischarge follow-up of EVALI patients.

That update involves six specific recommendations to determine readiness for discharge, which include “confirming no clinically significant fluctuations in vital signs for at least 24-48 hours before discharge [and] preparation for hospital discharge and postdischarge care coordination to reduce risk of rehospitalization and death,” Mary E. Evans, MD, and associates said in a separate CDC communication (MMWR. 2019 Dec. 20. 68[early release]:1-6).

As of Dec. 17, the CDC reports that 2,506 patients have been hospitalized with EVALI since March 31, 2019, and 54 deaths have been confirmed in 27 states and the District of Columbia. The outbreak appears to have peaked in September, but cases are still being reported: 13 during the week of Dec. 1-7 and one case for the week of Dec. 8-14.

[email protected]

SOURCE: Mikosz CA et al. MMWR. 2019 Dec. 20. 68[early release]:1-7.

At least a quarter of rehospitalizations for vaping-related lung injuries occurred within 2 days of initial discharge, and 13.5% of all deaths have occurred after patients left the hospital, according to the U.S. Centers for Disease Control and Prevention.

Those who required rehospitalization for e-cigarette or vaping product use–associated lung injury (EVALI) and those who died after discharge were more likely to have one or more chronic conditions than were other EVALI patients, and those “who died also were more likely to have been admitted to an intensive care unit, experienced respiratory failure necessitating intubation and mechanical ventilation, and were significantly older,” Christina A. Mikosz, MD, and associates wrote in the Morbidity and Mortality Weekly Report.

Their analysis included the 1,139 EVALI patients who were discharged on or after Oct. 31, 2019. Of that group, 31 (2.7%) patients were rehospitalized and subsequently discharged and another 7 died after the initial discharge. The median age was 54 years for those who died, 27 years for those who were rehospitalized, and 23 for those who survived without rehospitalization, said Dr. Mikosz of the CDC National Center for Injury Prevention and Control, Atlanta, and associates.

Those findings, along with the rates of one or more comorbidities – 83% for those who died, 71% for those who were rehospitalized, and 26% for those who did not die or get readmitted – prompted the CDC to update its guidance for postdischarge follow-up of EVALI patients.

That update involves six specific recommendations to determine readiness for discharge, which include “confirming no clinically significant fluctuations in vital signs for at least 24-48 hours before discharge [and] preparation for hospital discharge and postdischarge care coordination to reduce risk of rehospitalization and death,” Mary E. Evans, MD, and associates said in a separate CDC communication (MMWR. 2019 Dec. 20. 68[early release]:1-6).

As of Dec. 17, the CDC reports that 2,506 patients have been hospitalized with EVALI since March 31, 2019, and 54 deaths have been confirmed in 27 states and the District of Columbia. The outbreak appears to have peaked in September, but cases are still being reported: 13 during the week of Dec. 1-7 and one case for the week of Dec. 8-14.

[email protected]

SOURCE: Mikosz CA et al. MMWR. 2019 Dec. 20. 68[early release]:1-7.

Vitamin E acetate was found in fluid from the lungs of 94% of patients with electronic cigarette, or vaping, product use–associated lung injury, data from a convenience sample of 51 patients indicate. The findings were published in the New England Journal of Medicine.

Cases of electronic cigarette, or vaping, product use–associated lung injury (EVALI) were reported to the Centers for Disease Control and Prevention starting in early 2019, and numbers rose throughout the year, “which suggests new or increased exposure to one or more toxicants from the use of e-cigarette products,” wrote Benjamin C. Blount, PhD, of the National Center for Environmental Health at the CDC, and colleagues.

To further investigate potential toxins in patients with EVALI, the researchers examined bronchoalveolar-lavage (BAL) fluid from 51 EVALI patients and 99 healthy controls.

After the researchers used isotope dilution mass spectrometry on the samples, 48 of the 51 patients (94%) showed vitamin E acetate in their BAL samples. No other potential toxins – including plant oils, medium-chain triglyceride oil, petroleum distillates, and diluent terpenes – were identified. The samples of one patient each showed coconut oil and limonene.

A total of 47 of 51 patients for whom complete laboratory data were available either reported vaping tetrahydrocannabinol products within 90 days of becoming ill, or showed tetrahydrocannabinol or its metabolites in their BAL fluid. In addition, 30 of 47 patients showed nicotine or nicotine metabolites in their BAL fluid.

The average age of the patients was 23 years, 69% were male. Overall, 25 were confirmed EVALI cases and 26 were probable cases, and probable cases included the three patients who showed no vitamin E acetate.

The safety of inhaling vitamin E acetate, which is a common ingredient in dietary supplements and skin care creams, has not been well studied. It could contribute to lung injury when heated in e-cigarette products by splitting the acetate to create the reactive compound and potential lung irritant ketene, the researchers said.

The study findings were limited by several factors including the possibility that vitamin E acetate is a marker for exposure to other toxicants, a lack of data on the impact of heating vitamin e acetate, and the inability to assess the timing of the vitamin E acetate exposure compared to BAL sample collection, the researchers noted.

However, the results suggest that vitamin E acetate may play a role in EVALI because of the high detection rate in patients from across the United States, the biologically possible potential for lung injury from vitamin e acetate, and the timing of the rise of EVALI and the use of vitamin E acetate in vaping products, they concluded.

The research was supported by the National Cancer Institute, the FDA Center for Tobacco Products, and The Ohio State University Pelotonia intramural research program. The authors had no financial conflicts to disclose.

SOURCE: Blount BC et al. N Engl J Med. 2019 Dec 20. doi: 10.1056/NEJMoa1916433.

Vitamin E acetate was found in fluid from the lungs of 94% of patients with electronic cigarette, or vaping, product use–associated lung injury, data from a convenience sample of 51 patients indicate. The findings were published in the New England Journal of Medicine.

Cases of electronic cigarette, or vaping, product use–associated lung injury (EVALI) were reported to the Centers for Disease Control and Prevention starting in early 2019, and numbers rose throughout the year, “which suggests new or increased exposure to one or more toxicants from the use of e-cigarette products,” wrote Benjamin C. Blount, PhD, of the National Center for Environmental Health at the CDC, and colleagues.

To further investigate potential toxins in patients with EVALI, the researchers examined bronchoalveolar-lavage (BAL) fluid from 51 EVALI patients and 99 healthy controls.

After the researchers used isotope dilution mass spectrometry on the samples, 48 of the 51 patients (94%) showed vitamin E acetate in their BAL samples. No other potential toxins – including plant oils, medium-chain triglyceride oil, petroleum distillates, and diluent terpenes – were identified. The samples of one patient each showed coconut oil and limonene.

A total of 47 of 51 patients for whom complete laboratory data were available either reported vaping tetrahydrocannabinol products within 90 days of becoming ill, or showed tetrahydrocannabinol or its metabolites in their BAL fluid. In addition, 30 of 47 patients showed nicotine or nicotine metabolites in their BAL fluid.

The average age of the patients was 23 years, 69% were male. Overall, 25 were confirmed EVALI cases and 26 were probable cases, and probable cases included the three patients who showed no vitamin E acetate.

The safety of inhaling vitamin E acetate, which is a common ingredient in dietary supplements and skin care creams, has not been well studied. It could contribute to lung injury when heated in e-cigarette products by splitting the acetate to create the reactive compound and potential lung irritant ketene, the researchers said.

The study findings were limited by several factors including the possibility that vitamin E acetate is a marker for exposure to other toxicants, a lack of data on the impact of heating vitamin e acetate, and the inability to assess the timing of the vitamin E acetate exposure compared to BAL sample collection, the researchers noted.

However, the results suggest that vitamin E acetate may play a role in EVALI because of the high detection rate in patients from across the United States, the biologically possible potential for lung injury from vitamin e acetate, and the timing of the rise of EVALI and the use of vitamin E acetate in vaping products, they concluded.

The research was supported by the National Cancer Institute, the FDA Center for Tobacco Products, and The Ohio State University Pelotonia intramural research program. The authors had no financial conflicts to disclose.

SOURCE: Blount BC et al. N Engl J Med. 2019 Dec 20. doi: 10.1056/NEJMoa1916433.

Vitamin E acetate was found in fluid from the lungs of 94% of patients with electronic cigarette, or vaping, product use–associated lung injury, data from a convenience sample of 51 patients indicate. The findings were published in the New England Journal of Medicine.

Cases of electronic cigarette, or vaping, product use–associated lung injury (EVALI) were reported to the Centers for Disease Control and Prevention starting in early 2019, and numbers rose throughout the year, “which suggests new or increased exposure to one or more toxicants from the use of e-cigarette products,” wrote Benjamin C. Blount, PhD, of the National Center for Environmental Health at the CDC, and colleagues.

To further investigate potential toxins in patients with EVALI, the researchers examined bronchoalveolar-lavage (BAL) fluid from 51 EVALI patients and 99 healthy controls.

After the researchers used isotope dilution mass spectrometry on the samples, 48 of the 51 patients (94%) showed vitamin E acetate in their BAL samples. No other potential toxins – including plant oils, medium-chain triglyceride oil, petroleum distillates, and diluent terpenes – were identified. The samples of one patient each showed coconut oil and limonene.

A total of 47 of 51 patients for whom complete laboratory data were available either reported vaping tetrahydrocannabinol products within 90 days of becoming ill, or showed tetrahydrocannabinol or its metabolites in their BAL fluid. In addition, 30 of 47 patients showed nicotine or nicotine metabolites in their BAL fluid.

The average age of the patients was 23 years, 69% were male. Overall, 25 were confirmed EVALI cases and 26 were probable cases, and probable cases included the three patients who showed no vitamin E acetate.

The safety of inhaling vitamin E acetate, which is a common ingredient in dietary supplements and skin care creams, has not been well studied. It could contribute to lung injury when heated in e-cigarette products by splitting the acetate to create the reactive compound and potential lung irritant ketene, the researchers said.

The study findings were limited by several factors including the possibility that vitamin E acetate is a marker for exposure to other toxicants, a lack of data on the impact of heating vitamin e acetate, and the inability to assess the timing of the vitamin E acetate exposure compared to BAL sample collection, the researchers noted.

However, the results suggest that vitamin E acetate may play a role in EVALI because of the high detection rate in patients from across the United States, the biologically possible potential for lung injury from vitamin e acetate, and the timing of the rise of EVALI and the use of vitamin E acetate in vaping products, they concluded.

The research was supported by the National Cancer Institute, the FDA Center for Tobacco Products, and The Ohio State University Pelotonia intramural research program. The authors had no financial conflicts to disclose.

SOURCE: Blount BC et al. N Engl J Med. 2019 Dec 20. doi: 10.1056/NEJMoa1916433.

The 2019-2020 flu season continues its unusually early rise in activity, with the Centers for Disease Control and Prevention estimating that 3.7 million cases have occurred through Dec. 14.

Patients with influenza-like illness (ILI) accounted for an estimated 3.9% of all outpatient visits to health care professionals for the week of Dec. 8-14, which is up from 3.2% the previous week and is the sixth consecutive week that the United States has been at or above the national baseline of 2.4%, the CDC reported Dec. 20. This year’s 3.9% is the highest mid-December rate recorded since 2003, when it reached almost 7.4%.

Most of the influenza activity so far this season is being driven by influenza B/Victoria viruses. Nationwide testing puts influenza B prevalence at 68.5% of all positive specimens, exactly the same as last week, but A(H1N1) viruses “are increasing in proportion relative to other influenza viruses in some regions,” the CDC’s influenza division said.

A look at this week’s activity map shows that 21 states, compared with 12 last week, were in the “high” range of activity – that’s levels 8-10 on the CDC’s 1-10 scale. Twelve of those states, along with Puerto Rico, were at level 10, which was up from nine a week earlier, the CDC said.

The overall hospitalization rate through the week of Dec. 8-14 (5.5 per 100,000 population) “is similar to what has been seen at this time during recent seasons,” the CDC noted. The highest rates are occurring among adults over age 65 years (12.7 per 100,000) and children aged 0-4 years (10.9 per 100,000).

Three ILI-related deaths among children that occurred last week were reported, which brings the total for the 2019-2020 season to 19, the CDC said.

[email protected]

The 2019-2020 flu season continues its unusually early rise in activity, with the Centers for Disease Control and Prevention estimating that 3.7 million cases have occurred through Dec. 14.

Patients with influenza-like illness (ILI) accounted for an estimated 3.9% of all outpatient visits to health care professionals for the week of Dec. 8-14, which is up from 3.2% the previous week and is the sixth consecutive week that the United States has been at or above the national baseline of 2.4%, the CDC reported Dec. 20. This year’s 3.9% is the highest mid-December rate recorded since 2003, when it reached almost 7.4%.

Most of the influenza activity so far this season is being driven by influenza B/Victoria viruses. Nationwide testing puts influenza B prevalence at 68.5% of all positive specimens, exactly the same as last week, but A(H1N1) viruses “are increasing in proportion relative to other influenza viruses in some regions,” the CDC’s influenza division said.

A look at this week’s activity map shows that 21 states, compared with 12 last week, were in the “high” range of activity – that’s levels 8-10 on the CDC’s 1-10 scale. Twelve of those states, along with Puerto Rico, were at level 10, which was up from nine a week earlier, the CDC said.

The overall hospitalization rate through the week of Dec. 8-14 (5.5 per 100,000 population) “is similar to what has been seen at this time during recent seasons,” the CDC noted. The highest rates are occurring among adults over age 65 years (12.7 per 100,000) and children aged 0-4 years (10.9 per 100,000).

Three ILI-related deaths among children that occurred last week were reported, which brings the total for the 2019-2020 season to 19, the CDC said.

[email protected]

The 2019-2020 flu season continues its unusually early rise in activity, with the Centers for Disease Control and Prevention estimating that 3.7 million cases have occurred through Dec. 14.

Patients with influenza-like illness (ILI) accounted for an estimated 3.9% of all outpatient visits to health care professionals for the week of Dec. 8-14, which is up from 3.2% the previous week and is the sixth consecutive week that the United States has been at or above the national baseline of 2.4%, the CDC reported Dec. 20. This year’s 3.9% is the highest mid-December rate recorded since 2003, when it reached almost 7.4%.

Most of the influenza activity so far this season is being driven by influenza B/Victoria viruses. Nationwide testing puts influenza B prevalence at 68.5% of all positive specimens, exactly the same as last week, but A(H1N1) viruses “are increasing in proportion relative to other influenza viruses in some regions,” the CDC’s influenza division said.

A look at this week’s activity map shows that 21 states, compared with 12 last week, were in the “high” range of activity – that’s levels 8-10 on the CDC’s 1-10 scale. Twelve of those states, along with Puerto Rico, were at level 10, which was up from nine a week earlier, the CDC said.

The overall hospitalization rate through the week of Dec. 8-14 (5.5 per 100,000 population) “is similar to what has been seen at this time during recent seasons,” the CDC noted. The highest rates are occurring among adults over age 65 years (12.7 per 100,000) and children aged 0-4 years (10.9 per 100,000).

Three ILI-related deaths among children that occurred last week were reported, which brings the total for the 2019-2020 season to 19, the CDC said.

[email protected]

Vaping has expanded as a popular method of drug delivery for U.S. teenagers, and one in five students in grades 10 and 12 reported vaping marijuana in the past year, according to results of the 2019 Monitoring the Future survey conducted by the National Institute on Drug Abuse (NIDA).

licsiren/iStock/Getty Images

This year’s findings, announced Dec. 18, continue to illustrate “a clear shift in the pattern of drug taking among teenagers,” said NIDA Director Nora D. Volkow, MD, in a teleconference held to review the results.

Use of alcohol and drugs – including opioids and stimulants – continues to decline among teens, but vaping continues its significant rise, with a surge in marijuana vaping this year.

The increase in past-month marijuana vaping among 12th graders, from 7.5% in 2018 to 14% in 2019, represents the second-largest 1-year jump tracked for any substance in the survey’s history, Dr. Volkow said. The largest jump was the increase in past-month nicotine vaping among 12th-graders from 2017-2018.

Past-year marijuana vaping has more than doubled in the past 2 years, with rates this year of 20.8% among 12th-graders, 19.4% among 10th-graders, and 7.0% among 8th-graders.

“It is very unfortunate that we are seeing the steep rise in the use of vaping devices” because the devices deliver drugs in very high concentration, Dr. Volkow said. The growing popularity of vaping “threatens to undo years of progress protecting the health of adolescents in the U.S.,” Dr. Volkow said in a statement. The Monitoring the Future survey began including vaping questions in 2017.

Monitoring the Future is a national tool to assess drug and alcohol use and related attitudes among adolescent students across the United States. This year’s self-reported survey included 42,531 in grades 8, 10, and 12 from 396 public and private schools.

Nicotine vaping increased from 2018 to 2019 across all three grades; past-month nicotine use equated to 1 in 4, 1 in 5, and 1 in 10 (26%, 20%, and 10%) among 12th, 10th, and 8th graders, respectively, according to the survey. Daily nicotine vaping, measured for the first time this year because of public health concerns, was approximately 12% for 12th graders, 7% for 10th graders, and 2% for 8th graders. Daily marijuana vaping, also measured for the first time this year, was approximately 4%, 3%, and 1% among 12th, 10th, and 8th graders, respectively. Additional findings on the rise of vaping by U.S. teenagers were released Dec. 17 in a research letter published online in JAMA (doi: 10.1001/jama.2019.20185).

Meanwhile, positive trends in this year’s survey included a reduction in the misuse of prescription drugs, including OxyContin, Vicodin, and Adderall, and in the use of traditional cigarettes and other tobacco products, as well as alcohol, noted Richard A. Miech, PhD, MPH, of the University of Michigan, Ann Arbor, principal investigator for Monitoring the Future. However, the challenge of preventing and reducing vaping in teens remains “a whole new uncharted territory,” in part because the design of the vaping devices facilitates discreet use at home and at school, he said.

Physicians and parents have important roles to play in screening for vaping among teens, Dr. Volkow said in a question and answer session. Health care clinicians, including pediatricians and family physicians, “are in a unique position to communicate with their young patients” by educating them about the dangers of vaping, encouraging them to stop if they have started using these devices, and referring them for further treatment if they are showing signs of addiction, she said.

Monitoring the Future was funded by NIDA. The researchers had no disclosures.

Vaping has expanded as a popular method of drug delivery for U.S. teenagers, and one in five students in grades 10 and 12 reported vaping marijuana in the past year, according to results of the 2019 Monitoring the Future survey conducted by the National Institute on Drug Abuse (NIDA).

licsiren/iStock/Getty Images

This year’s findings, announced Dec. 18, continue to illustrate “a clear shift in the pattern of drug taking among teenagers,” said NIDA Director Nora D. Volkow, MD, in a teleconference held to review the results.

Use of alcohol and drugs – including opioids and stimulants – continues to decline among teens, but vaping continues its significant rise, with a surge in marijuana vaping this year.

The increase in past-month marijuana vaping among 12th graders, from 7.5% in 2018 to 14% in 2019, represents the second-largest 1-year jump tracked for any substance in the survey’s history, Dr. Volkow said. The largest jump was the increase in past-month nicotine vaping among 12th-graders from 2017-2018.

Past-year marijuana vaping has more than doubled in the past 2 years, with rates this year of 20.8% among 12th-graders, 19.4% among 10th-graders, and 7.0% among 8th-graders.

“It is very unfortunate that we are seeing the steep rise in the use of vaping devices” because the devices deliver drugs in very high concentration, Dr. Volkow said. The growing popularity of vaping “threatens to undo years of progress protecting the health of adolescents in the U.S.,” Dr. Volkow said in a statement. The Monitoring the Future survey began including vaping questions in 2017.

Monitoring the Future is a national tool to assess drug and alcohol use and related attitudes among adolescent students across the United States. This year’s self-reported survey included 42,531 in grades 8, 10, and 12 from 396 public and private schools.

Nicotine vaping increased from 2018 to 2019 across all three grades; past-month nicotine use equated to 1 in 4, 1 in 5, and 1 in 10 (26%, 20%, and 10%) among 12th, 10th, and 8th graders, respectively, according to the survey. Daily nicotine vaping, measured for the first time this year because of public health concerns, was approximately 12% for 12th graders, 7% for 10th graders, and 2% for 8th graders. Daily marijuana vaping, also measured for the first time this year, was approximately 4%, 3%, and 1% among 12th, 10th, and 8th graders, respectively. Additional findings on the rise of vaping by U.S. teenagers were released Dec. 17 in a research letter published online in JAMA (doi: 10.1001/jama.2019.20185).

Meanwhile, positive trends in this year’s survey included a reduction in the misuse of prescription drugs, including OxyContin, Vicodin, and Adderall, and in the use of traditional cigarettes and other tobacco products, as well as alcohol, noted Richard A. Miech, PhD, MPH, of the University of Michigan, Ann Arbor, principal investigator for Monitoring the Future. However, the challenge of preventing and reducing vaping in teens remains “a whole new uncharted territory,” in part because the design of the vaping devices facilitates discreet use at home and at school, he said.

Physicians and parents have important roles to play in screening for vaping among teens, Dr. Volkow said in a question and answer session. Health care clinicians, including pediatricians and family physicians, “are in a unique position to communicate with their young patients” by educating them about the dangers of vaping, encouraging them to stop if they have started using these devices, and referring them for further treatment if they are showing signs of addiction, she said.

Monitoring the Future was funded by NIDA. The researchers had no disclosures.

Vaping has expanded as a popular method of drug delivery for U.S. teenagers, and one in five students in grades 10 and 12 reported vaping marijuana in the past year, according to results of the 2019 Monitoring the Future survey conducted by the National Institute on Drug Abuse (NIDA).

licsiren/iStock/Getty Images

This year’s findings, announced Dec. 18, continue to illustrate “a clear shift in the pattern of drug taking among teenagers,” said NIDA Director Nora D. Volkow, MD, in a teleconference held to review the results.

Use of alcohol and drugs – including opioids and stimulants – continues to decline among teens, but vaping continues its significant rise, with a surge in marijuana vaping this year.

The increase in past-month marijuana vaping among 12th graders, from 7.5% in 2018 to 14% in 2019, represents the second-largest 1-year jump tracked for any substance in the survey’s history, Dr. Volkow said. The largest jump was the increase in past-month nicotine vaping among 12th-graders from 2017-2018.

Past-year marijuana vaping has more than doubled in the past 2 years, with rates this year of 20.8% among 12th-graders, 19.4% among 10th-graders, and 7.0% among 8th-graders.

“It is very unfortunate that we are seeing the steep rise in the use of vaping devices” because the devices deliver drugs in very high concentration, Dr. Volkow said. The growing popularity of vaping “threatens to undo years of progress protecting the health of adolescents in the U.S.,” Dr. Volkow said in a statement. The Monitoring the Future survey began including vaping questions in 2017.

Monitoring the Future is a national tool to assess drug and alcohol use and related attitudes among adolescent students across the United States. This year’s self-reported survey included 42,531 in grades 8, 10, and 12 from 396 public and private schools.

Nicotine vaping increased from 2018 to 2019 across all three grades; past-month nicotine use equated to 1 in 4, 1 in 5, and 1 in 10 (26%, 20%, and 10%) among 12th, 10th, and 8th graders, respectively, according to the survey. Daily nicotine vaping, measured for the first time this year because of public health concerns, was approximately 12% for 12th graders, 7% for 10th graders, and 2% for 8th graders. Daily marijuana vaping, also measured for the first time this year, was approximately 4%, 3%, and 1% among 12th, 10th, and 8th graders, respectively. Additional findings on the rise of vaping by U.S. teenagers were released Dec. 17 in a research letter published online in JAMA (doi: 10.1001/jama.2019.20185).

Meanwhile, positive trends in this year’s survey included a reduction in the misuse of prescription drugs, including OxyContin, Vicodin, and Adderall, and in the use of traditional cigarettes and other tobacco products, as well as alcohol, noted Richard A. Miech, PhD, MPH, of the University of Michigan, Ann Arbor, principal investigator for Monitoring the Future. However, the challenge of preventing and reducing vaping in teens remains “a whole new uncharted territory,” in part because the design of the vaping devices facilitates discreet use at home and at school, he said.

Physicians and parents have important roles to play in screening for vaping among teens, Dr. Volkow said in a question and answer session. Health care clinicians, including pediatricians and family physicians, “are in a unique position to communicate with their young patients” by educating them about the dangers of vaping, encouraging them to stop if they have started using these devices, and referring them for further treatment if they are showing signs of addiction, she said.

Monitoring the Future was funded by NIDA. The researchers had no disclosures.

A study using a new definition of early chronic obstructive pulmonary disease (COPD) has found that about 15% of Danish smokers under the age of 50 years meet the criteria.

The population-based cohort looked at individuals who had been exposed to at least 10 pack-years, and defined early COPD as the ratio of forced expiratory volume to forced vital capacity being less than the lower limit of normal (FEV₁/FVC less than LLN). The definition of early COPD, published in 2018 (Am J Resp and Crit Care Med. 2018;197:1540-51), also included the presence of abnormalities on a CT scan or a decline in FEV₁ (greater than 60 mL/year) that is accelerated relative to FVC, but the new population study did not include the latter two criteria.

The researchers, under corresponding author Peter Lange, MD, of the University of Copenhagen found that those with early COPD were more likely to have chronic respiratory symptoms, severe impairment of lung function, acute respirator hospitalization, and early mortality at baseline and at follow-up. The work was published in the American Journal of Respiratory and Critical Care Medicine.

“To dig through the smokers and try to figure out which smokers are more at risk than other smokers is probably the best way to summarize what they’ve done here,” said Robert Reed, MD, from the University of Maryland, Baltimore, in an interview. However, he added that he would like to see the research extended to an even younger population, as well as nonsmokers. “We don’t need all of this information to tell us that smoking is bad. I think nonsmokers would be really interesting – creating a definition of COPD that excludes patients that meet the usual definition for COPD would be of potential interest,” added Dr. Reed, who was not involved in the study.

Using a cohort of 105,630 randomly selected individuals from Danish nationwide health registries, the study identified 8,064 individuals aged under 50 years with 10 or more pack-years of tobacco exposure. In this group, 1,175 (15%) had early COPD, of whom 58% were current smokers. The cohort of smokers was followed for up to 14.4 years. Multivariate analyses found that those with early COPD, compared with smokers without COPD, were at substantially greater risk of acute obstructive lung disease hospitalization (hazard ratio, 6.42; 95% confidence interval, 3.39-12.2), acute pneumonia hospitalization (HR, 2.03; 95% CI, 1.43-2.88), and all-cause mortality (HR, 1.79; 95% CI, 1.28-2.52).

There is value in gaining a better understanding of which smokers are at greatest risk of COPD down the line, but data on younger people, even 30-year-olds, could guide therapeutic decisions when and if new drugs that can alter the state of the disease become available. Focusing more on younger, high-risk patients could also be used to create greater incentives to quit smoking, though Dr. Reed has mixed feelings even about that. “What if we identified 15% of smokers that are at risk of COPD, and the other 85% say, ‘I’ll keep smoking,’ and they fall over dead from a heart attack?” said Dr. Reed, noting that smoking has a wide range of known risks. “They should all stop,” he added.

The study also captures a wide range of patients, from some with early disease that will likely progress to COPD later in life along with some who already developed full-blown COPD in, for example, their early 40s. “Those are very different patients and to lump them together is potentially problematic,” said Dr. Reed. More granulated data could potentially inform more personalized medicine, and the discovery and verification of genetic risk factors.

Nevertheless, Dr. Reed expects the data to move the field forward. “They created a nice, rich database that I think will generate a lot more analysis and discussion.”

The study was funded by the Lundbeck Foundation. One of the authors has received support from the National Institute for Health Research Manchester (England) Biomedical Research Centre. Dr. Reed has no relevant financial disclosures.

SOURCE: Colak Y et al. Am J Resp Crit Care Med. 2019 Nov 26. doi: 10.1164/rccm.201908-1644OC

A study using a new definition of early chronic obstructive pulmonary disease (COPD) has found that about 15% of Danish smokers under the age of 50 years meet the criteria.

The population-based cohort looked at individuals who had been exposed to at least 10 pack-years, and defined early COPD as the ratio of forced expiratory volume to forced vital capacity being less than the lower limit of normal (FEV₁/FVC less than LLN). The definition of early COPD, published in 2018 (Am J Resp and Crit Care Med. 2018;197:1540-51), also included the presence of abnormalities on a CT scan or a decline in FEV₁ (greater than 60 mL/year) that is accelerated relative to FVC, but the new population study did not include the latter two criteria.

The researchers, under corresponding author Peter Lange, MD, of the University of Copenhagen found that those with early COPD were more likely to have chronic respiratory symptoms, severe impairment of lung function, acute respirator hospitalization, and early mortality at baseline and at follow-up. The work was published in the American Journal of Respiratory and Critical Care Medicine.

“To dig through the smokers and try to figure out which smokers are more at risk than other smokers is probably the best way to summarize what they’ve done here,” said Robert Reed, MD, from the University of Maryland, Baltimore, in an interview. However, he added that he would like to see the research extended to an even younger population, as well as nonsmokers. “We don’t need all of this information to tell us that smoking is bad. I think nonsmokers would be really interesting – creating a definition of COPD that excludes patients that meet the usual definition for COPD would be of potential interest,” added Dr. Reed, who was not involved in the study.

Using a cohort of 105,630 randomly selected individuals from Danish nationwide health registries, the study identified 8,064 individuals aged under 50 years with 10 or more pack-years of tobacco exposure. In this group, 1,175 (15%) had early COPD, of whom 58% were current smokers. The cohort of smokers was followed for up to 14.4 years. Multivariate analyses found that those with early COPD, compared with smokers without COPD, were at substantially greater risk of acute obstructive lung disease hospitalization (hazard ratio, 6.42; 95% confidence interval, 3.39-12.2), acute pneumonia hospitalization (HR, 2.03; 95% CI, 1.43-2.88), and all-cause mortality (HR, 1.79; 95% CI, 1.28-2.52).

There is value in gaining a better understanding of which smokers are at greatest risk of COPD down the line, but data on younger people, even 30-year-olds, could guide therapeutic decisions when and if new drugs that can alter the state of the disease become available. Focusing more on younger, high-risk patients could also be used to create greater incentives to quit smoking, though Dr. Reed has mixed feelings even about that. “What if we identified 15% of smokers that are at risk of COPD, and the other 85% say, ‘I’ll keep smoking,’ and they fall over dead from a heart attack?” said Dr. Reed, noting that smoking has a wide range of known risks. “They should all stop,” he added.

The study also captures a wide range of patients, from some with early disease that will likely progress to COPD later in life along with some who already developed full-blown COPD in, for example, their early 40s. “Those are very different patients and to lump them together is potentially problematic,” said Dr. Reed. More granulated data could potentially inform more personalized medicine, and the discovery and verification of genetic risk factors.

Nevertheless, Dr. Reed expects the data to move the field forward. “They created a nice, rich database that I think will generate a lot more analysis and discussion.”

The study was funded by the Lundbeck Foundation. One of the authors has received support from the National Institute for Health Research Manchester (England) Biomedical Research Centre. Dr. Reed has no relevant financial disclosures.

SOURCE: Colak Y et al. Am J Resp Crit Care Med. 2019 Nov 26. doi: 10.1164/rccm.201908-1644OC

A study using a new definition of early chronic obstructive pulmonary disease (COPD) has found that about 15% of Danish smokers under the age of 50 years meet the criteria.

The population-based cohort looked at individuals who had been exposed to at least 10 pack-years, and defined early COPD as the ratio of forced expiratory volume to forced vital capacity being less than the lower limit of normal (FEV₁/FVC less than LLN). The definition of early COPD, published in 2018 (Am J Resp and Crit Care Med. 2018;197:1540-51), also included the presence of abnormalities on a CT scan or a decline in FEV₁ (greater than 60 mL/year) that is accelerated relative to FVC, but the new population study did not include the latter two criteria.

The researchers, under corresponding author Peter Lange, MD, of the University of Copenhagen found that those with early COPD were more likely to have chronic respiratory symptoms, severe impairment of lung function, acute respirator hospitalization, and early mortality at baseline and at follow-up. The work was published in the American Journal of Respiratory and Critical Care Medicine.

“To dig through the smokers and try to figure out which smokers are more at risk than other smokers is probably the best way to summarize what they’ve done here,” said Robert Reed, MD, from the University of Maryland, Baltimore, in an interview. However, he added that he would like to see the research extended to an even younger population, as well as nonsmokers. “We don’t need all of this information to tell us that smoking is bad. I think nonsmokers would be really interesting – creating a definition of COPD that excludes patients that meet the usual definition for COPD would be of potential interest,” added Dr. Reed, who was not involved in the study.

Using a cohort of 105,630 randomly selected individuals from Danish nationwide health registries, the study identified 8,064 individuals aged under 50 years with 10 or more pack-years of tobacco exposure. In this group, 1,175 (15%) had early COPD, of whom 58% were current smokers. The cohort of smokers was followed for up to 14.4 years. Multivariate analyses found that those with early COPD, compared with smokers without COPD, were at substantially greater risk of acute obstructive lung disease hospitalization (hazard ratio, 6.42; 95% confidence interval, 3.39-12.2), acute pneumonia hospitalization (HR, 2.03; 95% CI, 1.43-2.88), and all-cause mortality (HR, 1.79; 95% CI, 1.28-2.52).

There is value in gaining a better understanding of which smokers are at greatest risk of COPD down the line, but data on younger people, even 30-year-olds, could guide therapeutic decisions when and if new drugs that can alter the state of the disease become available. Focusing more on younger, high-risk patients could also be used to create greater incentives to quit smoking, though Dr. Reed has mixed feelings even about that. “What if we identified 15% of smokers that are at risk of COPD, and the other 85% say, ‘I’ll keep smoking,’ and they fall over dead from a heart attack?” said Dr. Reed, noting that smoking has a wide range of known risks. “They should all stop,” he added.

The study also captures a wide range of patients, from some with early disease that will likely progress to COPD later in life along with some who already developed full-blown COPD in, for example, their early 40s. “Those are very different patients and to lump them together is potentially problematic,” said Dr. Reed. More granulated data could potentially inform more personalized medicine, and the discovery and verification of genetic risk factors.

Nevertheless, Dr. Reed expects the data to move the field forward. “They created a nice, rich database that I think will generate a lot more analysis and discussion.”

The study was funded by the Lundbeck Foundation. One of the authors has received support from the National Institute for Health Research Manchester (England) Biomedical Research Centre. Dr. Reed has no relevant financial disclosures.

SOURCE: Colak Y et al. Am J Resp Crit Care Med. 2019 Nov 26. doi: 10.1164/rccm.201908-1644OC

The unusually high levels of flu activity seen at the end of November have been followed by a decrease in activity, according to the Centers for Disease Control and Prevention.

Nationally, 3.2% of outpatient visits were for influenza-like illness (ILI) during the week of Dec. 1-7, the CDC reported. That is down from 3.4% the week before, which was the highest November rate in 10 years. The national baseline rate is 2.4%, and the current 3.2% marks the fifth consecutive week that the outpatient ILI rate has been at or above the baseline level, the CDC report noted.

The drop in activity “may be influenced in part by a reduction in routine healthcare visits surrounding the Thanksgiving holiday. … as has occurred during previous seasons,” the CDC influenza division said Dec. 13 in its weekly flu report.

The early spike in “activity is being caused mostly by influenza B/Victoria viruses, which is unusual for this time of year,” the report said. Since the beginning of the 2019-2020 season a little over 2 months ago, almost 70% of specimens that have been positive for influenza have been identified as type B.

The nationwide decline in activity doesn’t, however, show up at the state level. For the week ending Dec. 7, there were eight states along with Puerto Rico at level 10 on the CDC’s 1-10 scale of flu activity, as there were the previous week. Washington state moved up from 9 to 10, but Louisiana, which was at level 10 last week, had insufficient data to be included this week, the CDC data show.

There were four flu-related pediatric deaths reported to the CDC during the week ending Dec. 7, all occurring in previous weeks, which brings the total to 10 for the season. In 2018-2019, there were 143 pediatric deaths caused by influenza, the CDC said.

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The unusually high levels of flu activity seen at the end of November have been followed by a decrease in activity, according to the Centers for Disease Control and Prevention.

Nationally, 3.2% of outpatient visits were for influenza-like illness (ILI) during the week of Dec. 1-7, the CDC reported. That is down from 3.4% the week before, which was the highest November rate in 10 years. The national baseline rate is 2.4%, and the current 3.2% marks the fifth consecutive week that the outpatient ILI rate has been at or above the baseline level, the CDC report noted.

The drop in activity “may be influenced in part by a reduction in routine healthcare visits surrounding the Thanksgiving holiday. … as has occurred during previous seasons,” the CDC influenza division said Dec. 13 in its weekly flu report.

The early spike in “activity is being caused mostly by influenza B/Victoria viruses, which is unusual for this time of year,” the report said. Since the beginning of the 2019-2020 season a little over 2 months ago, almost 70% of specimens that have been positive for influenza have been identified as type B.

The nationwide decline in activity doesn’t, however, show up at the state level. For the week ending Dec. 7, there were eight states along with Puerto Rico at level 10 on the CDC’s 1-10 scale of flu activity, as there were the previous week. Washington state moved up from 9 to 10, but Louisiana, which was at level 10 last week, had insufficient data to be included this week, the CDC data show.

There were four flu-related pediatric deaths reported to the CDC during the week ending Dec. 7, all occurring in previous weeks, which brings the total to 10 for the season. In 2018-2019, there were 143 pediatric deaths caused by influenza, the CDC said.

[email protected]

The unusually high levels of flu activity seen at the end of November have been followed by a decrease in activity, according to the Centers for Disease Control and Prevention.

Nationally, 3.2% of outpatient visits were for influenza-like illness (ILI) during the week of Dec. 1-7, the CDC reported. That is down from 3.4% the week before, which was the highest November rate in 10 years. The national baseline rate is 2.4%, and the current 3.2% marks the fifth consecutive week that the outpatient ILI rate has been at or above the baseline level, the CDC report noted.

The drop in activity “may be influenced in part by a reduction in routine healthcare visits surrounding the Thanksgiving holiday. … as has occurred during previous seasons,” the CDC influenza division said Dec. 13 in its weekly flu report.

The early spike in “activity is being caused mostly by influenza B/Victoria viruses, which is unusual for this time of year,” the report said. Since the beginning of the 2019-2020 season a little over 2 months ago, almost 70% of specimens that have been positive for influenza have been identified as type B.

The nationwide decline in activity doesn’t, however, show up at the state level. For the week ending Dec. 7, there were eight states along with Puerto Rico at level 10 on the CDC’s 1-10 scale of flu activity, as there were the previous week. Washington state moved up from 9 to 10, but Louisiana, which was at level 10 last week, had insufficient data to be included this week, the CDC data show.

There were four flu-related pediatric deaths reported to the CDC during the week ending Dec. 7, all occurring in previous weeks, which brings the total to 10 for the season. In 2018-2019, there were 143 pediatric deaths caused by influenza, the CDC said.

[email protected]

Women with asthma who suffer asthma exacerbation while pregnant are at increased risk for complications during pregnancy and delivery, and their infants are at increased risk for respiratory problems, according to data from a longitudinal study of 58,524 women with asthma.

Vesnaandjic/E+/Getty Images

“Asthma exacerbation during pregnancy has been found to be associated with adverse perinatal and pregnancy outcomes such as low birth weight, small for gestational age, preterm delivery, congenital malformation, preeclampsia, and perinatal mortality,” but previous studies have been small and limited to comparisons of asthmatic and nonasthmatic women, wrote Kawsari Abdullah, PhD, of Children’s Hospital of Eastern Ontario, Ottawa, and colleagues.

To determine the impact of asthma exacerbation on maternal and fetal outcomes, the researchers analyzed data from the Ontario Asthma Surveillance Information System to identify women with asthma who had at least one pregnancy resulting in a live or still birth between 2006 and 2012.

Overall, significantly more women with exacerbated asthma had preeclampsia or pregnancy-induced hypertension, compared with asthmatic women who had no exacerbations, at 5% vs. 4% and 7% vs. 5%, respectively (P less than .001), according to the study published in the European Respiratory Journal.

Adverse perinatal outcomes were significantly more likely among babies of mothers with exacerbated asthma, compared with those who had no exacerbations, including low birth weight (7% vs. 5%), small for gestational age (3% vs. 2%), preterm birth (8% vs. 7%), and congenital malformation (6% vs. 5%). All P values were less than .001, except for small for gestational age, which was P = .008.

In addition, significantly more babies of asthmatic women with exacerbated asthma during pregnancy had respiratory problems including asthma and pneumonia, compared with those of asthmatic women who had no exacerbations during pregnancy, at 38% vs. 31% and 24% vs. 22% (P less than .001 for both). The researchers found no significant interactions between maternal age and smoking and asthma exacerbations.

The findings were limited by several factors, including the lack of a validated algorithm for asthma exacerbation, which the researchers defined as five or more visits to a general practice clinician for asthma during pregnancy. Other limitations included the lack of categorizing asthma exacerbation by severity, and the inability to include the potential effects of asthma medication on maternal and fetal outcomes, Dr. Abdullah and colleagues noted.

However, the results were strengthened by the large sample size and ability to follow babies from birth until 5 years of age, they said.

“Targeting women with asthma during pregnancy and ensuring appropriate asthma management and postpartum follow-up may help to reduce the risk of pregnancy complications, adverse perinatal outcomes, and early childhood respiratory disorders,” they concluded.

This study is important because asthma is a common, potentially serious medical condition that complicates approximately 4%-8% of pregnancies, and one in three women with asthma experience an exacerbation during pregnancy, Iris Krishna, MD, a specialist in maternal/fetal medicine at Emory University, Atlanta, said in an interview.

“This study is unique in that it uses population-level data to assess the association between an asthma exacerbation during pregnancy and adverse perinatal outcomes,” Dr. Krishna said. “After adjusting for confounders, and consistent with previous studies, study findings suggest an increased risk for women with asthma who have an asthma exacerbation during pregnancy for preeclampsia [odds ratio, 1.3; P less than .001], pregnancy-induced hypertension [OR, 1.17; P less than .05], low-birth-weight infant [OR, 1.14; P less than .05], preterm birth [OR, 1.14; P less than .05], and congenital malformations [OR, 1.21; P less than .001].”

Dr. Krishna also noted the impact on early childhood outcomes. “In this study, children born to women who had an asthma exacerbation during pregnancy had a 23% higher risk of developing asthma before 5 years of age, which is consistent with previous studies. [The] investigators also reported a 12% higher risk of having pneumonia during the first 5 years of life for children born to women who had an asthma exacerbation during pregnancy.”

“Previous studies have suggested children born to mothers with uncontrolled asthma have an increased risk for respiratory infections, but this study is the first to report an association with pneumonia,” she said. This increased risk for childhood respiratory disorders warrants further study.

Consequently, “Women with asthma during pregnancy should have appropriate management to ensure good control to optimize pregnancy outcome,” Dr. Krishna emphasized. “Women who experience asthma exacerbations in pregnancy are at increased risk for preeclampsia, [pregnancy-induced hypertension], low birth weight, and preterm delivery and may require closer monitoring.”

The study was supported by the Institute for Clinical Evaluative Sciences. The researchers and Dr. Krishna had no financial conflicts to disclose.

SOURCE: Abdullah K et al. Eur Respir J. 2019 Nov 26. doi: 10.1183/13993003.01335-2019.

Women with asthma who suffer asthma exacerbation while pregnant are at increased risk for complications during pregnancy and delivery, and their infants are at increased risk for respiratory problems, according to data from a longitudinal study of 58,524 women with asthma.

Vesnaandjic/E+/Getty Images

“Asthma exacerbation during pregnancy has been found to be associated with adverse perinatal and pregnancy outcomes such as low birth weight, small for gestational age, preterm delivery, congenital malformation, preeclampsia, and perinatal mortality,” but previous studies have been small and limited to comparisons of asthmatic and nonasthmatic women, wrote Kawsari Abdullah, PhD, of Children’s Hospital of Eastern Ontario, Ottawa, and colleagues.

To determine the impact of asthma exacerbation on maternal and fetal outcomes, the researchers analyzed data from the Ontario Asthma Surveillance Information System to identify women with asthma who had at least one pregnancy resulting in a live or still birth between 2006 and 2012.

Overall, significantly more women with exacerbated asthma had preeclampsia or pregnancy-induced hypertension, compared with asthmatic women who had no exacerbations, at 5% vs. 4% and 7% vs. 5%, respectively (P less than .001), according to the study published in the European Respiratory Journal.

Adverse perinatal outcomes were significantly more likely among babies of mothers with exacerbated asthma, compared with those who had no exacerbations, including low birth weight (7% vs. 5%), small for gestational age (3% vs. 2%), preterm birth (8% vs. 7%), and congenital malformation (6% vs. 5%). All P values were less than .001, except for small for gestational age, which was P = .008.

In addition, significantly more babies of asthmatic women with exacerbated asthma during pregnancy had respiratory problems including asthma and pneumonia, compared with those of asthmatic women who had no exacerbations during pregnancy, at 38% vs. 31% and 24% vs. 22% (P less than .001 for both). The researchers found no significant interactions between maternal age and smoking and asthma exacerbations.

The findings were limited by several factors, including the lack of a validated algorithm for asthma exacerbation, which the researchers defined as five or more visits to a general practice clinician for asthma during pregnancy. Other limitations included the lack of categorizing asthma exacerbation by severity, and the inability to include the potential effects of asthma medication on maternal and fetal outcomes, Dr. Abdullah and colleagues noted.

However, the results were strengthened by the large sample size and ability to follow babies from birth until 5 years of age, they said.

“Targeting women with asthma during pregnancy and ensuring appropriate asthma management and postpartum follow-up may help to reduce the risk of pregnancy complications, adverse perinatal outcomes, and early childhood respiratory disorders,” they concluded.

This study is important because asthma is a common, potentially serious medical condition that complicates approximately 4%-8% of pregnancies, and one in three women with asthma experience an exacerbation during pregnancy, Iris Krishna, MD, a specialist in maternal/fetal medicine at Emory University, Atlanta, said in an interview.

“This study is unique in that it uses population-level data to assess the association between an asthma exacerbation during pregnancy and adverse perinatal outcomes,” Dr. Krishna said. “After adjusting for confounders, and consistent with previous studies, study findings suggest an increased risk for women with asthma who have an asthma exacerbation during pregnancy for preeclampsia [odds ratio, 1.3; P less than .001], pregnancy-induced hypertension [OR, 1.17; P less than .05], low-birth-weight infant [OR, 1.14; P less than .05], preterm birth [OR, 1.14; P less than .05], and congenital malformations [OR, 1.21; P less than .001].”

Dr. Krishna also noted the impact on early childhood outcomes. “In this study, children born to women who had an asthma exacerbation during pregnancy had a 23% higher risk of developing asthma before 5 years of age, which is consistent with previous studies. [The] investigators also reported a 12% higher risk of having pneumonia during the first 5 years of life for children born to women who had an asthma exacerbation during pregnancy.”

“Previous studies have suggested children born to mothers with uncontrolled asthma have an increased risk for respiratory infections, but this study is the first to report an association with pneumonia,” she said. This increased risk for childhood respiratory disorders warrants further study.

Consequently, “Women with asthma during pregnancy should have appropriate management to ensure good control to optimize pregnancy outcome,” Dr. Krishna emphasized. “Women who experience asthma exacerbations in pregnancy are at increased risk for preeclampsia, [pregnancy-induced hypertension], low birth weight, and preterm delivery and may require closer monitoring.”

The study was supported by the Institute for Clinical Evaluative Sciences. The researchers and Dr. Krishna had no financial conflicts to disclose.

SOURCE: Abdullah K et al. Eur Respir J. 2019 Nov 26. doi: 10.1183/13993003.01335-2019.

Women with asthma who suffer asthma exacerbation while pregnant are at increased risk for complications during pregnancy and delivery, and their infants are at increased risk for respiratory problems, according to data from a longitudinal study of 58,524 women with asthma.

Vesnaandjic/E+/Getty Images

“Asthma exacerbation during pregnancy has been found to be associated with adverse perinatal and pregnancy outcomes such as low birth weight, small for gestational age, preterm delivery, congenital malformation, preeclampsia, and perinatal mortality,” but previous studies have been small and limited to comparisons of asthmatic and nonasthmatic women, wrote Kawsari Abdullah, PhD, of Children’s Hospital of Eastern Ontario, Ottawa, and colleagues.

To determine the impact of asthma exacerbation on maternal and fetal outcomes, the researchers analyzed data from the Ontario Asthma Surveillance Information System to identify women with asthma who had at least one pregnancy resulting in a live or still birth between 2006 and 2012.

Overall, significantly more women with exacerbated asthma had preeclampsia or pregnancy-induced hypertension, compared with asthmatic women who had no exacerbations, at 5% vs. 4% and 7% vs. 5%, respectively (P less than .001), according to the study published in the European Respiratory Journal.

Adverse perinatal outcomes were significantly more likely among babies of mothers with exacerbated asthma, compared with those who had no exacerbations, including low birth weight (7% vs. 5%), small for gestational age (3% vs. 2%), preterm birth (8% vs. 7%), and congenital malformation (6% vs. 5%). All P values were less than .001, except for small for gestational age, which was P = .008.

In addition, significantly more babies of asthmatic women with exacerbated asthma during pregnancy had respiratory problems including asthma and pneumonia, compared with those of asthmatic women who had no exacerbations during pregnancy, at 38% vs. 31% and 24% vs. 22% (P less than .001 for both). The researchers found no significant interactions between maternal age and smoking and asthma exacerbations.

The findings were limited by several factors, including the lack of a validated algorithm for asthma exacerbation, which the researchers defined as five or more visits to a general practice clinician for asthma during pregnancy. Other limitations included the lack of categorizing asthma exacerbation by severity, and the inability to include the potential effects of asthma medication on maternal and fetal outcomes, Dr. Abdullah and colleagues noted.

However, the results were strengthened by the large sample size and ability to follow babies from birth until 5 years of age, they said.

“Targeting women with asthma during pregnancy and ensuring appropriate asthma management and postpartum follow-up may help to reduce the risk of pregnancy complications, adverse perinatal outcomes, and early childhood respiratory disorders,” they concluded.

This study is important because asthma is a common, potentially serious medical condition that complicates approximately 4%-8% of pregnancies, and one in three women with asthma experience an exacerbation during pregnancy, Iris Krishna, MD, a specialist in maternal/fetal medicine at Emory University, Atlanta, said in an interview.

“This study is unique in that it uses population-level data to assess the association between an asthma exacerbation during pregnancy and adverse perinatal outcomes,” Dr. Krishna said. “After adjusting for confounders, and consistent with previous studies, study findings suggest an increased risk for women with asthma who have an asthma exacerbation during pregnancy for preeclampsia [odds ratio, 1.3; P less than .001], pregnancy-induced hypertension [OR, 1.17; P less than .05], low-birth-weight infant [OR, 1.14; P less than .05], preterm birth [OR, 1.14; P less than .05], and congenital malformations [OR, 1.21; P less than .001].”

Dr. Krishna also noted the impact on early childhood outcomes. “In this study, children born to women who had an asthma exacerbation during pregnancy had a 23% higher risk of developing asthma before 5 years of age, which is consistent with previous studies. [The] investigators also reported a 12% higher risk of having pneumonia during the first 5 years of life for children born to women who had an asthma exacerbation during pregnancy.”

“Previous studies have suggested children born to mothers with uncontrolled asthma have an increased risk for respiratory infections, but this study is the first to report an association with pneumonia,” she said. This increased risk for childhood respiratory disorders warrants further study.

Consequently, “Women with asthma during pregnancy should have appropriate management to ensure good control to optimize pregnancy outcome,” Dr. Krishna emphasized. “Women who experience asthma exacerbations in pregnancy are at increased risk for preeclampsia, [pregnancy-induced hypertension], low birth weight, and preterm delivery and may require closer monitoring.”

The study was supported by the Institute for Clinical Evaluative Sciences. The researchers and Dr. Krishna had no financial conflicts to disclose.

SOURCE: Abdullah K et al. Eur Respir J. 2019 Nov 26. doi: 10.1183/13993003.01335-2019.