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FDA: Newborns protected by whooping cough vaccine
The Food and Drug Administration has approved a whooping cough vaccine that protects newborns under 2 months of age.
The vaccine, manufactured by GlaxoSmithKline, was previously approved among pregnant people for their own protection.
“Infants younger than 2 months of age are too young to be protected by the childhood pertussis vaccine series,” Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, said in a press release. “This is the first vaccine approved specifically for use during pregnancy to prevent a disease in young infants whose mothers are vaccinated during pregnancy.”
Pertussis is a highly contagious respiratory tract infection caused by the bacterium Bordetella pertussis. Most cases that result in hospitalizations and death are among infants within 2 months of birth.
The FDA said its decision was based on data from observational studies, which included 108 cases of pertussis in infants younger than 2 months old. According to data evaluated by the agency, the vaccine was 78% effective in preventing whooping cough.
Boostrix is administered as a single 0.5-mL dose.
A version of this article first appeared on Medscape.com.
The Food and Drug Administration has approved a whooping cough vaccine that protects newborns under 2 months of age.
The vaccine, manufactured by GlaxoSmithKline, was previously approved among pregnant people for their own protection.
“Infants younger than 2 months of age are too young to be protected by the childhood pertussis vaccine series,” Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, said in a press release. “This is the first vaccine approved specifically for use during pregnancy to prevent a disease in young infants whose mothers are vaccinated during pregnancy.”
Pertussis is a highly contagious respiratory tract infection caused by the bacterium Bordetella pertussis. Most cases that result in hospitalizations and death are among infants within 2 months of birth.
The FDA said its decision was based on data from observational studies, which included 108 cases of pertussis in infants younger than 2 months old. According to data evaluated by the agency, the vaccine was 78% effective in preventing whooping cough.
Boostrix is administered as a single 0.5-mL dose.
A version of this article first appeared on Medscape.com.
The Food and Drug Administration has approved a whooping cough vaccine that protects newborns under 2 months of age.
The vaccine, manufactured by GlaxoSmithKline, was previously approved among pregnant people for their own protection.
“Infants younger than 2 months of age are too young to be protected by the childhood pertussis vaccine series,” Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, said in a press release. “This is the first vaccine approved specifically for use during pregnancy to prevent a disease in young infants whose mothers are vaccinated during pregnancy.”
Pertussis is a highly contagious respiratory tract infection caused by the bacterium Bordetella pertussis. Most cases that result in hospitalizations and death are among infants within 2 months of birth.
The FDA said its decision was based on data from observational studies, which included 108 cases of pertussis in infants younger than 2 months old. According to data evaluated by the agency, the vaccine was 78% effective in preventing whooping cough.
Boostrix is administered as a single 0.5-mL dose.
A version of this article first appeared on Medscape.com.
Is another COVID-19 booster really needed?
Many countries around the globe are starting to roll out another booster of the COVID-19 vaccine but, with public interest waning and a sense of normalcy firmly installed in our minds, this may prove an ill-fated effort, unless authorities can provide a coherent answer to the question “Is another jab really needed?” (The short answer is a firm “yes,” of course.)
In what we could call the “chronic” phase of the pandemic, most countries have now settled for a certain number of daily cases and a (relatively low) number of complications and deaths. It’s the vaccines that have afforded us this peace of mind, lest we forget. But they are different to other vaccines that we are more familiar with, such as the MMR that we get as kids and then forget about for the rest of our lives. As good as the different COVID-19 vaccines are, they never came with the promise of generating lifelong antibodies. We knew early on that the immunity they provide slowly wanes with time. That doesn’t mean that those who have their vaccination records up to date (which included a booster probably earlier in 2022) are suddenly exposed. Data suggest that although people several months past their last booster would now be more prone to getting reinfected, the protection against severe disease still hangs around 85%. In other words, their chances of ending up in the hospital are low.
Why worry, then, about further boosting the immune system? The same studies show that an additional jab would increase this percentage up to 99%. Is this roughly 10% improvement really worth another worldwide vaccination campaign? Well, this is a numbers game, after all. The current form of the virus is extremely infectious, and the Northern Hemisphere is heading toward the cold months of the year, which we have seen in past years increases COVID-19 contagions, as you would expect from any airborne virus. Thus, it’s easy to expect a new peak in the number of cases, especially considering that we are not going to apply any of the usual restrictions to prevent this. In these conditions, extending the safety net to a further 10% of the population would substantially reduce the total number of victims. It seems like a good investment of resources.
We can be more surgical about it and direct this new vaccination campaign to the population most likely to end up in the hospital. People with concomitant pathologies are at the top of the list, but it’s also an age issue. On the basis of different studies of the most common ages of admission, the cutoff point for the booster varies from country to country, with the lowest being 50 and in other cases hovering around 65 years of age. Given the safety of these vaccines, if we can afford it, the wider we cast the net, the better, but at least we should make every effort to fully vaccinate the higher age brackets.
The final question is which vaccine to give. There are confounding studies about the importance of switching to Omicron-specific jabs, which are finally available. Although this seems like a good idea, since Omicron infections elicit a more effective range of antibodies and new variants seem to better escape our defenses, recent studies suggest that there actually may not be so much difference with the old formula.
The conclusion? This regimen of yearly boosters for some may be the scenario for the upcoming years, similar to what we already do for the flu, so we should get used to it.
Dr. Macip is associate professor, department of molecular and cellular biology, University of Leicester (England). He reported no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
Many countries around the globe are starting to roll out another booster of the COVID-19 vaccine but, with public interest waning and a sense of normalcy firmly installed in our minds, this may prove an ill-fated effort, unless authorities can provide a coherent answer to the question “Is another jab really needed?” (The short answer is a firm “yes,” of course.)
In what we could call the “chronic” phase of the pandemic, most countries have now settled for a certain number of daily cases and a (relatively low) number of complications and deaths. It’s the vaccines that have afforded us this peace of mind, lest we forget. But they are different to other vaccines that we are more familiar with, such as the MMR that we get as kids and then forget about for the rest of our lives. As good as the different COVID-19 vaccines are, they never came with the promise of generating lifelong antibodies. We knew early on that the immunity they provide slowly wanes with time. That doesn’t mean that those who have their vaccination records up to date (which included a booster probably earlier in 2022) are suddenly exposed. Data suggest that although people several months past their last booster would now be more prone to getting reinfected, the protection against severe disease still hangs around 85%. In other words, their chances of ending up in the hospital are low.
Why worry, then, about further boosting the immune system? The same studies show that an additional jab would increase this percentage up to 99%. Is this roughly 10% improvement really worth another worldwide vaccination campaign? Well, this is a numbers game, after all. The current form of the virus is extremely infectious, and the Northern Hemisphere is heading toward the cold months of the year, which we have seen in past years increases COVID-19 contagions, as you would expect from any airborne virus. Thus, it’s easy to expect a new peak in the number of cases, especially considering that we are not going to apply any of the usual restrictions to prevent this. In these conditions, extending the safety net to a further 10% of the population would substantially reduce the total number of victims. It seems like a good investment of resources.
We can be more surgical about it and direct this new vaccination campaign to the population most likely to end up in the hospital. People with concomitant pathologies are at the top of the list, but it’s also an age issue. On the basis of different studies of the most common ages of admission, the cutoff point for the booster varies from country to country, with the lowest being 50 and in other cases hovering around 65 years of age. Given the safety of these vaccines, if we can afford it, the wider we cast the net, the better, but at least we should make every effort to fully vaccinate the higher age brackets.
The final question is which vaccine to give. There are confounding studies about the importance of switching to Omicron-specific jabs, which are finally available. Although this seems like a good idea, since Omicron infections elicit a more effective range of antibodies and new variants seem to better escape our defenses, recent studies suggest that there actually may not be so much difference with the old formula.
The conclusion? This regimen of yearly boosters for some may be the scenario for the upcoming years, similar to what we already do for the flu, so we should get used to it.
Dr. Macip is associate professor, department of molecular and cellular biology, University of Leicester (England). He reported no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
Many countries around the globe are starting to roll out another booster of the COVID-19 vaccine but, with public interest waning and a sense of normalcy firmly installed in our minds, this may prove an ill-fated effort, unless authorities can provide a coherent answer to the question “Is another jab really needed?” (The short answer is a firm “yes,” of course.)
In what we could call the “chronic” phase of the pandemic, most countries have now settled for a certain number of daily cases and a (relatively low) number of complications and deaths. It’s the vaccines that have afforded us this peace of mind, lest we forget. But they are different to other vaccines that we are more familiar with, such as the MMR that we get as kids and then forget about for the rest of our lives. As good as the different COVID-19 vaccines are, they never came with the promise of generating lifelong antibodies. We knew early on that the immunity they provide slowly wanes with time. That doesn’t mean that those who have their vaccination records up to date (which included a booster probably earlier in 2022) are suddenly exposed. Data suggest that although people several months past their last booster would now be more prone to getting reinfected, the protection against severe disease still hangs around 85%. In other words, their chances of ending up in the hospital are low.
Why worry, then, about further boosting the immune system? The same studies show that an additional jab would increase this percentage up to 99%. Is this roughly 10% improvement really worth another worldwide vaccination campaign? Well, this is a numbers game, after all. The current form of the virus is extremely infectious, and the Northern Hemisphere is heading toward the cold months of the year, which we have seen in past years increases COVID-19 contagions, as you would expect from any airborne virus. Thus, it’s easy to expect a new peak in the number of cases, especially considering that we are not going to apply any of the usual restrictions to prevent this. In these conditions, extending the safety net to a further 10% of the population would substantially reduce the total number of victims. It seems like a good investment of resources.
We can be more surgical about it and direct this new vaccination campaign to the population most likely to end up in the hospital. People with concomitant pathologies are at the top of the list, but it’s also an age issue. On the basis of different studies of the most common ages of admission, the cutoff point for the booster varies from country to country, with the lowest being 50 and in other cases hovering around 65 years of age. Given the safety of these vaccines, if we can afford it, the wider we cast the net, the better, but at least we should make every effort to fully vaccinate the higher age brackets.
The final question is which vaccine to give. There are confounding studies about the importance of switching to Omicron-specific jabs, which are finally available. Although this seems like a good idea, since Omicron infections elicit a more effective range of antibodies and new variants seem to better escape our defenses, recent studies suggest that there actually may not be so much difference with the old formula.
The conclusion? This regimen of yearly boosters for some may be the scenario for the upcoming years, similar to what we already do for the flu, so we should get used to it.
Dr. Macip is associate professor, department of molecular and cellular biology, University of Leicester (England). He reported no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
Death of son reinforces flu vaccination message
“It was what the CDC [Centers for Disease Control and Prevention] would call classic influenza-like illness,” Dr. Teichman said. “It was too late to start antivirals, so I gave him advice on symptomatic treatment. We texted the next day, and I was glad to hear that his fever was trending down and that he was feeling a little bit better.”
Two days later, his son called again.
“He said he was having trouble breathing, and over the phone I could hear him hyperventilating.” The retired pediatrician and health care executive told his son to seek medical care.
“Then I got the call that no parent wants to get.”
Brent’s cousin Jake called saying he couldn’t wake Brent up.
“I called Jake back a few minutes later and asked him to hold up the phone,” Dr. Teichman said. “I listened to EMS working on my son, calling for round after round of many medications. He was in arrest and they couldn’t revive him.”
“To this day when I close my eyes at night, I still hear the beeping of those monitors.”
Brent had no health conditions to put him at higher risk for complications of the flu. “Brent was a wonderful son, brother, uncle, and friend. He had a passion for everything he did, and that included his chosen calling of the culinary arts but also included University of Kentucky sports,” Dr. Teichman said.
Brent planned to get a flu vaccine but had not done it yet. “In his obituary, we requested that, in lieu of flowers or donations, people go get their flu shot,” Dr. Teichman said.
“I’m here today to put a face on influenza,” Dr. Teichman said at a news briefing Oct. 4 on preventing the flu and pneumococcal disease, sponsored by the National Foundation for Infectious Diseases.
New survey numbers ‘alarming’
The NFID commissioned a national survey of more than 1,000 U.S. adults to better understand their knowledge and attitudes about the flu, pneumococcal disease, vaccines, and the impact of COVID-19.
“We were alarmed to learn that only 49% of U.S. adults plan to get their flu vaccine this season,” said Patricia A. “Patsy” Stinchfield, a registered nurse, NFID president, and moderator of the news briefing. “That is not good enough.”
In addition, 22% of people at higher risk for flu-related complications do not plan to get vaccinated this season. “That’s a dangerous risk to take,” Ms. Stinchfield said.
An encouraging finding, she said, is that 69% of adults surveyed recognize that an annual flu vaccination is the best way to prevent flu-related hospitalizations and death.
“So, most people know what to do. We just need to do it,” she said.
The top reason for not getting a flu shot in 2022 mentioned by 41% of people surveyed, is they do not think vaccines work very well. Another 39% are concerned about vaccine side effects, and 28% skip the vaccine because they “never get the flu.”
The experts on the panel emphasized the recommendation that all Americans 6 months or older get the flu vaccine, preferably by the end of October. Vaccination is especially important for those at higher risk of complications from the flu, including children under 5, pregnant women, people with one or more health conditions, the immunocompromised, and Americans 65 years and older.
Ms. Stinchfield acknowledged that the effectiveness of the flu vaccine varies season to season, but even if the vaccine does not completely match the circulating viruses, it can help prevent serious outcomes like hospitalization and death. One of the serious potential complications is pneumonia or “pneumococcal disease.”
“Our survey shows that only 29% of those at risk have been advised to receive a pneumococcal vaccine,” Ms. Stinchfield said. “The good news is that, among those who were advised to get the vaccine, 74% did receive their pneumococcal vaccine,” she said. “This underscores a key point to you, my fellow clinicians: As health professionals, our recommendations matter.”
Higher doses for 65+ Americans
The CDC updated recommendations this flu season for adults 65 and older to receive one of three preferentially recommended flu vaccines, said CDC Director Rochelle Walensky, MD. The CDC is recommending higher-dose, stronger vaccines for older Americans “based on a review of the available studies, which suggested that in this age group, these vaccines are potentially more effective than standard-dose ... vaccines.”
During most seasons, people 65 and older bear the greatest burden of severe flu disease, accounting for most flu-related hospitalizations and deaths.
“They are the largest vulnerable segment of our society,” Dr. Walensky said.
What will this flu season be like?
Health officials in the flu vaccine business also tend to be in the flu season prediction business. That includes Dr. Walensky.
“While we will never exactly know what each flu season will hold, we do know that every year, the best way you can protect yourself and those around you is to get your annual flu vaccine,” she said while taking part remotely in the briefing.
How severe will the flu season be in 2022-23? William Schaffner, MD, said he gets that question a lot. “Don’t think about that. Just focus on the fact that flu will be with us each year.
“We were a little bit spoiled. We’ve had two mild influenza seasons,” said Dr. Schaffner, medical director of NFID and a professor of infectious diseases and preventive medicine at Vanderbilt University, Nashville, Tenn. “I think with all the interest in COVID, people have rather forgotten about influenza. I’ve had to remind them that this is yet another serious winter respiratory virus.
“As I like to say, flu is fickle. It’s difficult to predict how serious this next outbreak of influenza this season is going to be. We could look at what happened in the Southern Hemisphere,” he said.
For example, Australia had the worst influenza season in the past 5 years, Schaffner said. “If you want a hint of what might happen here and you want yet another reason to be vaccinated, there it is.”
What we do know, Dr. Walensky said, is that the timing and severity of the past two flu seasons in the U.S. have been different than typical flu seasons. “And this is likely due to the COVID mitigation measures and other changes in circulating respiratory viruses.” Also, although last flu season was “relatively mild,” there was more flu activity than in the prior, 2020-21 season.
Also, Dr. Walensky said, last season’s flu cases began to increase in November and remained elevated until mid-June, “making it the latest season on record.”
The official cause of Brent Teichman’s death was multilobar pneumonia, cause undetermined. “But after 30-plus years as a pediatrician ... I know influenza when I see it,” Dr. Teichman said.
“There’s a hole in our hearts that will never heal. Loss of a child is devastating,” he said. The flu “can take the life of a healthy young person, as it did to my son.
“And for all those listening to my story who are vaccine hesitant, do it for those who love you. So that they won’t walk the path that we and many other families in this country have walked.”
To prove their point, Dr. Teichman and Ms. Stinchfield raised their sleeves and received flu shots during the news briefing.
“This one is for Brent,” Dr. Teichman said.
A version of this article first appeared on WebMD.com.
“It was what the CDC [Centers for Disease Control and Prevention] would call classic influenza-like illness,” Dr. Teichman said. “It was too late to start antivirals, so I gave him advice on symptomatic treatment. We texted the next day, and I was glad to hear that his fever was trending down and that he was feeling a little bit better.”
Two days later, his son called again.
“He said he was having trouble breathing, and over the phone I could hear him hyperventilating.” The retired pediatrician and health care executive told his son to seek medical care.
“Then I got the call that no parent wants to get.”
Brent’s cousin Jake called saying he couldn’t wake Brent up.
“I called Jake back a few minutes later and asked him to hold up the phone,” Dr. Teichman said. “I listened to EMS working on my son, calling for round after round of many medications. He was in arrest and they couldn’t revive him.”
“To this day when I close my eyes at night, I still hear the beeping of those monitors.”
Brent had no health conditions to put him at higher risk for complications of the flu. “Brent was a wonderful son, brother, uncle, and friend. He had a passion for everything he did, and that included his chosen calling of the culinary arts but also included University of Kentucky sports,” Dr. Teichman said.
Brent planned to get a flu vaccine but had not done it yet. “In his obituary, we requested that, in lieu of flowers or donations, people go get their flu shot,” Dr. Teichman said.
“I’m here today to put a face on influenza,” Dr. Teichman said at a news briefing Oct. 4 on preventing the flu and pneumococcal disease, sponsored by the National Foundation for Infectious Diseases.
New survey numbers ‘alarming’
The NFID commissioned a national survey of more than 1,000 U.S. adults to better understand their knowledge and attitudes about the flu, pneumococcal disease, vaccines, and the impact of COVID-19.
“We were alarmed to learn that only 49% of U.S. adults plan to get their flu vaccine this season,” said Patricia A. “Patsy” Stinchfield, a registered nurse, NFID president, and moderator of the news briefing. “That is not good enough.”
In addition, 22% of people at higher risk for flu-related complications do not plan to get vaccinated this season. “That’s a dangerous risk to take,” Ms. Stinchfield said.
An encouraging finding, she said, is that 69% of adults surveyed recognize that an annual flu vaccination is the best way to prevent flu-related hospitalizations and death.
“So, most people know what to do. We just need to do it,” she said.
The top reason for not getting a flu shot in 2022 mentioned by 41% of people surveyed, is they do not think vaccines work very well. Another 39% are concerned about vaccine side effects, and 28% skip the vaccine because they “never get the flu.”
The experts on the panel emphasized the recommendation that all Americans 6 months or older get the flu vaccine, preferably by the end of October. Vaccination is especially important for those at higher risk of complications from the flu, including children under 5, pregnant women, people with one or more health conditions, the immunocompromised, and Americans 65 years and older.
Ms. Stinchfield acknowledged that the effectiveness of the flu vaccine varies season to season, but even if the vaccine does not completely match the circulating viruses, it can help prevent serious outcomes like hospitalization and death. One of the serious potential complications is pneumonia or “pneumococcal disease.”
“Our survey shows that only 29% of those at risk have been advised to receive a pneumococcal vaccine,” Ms. Stinchfield said. “The good news is that, among those who were advised to get the vaccine, 74% did receive their pneumococcal vaccine,” she said. “This underscores a key point to you, my fellow clinicians: As health professionals, our recommendations matter.”
Higher doses for 65+ Americans
The CDC updated recommendations this flu season for adults 65 and older to receive one of three preferentially recommended flu vaccines, said CDC Director Rochelle Walensky, MD. The CDC is recommending higher-dose, stronger vaccines for older Americans “based on a review of the available studies, which suggested that in this age group, these vaccines are potentially more effective than standard-dose ... vaccines.”
During most seasons, people 65 and older bear the greatest burden of severe flu disease, accounting for most flu-related hospitalizations and deaths.
“They are the largest vulnerable segment of our society,” Dr. Walensky said.
What will this flu season be like?
Health officials in the flu vaccine business also tend to be in the flu season prediction business. That includes Dr. Walensky.
“While we will never exactly know what each flu season will hold, we do know that every year, the best way you can protect yourself and those around you is to get your annual flu vaccine,” she said while taking part remotely in the briefing.
How severe will the flu season be in 2022-23? William Schaffner, MD, said he gets that question a lot. “Don’t think about that. Just focus on the fact that flu will be with us each year.
“We were a little bit spoiled. We’ve had two mild influenza seasons,” said Dr. Schaffner, medical director of NFID and a professor of infectious diseases and preventive medicine at Vanderbilt University, Nashville, Tenn. “I think with all the interest in COVID, people have rather forgotten about influenza. I’ve had to remind them that this is yet another serious winter respiratory virus.
“As I like to say, flu is fickle. It’s difficult to predict how serious this next outbreak of influenza this season is going to be. We could look at what happened in the Southern Hemisphere,” he said.
For example, Australia had the worst influenza season in the past 5 years, Schaffner said. “If you want a hint of what might happen here and you want yet another reason to be vaccinated, there it is.”
What we do know, Dr. Walensky said, is that the timing and severity of the past two flu seasons in the U.S. have been different than typical flu seasons. “And this is likely due to the COVID mitigation measures and other changes in circulating respiratory viruses.” Also, although last flu season was “relatively mild,” there was more flu activity than in the prior, 2020-21 season.
Also, Dr. Walensky said, last season’s flu cases began to increase in November and remained elevated until mid-June, “making it the latest season on record.”
The official cause of Brent Teichman’s death was multilobar pneumonia, cause undetermined. “But after 30-plus years as a pediatrician ... I know influenza when I see it,” Dr. Teichman said.
“There’s a hole in our hearts that will never heal. Loss of a child is devastating,” he said. The flu “can take the life of a healthy young person, as it did to my son.
“And for all those listening to my story who are vaccine hesitant, do it for those who love you. So that they won’t walk the path that we and many other families in this country have walked.”
To prove their point, Dr. Teichman and Ms. Stinchfield raised their sleeves and received flu shots during the news briefing.
“This one is for Brent,” Dr. Teichman said.
A version of this article first appeared on WebMD.com.
“It was what the CDC [Centers for Disease Control and Prevention] would call classic influenza-like illness,” Dr. Teichman said. “It was too late to start antivirals, so I gave him advice on symptomatic treatment. We texted the next day, and I was glad to hear that his fever was trending down and that he was feeling a little bit better.”
Two days later, his son called again.
“He said he was having trouble breathing, and over the phone I could hear him hyperventilating.” The retired pediatrician and health care executive told his son to seek medical care.
“Then I got the call that no parent wants to get.”
Brent’s cousin Jake called saying he couldn’t wake Brent up.
“I called Jake back a few minutes later and asked him to hold up the phone,” Dr. Teichman said. “I listened to EMS working on my son, calling for round after round of many medications. He was in arrest and they couldn’t revive him.”
“To this day when I close my eyes at night, I still hear the beeping of those monitors.”
Brent had no health conditions to put him at higher risk for complications of the flu. “Brent was a wonderful son, brother, uncle, and friend. He had a passion for everything he did, and that included his chosen calling of the culinary arts but also included University of Kentucky sports,” Dr. Teichman said.
Brent planned to get a flu vaccine but had not done it yet. “In his obituary, we requested that, in lieu of flowers or donations, people go get their flu shot,” Dr. Teichman said.
“I’m here today to put a face on influenza,” Dr. Teichman said at a news briefing Oct. 4 on preventing the flu and pneumococcal disease, sponsored by the National Foundation for Infectious Diseases.
New survey numbers ‘alarming’
The NFID commissioned a national survey of more than 1,000 U.S. adults to better understand their knowledge and attitudes about the flu, pneumococcal disease, vaccines, and the impact of COVID-19.
“We were alarmed to learn that only 49% of U.S. adults plan to get their flu vaccine this season,” said Patricia A. “Patsy” Stinchfield, a registered nurse, NFID president, and moderator of the news briefing. “That is not good enough.”
In addition, 22% of people at higher risk for flu-related complications do not plan to get vaccinated this season. “That’s a dangerous risk to take,” Ms. Stinchfield said.
An encouraging finding, she said, is that 69% of adults surveyed recognize that an annual flu vaccination is the best way to prevent flu-related hospitalizations and death.
“So, most people know what to do. We just need to do it,” she said.
The top reason for not getting a flu shot in 2022 mentioned by 41% of people surveyed, is they do not think vaccines work very well. Another 39% are concerned about vaccine side effects, and 28% skip the vaccine because they “never get the flu.”
The experts on the panel emphasized the recommendation that all Americans 6 months or older get the flu vaccine, preferably by the end of October. Vaccination is especially important for those at higher risk of complications from the flu, including children under 5, pregnant women, people with one or more health conditions, the immunocompromised, and Americans 65 years and older.
Ms. Stinchfield acknowledged that the effectiveness of the flu vaccine varies season to season, but even if the vaccine does not completely match the circulating viruses, it can help prevent serious outcomes like hospitalization and death. One of the serious potential complications is pneumonia or “pneumococcal disease.”
“Our survey shows that only 29% of those at risk have been advised to receive a pneumococcal vaccine,” Ms. Stinchfield said. “The good news is that, among those who were advised to get the vaccine, 74% did receive their pneumococcal vaccine,” she said. “This underscores a key point to you, my fellow clinicians: As health professionals, our recommendations matter.”
Higher doses for 65+ Americans
The CDC updated recommendations this flu season for adults 65 and older to receive one of three preferentially recommended flu vaccines, said CDC Director Rochelle Walensky, MD. The CDC is recommending higher-dose, stronger vaccines for older Americans “based on a review of the available studies, which suggested that in this age group, these vaccines are potentially more effective than standard-dose ... vaccines.”
During most seasons, people 65 and older bear the greatest burden of severe flu disease, accounting for most flu-related hospitalizations and deaths.
“They are the largest vulnerable segment of our society,” Dr. Walensky said.
What will this flu season be like?
Health officials in the flu vaccine business also tend to be in the flu season prediction business. That includes Dr. Walensky.
“While we will never exactly know what each flu season will hold, we do know that every year, the best way you can protect yourself and those around you is to get your annual flu vaccine,” she said while taking part remotely in the briefing.
How severe will the flu season be in 2022-23? William Schaffner, MD, said he gets that question a lot. “Don’t think about that. Just focus on the fact that flu will be with us each year.
“We were a little bit spoiled. We’ve had two mild influenza seasons,” said Dr. Schaffner, medical director of NFID and a professor of infectious diseases and preventive medicine at Vanderbilt University, Nashville, Tenn. “I think with all the interest in COVID, people have rather forgotten about influenza. I’ve had to remind them that this is yet another serious winter respiratory virus.
“As I like to say, flu is fickle. It’s difficult to predict how serious this next outbreak of influenza this season is going to be. We could look at what happened in the Southern Hemisphere,” he said.
For example, Australia had the worst influenza season in the past 5 years, Schaffner said. “If you want a hint of what might happen here and you want yet another reason to be vaccinated, there it is.”
What we do know, Dr. Walensky said, is that the timing and severity of the past two flu seasons in the U.S. have been different than typical flu seasons. “And this is likely due to the COVID mitigation measures and other changes in circulating respiratory viruses.” Also, although last flu season was “relatively mild,” there was more flu activity than in the prior, 2020-21 season.
Also, Dr. Walensky said, last season’s flu cases began to increase in November and remained elevated until mid-June, “making it the latest season on record.”
The official cause of Brent Teichman’s death was multilobar pneumonia, cause undetermined. “But after 30-plus years as a pediatrician ... I know influenza when I see it,” Dr. Teichman said.
“There’s a hole in our hearts that will never heal. Loss of a child is devastating,” he said. The flu “can take the life of a healthy young person, as it did to my son.
“And for all those listening to my story who are vaccine hesitant, do it for those who love you. So that they won’t walk the path that we and many other families in this country have walked.”
To prove their point, Dr. Teichman and Ms. Stinchfield raised their sleeves and received flu shots during the news briefing.
“This one is for Brent,” Dr. Teichman said.
A version of this article first appeared on WebMD.com.
Antifibrotic shows mixed results in RA-ILD
The antifibrotic pirfenidone (Esbriet) did not change the decline in forced vital capacity percentage (FVC%) from baseline of 10% or more or the risk of death compared with placebo in patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD). However, the drug appeared to slow the rate of decline in lung function, a phase 2 study indicated.
“This is the first randomized double-blind, placebo-controlled trial focused only on patients with RA-ILD,” observed Joshua Solomon, MD, National Jewish Health, Denver, and fellow TRAIL1 Network investigators.
in patients with rheumatoid arthritis and evidence of fibrotic interstitial lung disease and the totality of the evidence suggests that pirfenidone is effective in the treatment of RA-ILD,” they suggest.
The study was published online in the Lancet Respiratory Medicine.
TRAIL1
The treatment for Rheumatoid Arthritis and Interstitial Lung Disease 1 (TRAIL1) was carried out in 34 academic centers specializing in ILD. Patients had RA and the presence of ILD on high-resolution CT scan and, where possible, lung biopsy. A total of 231 patients were randomly assigned to the pirfenidone group and the remainder to placebo. The mean age of patients was 66 (interquartile range (IQR, 61.0-74.0) in the pirfenidone group and 69.56 (IQR, 63.-74.5) among placebo controls.
Patients received pirfenidone at a dose of 2,403 mg per day, given in divided doses of three 267-mg tablets, three times a day, titrated to full dose over the course of 2 weeks. High-resolution CT scans were done at the beginning and the end of the study interval. Several disease-modifying antirheumatic drugs (DMARDS) were used for the treatment of RA but no differences were observed between treatment groups accounting for the DMARD classes.
“The primary endpoint was the incidence of the composite endpoint of a decline from baseline in [FVC%] of 10% or more or death during the 52-week treatment period,” Dr. Solomon and colleagues observed. The primary outcome was measured in the intent-to-treat (ITT) population.
Some 11% of patients in the active treatment group vs. 15% of patients in the placebo group met the composite primary endpoint, as investigators reported. For the secondary endpoint of the change in FVC over 52 weeks, patients treated with pirfenidone had a slow rate of decline in lung function compared with placebo patients as measured by estimated annual change in absolute FVC (–66 ml vs. –146 mL; P = .0082).
Moreover, in a post hoc analysis by CT pattern, the effect of the antifibrotic therapy on decline in FVC was more pronounced in those with usual interstitial pneumonia pattern on imaging compared with those with any pattern of ILD, the investigators observed. Indeed, approximately half of patients with the usual interstitial pneumonia in the pirfenidone group had a significantly smaller reduction in annual change in FVC at 52 weeks compared with over three-quarters of patients with usual interstitial pneumonia treated with placebo.
In contrast, the two groups were similar with regard to the decline in FVC% by 10% more or the frequency of progression. All-cause mortality rates were similar between the two groups. Adverse events thought to be related to treatment were more frequently reported in the pirfenidone group at 44% vs. 30% of placebo patients, the most frequent of which were nausea, fatigue, and diarrhea.
“These adverse events were generally grade 1 and were not clinically significant,” as the authors emphasized, although 24% of patients receiving pirfenidone discontinued treatment because of AEs vs. only 10% of placebo patients.
Limitations of the trial included early termination because of slow recruitment and the COVID-19 pandemic. This led to underpowering of the study.
Wrong endpoint?
In an accompanying editorial, Marco Sebastiani and Andreina Manfredi, MD, said that the choice of the primary outcome of an FVC decline from a baseline of 10% or more could have negatively influenced results because an FVC decline of 10% or more was probably too challenging to show a difference between the two groups. Indeed, the updated 2022 guidelines proposed a decline of 5% or more in FVC as a “significant threshold” for disease progression in patients with progressive pulmonary fibrosis, as the editorialists pointed out.
Nevertheless, the editorialists felt that the effect of pirfenidone on the decline in FVC seems to be significant, particularly when patients with usual interstitial pneumonia are considered. ”The magnitude of the effect of pirfenidone in patients with usual interstitial pneumonia-rheumatoid arthritis-interstitial lung disease and idiopathic pulmonary fibrosis [enrolled in a different study] was very similar,” they noted, “suggesting that a careful identification of usual interstitial pneumonia pattern at HRCT [high resolution CT] could be relevant in patients with RA-ILD. Moreover, given that pirfenidone did not modify its safety in these patients, the fact that pirfenidone can be safely used with DMARD therapy is important in clinical practice.
Dr. Solomon had no conflicts of interest to declare. Dr. Sebastiani disclosed ties with Bristol Myers Squibb, Pfizer, Boehringer-Ingelheim, Lilly, Amgen, Janssen, and Celltrion. Dr. Manfredi disclosed ties with Bristol Myers Squibb, Lilly, and Boehringer-Ingelheim. The study was funded by Genentech.
The antifibrotic pirfenidone (Esbriet) did not change the decline in forced vital capacity percentage (FVC%) from baseline of 10% or more or the risk of death compared with placebo in patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD). However, the drug appeared to slow the rate of decline in lung function, a phase 2 study indicated.
“This is the first randomized double-blind, placebo-controlled trial focused only on patients with RA-ILD,” observed Joshua Solomon, MD, National Jewish Health, Denver, and fellow TRAIL1 Network investigators.
in patients with rheumatoid arthritis and evidence of fibrotic interstitial lung disease and the totality of the evidence suggests that pirfenidone is effective in the treatment of RA-ILD,” they suggest.
The study was published online in the Lancet Respiratory Medicine.
TRAIL1
The treatment for Rheumatoid Arthritis and Interstitial Lung Disease 1 (TRAIL1) was carried out in 34 academic centers specializing in ILD. Patients had RA and the presence of ILD on high-resolution CT scan and, where possible, lung biopsy. A total of 231 patients were randomly assigned to the pirfenidone group and the remainder to placebo. The mean age of patients was 66 (interquartile range (IQR, 61.0-74.0) in the pirfenidone group and 69.56 (IQR, 63.-74.5) among placebo controls.
Patients received pirfenidone at a dose of 2,403 mg per day, given in divided doses of three 267-mg tablets, three times a day, titrated to full dose over the course of 2 weeks. High-resolution CT scans were done at the beginning and the end of the study interval. Several disease-modifying antirheumatic drugs (DMARDS) were used for the treatment of RA but no differences were observed between treatment groups accounting for the DMARD classes.
“The primary endpoint was the incidence of the composite endpoint of a decline from baseline in [FVC%] of 10% or more or death during the 52-week treatment period,” Dr. Solomon and colleagues observed. The primary outcome was measured in the intent-to-treat (ITT) population.
Some 11% of patients in the active treatment group vs. 15% of patients in the placebo group met the composite primary endpoint, as investigators reported. For the secondary endpoint of the change in FVC over 52 weeks, patients treated with pirfenidone had a slow rate of decline in lung function compared with placebo patients as measured by estimated annual change in absolute FVC (–66 ml vs. –146 mL; P = .0082).
Moreover, in a post hoc analysis by CT pattern, the effect of the antifibrotic therapy on decline in FVC was more pronounced in those with usual interstitial pneumonia pattern on imaging compared with those with any pattern of ILD, the investigators observed. Indeed, approximately half of patients with the usual interstitial pneumonia in the pirfenidone group had a significantly smaller reduction in annual change in FVC at 52 weeks compared with over three-quarters of patients with usual interstitial pneumonia treated with placebo.
In contrast, the two groups were similar with regard to the decline in FVC% by 10% more or the frequency of progression. All-cause mortality rates were similar between the two groups. Adverse events thought to be related to treatment were more frequently reported in the pirfenidone group at 44% vs. 30% of placebo patients, the most frequent of which were nausea, fatigue, and diarrhea.
“These adverse events were generally grade 1 and were not clinically significant,” as the authors emphasized, although 24% of patients receiving pirfenidone discontinued treatment because of AEs vs. only 10% of placebo patients.
Limitations of the trial included early termination because of slow recruitment and the COVID-19 pandemic. This led to underpowering of the study.
Wrong endpoint?
In an accompanying editorial, Marco Sebastiani and Andreina Manfredi, MD, said that the choice of the primary outcome of an FVC decline from a baseline of 10% or more could have negatively influenced results because an FVC decline of 10% or more was probably too challenging to show a difference between the two groups. Indeed, the updated 2022 guidelines proposed a decline of 5% or more in FVC as a “significant threshold” for disease progression in patients with progressive pulmonary fibrosis, as the editorialists pointed out.
Nevertheless, the editorialists felt that the effect of pirfenidone on the decline in FVC seems to be significant, particularly when patients with usual interstitial pneumonia are considered. ”The magnitude of the effect of pirfenidone in patients with usual interstitial pneumonia-rheumatoid arthritis-interstitial lung disease and idiopathic pulmonary fibrosis [enrolled in a different study] was very similar,” they noted, “suggesting that a careful identification of usual interstitial pneumonia pattern at HRCT [high resolution CT] could be relevant in patients with RA-ILD. Moreover, given that pirfenidone did not modify its safety in these patients, the fact that pirfenidone can be safely used with DMARD therapy is important in clinical practice.
Dr. Solomon had no conflicts of interest to declare. Dr. Sebastiani disclosed ties with Bristol Myers Squibb, Pfizer, Boehringer-Ingelheim, Lilly, Amgen, Janssen, and Celltrion. Dr. Manfredi disclosed ties with Bristol Myers Squibb, Lilly, and Boehringer-Ingelheim. The study was funded by Genentech.
The antifibrotic pirfenidone (Esbriet) did not change the decline in forced vital capacity percentage (FVC%) from baseline of 10% or more or the risk of death compared with placebo in patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD). However, the drug appeared to slow the rate of decline in lung function, a phase 2 study indicated.
“This is the first randomized double-blind, placebo-controlled trial focused only on patients with RA-ILD,” observed Joshua Solomon, MD, National Jewish Health, Denver, and fellow TRAIL1 Network investigators.
in patients with rheumatoid arthritis and evidence of fibrotic interstitial lung disease and the totality of the evidence suggests that pirfenidone is effective in the treatment of RA-ILD,” they suggest.
The study was published online in the Lancet Respiratory Medicine.
TRAIL1
The treatment for Rheumatoid Arthritis and Interstitial Lung Disease 1 (TRAIL1) was carried out in 34 academic centers specializing in ILD. Patients had RA and the presence of ILD on high-resolution CT scan and, where possible, lung biopsy. A total of 231 patients were randomly assigned to the pirfenidone group and the remainder to placebo. The mean age of patients was 66 (interquartile range (IQR, 61.0-74.0) in the pirfenidone group and 69.56 (IQR, 63.-74.5) among placebo controls.
Patients received pirfenidone at a dose of 2,403 mg per day, given in divided doses of three 267-mg tablets, three times a day, titrated to full dose over the course of 2 weeks. High-resolution CT scans were done at the beginning and the end of the study interval. Several disease-modifying antirheumatic drugs (DMARDS) were used for the treatment of RA but no differences were observed between treatment groups accounting for the DMARD classes.
“The primary endpoint was the incidence of the composite endpoint of a decline from baseline in [FVC%] of 10% or more or death during the 52-week treatment period,” Dr. Solomon and colleagues observed. The primary outcome was measured in the intent-to-treat (ITT) population.
Some 11% of patients in the active treatment group vs. 15% of patients in the placebo group met the composite primary endpoint, as investigators reported. For the secondary endpoint of the change in FVC over 52 weeks, patients treated with pirfenidone had a slow rate of decline in lung function compared with placebo patients as measured by estimated annual change in absolute FVC (–66 ml vs. –146 mL; P = .0082).
Moreover, in a post hoc analysis by CT pattern, the effect of the antifibrotic therapy on decline in FVC was more pronounced in those with usual interstitial pneumonia pattern on imaging compared with those with any pattern of ILD, the investigators observed. Indeed, approximately half of patients with the usual interstitial pneumonia in the pirfenidone group had a significantly smaller reduction in annual change in FVC at 52 weeks compared with over three-quarters of patients with usual interstitial pneumonia treated with placebo.
In contrast, the two groups were similar with regard to the decline in FVC% by 10% more or the frequency of progression. All-cause mortality rates were similar between the two groups. Adverse events thought to be related to treatment were more frequently reported in the pirfenidone group at 44% vs. 30% of placebo patients, the most frequent of which were nausea, fatigue, and diarrhea.
“These adverse events were generally grade 1 and were not clinically significant,” as the authors emphasized, although 24% of patients receiving pirfenidone discontinued treatment because of AEs vs. only 10% of placebo patients.
Limitations of the trial included early termination because of slow recruitment and the COVID-19 pandemic. This led to underpowering of the study.
Wrong endpoint?
In an accompanying editorial, Marco Sebastiani and Andreina Manfredi, MD, said that the choice of the primary outcome of an FVC decline from a baseline of 10% or more could have negatively influenced results because an FVC decline of 10% or more was probably too challenging to show a difference between the two groups. Indeed, the updated 2022 guidelines proposed a decline of 5% or more in FVC as a “significant threshold” for disease progression in patients with progressive pulmonary fibrosis, as the editorialists pointed out.
Nevertheless, the editorialists felt that the effect of pirfenidone on the decline in FVC seems to be significant, particularly when patients with usual interstitial pneumonia are considered. ”The magnitude of the effect of pirfenidone in patients with usual interstitial pneumonia-rheumatoid arthritis-interstitial lung disease and idiopathic pulmonary fibrosis [enrolled in a different study] was very similar,” they noted, “suggesting that a careful identification of usual interstitial pneumonia pattern at HRCT [high resolution CT] could be relevant in patients with RA-ILD. Moreover, given that pirfenidone did not modify its safety in these patients, the fact that pirfenidone can be safely used with DMARD therapy is important in clinical practice.
Dr. Solomon had no conflicts of interest to declare. Dr. Sebastiani disclosed ties with Bristol Myers Squibb, Pfizer, Boehringer-Ingelheim, Lilly, Amgen, Janssen, and Celltrion. Dr. Manfredi disclosed ties with Bristol Myers Squibb, Lilly, and Boehringer-Ingelheim. The study was funded by Genentech.
FROM THE LANCET RESPIRATORY MEDICINE
Pulmonology Data Trends 2022
CHEST Physician presents the 2022 edition of Pulmonology Data Trends (click to view the digital edition). This special issue provides updates on hot topics in pulmonology through original infographics and visual storytelling.
Inside this issue:
- Comorbidities, Racial Disparities, and Geographic Differences in Asthma
Navitha Ramesh, MD, FCCP - Post-COVID-19 Effects
Viren Kaul, MD, FCCP, FACP - New Pathogens, COVID-19, and Antibiotic Resistance in the Field of Pneumonia
Marcos I. Restrepo, MD, MSc, PhD, FCCP - COPD Characteristics and Health Disparities
Muhammad Adrish, MD, MBA, FCCP - Reducing Tuberculosis Globally and the Impact of COVID-19
Patricio Escalante, MD, MSc, FCCP and Paige K. Marty, MD - New Treatment Pathways for Cystic Fibrosis
David Finklea, MD - Risk Assessment in Pulmonary Arterial Hypertension
Sandeep Sahay, MD, MSc, FCCP, ATSF - Rising Incidence of Bronchiectasis and Associated Burdens
Anne E. O'Donnell, MD, FCCP - ILD: Diagnostic Considerations and Socioeconomic Barriers
Daniel Dilling, MD, FCCP, FACP, FAST - Advances in Lung Cancer Diagnostics and Treatment
Eric S. Edell, MD, FCCP
CHEST Physician presents the 2022 edition of Pulmonology Data Trends (click to view the digital edition). This special issue provides updates on hot topics in pulmonology through original infographics and visual storytelling.
Inside this issue:
- Comorbidities, Racial Disparities, and Geographic Differences in Asthma
Navitha Ramesh, MD, FCCP - Post-COVID-19 Effects
Viren Kaul, MD, FCCP, FACP - New Pathogens, COVID-19, and Antibiotic Resistance in the Field of Pneumonia
Marcos I. Restrepo, MD, MSc, PhD, FCCP - COPD Characteristics and Health Disparities
Muhammad Adrish, MD, MBA, FCCP - Reducing Tuberculosis Globally and the Impact of COVID-19
Patricio Escalante, MD, MSc, FCCP and Paige K. Marty, MD - New Treatment Pathways for Cystic Fibrosis
David Finklea, MD - Risk Assessment in Pulmonary Arterial Hypertension
Sandeep Sahay, MD, MSc, FCCP, ATSF - Rising Incidence of Bronchiectasis and Associated Burdens
Anne E. O'Donnell, MD, FCCP - ILD: Diagnostic Considerations and Socioeconomic Barriers
Daniel Dilling, MD, FCCP, FACP, FAST - Advances in Lung Cancer Diagnostics and Treatment
Eric S. Edell, MD, FCCP
CHEST Physician presents the 2022 edition of Pulmonology Data Trends (click to view the digital edition). This special issue provides updates on hot topics in pulmonology through original infographics and visual storytelling.
Inside this issue:
- Comorbidities, Racial Disparities, and Geographic Differences in Asthma
Navitha Ramesh, MD, FCCP - Post-COVID-19 Effects
Viren Kaul, MD, FCCP, FACP - New Pathogens, COVID-19, and Antibiotic Resistance in the Field of Pneumonia
Marcos I. Restrepo, MD, MSc, PhD, FCCP - COPD Characteristics and Health Disparities
Muhammad Adrish, MD, MBA, FCCP - Reducing Tuberculosis Globally and the Impact of COVID-19
Patricio Escalante, MD, MSc, FCCP and Paige K. Marty, MD - New Treatment Pathways for Cystic Fibrosis
David Finklea, MD - Risk Assessment in Pulmonary Arterial Hypertension
Sandeep Sahay, MD, MSc, FCCP, ATSF - Rising Incidence of Bronchiectasis and Associated Burdens
Anne E. O'Donnell, MD, FCCP - ILD: Diagnostic Considerations and Socioeconomic Barriers
Daniel Dilling, MD, FCCP, FACP, FAST - Advances in Lung Cancer Diagnostics and Treatment
Eric S. Edell, MD, FCCP
Meet our newest genetically engineered frenemy, herpes
Herpes to the rescue
Let’s face it: When people hear the word “herpes,” their first thoughts are not positive. But what if herpes could be a hero?
Scientists have found a way to make a strain of herpes that kills cancer because, hey, it’s 2022, and anything is possible. Trials have been going well and this seems like a safe and effective way to fight cancer.
Viruses may be one of our oldest enemies, but it’s also been said that the enemy of my enemy is my friend. So why not make herpes the enemy of cancer, thereby turning it into our friend? The genetically modified herpes virus is injected directly into tumors, where it destroys cancer cells from within. But wait, there’s more! The patient’s immune system also senses the virus and springs into action against it and the cancer in which it is residing.
During the phase 1 trial, three of the nine patients saw tumor reduction and the therapy proved safe as well. Future trials will be able to more specifically target various cancer types and make the treatment better. For once, we are rooting for you, herpes.
A breath of not-so-fresh air
There’s nothing quite like that first real warm day of spring. You can finally open the windows and clear out the old stuffy air that’s been hanging around all winter long. It’s a ritual that’s now backed up with some science in the form of a new study. Turns out that there’s actually a fair amount of smog in the average home. That’s right, smog’s not just for the big city anymore.
As part of the HOMEChem project, a whole host of scientists gathered together under one roof in a typical suburban house and immediately started doing chores. Cooking, cleaning, the works. No, it wasn’t because they had trashed the place the night before. They had set up instrumentation all around the house to measure the chemical makeup of the air inside. A scientist’s idea of a wild party.
The results are perhaps not all that surprising, but interesting nonetheless. Your homemade smog certainly won’t kill you, but there’s both an increased amount and higher concentration of airborne toxins in indoor air, compared with outdoors. Benzene and formaldehyde were common, as were acrolein (a pulmonary toxicant emitted by lumber and burning fats) and isocyanic acid (which can react with proteins in the human body). The researchers noted that most of these chemicals can be removed with proper ventilation.
Although cleaning is certainly responsible for a fair share of the chemicals, cooking generally produced more toxic compounds, similar to what’s found in wildfire smoke. One of the researchers said this makes sense, since a wildfire can be considered an “extreme form of cooking.” Scientists may not know how to party, but their idea of a barbecue sounds … interesting. We’re looking forward to an upcoming study out of California: Can a 1-million acre wildfire adequately cook a ribeye steak?
We’re dying to try composting ... with humans, that is
We here at LOTME are not really fans of politicians, except as objects of ridicule. That is kind of fun. Whether we’re watching Fox News, listening to NPR, or reading Vladimir Putin’s fashion blog, one thing remains clear: If you want actual information, don’t ask a politician.
There are, of course, always exceptions, and we just found one: California state representative Cristina Garcia. Rep. Garcia sponsored a bill just signed into law by Gov. Gavin Newsom that legalizes the practice of human composting, the reduction of remains by “placing bodies in individual vessels and fostering gentle transformation into a nutrient-dense soil.”
Since we’ve written about this sort of thing before – Washington was the first state to legalize the process back in 2019 – we’re more interested now in what Rep. Garcia told NBC News while describing her motivation: “I’ve always wanted to be a tree. The idea of having my family sitting under my shade one day – that brings a lot of joy.” How great is that? Tree-hugging is just not enough. Be the tree.
California is the fifth state to provide its residents with the human composting option, the other three being Colorado, Oregon, and Vermont. The process “typically involves putting a body into a steel vessel, then covering it with organic materials like straw, wood chips and alfalfa. Microbes break down the corpse and the plant matter, transforming the various components into nutrient-rich soil in roughly 30 days,” Smithsonian Magazine explained.
We just happen to have some good news for Rep. Garcia about that wanting-to-be-a-tree business. She’s already pretty close. For more on that, we go to our correspondent from beyond the grave, Carl Sagan, who shares a thought about trees. And no, we couldn’t just write out his quote here. You have to hear it in Dr. Sagan’s own voice.
That’ll be one pandemic with extra distress. Hold the goals
When the COVID-19 pandemic first hit it put a lot of stuff on hold for everyone. Couldn’t eat inside at your favorite restaurant, attend that long-awaited concert, or travel out of the country. Those were all pretty bad, but it was the disruption of pursuing long-term goals that seemed to have the most effect on people’s mental health.
Investigators from the University of Waterloo (Ont.) looked at how putting such goals on hold affected people’s mental well-being. The study’s 226 participants were asked about their “COVID-frozen” goals and the degree to which they were able to actively pursue each goal and how committed they were to achieving it.
What they found was that the participants’ COVID-frozen goals were associated with feelings of psychological distress, such as anxiety, depressive symptoms, stress, and lowered life satisfaction. It was only when participants were able to disengage from goal rumination that well-being was impacted positively.
“Goal rumination is compulsive and can aggravate worries and frustrations while also taking away mental resources from other goals,” Candice Hubley, lead author and a PhD candidate in psychology, said in a written statement. So in short, you’re only stressing yourself out more about something that is far off in the distance when you could be focusing more on short-term, tangible goals instead.
Now, no one is saying to give up on your goals. Just take them one at a time. You’ll have better life satisfaction and your COVID-frozen goals will thaw out before you know it.
Herpes to the rescue
Let’s face it: When people hear the word “herpes,” their first thoughts are not positive. But what if herpes could be a hero?
Scientists have found a way to make a strain of herpes that kills cancer because, hey, it’s 2022, and anything is possible. Trials have been going well and this seems like a safe and effective way to fight cancer.
Viruses may be one of our oldest enemies, but it’s also been said that the enemy of my enemy is my friend. So why not make herpes the enemy of cancer, thereby turning it into our friend? The genetically modified herpes virus is injected directly into tumors, where it destroys cancer cells from within. But wait, there’s more! The patient’s immune system also senses the virus and springs into action against it and the cancer in which it is residing.
During the phase 1 trial, three of the nine patients saw tumor reduction and the therapy proved safe as well. Future trials will be able to more specifically target various cancer types and make the treatment better. For once, we are rooting for you, herpes.
A breath of not-so-fresh air
There’s nothing quite like that first real warm day of spring. You can finally open the windows and clear out the old stuffy air that’s been hanging around all winter long. It’s a ritual that’s now backed up with some science in the form of a new study. Turns out that there’s actually a fair amount of smog in the average home. That’s right, smog’s not just for the big city anymore.
As part of the HOMEChem project, a whole host of scientists gathered together under one roof in a typical suburban house and immediately started doing chores. Cooking, cleaning, the works. No, it wasn’t because they had trashed the place the night before. They had set up instrumentation all around the house to measure the chemical makeup of the air inside. A scientist’s idea of a wild party.
The results are perhaps not all that surprising, but interesting nonetheless. Your homemade smog certainly won’t kill you, but there’s both an increased amount and higher concentration of airborne toxins in indoor air, compared with outdoors. Benzene and formaldehyde were common, as were acrolein (a pulmonary toxicant emitted by lumber and burning fats) and isocyanic acid (which can react with proteins in the human body). The researchers noted that most of these chemicals can be removed with proper ventilation.
Although cleaning is certainly responsible for a fair share of the chemicals, cooking generally produced more toxic compounds, similar to what’s found in wildfire smoke. One of the researchers said this makes sense, since a wildfire can be considered an “extreme form of cooking.” Scientists may not know how to party, but their idea of a barbecue sounds … interesting. We’re looking forward to an upcoming study out of California: Can a 1-million acre wildfire adequately cook a ribeye steak?
We’re dying to try composting ... with humans, that is
We here at LOTME are not really fans of politicians, except as objects of ridicule. That is kind of fun. Whether we’re watching Fox News, listening to NPR, or reading Vladimir Putin’s fashion blog, one thing remains clear: If you want actual information, don’t ask a politician.
There are, of course, always exceptions, and we just found one: California state representative Cristina Garcia. Rep. Garcia sponsored a bill just signed into law by Gov. Gavin Newsom that legalizes the practice of human composting, the reduction of remains by “placing bodies in individual vessels and fostering gentle transformation into a nutrient-dense soil.”
Since we’ve written about this sort of thing before – Washington was the first state to legalize the process back in 2019 – we’re more interested now in what Rep. Garcia told NBC News while describing her motivation: “I’ve always wanted to be a tree. The idea of having my family sitting under my shade one day – that brings a lot of joy.” How great is that? Tree-hugging is just not enough. Be the tree.
California is the fifth state to provide its residents with the human composting option, the other three being Colorado, Oregon, and Vermont. The process “typically involves putting a body into a steel vessel, then covering it with organic materials like straw, wood chips and alfalfa. Microbes break down the corpse and the plant matter, transforming the various components into nutrient-rich soil in roughly 30 days,” Smithsonian Magazine explained.
We just happen to have some good news for Rep. Garcia about that wanting-to-be-a-tree business. She’s already pretty close. For more on that, we go to our correspondent from beyond the grave, Carl Sagan, who shares a thought about trees. And no, we couldn’t just write out his quote here. You have to hear it in Dr. Sagan’s own voice.
That’ll be one pandemic with extra distress. Hold the goals
When the COVID-19 pandemic first hit it put a lot of stuff on hold for everyone. Couldn’t eat inside at your favorite restaurant, attend that long-awaited concert, or travel out of the country. Those were all pretty bad, but it was the disruption of pursuing long-term goals that seemed to have the most effect on people’s mental health.
Investigators from the University of Waterloo (Ont.) looked at how putting such goals on hold affected people’s mental well-being. The study’s 226 participants were asked about their “COVID-frozen” goals and the degree to which they were able to actively pursue each goal and how committed they were to achieving it.
What they found was that the participants’ COVID-frozen goals were associated with feelings of psychological distress, such as anxiety, depressive symptoms, stress, and lowered life satisfaction. It was only when participants were able to disengage from goal rumination that well-being was impacted positively.
“Goal rumination is compulsive and can aggravate worries and frustrations while also taking away mental resources from other goals,” Candice Hubley, lead author and a PhD candidate in psychology, said in a written statement. So in short, you’re only stressing yourself out more about something that is far off in the distance when you could be focusing more on short-term, tangible goals instead.
Now, no one is saying to give up on your goals. Just take them one at a time. You’ll have better life satisfaction and your COVID-frozen goals will thaw out before you know it.
Herpes to the rescue
Let’s face it: When people hear the word “herpes,” their first thoughts are not positive. But what if herpes could be a hero?
Scientists have found a way to make a strain of herpes that kills cancer because, hey, it’s 2022, and anything is possible. Trials have been going well and this seems like a safe and effective way to fight cancer.
Viruses may be one of our oldest enemies, but it’s also been said that the enemy of my enemy is my friend. So why not make herpes the enemy of cancer, thereby turning it into our friend? The genetically modified herpes virus is injected directly into tumors, where it destroys cancer cells from within. But wait, there’s more! The patient’s immune system also senses the virus and springs into action against it and the cancer in which it is residing.
During the phase 1 trial, three of the nine patients saw tumor reduction and the therapy proved safe as well. Future trials will be able to more specifically target various cancer types and make the treatment better. For once, we are rooting for you, herpes.
A breath of not-so-fresh air
There’s nothing quite like that first real warm day of spring. You can finally open the windows and clear out the old stuffy air that’s been hanging around all winter long. It’s a ritual that’s now backed up with some science in the form of a new study. Turns out that there’s actually a fair amount of smog in the average home. That’s right, smog’s not just for the big city anymore.
As part of the HOMEChem project, a whole host of scientists gathered together under one roof in a typical suburban house and immediately started doing chores. Cooking, cleaning, the works. No, it wasn’t because they had trashed the place the night before. They had set up instrumentation all around the house to measure the chemical makeup of the air inside. A scientist’s idea of a wild party.
The results are perhaps not all that surprising, but interesting nonetheless. Your homemade smog certainly won’t kill you, but there’s both an increased amount and higher concentration of airborne toxins in indoor air, compared with outdoors. Benzene and formaldehyde were common, as were acrolein (a pulmonary toxicant emitted by lumber and burning fats) and isocyanic acid (which can react with proteins in the human body). The researchers noted that most of these chemicals can be removed with proper ventilation.
Although cleaning is certainly responsible for a fair share of the chemicals, cooking generally produced more toxic compounds, similar to what’s found in wildfire smoke. One of the researchers said this makes sense, since a wildfire can be considered an “extreme form of cooking.” Scientists may not know how to party, but their idea of a barbecue sounds … interesting. We’re looking forward to an upcoming study out of California: Can a 1-million acre wildfire adequately cook a ribeye steak?
We’re dying to try composting ... with humans, that is
We here at LOTME are not really fans of politicians, except as objects of ridicule. That is kind of fun. Whether we’re watching Fox News, listening to NPR, or reading Vladimir Putin’s fashion blog, one thing remains clear: If you want actual information, don’t ask a politician.
There are, of course, always exceptions, and we just found one: California state representative Cristina Garcia. Rep. Garcia sponsored a bill just signed into law by Gov. Gavin Newsom that legalizes the practice of human composting, the reduction of remains by “placing bodies in individual vessels and fostering gentle transformation into a nutrient-dense soil.”
Since we’ve written about this sort of thing before – Washington was the first state to legalize the process back in 2019 – we’re more interested now in what Rep. Garcia told NBC News while describing her motivation: “I’ve always wanted to be a tree. The idea of having my family sitting under my shade one day – that brings a lot of joy.” How great is that? Tree-hugging is just not enough. Be the tree.
California is the fifth state to provide its residents with the human composting option, the other three being Colorado, Oregon, and Vermont. The process “typically involves putting a body into a steel vessel, then covering it with organic materials like straw, wood chips and alfalfa. Microbes break down the corpse and the plant matter, transforming the various components into nutrient-rich soil in roughly 30 days,” Smithsonian Magazine explained.
We just happen to have some good news for Rep. Garcia about that wanting-to-be-a-tree business. She’s already pretty close. For more on that, we go to our correspondent from beyond the grave, Carl Sagan, who shares a thought about trees. And no, we couldn’t just write out his quote here. You have to hear it in Dr. Sagan’s own voice.
That’ll be one pandemic with extra distress. Hold the goals
When the COVID-19 pandemic first hit it put a lot of stuff on hold for everyone. Couldn’t eat inside at your favorite restaurant, attend that long-awaited concert, or travel out of the country. Those were all pretty bad, but it was the disruption of pursuing long-term goals that seemed to have the most effect on people’s mental health.
Investigators from the University of Waterloo (Ont.) looked at how putting such goals on hold affected people’s mental well-being. The study’s 226 participants were asked about their “COVID-frozen” goals and the degree to which they were able to actively pursue each goal and how committed they were to achieving it.
What they found was that the participants’ COVID-frozen goals were associated with feelings of psychological distress, such as anxiety, depressive symptoms, stress, and lowered life satisfaction. It was only when participants were able to disengage from goal rumination that well-being was impacted positively.
“Goal rumination is compulsive and can aggravate worries and frustrations while also taking away mental resources from other goals,” Candice Hubley, lead author and a PhD candidate in psychology, said in a written statement. So in short, you’re only stressing yourself out more about something that is far off in the distance when you could be focusing more on short-term, tangible goals instead.
Now, no one is saying to give up on your goals. Just take them one at a time. You’ll have better life satisfaction and your COVID-frozen goals will thaw out before you know it.
Newer 3D lung models starting to remake research
Pulmonologist-scientist Veena B. Antony, MD, professor of medicine at the University of Alabama in Birmingham, grows “pulmospheres” in her lab. The tiny spheres, about 1 mL in diameter, contain cells representing all of the cell types in a lung struck with pulmonary fibrosis.
They are a three-dimensional model of idiopathic pulmonary fibrosis (IPF) that can be used to study the behavior of invasive myofibroblasts and to predict in vivo responsiveness to antifibrotic drugs; 
“The utility is extensive, including looking at the impact of early-life exposures on mid-life lung disease. We can ask all kinds of questions and answer them much faster, and with more accuracy, than with any 2D model,” said Dr. Antony, also professor of environmental health sciences and director of UAB’s program for environmental and translational medicine.
“The future of 3D modeling of the lung will happen step by step ... but we’re right at the edge of a prime explosion of information coming from these models, in all kinds of lung diseases,” she said.
Two-dimensional model systems – mainly monolayer cell cultures where cells adhere to and grow on a plate – cannot approximate the variety of cell types and architecture found in tissue, nor can they recapitulate cell-cell communication, biochemical cues, and other factors that are key to lung development and the pathogenesis of disease.
Dr. Antony’s pulmospheres resemble what have come to be known as organoids – 3D tissue cultures emanating from induced pluripotent stem cells (iPSC) or adult stem cells, in which multiple cell types self-organize, usually while suspended in natural or synthetic extracellular matrix (with or without a scaffold of some kind).
Lung-on-a-chip
In lung-on-a-chip (LOC) models, multiple cell types are seeded into miniature chambers, or “chips,” that contain networks of microfabricated channels designed to deliver and remove fluids, chemical cues, oxygen, and biomechanical forces. LOCs and other organs-on-chips – also called tissues-on-chips – can be continuously perfused and are highly structured and precisely controlled.
It’s the organs-on-chip model – or potential fusions of the organoid and organs-on-chip models – that will likely impact drug development. Almost 9 out of 10 investigational drugs fail in clinical trials – approximately 60% because of lack of efficacy and 30% because of toxicity. More reliable and predictive preclinical investigation is key, said Danilo A. Tagle, PhD, director of the Office of Special Initiatives in the National Center for Advancing Translational Sciences, of the National Institutes of Health.
“We have so many candidate drugs that go through preclinical safety testing, and that do relatively well in animal studies of efficacy, but then fail in clinical trials,” Dr. Tagle said. “We need better preclinical models.”
In its 10 years of life, the Tissue Chip for Drug Screening Program led by the NCATS – and funded by the NIH and Defense Advanced Research Projects Agency – has shown that organs-on-chips can be used to model disease and to predict both the safety and efficacy of clinical compounds, he said.
Lung organoids
Dr. Antony’s pulmospheres emanate not from stem cells but from primary tissue obtained from diseased lung. “We reconstitute the lung cells in single-cell suspensions, and then we allow them to come back together to form lung tissue,” she said. The pulmospheres take about 3 days to grow.
In a study published 5 years ago of pulmospheres of 20 patients with IPF and 9 control subjects, Dr. Antony and colleagues quantitated invasiveness and found “remarkable” differences in the invasiveness of IPF pulmospheres following exposure to the Food and Drug Administration–approved antifibrotic drugs nintedanib and pirfenidone. Some pulmospheres responded to one or the other drug, some to both, and two to neither – findings that Dr. Antony said offer hope for the goals of personalizing therapy and assessing new drugs.
Moreover, clinical disease progression correlated with invasiveness of the pulmospheres, showing that the organoid-like structures “do give us a model that [reflects] what’s happening in the clinical setting,” she said. (Lung tissue for the study was obtained via video-assisted thoracic surgery biopsy of IPF patients and from failed donor lung explants, but bronchoscopic forceps biopsies have become a useful method for obtaining tissue.)
The pulmospheres are not yet in clinical use, Dr. Antony said, but her lab is testing other fibrosis modifiers and continuing to use the model as a research tool.
One state to the east, at Vanderbilt University, Nashville, Tenn., Amanda Linkous, PhD, grows “branching lung organoids” and brain organoids to study the biology of small cell lung cancer (SCLC).
“We want to understand how [SCLC] cells change in the primary organ site, compared with metastatic sites like the brain. ... Are different transcription factors expressed [for instance] depending on where the tumor is growing?” said Dr. Linkous, scientific center manager of the National Cancer Institute’s Center for Systems Biology of SCLC at Vanderbilt. “Then we hope to start drug screening within the next year.”
Her lung organoids take shape from either human embryonic stem cells or iPSCs. Within commercially available media, the cells mature through several stages of differentiation, forming definitive endoderm, anterior foregut endoderm, and then circular lung bud structures – the latter of which are then placed into droplets of Matrigel, an extracellular matrix gel.
“In the Matrigel droplets, the lung bud cells will develop proximal and distal-like branching structures that express things like EPCAM, MUC1, SOX2, SOX9, and NKX2.1 – key markers that you should see in a more mature lung microenvironment,” she said. Tumor cells from established SCLC cell lines will then easily invade the branching lung organoid.
Dr. Linkous said she has found her organoid models highly reproducible and values their long-lasting nature – especially for future drug screening. “We can keep organoids going for months at a time,” said Dr. Linkous, a research associate professor in Vanderbilt’s department of biochemistry.
Like Dr. Antony, she envisions personalizing treatment in the future. “SCLC is a very heterogeneous tumor with many different cell types, so what works for one patient may not work well at all for another patient,” she said.
As recently as 5 years ago, “many in the cancer field would have been resistant to moving away from mouse models,” Dr. Linkous noted. “But preclinical studies in mice often don’t pan out in the clinic ... so we’re moving toward a human microenvironment to study human disease.”
The greatest challenge, Dr. Linkous and Dr. Antony said, lies in integrating both vascular blood flow and air into these models. “We just don’t have that combination as of yet,” Dr. Antony said.
LOC models
One of the first LOC models – and a galvanizing event for organs-on-chips more broadly – was a 1- to 2-cm–long model of the alveolar-capillary interface developed at the Wyss Institute for Biologically Inspired Engineering at Harvard Medical School, Boston.
Microchannels ran alongside a porous membrane coated with extracellular matrix, with alveolar cells seeded on one side and lung endothelial cells on the other side. When a vacuum was applied rhythmically to the channels, the cell-lined membrane stretched and relaxed, mimicking breathing movements.
Lead investigator Dongeun (Dan) Huh, PhD, then a postdoctoral student working with Donald E. Ingber, MD, PhD, founding director of the institute, ran tests showing that the model could reproduce organ-level responses to bacteria and inflammatory cytokines, as well as to silica nanoparticles. The widely cited paper was published in 2010 (Science. 2010;328[5986]:1662-8), and was followed by another study published in 2012 (Sci Transl Med. 2012;4[159]:159ra147) that used the LOC device to reproduce drug toxicity–induced pulmonary edema. “Here we were demonstrating for the first time that we could use the lung-on-chip to model human lung disease,” said Dr. Huh, who started his own lab at the University of Pennsylvania, Philadelphia, in 2013.
Since then, “as a field we’ve come a long way in modeling the complexity of human lung tissues ... with more advanced devices that can be used to mimic different parts of the lung and different processes, like immune responses in asthma and viral infections,” said Dr. Huh, “and with several studies using primary human cells taken from lung disease patients.”
Among Dr. Huh’s latest devices, built with NIH funding, is an asthma-on-a-chip device. Lung cells isolated from asthma patients are grown in a microfabricated device to create multilayered airway tissue, with airspace, that contains a fully differentiated epithelium and a vascularized stroma. “We can compress the entire engineered area of asthmatic human tissue in a lateral direction to mimic bronchoconstriction that happens during an asthma attack,” he said.
A paper soon to be published will describe how “abnormal pathophysiologic compressive forces due to bronchoconstriction in asthmatic lungs can make the lungs fibrotic, and how those mechanical forces also can induce increased vascularity,” said Dr. Huh, associate professor in the university’s department of bioengineering. “The increased vascular density can also change the phenotype of blood vessels in asthmatic airways.”
Dr. Huh also has an $8.3 million contract with the government’s Biomedical Advanced Research and Development Authority to study how chlorine gas damages lung tissues and identify biomarkers of chlorine gas–induced lung injury, with the goal of developing therapeutics.
Dr. Ingber and associates have developed a device modeling cystic fibrosis (CF). The chip is lined with primary human CF bronchial epithelial cells grown under an air-liquid interface and interfaced with primary lung microvascular endothelium that are exposed to fluid flow.
The chip reproduced, “with high fidelity, many of the structural, biochemical, and pathophysiological features of the human CF lung airway and its response to pathogens and circulating immune cells in vitro,” Dr. Ingber and colleagues reported (J Cyst Fibros. 2022;21:605-15).
Government investment in tissue chips
Efforts to commercialize organs-on-chip platforms and translate them for nonengineers have also picked in recent years. Several companies in the United States (including Emulate, a Wyss start-up) and in Europe now offer microengineered lung tissue models that can be used for research and drug testing. And some large pharmaceutical companies, said Dr. Tagle, have begun integrating tissue chip technology into their drug development programs.
The FDA, meanwhile, “has come to embrace the technology and see its promise,” Dr. Tagle said. An FDA pilot program announced in 2021 – called ISTAND (Innovative Science and Technology Approaches for New Drugs) – allows for tissue chip data to be submitted, as standalone data, for some drug applications.
The first 5 years of the government’s Tissue Chip for Drug Screening Program focused on safety and toxicity, and it “was successful in that model organ systems were able to capture the human response that [had been missed in] animal models,” he said.
For example, when a liver-tissue model was used to test several compounds that had passed animal testing for toxicity/safety but then failed in human clinical trials – killing some of the participants – the model showed a 100% sensitivity and a 87% specificity in predicting the human response, said Dr. Tagle, who recently coauthored a review on the future of organs-on-chips (Nature Reviews I Drug Discovery. 2021;20:345-61).
The second 5 years of the program, currently winding down, have focused on efficacy – the ability of organs-on-chip models to recreate the pathophysiology of chronic obstructive pulmonary disease, influenza, and other diseases, so that potential drugs can be assessed. In 2020, with extra support from the Coronavirus Aid, Relief, and Economic Security Act, NCATS funded academic labs to use organs-on-chip technology to evaluate SARS-CoV-2 and potential therapeutics.
Dr. Ingbar was one of the grantees. His team screened a number of FDA-approved drugs for potential repurposing using a bronchial-airway-on-a-chip and compared results with 2D model systems (Nat Biomed Eng. 2021;5:815-29). Amodiaquine inhibited infection in the 3D model and is now in phase 2 COVID trials. Several other drugs showed effectiveness in a 2D model but not in the chip.
Now, in a next phase of study at NCATS, coined Clinical Trials on a Chip, the center has awarded $35.5 million for investigators to test candidate therapies, often in parallel to ongoing clinical trials. The hope is that organs-on-chips can improve clinical trial design, from enrollment criteria and patient stratification to endpoints and the use of biomarkers. And in his lab, Dr. Huh is now engineering a shift to “organoids-on-a-chip” that combines the best features of each approach. “The idea,” he said, “is to grow organoids, and maintain the organoids in the microengineered systems where we can control their environment better ... and apply cues to allow them to develop into even more realistic tissues.”
Drs. Antony, Linkous, and Tagle reported no relevant disclosures. Dr. Huh is a co-founder of Vivodyne Inc, and owns shares in Vivodyne Inc. and Emulate Inc.
Pulmonologist-scientist Veena B. Antony, MD, professor of medicine at the University of Alabama in Birmingham, grows “pulmospheres” in her lab. The tiny spheres, about 1 mL in diameter, contain cells representing all of the cell types in a lung struck with pulmonary fibrosis.
They are a three-dimensional model of idiopathic pulmonary fibrosis (IPF) that can be used to study the behavior of invasive myofibroblasts and to predict in vivo responsiveness to antifibrotic drugs;
“The utility is extensive, including looking at the impact of early-life exposures on mid-life lung disease. We can ask all kinds of questions and answer them much faster, and with more accuracy, than with any 2D model,” said Dr. Antony, also professor of environmental health sciences and director of UAB’s program for environmental and translational medicine.
“The future of 3D modeling of the lung will happen step by step ... but we’re right at the edge of a prime explosion of information coming from these models, in all kinds of lung diseases,” she said.
Two-dimensional model systems – mainly monolayer cell cultures where cells adhere to and grow on a plate – cannot approximate the variety of cell types and architecture found in tissue, nor can they recapitulate cell-cell communication, biochemical cues, and other factors that are key to lung development and the pathogenesis of disease.
Dr. Antony’s pulmospheres resemble what have come to be known as organoids – 3D tissue cultures emanating from induced pluripotent stem cells (iPSC) or adult stem cells, in which multiple cell types self-organize, usually while suspended in natural or synthetic extracellular matrix (with or without a scaffold of some kind).
Lung-on-a-chip
In lung-on-a-chip (LOC) models, multiple cell types are seeded into miniature chambers, or “chips,” that contain networks of microfabricated channels designed to deliver and remove fluids, chemical cues, oxygen, and biomechanical forces. LOCs and other organs-on-chips – also called tissues-on-chips – can be continuously perfused and are highly structured and precisely controlled.
It’s the organs-on-chip model – or potential fusions of the organoid and organs-on-chip models – that will likely impact drug development. Almost 9 out of 10 investigational drugs fail in clinical trials – approximately 60% because of lack of efficacy and 30% because of toxicity. More reliable and predictive preclinical investigation is key, said Danilo A. Tagle, PhD, director of the Office of Special Initiatives in the National Center for Advancing Translational Sciences, of the National Institutes of Health.
“We have so many candidate drugs that go through preclinical safety testing, and that do relatively well in animal studies of efficacy, but then fail in clinical trials,” Dr. Tagle said. “We need better preclinical models.”
In its 10 years of life, the Tissue Chip for Drug Screening Program led by the NCATS – and funded by the NIH and Defense Advanced Research Projects Agency – has shown that organs-on-chips can be used to model disease and to predict both the safety and efficacy of clinical compounds, he said.
Lung organoids
Dr. Antony’s pulmospheres emanate not from stem cells but from primary tissue obtained from diseased lung. “We reconstitute the lung cells in single-cell suspensions, and then we allow them to come back together to form lung tissue,” she said. The pulmospheres take about 3 days to grow.
In a study published 5 years ago of pulmospheres of 20 patients with IPF and 9 control subjects, Dr. Antony and colleagues quantitated invasiveness and found “remarkable” differences in the invasiveness of IPF pulmospheres following exposure to the Food and Drug Administration–approved antifibrotic drugs nintedanib and pirfenidone. Some pulmospheres responded to one or the other drug, some to both, and two to neither – findings that Dr. Antony said offer hope for the goals of personalizing therapy and assessing new drugs.
Moreover, clinical disease progression correlated with invasiveness of the pulmospheres, showing that the organoid-like structures “do give us a model that [reflects] what’s happening in the clinical setting,” she said. (Lung tissue for the study was obtained via video-assisted thoracic surgery biopsy of IPF patients and from failed donor lung explants, but bronchoscopic forceps biopsies have become a useful method for obtaining tissue.)
The pulmospheres are not yet in clinical use, Dr. Antony said, but her lab is testing other fibrosis modifiers and continuing to use the model as a research tool.
One state to the east, at Vanderbilt University, Nashville, Tenn., Amanda Linkous, PhD, grows “branching lung organoids” and brain organoids to study the biology of small cell lung cancer (SCLC).
“We want to understand how [SCLC] cells change in the primary organ site, compared with metastatic sites like the brain. ... Are different transcription factors expressed [for instance] depending on where the tumor is growing?” said Dr. Linkous, scientific center manager of the National Cancer Institute’s Center for Systems Biology of SCLC at Vanderbilt. “Then we hope to start drug screening within the next year.”
Her lung organoids take shape from either human embryonic stem cells or iPSCs. Within commercially available media, the cells mature through several stages of differentiation, forming definitive endoderm, anterior foregut endoderm, and then circular lung bud structures – the latter of which are then placed into droplets of Matrigel, an extracellular matrix gel.
“In the Matrigel droplets, the lung bud cells will develop proximal and distal-like branching structures that express things like EPCAM, MUC1, SOX2, SOX9, and NKX2.1 – key markers that you should see in a more mature lung microenvironment,” she said. Tumor cells from established SCLC cell lines will then easily invade the branching lung organoid.
Dr. Linkous said she has found her organoid models highly reproducible and values their long-lasting nature – especially for future drug screening. “We can keep organoids going for months at a time,” said Dr. Linkous, a research associate professor in Vanderbilt’s department of biochemistry.
Like Dr. Antony, she envisions personalizing treatment in the future. “SCLC is a very heterogeneous tumor with many different cell types, so what works for one patient may not work well at all for another patient,” she said.
As recently as 5 years ago, “many in the cancer field would have been resistant to moving away from mouse models,” Dr. Linkous noted. “But preclinical studies in mice often don’t pan out in the clinic ... so we’re moving toward a human microenvironment to study human disease.”
The greatest challenge, Dr. Linkous and Dr. Antony said, lies in integrating both vascular blood flow and air into these models. “We just don’t have that combination as of yet,” Dr. Antony said.
LOC models
One of the first LOC models – and a galvanizing event for organs-on-chips more broadly – was a 1- to 2-cm–long model of the alveolar-capillary interface developed at the Wyss Institute for Biologically Inspired Engineering at Harvard Medical School, Boston.
Microchannels ran alongside a porous membrane coated with extracellular matrix, with alveolar cells seeded on one side and lung endothelial cells on the other side. When a vacuum was applied rhythmically to the channels, the cell-lined membrane stretched and relaxed, mimicking breathing movements.
Lead investigator Dongeun (Dan) Huh, PhD, then a postdoctoral student working with Donald E. Ingber, MD, PhD, founding director of the institute, ran tests showing that the model could reproduce organ-level responses to bacteria and inflammatory cytokines, as well as to silica nanoparticles. The widely cited paper was published in 2010 (Science. 2010;328[5986]:1662-8), and was followed by another study published in 2012 (Sci Transl Med. 2012;4[159]:159ra147) that used the LOC device to reproduce drug toxicity–induced pulmonary edema. “Here we were demonstrating for the first time that we could use the lung-on-chip to model human lung disease,” said Dr. Huh, who started his own lab at the University of Pennsylvania, Philadelphia, in 2013.
Since then, “as a field we’ve come a long way in modeling the complexity of human lung tissues ... with more advanced devices that can be used to mimic different parts of the lung and different processes, like immune responses in asthma and viral infections,” said Dr. Huh, “and with several studies using primary human cells taken from lung disease patients.”
Among Dr. Huh’s latest devices, built with NIH funding, is an asthma-on-a-chip device. Lung cells isolated from asthma patients are grown in a microfabricated device to create multilayered airway tissue, with airspace, that contains a fully differentiated epithelium and a vascularized stroma. “We can compress the entire engineered area of asthmatic human tissue in a lateral direction to mimic bronchoconstriction that happens during an asthma attack,” he said.
A paper soon to be published will describe how “abnormal pathophysiologic compressive forces due to bronchoconstriction in asthmatic lungs can make the lungs fibrotic, and how those mechanical forces also can induce increased vascularity,” said Dr. Huh, associate professor in the university’s department of bioengineering. “The increased vascular density can also change the phenotype of blood vessels in asthmatic airways.”
Dr. Huh also has an $8.3 million contract with the government’s Biomedical Advanced Research and Development Authority to study how chlorine gas damages lung tissues and identify biomarkers of chlorine gas–induced lung injury, with the goal of developing therapeutics.
Dr. Ingber and associates have developed a device modeling cystic fibrosis (CF). The chip is lined with primary human CF bronchial epithelial cells grown under an air-liquid interface and interfaced with primary lung microvascular endothelium that are exposed to fluid flow.
The chip reproduced, “with high fidelity, many of the structural, biochemical, and pathophysiological features of the human CF lung airway and its response to pathogens and circulating immune cells in vitro,” Dr. Ingber and colleagues reported (J Cyst Fibros. 2022;21:605-15).
Government investment in tissue chips
Efforts to commercialize organs-on-chip platforms and translate them for nonengineers have also picked in recent years. Several companies in the United States (including Emulate, a Wyss start-up) and in Europe now offer microengineered lung tissue models that can be used for research and drug testing. And some large pharmaceutical companies, said Dr. Tagle, have begun integrating tissue chip technology into their drug development programs.
The FDA, meanwhile, “has come to embrace the technology and see its promise,” Dr. Tagle said. An FDA pilot program announced in 2021 – called ISTAND (Innovative Science and Technology Approaches for New Drugs) – allows for tissue chip data to be submitted, as standalone data, for some drug applications.
The first 5 years of the government’s Tissue Chip for Drug Screening Program focused on safety and toxicity, and it “was successful in that model organ systems were able to capture the human response that [had been missed in] animal models,” he said.
For example, when a liver-tissue model was used to test several compounds that had passed animal testing for toxicity/safety but then failed in human clinical trials – killing some of the participants – the model showed a 100% sensitivity and a 87% specificity in predicting the human response, said Dr. Tagle, who recently coauthored a review on the future of organs-on-chips (Nature Reviews I Drug Discovery. 2021;20:345-61).
The second 5 years of the program, currently winding down, have focused on efficacy – the ability of organs-on-chip models to recreate the pathophysiology of chronic obstructive pulmonary disease, influenza, and other diseases, so that potential drugs can be assessed. In 2020, with extra support from the Coronavirus Aid, Relief, and Economic Security Act, NCATS funded academic labs to use organs-on-chip technology to evaluate SARS-CoV-2 and potential therapeutics.
Dr. Ingbar was one of the grantees. His team screened a number of FDA-approved drugs for potential repurposing using a bronchial-airway-on-a-chip and compared results with 2D model systems (Nat Biomed Eng. 2021;5:815-29). Amodiaquine inhibited infection in the 3D model and is now in phase 2 COVID trials. Several other drugs showed effectiveness in a 2D model but not in the chip.
Now, in a next phase of study at NCATS, coined Clinical Trials on a Chip, the center has awarded $35.5 million for investigators to test candidate therapies, often in parallel to ongoing clinical trials. The hope is that organs-on-chips can improve clinical trial design, from enrollment criteria and patient stratification to endpoints and the use of biomarkers. And in his lab, Dr. Huh is now engineering a shift to “organoids-on-a-chip” that combines the best features of each approach. “The idea,” he said, “is to grow organoids, and maintain the organoids in the microengineered systems where we can control their environment better ... and apply cues to allow them to develop into even more realistic tissues.”
Drs. Antony, Linkous, and Tagle reported no relevant disclosures. Dr. Huh is a co-founder of Vivodyne Inc, and owns shares in Vivodyne Inc. and Emulate Inc.
Pulmonologist-scientist Veena B. Antony, MD, professor of medicine at the University of Alabama in Birmingham, grows “pulmospheres” in her lab. The tiny spheres, about 1 mL in diameter, contain cells representing all of the cell types in a lung struck with pulmonary fibrosis.
They are a three-dimensional model of idiopathic pulmonary fibrosis (IPF) that can be used to study the behavior of invasive myofibroblasts and to predict in vivo responsiveness to antifibrotic drugs;
“The utility is extensive, including looking at the impact of early-life exposures on mid-life lung disease. We can ask all kinds of questions and answer them much faster, and with more accuracy, than with any 2D model,” said Dr. Antony, also professor of environmental health sciences and director of UAB’s program for environmental and translational medicine.
“The future of 3D modeling of the lung will happen step by step ... but we’re right at the edge of a prime explosion of information coming from these models, in all kinds of lung diseases,” she said.
Two-dimensional model systems – mainly monolayer cell cultures where cells adhere to and grow on a plate – cannot approximate the variety of cell types and architecture found in tissue, nor can they recapitulate cell-cell communication, biochemical cues, and other factors that are key to lung development and the pathogenesis of disease.
Dr. Antony’s pulmospheres resemble what have come to be known as organoids – 3D tissue cultures emanating from induced pluripotent stem cells (iPSC) or adult stem cells, in which multiple cell types self-organize, usually while suspended in natural or synthetic extracellular matrix (with or without a scaffold of some kind).
Lung-on-a-chip
In lung-on-a-chip (LOC) models, multiple cell types are seeded into miniature chambers, or “chips,” that contain networks of microfabricated channels designed to deliver and remove fluids, chemical cues, oxygen, and biomechanical forces. LOCs and other organs-on-chips – also called tissues-on-chips – can be continuously perfused and are highly structured and precisely controlled.
It’s the organs-on-chip model – or potential fusions of the organoid and organs-on-chip models – that will likely impact drug development. Almost 9 out of 10 investigational drugs fail in clinical trials – approximately 60% because of lack of efficacy and 30% because of toxicity. More reliable and predictive preclinical investigation is key, said Danilo A. Tagle, PhD, director of the Office of Special Initiatives in the National Center for Advancing Translational Sciences, of the National Institutes of Health.
“We have so many candidate drugs that go through preclinical safety testing, and that do relatively well in animal studies of efficacy, but then fail in clinical trials,” Dr. Tagle said. “We need better preclinical models.”
In its 10 years of life, the Tissue Chip for Drug Screening Program led by the NCATS – and funded by the NIH and Defense Advanced Research Projects Agency – has shown that organs-on-chips can be used to model disease and to predict both the safety and efficacy of clinical compounds, he said.
Lung organoids
Dr. Antony’s pulmospheres emanate not from stem cells but from primary tissue obtained from diseased lung. “We reconstitute the lung cells in single-cell suspensions, and then we allow them to come back together to form lung tissue,” she said. The pulmospheres take about 3 days to grow.
In a study published 5 years ago of pulmospheres of 20 patients with IPF and 9 control subjects, Dr. Antony and colleagues quantitated invasiveness and found “remarkable” differences in the invasiveness of IPF pulmospheres following exposure to the Food and Drug Administration–approved antifibrotic drugs nintedanib and pirfenidone. Some pulmospheres responded to one or the other drug, some to both, and two to neither – findings that Dr. Antony said offer hope for the goals of personalizing therapy and assessing new drugs.
Moreover, clinical disease progression correlated with invasiveness of the pulmospheres, showing that the organoid-like structures “do give us a model that [reflects] what’s happening in the clinical setting,” she said. (Lung tissue for the study was obtained via video-assisted thoracic surgery biopsy of IPF patients and from failed donor lung explants, but bronchoscopic forceps biopsies have become a useful method for obtaining tissue.)
The pulmospheres are not yet in clinical use, Dr. Antony said, but her lab is testing other fibrosis modifiers and continuing to use the model as a research tool.
One state to the east, at Vanderbilt University, Nashville, Tenn., Amanda Linkous, PhD, grows “branching lung organoids” and brain organoids to study the biology of small cell lung cancer (SCLC).
“We want to understand how [SCLC] cells change in the primary organ site, compared with metastatic sites like the brain. ... Are different transcription factors expressed [for instance] depending on where the tumor is growing?” said Dr. Linkous, scientific center manager of the National Cancer Institute’s Center for Systems Biology of SCLC at Vanderbilt. “Then we hope to start drug screening within the next year.”
Her lung organoids take shape from either human embryonic stem cells or iPSCs. Within commercially available media, the cells mature through several stages of differentiation, forming definitive endoderm, anterior foregut endoderm, and then circular lung bud structures – the latter of which are then placed into droplets of Matrigel, an extracellular matrix gel.
“In the Matrigel droplets, the lung bud cells will develop proximal and distal-like branching structures that express things like EPCAM, MUC1, SOX2, SOX9, and NKX2.1 – key markers that you should see in a more mature lung microenvironment,” she said. Tumor cells from established SCLC cell lines will then easily invade the branching lung organoid.
Dr. Linkous said she has found her organoid models highly reproducible and values their long-lasting nature – especially for future drug screening. “We can keep organoids going for months at a time,” said Dr. Linkous, a research associate professor in Vanderbilt’s department of biochemistry.
Like Dr. Antony, she envisions personalizing treatment in the future. “SCLC is a very heterogeneous tumor with many different cell types, so what works for one patient may not work well at all for another patient,” she said.
As recently as 5 years ago, “many in the cancer field would have been resistant to moving away from mouse models,” Dr. Linkous noted. “But preclinical studies in mice often don’t pan out in the clinic ... so we’re moving toward a human microenvironment to study human disease.”
The greatest challenge, Dr. Linkous and Dr. Antony said, lies in integrating both vascular blood flow and air into these models. “We just don’t have that combination as of yet,” Dr. Antony said.
LOC models
One of the first LOC models – and a galvanizing event for organs-on-chips more broadly – was a 1- to 2-cm–long model of the alveolar-capillary interface developed at the Wyss Institute for Biologically Inspired Engineering at Harvard Medical School, Boston.
Microchannels ran alongside a porous membrane coated with extracellular matrix, with alveolar cells seeded on one side and lung endothelial cells on the other side. When a vacuum was applied rhythmically to the channels, the cell-lined membrane stretched and relaxed, mimicking breathing movements.
Lead investigator Dongeun (Dan) Huh, PhD, then a postdoctoral student working with Donald E. Ingber, MD, PhD, founding director of the institute, ran tests showing that the model could reproduce organ-level responses to bacteria and inflammatory cytokines, as well as to silica nanoparticles. The widely cited paper was published in 2010 (Science. 2010;328[5986]:1662-8), and was followed by another study published in 2012 (Sci Transl Med. 2012;4[159]:159ra147) that used the LOC device to reproduce drug toxicity–induced pulmonary edema. “Here we were demonstrating for the first time that we could use the lung-on-chip to model human lung disease,” said Dr. Huh, who started his own lab at the University of Pennsylvania, Philadelphia, in 2013.
Since then, “as a field we’ve come a long way in modeling the complexity of human lung tissues ... with more advanced devices that can be used to mimic different parts of the lung and different processes, like immune responses in asthma and viral infections,” said Dr. Huh, “and with several studies using primary human cells taken from lung disease patients.”
Among Dr. Huh’s latest devices, built with NIH funding, is an asthma-on-a-chip device. Lung cells isolated from asthma patients are grown in a microfabricated device to create multilayered airway tissue, with airspace, that contains a fully differentiated epithelium and a vascularized stroma. “We can compress the entire engineered area of asthmatic human tissue in a lateral direction to mimic bronchoconstriction that happens during an asthma attack,” he said.
A paper soon to be published will describe how “abnormal pathophysiologic compressive forces due to bronchoconstriction in asthmatic lungs can make the lungs fibrotic, and how those mechanical forces also can induce increased vascularity,” said Dr. Huh, associate professor in the university’s department of bioengineering. “The increased vascular density can also change the phenotype of blood vessels in asthmatic airways.”
Dr. Huh also has an $8.3 million contract with the government’s Biomedical Advanced Research and Development Authority to study how chlorine gas damages lung tissues and identify biomarkers of chlorine gas–induced lung injury, with the goal of developing therapeutics.
Dr. Ingber and associates have developed a device modeling cystic fibrosis (CF). The chip is lined with primary human CF bronchial epithelial cells grown under an air-liquid interface and interfaced with primary lung microvascular endothelium that are exposed to fluid flow.
The chip reproduced, “with high fidelity, many of the structural, biochemical, and pathophysiological features of the human CF lung airway and its response to pathogens and circulating immune cells in vitro,” Dr. Ingber and colleagues reported (J Cyst Fibros. 2022;21:605-15).
Government investment in tissue chips
Efforts to commercialize organs-on-chip platforms and translate them for nonengineers have also picked in recent years. Several companies in the United States (including Emulate, a Wyss start-up) and in Europe now offer microengineered lung tissue models that can be used for research and drug testing. And some large pharmaceutical companies, said Dr. Tagle, have begun integrating tissue chip technology into their drug development programs.
The FDA, meanwhile, “has come to embrace the technology and see its promise,” Dr. Tagle said. An FDA pilot program announced in 2021 – called ISTAND (Innovative Science and Technology Approaches for New Drugs) – allows for tissue chip data to be submitted, as standalone data, for some drug applications.
The first 5 years of the government’s Tissue Chip for Drug Screening Program focused on safety and toxicity, and it “was successful in that model organ systems were able to capture the human response that [had been missed in] animal models,” he said.
For example, when a liver-tissue model was used to test several compounds that had passed animal testing for toxicity/safety but then failed in human clinical trials – killing some of the participants – the model showed a 100% sensitivity and a 87% specificity in predicting the human response, said Dr. Tagle, who recently coauthored a review on the future of organs-on-chips (Nature Reviews I Drug Discovery. 2021;20:345-61).
The second 5 years of the program, currently winding down, have focused on efficacy – the ability of organs-on-chip models to recreate the pathophysiology of chronic obstructive pulmonary disease, influenza, and other diseases, so that potential drugs can be assessed. In 2020, with extra support from the Coronavirus Aid, Relief, and Economic Security Act, NCATS funded academic labs to use organs-on-chip technology to evaluate SARS-CoV-2 and potential therapeutics.
Dr. Ingbar was one of the grantees. His team screened a number of FDA-approved drugs for potential repurposing using a bronchial-airway-on-a-chip and compared results with 2D model systems (Nat Biomed Eng. 2021;5:815-29). Amodiaquine inhibited infection in the 3D model and is now in phase 2 COVID trials. Several other drugs showed effectiveness in a 2D model but not in the chip.
Now, in a next phase of study at NCATS, coined Clinical Trials on a Chip, the center has awarded $35.5 million for investigators to test candidate therapies, often in parallel to ongoing clinical trials. The hope is that organs-on-chips can improve clinical trial design, from enrollment criteria and patient stratification to endpoints and the use of biomarkers. And in his lab, Dr. Huh is now engineering a shift to “organoids-on-a-chip” that combines the best features of each approach. “The idea,” he said, “is to grow organoids, and maintain the organoids in the microengineered systems where we can control their environment better ... and apply cues to allow them to develop into even more realistic tissues.”
Drs. Antony, Linkous, and Tagle reported no relevant disclosures. Dr. Huh is a co-founder of Vivodyne Inc, and owns shares in Vivodyne Inc. and Emulate Inc.
Increasing primary care doctors’ knowledge of IPF could speed up diagnoses, suggests white paper
The nonspecific nature of the symptoms of idiopathic pulmonary fibrosis (IPF) especially in early stages, and the relative rarity of IPF compared with other conditions that have similar symptoms, may contribute to a delay in diagnosis in the primary care setting, wrote Daniel F. Dilling, MD, of Loyola University Chicago, Maywood, Ill., and colleagues in Chest: Clinical Perspectives (Dilling et al. State of Practice: Factors Driving Diagnostic Delays in Idiopathic Pulmonary Fibrosis. Chest. 2022).
“We have learned over and over again through research, and also through talking with our own patients with IPF, that there is often a long lag between the first signs of the disease and a diagnosis of IPF,” corresponding author Dr. Dilling said in an interview.
“Even some pulmonary specialists can be uncertain about how to approach the diagnosis when a CT scan or other test first suggests the possibility; this can cost a patient precious time, as being on drug therapy earlier can result in preservation of lung function,” he said. “By sounding the alarm bell with this paper, we hope to promote awareness and education/training within the primary care community as well as the pulmonary community, and also to make all of them aware of the possibility of referral to specialty ILD [interstitial lung disease] centers when desired and possible,” he added.
The researchers conducted a pair of online surveys to inform the development of improving education on IPF among primary care providers.
In the white paper, which can be accessed online, the authors reported results of the surveys. One included 100 general pulmonologists and the other included 306 primary care physicians (156 practiced family physicians and 150 practiced general internal medicine). The data were collected between April 11, 2022, and May 16, 2022. Participants were asked to respond to a patient case scenario of a 55-year-old woman with nonspecific symptoms such as shortness of breath on moderate exertion, cough, exhaustion, and trouble sleeping.
The PCPs were most likely to evaluate the patient for a cardiac condition (46%), 25% would evaluate for chronic obstructive pulmonary disease (COPD), and 23% for asthma. More than half (58%) ranked progressive fibrosing ILD as one of their bottom two diagnoses.
A total of 87% of PCPs said they would begin a diagnostic workup to evaluate symptoms if the patient had no preexisting respiratory disease, compared with 61% for patients with a respiratory diagnosis.
Although 93% of PCPs cited a chest x-ray as part of the initial patient workup, fewer than half said they would order an echocardiogram, spirometry, or pulmonary function test (PFT), and 11% said they would include diffusion capacity testing in the initial workup.
In addition, PCPs were less likely to ask patients about issues that might prompt an IPF diagnosis, such as exposures to agents through work, hobbies, the environment, or comorbidities.
In the pulmonology survey, more than 75% of respondents cited patient history, high-resolution tomography scan, serologic testing, and review for autoimmune disease symptoms as first steps in a diagnostic response to patients with suspected IPF.
Differences between PCPs’ and pulmonolgists’ responses
Both PCPs and pulmonologists responded to several questions to assess knowledge and opinion gaps related to IPF. Overall, pulmonologists were more likely than PCPs to cite both imaging and testing issues and waiting 6-8 weeks after symptom onset before imaging as contributing factors to diagnostic delays.
PCPs more often expressed beliefs that delayed diagnosis had little impact on a patient with IPF, and that the treatments may be worse than the disease.
Dr. Dilling said he was not surprised by the survey findings, as similar clues about the underdiagnosis of IPF have surfaced in prior studies.
“We need to get the word out to primary care physicians, to pulmonary physicians, and even to the public, that idiopathic pulmonary fibrosis and other forms of interstitial lung disease are out there and prevalent, and that making the right diagnosis in a timely way can lead to better outcomes for patients,” he said.
The take-home message for primary care is to think outside the COPD box, said Dr. Dilling. “Just because someone has shortness of breath or cough and used to smoke does not automatically mean that they have COPD,” he emphasized. “Listen carefully for crackles (rales) on exam. Get spirometry or PFTs before you secure the diagnosis of COPD, or else you will be missing all of your cases of pulmonary fibrosis; think of pulmonary fibrosis and use imaging to help guide your diagnosis,” he said.
The authors suggested several education goals for PCPs, including establishing the importance of early evaluation, outlining the correct approach to a patient workup, encouraging prompt referral, and empowering PCPs as part of the team approach to IPF patients’ care. For pulmonologists, only 11% of those surveyed said they were aware of the latest developments in antifibrotic research, and education efforts might include information about drug pipelines and clinical trials, as well as technology.
Looking ahead, “We need to better understand how to find the pulmonary fibrosis in the community,” Dr. Dilling said. This understanding may come in part from greater education and awareness, he noted. However, eventually there may be ways to enhance the reading of PFTs and of CT scans through artificial intelligence technologies that would not only prompt clinicians to recognize what they are seeing, but would prompt them to refer and send the patient on the correct diagnostic path as soon as possible, he added.
Key message: Include ILD in differential diagnosis of patients with shortness of breath and/or cough
Advances in diagnostics and therapies for interstitial lung disease can take time to be absorbed and adopted, and patients with ILD and pulmonologists caring for ILD, specifically IPF, continue to report delays in diagnosis and therapy, said Krishna Thavarajah, MD, a pulmonologist at Henry Ford Hospital, Detroit, Mich., in an interview.
The current study findings of the time to diagnosis and the approach to patient workups echo her own clinical experience, Dr. Thavarajah said. “There is a delay in IPF diagnosis as physicians look to more common diagnoses, such as cardiac disease or chronic obstructive pulmonary disease, prior to pursuit of additional workup, and the attitude toward treatment has, in some ways, lagged behind advances in therapy, including timing and feasibility of therapy for IPF,” she said.
The key message for primary care physicians is to include ILD in the differential diagnosis of patients with shortness of breath and/or cough, especially if the initial cardiac and pulmonary test (meaning at least a chest x-ray and pulmonary function tests, including a diffusion capacity) are not pointing to an alternative cause within 3 months of presentation, Dr. Thavarajah said.
Once IPF is diagnosed, primary care clinicians should know that there are FDA-approved therapies that improve survival, said Dr. Thavarajah. “There are identifiable and treatable comorbid conditions,” she added. “The statement of ‘time lost is lung lost’ sums up the care of an IPF patient; partnerships between primary care clinicians, pulmonologists, and referral centers can provide the patient multiple levels of support with quality-of-life interventions, treatments, and also clinical trials, delivered by a team of providers,” she said.
In the wake of the current study, more research is needed with outcome studies regarding educational interventions targeting primary care and pulmonologists on appropriate workup, timing of workup, and current therapy for IPF patients, she added.
The white paper received no outside funding. The authors and Dr. Thavarajah had no financial conflicts to disclose.
The nonspecific nature of the symptoms of idiopathic pulmonary fibrosis (IPF) especially in early stages, and the relative rarity of IPF compared with other conditions that have similar symptoms, may contribute to a delay in diagnosis in the primary care setting, wrote Daniel F. Dilling, MD, of Loyola University Chicago, Maywood, Ill., and colleagues in Chest: Clinical Perspectives (Dilling et al. State of Practice: Factors Driving Diagnostic Delays in Idiopathic Pulmonary Fibrosis. Chest. 2022).
“We have learned over and over again through research, and also through talking with our own patients with IPF, that there is often a long lag between the first signs of the disease and a diagnosis of IPF,” corresponding author Dr. Dilling said in an interview.
“Even some pulmonary specialists can be uncertain about how to approach the diagnosis when a CT scan or other test first suggests the possibility; this can cost a patient precious time, as being on drug therapy earlier can result in preservation of lung function,” he said. “By sounding the alarm bell with this paper, we hope to promote awareness and education/training within the primary care community as well as the pulmonary community, and also to make all of them aware of the possibility of referral to specialty ILD [interstitial lung disease] centers when desired and possible,” he added.
The researchers conducted a pair of online surveys to inform the development of improving education on IPF among primary care providers.
In the white paper, which can be accessed online, the authors reported results of the surveys. One included 100 general pulmonologists and the other included 306 primary care physicians (156 practiced family physicians and 150 practiced general internal medicine). The data were collected between April 11, 2022, and May 16, 2022. Participants were asked to respond to a patient case scenario of a 55-year-old woman with nonspecific symptoms such as shortness of breath on moderate exertion, cough, exhaustion, and trouble sleeping.
The PCPs were most likely to evaluate the patient for a cardiac condition (46%), 25% would evaluate for chronic obstructive pulmonary disease (COPD), and 23% for asthma. More than half (58%) ranked progressive fibrosing ILD as one of their bottom two diagnoses.
A total of 87% of PCPs said they would begin a diagnostic workup to evaluate symptoms if the patient had no preexisting respiratory disease, compared with 61% for patients with a respiratory diagnosis.
Although 93% of PCPs cited a chest x-ray as part of the initial patient workup, fewer than half said they would order an echocardiogram, spirometry, or pulmonary function test (PFT), and 11% said they would include diffusion capacity testing in the initial workup.
In addition, PCPs were less likely to ask patients about issues that might prompt an IPF diagnosis, such as exposures to agents through work, hobbies, the environment, or comorbidities.
In the pulmonology survey, more than 75% of respondents cited patient history, high-resolution tomography scan, serologic testing, and review for autoimmune disease symptoms as first steps in a diagnostic response to patients with suspected IPF.
Differences between PCPs’ and pulmonolgists’ responses
Both PCPs and pulmonologists responded to several questions to assess knowledge and opinion gaps related to IPF. Overall, pulmonologists were more likely than PCPs to cite both imaging and testing issues and waiting 6-8 weeks after symptom onset before imaging as contributing factors to diagnostic delays.
PCPs more often expressed beliefs that delayed diagnosis had little impact on a patient with IPF, and that the treatments may be worse than the disease.
Dr. Dilling said he was not surprised by the survey findings, as similar clues about the underdiagnosis of IPF have surfaced in prior studies.
“We need to get the word out to primary care physicians, to pulmonary physicians, and even to the public, that idiopathic pulmonary fibrosis and other forms of interstitial lung disease are out there and prevalent, and that making the right diagnosis in a timely way can lead to better outcomes for patients,” he said.
The take-home message for primary care is to think outside the COPD box, said Dr. Dilling. “Just because someone has shortness of breath or cough and used to smoke does not automatically mean that they have COPD,” he emphasized. “Listen carefully for crackles (rales) on exam. Get spirometry or PFTs before you secure the diagnosis of COPD, or else you will be missing all of your cases of pulmonary fibrosis; think of pulmonary fibrosis and use imaging to help guide your diagnosis,” he said.
The authors suggested several education goals for PCPs, including establishing the importance of early evaluation, outlining the correct approach to a patient workup, encouraging prompt referral, and empowering PCPs as part of the team approach to IPF patients’ care. For pulmonologists, only 11% of those surveyed said they were aware of the latest developments in antifibrotic research, and education efforts might include information about drug pipelines and clinical trials, as well as technology.
Looking ahead, “We need to better understand how to find the pulmonary fibrosis in the community,” Dr. Dilling said. This understanding may come in part from greater education and awareness, he noted. However, eventually there may be ways to enhance the reading of PFTs and of CT scans through artificial intelligence technologies that would not only prompt clinicians to recognize what they are seeing, but would prompt them to refer and send the patient on the correct diagnostic path as soon as possible, he added.
Key message: Include ILD in differential diagnosis of patients with shortness of breath and/or cough
Advances in diagnostics and therapies for interstitial lung disease can take time to be absorbed and adopted, and patients with ILD and pulmonologists caring for ILD, specifically IPF, continue to report delays in diagnosis and therapy, said Krishna Thavarajah, MD, a pulmonologist at Henry Ford Hospital, Detroit, Mich., in an interview.
The current study findings of the time to diagnosis and the approach to patient workups echo her own clinical experience, Dr. Thavarajah said. “There is a delay in IPF diagnosis as physicians look to more common diagnoses, such as cardiac disease or chronic obstructive pulmonary disease, prior to pursuit of additional workup, and the attitude toward treatment has, in some ways, lagged behind advances in therapy, including timing and feasibility of therapy for IPF,” she said.
The key message for primary care physicians is to include ILD in the differential diagnosis of patients with shortness of breath and/or cough, especially if the initial cardiac and pulmonary test (meaning at least a chest x-ray and pulmonary function tests, including a diffusion capacity) are not pointing to an alternative cause within 3 months of presentation, Dr. Thavarajah said.
Once IPF is diagnosed, primary care clinicians should know that there are FDA-approved therapies that improve survival, said Dr. Thavarajah. “There are identifiable and treatable comorbid conditions,” she added. “The statement of ‘time lost is lung lost’ sums up the care of an IPF patient; partnerships between primary care clinicians, pulmonologists, and referral centers can provide the patient multiple levels of support with quality-of-life interventions, treatments, and also clinical trials, delivered by a team of providers,” she said.
In the wake of the current study, more research is needed with outcome studies regarding educational interventions targeting primary care and pulmonologists on appropriate workup, timing of workup, and current therapy for IPF patients, she added.
The white paper received no outside funding. The authors and Dr. Thavarajah had no financial conflicts to disclose.
The nonspecific nature of the symptoms of idiopathic pulmonary fibrosis (IPF) especially in early stages, and the relative rarity of IPF compared with other conditions that have similar symptoms, may contribute to a delay in diagnosis in the primary care setting, wrote Daniel F. Dilling, MD, of Loyola University Chicago, Maywood, Ill., and colleagues in Chest: Clinical Perspectives (Dilling et al. State of Practice: Factors Driving Diagnostic Delays in Idiopathic Pulmonary Fibrosis. Chest. 2022).
“We have learned over and over again through research, and also through talking with our own patients with IPF, that there is often a long lag between the first signs of the disease and a diagnosis of IPF,” corresponding author Dr. Dilling said in an interview.
“Even some pulmonary specialists can be uncertain about how to approach the diagnosis when a CT scan or other test first suggests the possibility; this can cost a patient precious time, as being on drug therapy earlier can result in preservation of lung function,” he said. “By sounding the alarm bell with this paper, we hope to promote awareness and education/training within the primary care community as well as the pulmonary community, and also to make all of them aware of the possibility of referral to specialty ILD [interstitial lung disease] centers when desired and possible,” he added.
The researchers conducted a pair of online surveys to inform the development of improving education on IPF among primary care providers.
In the white paper, which can be accessed online, the authors reported results of the surveys. One included 100 general pulmonologists and the other included 306 primary care physicians (156 practiced family physicians and 150 practiced general internal medicine). The data were collected between April 11, 2022, and May 16, 2022. Participants were asked to respond to a patient case scenario of a 55-year-old woman with nonspecific symptoms such as shortness of breath on moderate exertion, cough, exhaustion, and trouble sleeping.
The PCPs were most likely to evaluate the patient for a cardiac condition (46%), 25% would evaluate for chronic obstructive pulmonary disease (COPD), and 23% for asthma. More than half (58%) ranked progressive fibrosing ILD as one of their bottom two diagnoses.
A total of 87% of PCPs said they would begin a diagnostic workup to evaluate symptoms if the patient had no preexisting respiratory disease, compared with 61% for patients with a respiratory diagnosis.
Although 93% of PCPs cited a chest x-ray as part of the initial patient workup, fewer than half said they would order an echocardiogram, spirometry, or pulmonary function test (PFT), and 11% said they would include diffusion capacity testing in the initial workup.
In addition, PCPs were less likely to ask patients about issues that might prompt an IPF diagnosis, such as exposures to agents through work, hobbies, the environment, or comorbidities.
In the pulmonology survey, more than 75% of respondents cited patient history, high-resolution tomography scan, serologic testing, and review for autoimmune disease symptoms as first steps in a diagnostic response to patients with suspected IPF.
Differences between PCPs’ and pulmonolgists’ responses
Both PCPs and pulmonologists responded to several questions to assess knowledge and opinion gaps related to IPF. Overall, pulmonologists were more likely than PCPs to cite both imaging and testing issues and waiting 6-8 weeks after symptom onset before imaging as contributing factors to diagnostic delays.
PCPs more often expressed beliefs that delayed diagnosis had little impact on a patient with IPF, and that the treatments may be worse than the disease.
Dr. Dilling said he was not surprised by the survey findings, as similar clues about the underdiagnosis of IPF have surfaced in prior studies.
“We need to get the word out to primary care physicians, to pulmonary physicians, and even to the public, that idiopathic pulmonary fibrosis and other forms of interstitial lung disease are out there and prevalent, and that making the right diagnosis in a timely way can lead to better outcomes for patients,” he said.
The take-home message for primary care is to think outside the COPD box, said Dr. Dilling. “Just because someone has shortness of breath or cough and used to smoke does not automatically mean that they have COPD,” he emphasized. “Listen carefully for crackles (rales) on exam. Get spirometry or PFTs before you secure the diagnosis of COPD, or else you will be missing all of your cases of pulmonary fibrosis; think of pulmonary fibrosis and use imaging to help guide your diagnosis,” he said.
The authors suggested several education goals for PCPs, including establishing the importance of early evaluation, outlining the correct approach to a patient workup, encouraging prompt referral, and empowering PCPs as part of the team approach to IPF patients’ care. For pulmonologists, only 11% of those surveyed said they were aware of the latest developments in antifibrotic research, and education efforts might include information about drug pipelines and clinical trials, as well as technology.
Looking ahead, “We need to better understand how to find the pulmonary fibrosis in the community,” Dr. Dilling said. This understanding may come in part from greater education and awareness, he noted. However, eventually there may be ways to enhance the reading of PFTs and of CT scans through artificial intelligence technologies that would not only prompt clinicians to recognize what they are seeing, but would prompt them to refer and send the patient on the correct diagnostic path as soon as possible, he added.
Key message: Include ILD in differential diagnosis of patients with shortness of breath and/or cough
Advances in diagnostics and therapies for interstitial lung disease can take time to be absorbed and adopted, and patients with ILD and pulmonologists caring for ILD, specifically IPF, continue to report delays in diagnosis and therapy, said Krishna Thavarajah, MD, a pulmonologist at Henry Ford Hospital, Detroit, Mich., in an interview.
The current study findings of the time to diagnosis and the approach to patient workups echo her own clinical experience, Dr. Thavarajah said. “There is a delay in IPF diagnosis as physicians look to more common diagnoses, such as cardiac disease or chronic obstructive pulmonary disease, prior to pursuit of additional workup, and the attitude toward treatment has, in some ways, lagged behind advances in therapy, including timing and feasibility of therapy for IPF,” she said.
The key message for primary care physicians is to include ILD in the differential diagnosis of patients with shortness of breath and/or cough, especially if the initial cardiac and pulmonary test (meaning at least a chest x-ray and pulmonary function tests, including a diffusion capacity) are not pointing to an alternative cause within 3 months of presentation, Dr. Thavarajah said.
Once IPF is diagnosed, primary care clinicians should know that there are FDA-approved therapies that improve survival, said Dr. Thavarajah. “There are identifiable and treatable comorbid conditions,” she added. “The statement of ‘time lost is lung lost’ sums up the care of an IPF patient; partnerships between primary care clinicians, pulmonologists, and referral centers can provide the patient multiple levels of support with quality-of-life interventions, treatments, and also clinical trials, delivered by a team of providers,” she said.
In the wake of the current study, more research is needed with outcome studies regarding educational interventions targeting primary care and pulmonologists on appropriate workup, timing of workup, and current therapy for IPF patients, she added.
The white paper received no outside funding. The authors and Dr. Thavarajah had no financial conflicts to disclose.
FROM CHEST CLINICAL PERSPECTIVES
Esophageal motility issues may promote respiratory disease
Individuals with esophageal dysmotility had significantly higher scores on measures of airway reflux symptoms, based on data from 441 patients.
Many patients with chronic respiratory diseases experience persistent symptoms despite optimal treatment, and the reason is often unclear and frustrating for clinicians and patients, Dominic L. Sykes, MD, of Hull (England) University Teaching Hospitals NHS Trust, and colleagues wrote.
Although more studies in recent years have explored the association between gastroesophageal reflux and respiratory diseases such as asthma and chronic obstructive pulmonary disease, data on a potential link between esophageal motility and respiratory disease in adults are limited, they noted.
In a study published in Respiratory Medicine, the researchers reviewed data from 441 adults with refractory respiratory symptoms who were treated at a single center between Jan. 1, 2011, and Dec. 1, 2021. Symptoms included persistent cough and breathlessness despite optimal medication. The participants underwent examination with high-resolution esophageal manometry (HROM). Airway reflux was measured using the Hull Airways Reflux Questionnaire (HARQ). The mean age of the patients was 56.5 years, and 64% were women.
Overall, the most common diagnoses were chronic cough (77%), asthma (10%), and interstitial lung disease (7%). The prevalence of esophageal dysmotility was 66%. Patients with esophageal dysmotility had significantly higher HARQ scores than those with normal motility (40.6 vs. 35.3; P < .001). Approximately one-third of the patients had normal motility (34.5%) on HROM, 54% had ineffective esophageal motility, 7.3% had absent contractility, 3.2% had esophageal-gastric junction outflow obstruction, 0.5% had distal esophageal spasm, 0.5% has achalasia, and one patient had hypercontractile esophagus.
No significant differences in manometric diagnoses appeared between men and women. In addition, HARQ scores showed a significant inverse correlation with esophageal contractility as measured by distal contractile integral (DCI).
“The proportion of patients with esophageal dysmotility is consistently high over a range of respiratory diseases, including interstitial lung disease (72%), airways disease (57%), and chronic cough (68%),” and the findings suggest that esophageal disease may play a role in patients with persistent respiratory symptoms, they noted.
The study authors proposed that “impaired peristaltic activity of the esophagus, leading to aspiration of gaseous nonacidic refluxate into the airways, may be a contributor in the development and progression of respiratory disease.” They added that the HARQ offers clinicians a useful screening tool for assessing the need for esophageal study in patients with persistent respiratory symptoms that should be used before considering antireflux surgery.
The study findings were limited by several factors including the lack of lung function data for patients with airway disease and ILD and the inability to show causality between esophageal dysmotility and refractory respiratory symptoms, the researchers noted. Other limitations include the retrospective design, and the lack of data on symptom severity and the subsequent impact on outcomes.
However, the results support the need for additional research into the relationship between esophageal dysmotility, lung function, and symptom burden in chronic respiratory disease, and may inform investigations of therapeutic targets, they concluded.
The study received no outside funding. The researchers had no financial conflicts to disclose.
Individuals with esophageal dysmotility had significantly higher scores on measures of airway reflux symptoms, based on data from 441 patients.
Many patients with chronic respiratory diseases experience persistent symptoms despite optimal treatment, and the reason is often unclear and frustrating for clinicians and patients, Dominic L. Sykes, MD, of Hull (England) University Teaching Hospitals NHS Trust, and colleagues wrote.
Although more studies in recent years have explored the association between gastroesophageal reflux and respiratory diseases such as asthma and chronic obstructive pulmonary disease, data on a potential link between esophageal motility and respiratory disease in adults are limited, they noted.
In a study published in Respiratory Medicine, the researchers reviewed data from 441 adults with refractory respiratory symptoms who were treated at a single center between Jan. 1, 2011, and Dec. 1, 2021. Symptoms included persistent cough and breathlessness despite optimal medication. The participants underwent examination with high-resolution esophageal manometry (HROM). Airway reflux was measured using the Hull Airways Reflux Questionnaire (HARQ). The mean age of the patients was 56.5 years, and 64% were women.
Overall, the most common diagnoses were chronic cough (77%), asthma (10%), and interstitial lung disease (7%). The prevalence of esophageal dysmotility was 66%. Patients with esophageal dysmotility had significantly higher HARQ scores than those with normal motility (40.6 vs. 35.3; P < .001). Approximately one-third of the patients had normal motility (34.5%) on HROM, 54% had ineffective esophageal motility, 7.3% had absent contractility, 3.2% had esophageal-gastric junction outflow obstruction, 0.5% had distal esophageal spasm, 0.5% has achalasia, and one patient had hypercontractile esophagus.
No significant differences in manometric diagnoses appeared between men and women. In addition, HARQ scores showed a significant inverse correlation with esophageal contractility as measured by distal contractile integral (DCI).
“The proportion of patients with esophageal dysmotility is consistently high over a range of respiratory diseases, including interstitial lung disease (72%), airways disease (57%), and chronic cough (68%),” and the findings suggest that esophageal disease may play a role in patients with persistent respiratory symptoms, they noted.
The study authors proposed that “impaired peristaltic activity of the esophagus, leading to aspiration of gaseous nonacidic refluxate into the airways, may be a contributor in the development and progression of respiratory disease.” They added that the HARQ offers clinicians a useful screening tool for assessing the need for esophageal study in patients with persistent respiratory symptoms that should be used before considering antireflux surgery.
The study findings were limited by several factors including the lack of lung function data for patients with airway disease and ILD and the inability to show causality between esophageal dysmotility and refractory respiratory symptoms, the researchers noted. Other limitations include the retrospective design, and the lack of data on symptom severity and the subsequent impact on outcomes.
However, the results support the need for additional research into the relationship between esophageal dysmotility, lung function, and symptom burden in chronic respiratory disease, and may inform investigations of therapeutic targets, they concluded.
The study received no outside funding. The researchers had no financial conflicts to disclose.
Individuals with esophageal dysmotility had significantly higher scores on measures of airway reflux symptoms, based on data from 441 patients.
Many patients with chronic respiratory diseases experience persistent symptoms despite optimal treatment, and the reason is often unclear and frustrating for clinicians and patients, Dominic L. Sykes, MD, of Hull (England) University Teaching Hospitals NHS Trust, and colleagues wrote.
Although more studies in recent years have explored the association between gastroesophageal reflux and respiratory diseases such as asthma and chronic obstructive pulmonary disease, data on a potential link between esophageal motility and respiratory disease in adults are limited, they noted.
In a study published in Respiratory Medicine, the researchers reviewed data from 441 adults with refractory respiratory symptoms who were treated at a single center between Jan. 1, 2011, and Dec. 1, 2021. Symptoms included persistent cough and breathlessness despite optimal medication. The participants underwent examination with high-resolution esophageal manometry (HROM). Airway reflux was measured using the Hull Airways Reflux Questionnaire (HARQ). The mean age of the patients was 56.5 years, and 64% were women.
Overall, the most common diagnoses were chronic cough (77%), asthma (10%), and interstitial lung disease (7%). The prevalence of esophageal dysmotility was 66%. Patients with esophageal dysmotility had significantly higher HARQ scores than those with normal motility (40.6 vs. 35.3; P < .001). Approximately one-third of the patients had normal motility (34.5%) on HROM, 54% had ineffective esophageal motility, 7.3% had absent contractility, 3.2% had esophageal-gastric junction outflow obstruction, 0.5% had distal esophageal spasm, 0.5% has achalasia, and one patient had hypercontractile esophagus.
No significant differences in manometric diagnoses appeared between men and women. In addition, HARQ scores showed a significant inverse correlation with esophageal contractility as measured by distal contractile integral (DCI).
“The proportion of patients with esophageal dysmotility is consistently high over a range of respiratory diseases, including interstitial lung disease (72%), airways disease (57%), and chronic cough (68%),” and the findings suggest that esophageal disease may play a role in patients with persistent respiratory symptoms, they noted.
The study authors proposed that “impaired peristaltic activity of the esophagus, leading to aspiration of gaseous nonacidic refluxate into the airways, may be a contributor in the development and progression of respiratory disease.” They added that the HARQ offers clinicians a useful screening tool for assessing the need for esophageal study in patients with persistent respiratory symptoms that should be used before considering antireflux surgery.
The study findings were limited by several factors including the lack of lung function data for patients with airway disease and ILD and the inability to show causality between esophageal dysmotility and refractory respiratory symptoms, the researchers noted. Other limitations include the retrospective design, and the lack of data on symptom severity and the subsequent impact on outcomes.
However, the results support the need for additional research into the relationship between esophageal dysmotility, lung function, and symptom burden in chronic respiratory disease, and may inform investigations of therapeutic targets, they concluded.
The study received no outside funding. The researchers had no financial conflicts to disclose.
FROM RESPIRATORY MEDICINE
New ESC guidelines for cutting CV risk in noncardiac surgery
The European Society of Cardiology guidelines on cardiovascular assessment and management of patients undergoing noncardiac surgery have seen extensive revision since the 2014 version.
They still have the same aim – to prevent surgery-related bleeding complications, perioperative myocardial infarction/injury (PMI), stent thrombosis, acute heart failure, arrhythmias, pulmonary embolism, ischemic stroke, and cardiovascular (CV) death.
Cochairpersons Sigrun Halvorsen, MD, PhD, and Julinda Mehilli, MD, presented highlights from the guidelines at the annual congress of the European Society of Cardiology and the document was simultaneously published online in the European Heart Journal.
The document classifies noncardiac surgery into three levels of 30-day risk of CV death, MI, or stroke. Low (< 1%) risk includes eye or thyroid surgery; intermediate (1%-5%) risk includes knee or hip replacement or renal transplant; and high (> 5%) risk includes aortic aneurysm, lung transplant, or pancreatic or bladder cancer surgery (see more examples below).
It classifies patients as low risk if they are younger than 65 without CV disease or CV risk factors (smoking, hypertension, diabetes, dyslipidemia, family history); intermediate risk if they are 65 or older or have CV risk factors; and high risk if they have CVD.
In an interview, Dr. Halvorsen, professor in cardiology, University of Oslo, zeroed in on three important revisions:
First, recommendations for preoperative ECG and biomarkers are more specific, he noted.
The guidelines advise that before intermediate- or high-risk noncardiac surgery, in patients who have known CVD, CV risk factors (including age 65 or older), or symptoms suggestive of CVD:
- It is recommended to obtain a preoperative 12-lead ECG (class I).
- It is recommended to measure high-sensitivity cardiac troponin T (hs-cTn T) or high-sensitivity cardiac troponin I (hs-cTn I). It is also recommended to measure these biomarkers at 24 hours and 48 hours post surgery (class I).
- It should be considered to measure B-type natriuretic peptide or N-terminal of the prohormone BNP (NT-proBNP).
However, for low-risk patients undergoing low- and intermediate-risk noncardiac surgery, it is not recommended to routinely obtain preoperative ECG, hs-cTn T/I, or BNP/NT-proBNP concentrations (class III).
Troponins have a stronger class I recommendation, compared with the IIA recommendation for BNP, because they are useful for preoperative risk stratification and for diagnosis of PMI, Dr. Halvorsen explained. “Patients receive painkillers after surgery and may have no pain,” she noted, but they may have PMI, which has a bad prognosis.
Second, the guidelines recommend that “all patients should stop smoking 4 weeks before noncardiac surgery [class I],” she noted. Clinicians should also “measure hemoglobin, and if the patient is anemic, treat the anemia.”
Third, the sections on antithrombotic treatment have been significantly revised. “Bridging – stopping an oral antithrombotic drug and switching to a subcutaneous or IV drug – has been common,” Dr. Halvorsen said, “but recently we have new evidence that in most cases that increases the risk of bleeding.”
“We are [now] much more restrictive with respect to bridging” with unfractionated heparin or low-molecular-weight heparin, she said. “We recommend against bridging in patients with low to moderate thrombotic risk,” and bridging should only be considered in patients with mechanical prosthetic heart valves or with very high thrombotic risk.
More preoperative recommendations
In the guideline overview session at the congress, Dr. Halverson highlighted some of the new recommendations for preoperative risk assessment.
If time allows, it is recommended to optimize guideline-recommended treatment of CVD and control of CV risk factors including blood pressure, dyslipidemia, and diabetes, before noncardiac surgery (class I).
Patients commonly have “murmurs, chest pain, dyspnea, and edema that may suggest severe CVD, but may also be caused by noncardiac disease,” she noted. The guidelines state that “for patients with a newly detected murmur and symptoms or signs of CVD, transthoracic echocardiography is recommended before noncardiac surgery (class I).
“Many studies have been performed to try to find out if initiation of specific drugs before surgery could reduce the risk of complications,” Dr. Halvorsen noted. However, few have shown any benefit and “the question of presurgery initiation of beta-blockers has been greatly debated,” she said. “We have again reviewed the literature and concluded ‘Routine initiation of beta-blockers perioperatively is not recommended (class IIIA).’ “
“We adhere to the guidelines on acute and chronic coronary syndrome recommending 6-12 months of dual antiplatelet treatment as a standard before elective surgery,” she said. “However, in case of time-sensitive surgery, the duration of that treatment can be shortened down to a minimum of 1 month after elective PCI and a minimum of 3 months after PCI and ACS.”
Patients with specific types of CVD
Dr. Mehilli, a professor at Landshut-Achdorf (Germany) Hospital, highlighted some new guideline recommendations for patients who have specific types of cardiovascular disease.
Coronary artery disease (CAD). “For chronic coronary syndrome, a cardiac workup is recommended only for patients undergoing intermediate risk or high-risk noncardiac surgery.”
“Stress imaging should be considered before any high risk, noncardiac surgery in asymptomatic patients with poor functional capacity and prior PCI or coronary artery bypass graft (new recommendation, class IIa).”
Mitral valve regurgitation. For patients undergoing scheduled noncardiac surgery, who remain symptomatic despite guideline-directed medical treatment for mitral valve regurgitation (including resynchronization and myocardial revascularization), consider a valve intervention – either transcatheter or surgical – before noncardiac surgery in eligible patients with acceptable procedural risk (new recommendation).
Cardiac implantable electronic devices (CIED). For high-risk patients with CIEDs undergoing noncardiac surgery with high probability of electromagnetic interference, a CIED checkup and necessary reprogramming immediately before the procedure should be considered (new recommendation).
Arrhythmias. “I want only to stress,” Dr. Mehilli said, “in patients with atrial fibrillation with acute or worsening hemodynamic instability undergoing noncardiac surgery, an emergency electrical cardioversion is recommended (class I).”
Peripheral artery disease (PAD) and abdominal aortic aneurysm. For these patients “we do not recommend a routine referral for a cardiac workup. But we recommend it for patients with poor functional capacity or with significant risk factors or symptoms (new recommendations).”
Chronic arterial hypertension. “We have modified the recommendation, recommending avoidance of large perioperative fluctuations in blood pressure, and we do not recommend deferring noncardiac surgery in patients with stage 1 or 2 hypertension,” she said.
Postoperative cardiovascular complications
The most frequent postoperative cardiovascular complication is PMI, Dr. Mehilli noted.
“In the BASEL-PMI registry, the incidence of this complication around intermediate or high-risk noncardiac surgery was up to 15% among patients older than 65 years or with a history of CAD or PAD, which makes this kind of complication really important to prevent, to assess, and to know how to treat.”
“It is recommended to have a high awareness for perioperative cardiovascular complications, combined with surveillance for PMI in patients undergoing intermediate- or high-risk noncardiac surgery” based on serial measurements of high-sensitivity cardiac troponin.
The guidelines define PMI as “an increase in the delta of high-sensitivity troponin more than the upper level of normal,” Dr. Mehilli said. “It’s different from the one used in a rule-in algorithm for non-STEMI acute coronary syndrome.”
Postoperative atrial fibrillation (AFib) is observed in 2%-30% of noncardiac surgery patients in different registries, particularly in patients undergoing intermediate or high-risk noncardiac surgery, she noted.
“We propose an algorithm on how to prevent and treat this complication. I want to highlight that in patients with hemodynamic unstable postoperative AF[ib], an emergency cardioversion is indicated. For the others, a rate control with the target heart rate of less than 110 beats per minute is indicated.”
In patients with postoperative AFib, long-term oral anticoagulation therapy should be considered in all patients at risk for stroke, considering the anticipated net clinical benefit of oral anticoagulation therapy as well as informed patient preference (new recommendations).
Routine use of beta-blockers to prevent postoperative AFib in patients undergoing noncardiac surgery is not recommended.
The document also covers the management of patients with kidney disease, diabetes, cancer, obesity, and COVID-19. In general, elective noncardiac surgery should be postponed after a patient has COVID-19, until he or she recovers completely, and coexisting conditions are optimized.
The guidelines are available from the ESC website in several formats: pocket guidelines, pocket guidelines smartphone app, guidelines slide set, essential messages, and the European Heart Journal article.
Noncardiac surgery risk categories
The guideline includes a table that classifies noncardiac surgeries into three groups, based on the associated 30-day risk of death, MI, or stroke:
- Low (< 1%): breast, dental, eye, thyroid, and minor gynecologic, orthopedic, and urologic surgery.
- Intermediate (1%-5%): carotid surgery, endovascular aortic aneurysm repair, gallbladder surgery, head or neck surgery, hernia repair, peripheral arterial angioplasty, renal transplant, major gynecologic, orthopedic, or neurologic (hip or spine) surgery, or urologic surgery
- High (> 5%): aortic and major vascular surgery (including aortic aneurysm), bladder removal (usually as a result of cancer), limb amputation, lung or liver transplant, pancreatic surgery, or perforated bowel repair.
The guidelines were endorsed by the European Society of Anaesthesiology and Intensive Care. The guideline authors reported numerous disclosures.
A version of this article first appeared on Medscape.com.
The European Society of Cardiology guidelines on cardiovascular assessment and management of patients undergoing noncardiac surgery have seen extensive revision since the 2014 version.
They still have the same aim – to prevent surgery-related bleeding complications, perioperative myocardial infarction/injury (PMI), stent thrombosis, acute heart failure, arrhythmias, pulmonary embolism, ischemic stroke, and cardiovascular (CV) death.
Cochairpersons Sigrun Halvorsen, MD, PhD, and Julinda Mehilli, MD, presented highlights from the guidelines at the annual congress of the European Society of Cardiology and the document was simultaneously published online in the European Heart Journal.
The document classifies noncardiac surgery into three levels of 30-day risk of CV death, MI, or stroke. Low (< 1%) risk includes eye or thyroid surgery; intermediate (1%-5%) risk includes knee or hip replacement or renal transplant; and high (> 5%) risk includes aortic aneurysm, lung transplant, or pancreatic or bladder cancer surgery (see more examples below).
It classifies patients as low risk if they are younger than 65 without CV disease or CV risk factors (smoking, hypertension, diabetes, dyslipidemia, family history); intermediate risk if they are 65 or older or have CV risk factors; and high risk if they have CVD.
In an interview, Dr. Halvorsen, professor in cardiology, University of Oslo, zeroed in on three important revisions:
First, recommendations for preoperative ECG and biomarkers are more specific, he noted.
The guidelines advise that before intermediate- or high-risk noncardiac surgery, in patients who have known CVD, CV risk factors (including age 65 or older), or symptoms suggestive of CVD:
- It is recommended to obtain a preoperative 12-lead ECG (class I).
- It is recommended to measure high-sensitivity cardiac troponin T (hs-cTn T) or high-sensitivity cardiac troponin I (hs-cTn I). It is also recommended to measure these biomarkers at 24 hours and 48 hours post surgery (class I).
- It should be considered to measure B-type natriuretic peptide or N-terminal of the prohormone BNP (NT-proBNP).
However, for low-risk patients undergoing low- and intermediate-risk noncardiac surgery, it is not recommended to routinely obtain preoperative ECG, hs-cTn T/I, or BNP/NT-proBNP concentrations (class III).
Troponins have a stronger class I recommendation, compared with the IIA recommendation for BNP, because they are useful for preoperative risk stratification and for diagnosis of PMI, Dr. Halvorsen explained. “Patients receive painkillers after surgery and may have no pain,” she noted, but they may have PMI, which has a bad prognosis.
Second, the guidelines recommend that “all patients should stop smoking 4 weeks before noncardiac surgery [class I],” she noted. Clinicians should also “measure hemoglobin, and if the patient is anemic, treat the anemia.”
Third, the sections on antithrombotic treatment have been significantly revised. “Bridging – stopping an oral antithrombotic drug and switching to a subcutaneous or IV drug – has been common,” Dr. Halvorsen said, “but recently we have new evidence that in most cases that increases the risk of bleeding.”
“We are [now] much more restrictive with respect to bridging” with unfractionated heparin or low-molecular-weight heparin, she said. “We recommend against bridging in patients with low to moderate thrombotic risk,” and bridging should only be considered in patients with mechanical prosthetic heart valves or with very high thrombotic risk.
More preoperative recommendations
In the guideline overview session at the congress, Dr. Halverson highlighted some of the new recommendations for preoperative risk assessment.
If time allows, it is recommended to optimize guideline-recommended treatment of CVD and control of CV risk factors including blood pressure, dyslipidemia, and diabetes, before noncardiac surgery (class I).
Patients commonly have “murmurs, chest pain, dyspnea, and edema that may suggest severe CVD, but may also be caused by noncardiac disease,” she noted. The guidelines state that “for patients with a newly detected murmur and symptoms or signs of CVD, transthoracic echocardiography is recommended before noncardiac surgery (class I).
“Many studies have been performed to try to find out if initiation of specific drugs before surgery could reduce the risk of complications,” Dr. Halvorsen noted. However, few have shown any benefit and “the question of presurgery initiation of beta-blockers has been greatly debated,” she said. “We have again reviewed the literature and concluded ‘Routine initiation of beta-blockers perioperatively is not recommended (class IIIA).’ “
“We adhere to the guidelines on acute and chronic coronary syndrome recommending 6-12 months of dual antiplatelet treatment as a standard before elective surgery,” she said. “However, in case of time-sensitive surgery, the duration of that treatment can be shortened down to a minimum of 1 month after elective PCI and a minimum of 3 months after PCI and ACS.”
Patients with specific types of CVD
Dr. Mehilli, a professor at Landshut-Achdorf (Germany) Hospital, highlighted some new guideline recommendations for patients who have specific types of cardiovascular disease.
Coronary artery disease (CAD). “For chronic coronary syndrome, a cardiac workup is recommended only for patients undergoing intermediate risk or high-risk noncardiac surgery.”
“Stress imaging should be considered before any high risk, noncardiac surgery in asymptomatic patients with poor functional capacity and prior PCI or coronary artery bypass graft (new recommendation, class IIa).”
Mitral valve regurgitation. For patients undergoing scheduled noncardiac surgery, who remain symptomatic despite guideline-directed medical treatment for mitral valve regurgitation (including resynchronization and myocardial revascularization), consider a valve intervention – either transcatheter or surgical – before noncardiac surgery in eligible patients with acceptable procedural risk (new recommendation).
Cardiac implantable electronic devices (CIED). For high-risk patients with CIEDs undergoing noncardiac surgery with high probability of electromagnetic interference, a CIED checkup and necessary reprogramming immediately before the procedure should be considered (new recommendation).
Arrhythmias. “I want only to stress,” Dr. Mehilli said, “in patients with atrial fibrillation with acute or worsening hemodynamic instability undergoing noncardiac surgery, an emergency electrical cardioversion is recommended (class I).”
Peripheral artery disease (PAD) and abdominal aortic aneurysm. For these patients “we do not recommend a routine referral for a cardiac workup. But we recommend it for patients with poor functional capacity or with significant risk factors or symptoms (new recommendations).”
Chronic arterial hypertension. “We have modified the recommendation, recommending avoidance of large perioperative fluctuations in blood pressure, and we do not recommend deferring noncardiac surgery in patients with stage 1 or 2 hypertension,” she said.
Postoperative cardiovascular complications
The most frequent postoperative cardiovascular complication is PMI, Dr. Mehilli noted.
“In the BASEL-PMI registry, the incidence of this complication around intermediate or high-risk noncardiac surgery was up to 15% among patients older than 65 years or with a history of CAD or PAD, which makes this kind of complication really important to prevent, to assess, and to know how to treat.”
“It is recommended to have a high awareness for perioperative cardiovascular complications, combined with surveillance for PMI in patients undergoing intermediate- or high-risk noncardiac surgery” based on serial measurements of high-sensitivity cardiac troponin.
The guidelines define PMI as “an increase in the delta of high-sensitivity troponin more than the upper level of normal,” Dr. Mehilli said. “It’s different from the one used in a rule-in algorithm for non-STEMI acute coronary syndrome.”
Postoperative atrial fibrillation (AFib) is observed in 2%-30% of noncardiac surgery patients in different registries, particularly in patients undergoing intermediate or high-risk noncardiac surgery, she noted.
“We propose an algorithm on how to prevent and treat this complication. I want to highlight that in patients with hemodynamic unstable postoperative AF[ib], an emergency cardioversion is indicated. For the others, a rate control with the target heart rate of less than 110 beats per minute is indicated.”
In patients with postoperative AFib, long-term oral anticoagulation therapy should be considered in all patients at risk for stroke, considering the anticipated net clinical benefit of oral anticoagulation therapy as well as informed patient preference (new recommendations).
Routine use of beta-blockers to prevent postoperative AFib in patients undergoing noncardiac surgery is not recommended.
The document also covers the management of patients with kidney disease, diabetes, cancer, obesity, and COVID-19. In general, elective noncardiac surgery should be postponed after a patient has COVID-19, until he or she recovers completely, and coexisting conditions are optimized.
The guidelines are available from the ESC website in several formats: pocket guidelines, pocket guidelines smartphone app, guidelines slide set, essential messages, and the European Heart Journal article.
Noncardiac surgery risk categories
The guideline includes a table that classifies noncardiac surgeries into three groups, based on the associated 30-day risk of death, MI, or stroke:
- Low (< 1%): breast, dental, eye, thyroid, and minor gynecologic, orthopedic, and urologic surgery.
- Intermediate (1%-5%): carotid surgery, endovascular aortic aneurysm repair, gallbladder surgery, head or neck surgery, hernia repair, peripheral arterial angioplasty, renal transplant, major gynecologic, orthopedic, or neurologic (hip or spine) surgery, or urologic surgery
- High (> 5%): aortic and major vascular surgery (including aortic aneurysm), bladder removal (usually as a result of cancer), limb amputation, lung or liver transplant, pancreatic surgery, or perforated bowel repair.
The guidelines were endorsed by the European Society of Anaesthesiology and Intensive Care. The guideline authors reported numerous disclosures.
A version of this article first appeared on Medscape.com.
The European Society of Cardiology guidelines on cardiovascular assessment and management of patients undergoing noncardiac surgery have seen extensive revision since the 2014 version.
They still have the same aim – to prevent surgery-related bleeding complications, perioperative myocardial infarction/injury (PMI), stent thrombosis, acute heart failure, arrhythmias, pulmonary embolism, ischemic stroke, and cardiovascular (CV) death.
Cochairpersons Sigrun Halvorsen, MD, PhD, and Julinda Mehilli, MD, presented highlights from the guidelines at the annual congress of the European Society of Cardiology and the document was simultaneously published online in the European Heart Journal.
The document classifies noncardiac surgery into three levels of 30-day risk of CV death, MI, or stroke. Low (< 1%) risk includes eye or thyroid surgery; intermediate (1%-5%) risk includes knee or hip replacement or renal transplant; and high (> 5%) risk includes aortic aneurysm, lung transplant, or pancreatic or bladder cancer surgery (see more examples below).
It classifies patients as low risk if they are younger than 65 without CV disease or CV risk factors (smoking, hypertension, diabetes, dyslipidemia, family history); intermediate risk if they are 65 or older or have CV risk factors; and high risk if they have CVD.
In an interview, Dr. Halvorsen, professor in cardiology, University of Oslo, zeroed in on three important revisions:
First, recommendations for preoperative ECG and biomarkers are more specific, he noted.
The guidelines advise that before intermediate- or high-risk noncardiac surgery, in patients who have known CVD, CV risk factors (including age 65 or older), or symptoms suggestive of CVD:
- It is recommended to obtain a preoperative 12-lead ECG (class I).
- It is recommended to measure high-sensitivity cardiac troponin T (hs-cTn T) or high-sensitivity cardiac troponin I (hs-cTn I). It is also recommended to measure these biomarkers at 24 hours and 48 hours post surgery (class I).
- It should be considered to measure B-type natriuretic peptide or N-terminal of the prohormone BNP (NT-proBNP).
However, for low-risk patients undergoing low- and intermediate-risk noncardiac surgery, it is not recommended to routinely obtain preoperative ECG, hs-cTn T/I, or BNP/NT-proBNP concentrations (class III).
Troponins have a stronger class I recommendation, compared with the IIA recommendation for BNP, because they are useful for preoperative risk stratification and for diagnosis of PMI, Dr. Halvorsen explained. “Patients receive painkillers after surgery and may have no pain,” she noted, but they may have PMI, which has a bad prognosis.
Second, the guidelines recommend that “all patients should stop smoking 4 weeks before noncardiac surgery [class I],” she noted. Clinicians should also “measure hemoglobin, and if the patient is anemic, treat the anemia.”
Third, the sections on antithrombotic treatment have been significantly revised. “Bridging – stopping an oral antithrombotic drug and switching to a subcutaneous or IV drug – has been common,” Dr. Halvorsen said, “but recently we have new evidence that in most cases that increases the risk of bleeding.”
“We are [now] much more restrictive with respect to bridging” with unfractionated heparin or low-molecular-weight heparin, she said. “We recommend against bridging in patients with low to moderate thrombotic risk,” and bridging should only be considered in patients with mechanical prosthetic heart valves or with very high thrombotic risk.
More preoperative recommendations
In the guideline overview session at the congress, Dr. Halverson highlighted some of the new recommendations for preoperative risk assessment.
If time allows, it is recommended to optimize guideline-recommended treatment of CVD and control of CV risk factors including blood pressure, dyslipidemia, and diabetes, before noncardiac surgery (class I).
Patients commonly have “murmurs, chest pain, dyspnea, and edema that may suggest severe CVD, but may also be caused by noncardiac disease,” she noted. The guidelines state that “for patients with a newly detected murmur and symptoms or signs of CVD, transthoracic echocardiography is recommended before noncardiac surgery (class I).
“Many studies have been performed to try to find out if initiation of specific drugs before surgery could reduce the risk of complications,” Dr. Halvorsen noted. However, few have shown any benefit and “the question of presurgery initiation of beta-blockers has been greatly debated,” she said. “We have again reviewed the literature and concluded ‘Routine initiation of beta-blockers perioperatively is not recommended (class IIIA).’ “
“We adhere to the guidelines on acute and chronic coronary syndrome recommending 6-12 months of dual antiplatelet treatment as a standard before elective surgery,” she said. “However, in case of time-sensitive surgery, the duration of that treatment can be shortened down to a minimum of 1 month after elective PCI and a minimum of 3 months after PCI and ACS.”
Patients with specific types of CVD
Dr. Mehilli, a professor at Landshut-Achdorf (Germany) Hospital, highlighted some new guideline recommendations for patients who have specific types of cardiovascular disease.
Coronary artery disease (CAD). “For chronic coronary syndrome, a cardiac workup is recommended only for patients undergoing intermediate risk or high-risk noncardiac surgery.”
“Stress imaging should be considered before any high risk, noncardiac surgery in asymptomatic patients with poor functional capacity and prior PCI or coronary artery bypass graft (new recommendation, class IIa).”
Mitral valve regurgitation. For patients undergoing scheduled noncardiac surgery, who remain symptomatic despite guideline-directed medical treatment for mitral valve regurgitation (including resynchronization and myocardial revascularization), consider a valve intervention – either transcatheter or surgical – before noncardiac surgery in eligible patients with acceptable procedural risk (new recommendation).
Cardiac implantable electronic devices (CIED). For high-risk patients with CIEDs undergoing noncardiac surgery with high probability of electromagnetic interference, a CIED checkup and necessary reprogramming immediately before the procedure should be considered (new recommendation).
Arrhythmias. “I want only to stress,” Dr. Mehilli said, “in patients with atrial fibrillation with acute or worsening hemodynamic instability undergoing noncardiac surgery, an emergency electrical cardioversion is recommended (class I).”
Peripheral artery disease (PAD) and abdominal aortic aneurysm. For these patients “we do not recommend a routine referral for a cardiac workup. But we recommend it for patients with poor functional capacity or with significant risk factors or symptoms (new recommendations).”
Chronic arterial hypertension. “We have modified the recommendation, recommending avoidance of large perioperative fluctuations in blood pressure, and we do not recommend deferring noncardiac surgery in patients with stage 1 or 2 hypertension,” she said.
Postoperative cardiovascular complications
The most frequent postoperative cardiovascular complication is PMI, Dr. Mehilli noted.
“In the BASEL-PMI registry, the incidence of this complication around intermediate or high-risk noncardiac surgery was up to 15% among patients older than 65 years or with a history of CAD or PAD, which makes this kind of complication really important to prevent, to assess, and to know how to treat.”
“It is recommended to have a high awareness for perioperative cardiovascular complications, combined with surveillance for PMI in patients undergoing intermediate- or high-risk noncardiac surgery” based on serial measurements of high-sensitivity cardiac troponin.
The guidelines define PMI as “an increase in the delta of high-sensitivity troponin more than the upper level of normal,” Dr. Mehilli said. “It’s different from the one used in a rule-in algorithm for non-STEMI acute coronary syndrome.”
Postoperative atrial fibrillation (AFib) is observed in 2%-30% of noncardiac surgery patients in different registries, particularly in patients undergoing intermediate or high-risk noncardiac surgery, she noted.
“We propose an algorithm on how to prevent and treat this complication. I want to highlight that in patients with hemodynamic unstable postoperative AF[ib], an emergency cardioversion is indicated. For the others, a rate control with the target heart rate of less than 110 beats per minute is indicated.”
In patients with postoperative AFib, long-term oral anticoagulation therapy should be considered in all patients at risk for stroke, considering the anticipated net clinical benefit of oral anticoagulation therapy as well as informed patient preference (new recommendations).
Routine use of beta-blockers to prevent postoperative AFib in patients undergoing noncardiac surgery is not recommended.
The document also covers the management of patients with kidney disease, diabetes, cancer, obesity, and COVID-19. In general, elective noncardiac surgery should be postponed after a patient has COVID-19, until he or she recovers completely, and coexisting conditions are optimized.
The guidelines are available from the ESC website in several formats: pocket guidelines, pocket guidelines smartphone app, guidelines slide set, essential messages, and the European Heart Journal article.
Noncardiac surgery risk categories
The guideline includes a table that classifies noncardiac surgeries into three groups, based on the associated 30-day risk of death, MI, or stroke:
- Low (< 1%): breast, dental, eye, thyroid, and minor gynecologic, orthopedic, and urologic surgery.
- Intermediate (1%-5%): carotid surgery, endovascular aortic aneurysm repair, gallbladder surgery, head or neck surgery, hernia repair, peripheral arterial angioplasty, renal transplant, major gynecologic, orthopedic, or neurologic (hip or spine) surgery, or urologic surgery
- High (> 5%): aortic and major vascular surgery (including aortic aneurysm), bladder removal (usually as a result of cancer), limb amputation, lung or liver transplant, pancreatic surgery, or perforated bowel repair.
The guidelines were endorsed by the European Society of Anaesthesiology and Intensive Care. The guideline authors reported numerous disclosures.
A version of this article first appeared on Medscape.com.
FROM ESC CONGRESS 2022