Pulmonology

Tuberculosis cases are increasing in Washington, which has put public health officials on “heightened alert,” according to a recent announcement from the Washington State Department of Health.

Widespread disruptions in health care and missed tuberculosis diagnoses during the COVID-19 pandemic have likely added to the increase – both locally and globally.

“It’s been 20 years since we saw a cluster of TB cases like this,” Tao Sheng Kwan-Gett, MD, the state’s chief science officer, said in the announcement.

“The pandemic has likely contributed to the rise in cases and the outbreak in at least one correctional facility,” he said. “Increased access to TB testing and treatment in the community is going to be key to getting TB under control.”

Case numbers appeared to fall in Washington during the first year of the pandemic, possibly because of less reporting and missed diagnoses. But in 2021, cases rose quickly. The state reported 199 cases, marking a 22% increase from 2020.

So far this year, 70 cases have been reported, including 17 new cases that all have connections with each other and several state prisons.

The state’s Department of Corrections, Department of Health, and the Centers for Disease Control and Prevention are working together on testing and decreasing spread, MaryAnn Curl, MD, the chief medical officer for the Department of Corrections, said in the statement.

Tuberculosis cases are increasing worldwide. For the first time in more than a decade, TB deaths increased to about 1.5 million, according to the World Health Organization’s 2021 Global Tuberculosis Report.

Across the U.S., the number of reported TB cases significantly declined at the beginning of the pandemic in 2020 but increased again in 2021, according to a recent CDC study.

The Kansas Department of Health also reported an outbreak of TB cases in March, according to USA Today.

At the beginning of the pandemic, some people with TB may have been diagnosed with COVID-19 because both are infectious diseases that attack the lungs and have similar symptoms, the Washington Health Department said.

Like COVID-19, tuberculosis can spread through the air when an infected person coughs or sneezes. But unlike COVID-19, TB typically requires that you have prolonged exposure to become infected.

Symptoms of tuberculosis can include chest pain and coughing, with or without blood, as well as fever, night sweats, weight loss, and fatigue.

Tuberculosis is preventable, treatable, and curable, the Washington Health Department said. Those who travel to countries where TB is more common face higher risks for exposure, as well as those who live or work in settings where TB may spread, such as homeless shelters, prisons, jails, and nursing homes.

People can develop inactive TB, also called latent TB, which doesn’t have any symptoms and isn’t contagious. If people with inactive TB don’t get quick diagnosis or treatment, the infection can become active TB and cause symptoms. State health officials estimated that about 200,000 people in Washington have inactive TB.

Tuberculosis treatment can take a minimum of 6 months, and if it’s not followed carefully, symptoms can become more severe, the Health Department said. Incomplete treatment can also contribute to the spread of antibiotic-resistant strains of tuberculosis.

A version of this article first appeared on WebMD.com.

Tuberculosis cases are increasing in Washington, which has put public health officials on “heightened alert,” according to a recent announcement from the Washington State Department of Health.

Widespread disruptions in health care and missed tuberculosis diagnoses during the COVID-19 pandemic have likely added to the increase – both locally and globally.

“It’s been 20 years since we saw a cluster of TB cases like this,” Tao Sheng Kwan-Gett, MD, the state’s chief science officer, said in the announcement.

“The pandemic has likely contributed to the rise in cases and the outbreak in at least one correctional facility,” he said. “Increased access to TB testing and treatment in the community is going to be key to getting TB under control.”

Case numbers appeared to fall in Washington during the first year of the pandemic, possibly because of less reporting and missed diagnoses. But in 2021, cases rose quickly. The state reported 199 cases, marking a 22% increase from 2020.

So far this year, 70 cases have been reported, including 17 new cases that all have connections with each other and several state prisons.

The state’s Department of Corrections, Department of Health, and the Centers for Disease Control and Prevention are working together on testing and decreasing spread, MaryAnn Curl, MD, the chief medical officer for the Department of Corrections, said in the statement.

Tuberculosis cases are increasing worldwide. For the first time in more than a decade, TB deaths increased to about 1.5 million, according to the World Health Organization’s 2021 Global Tuberculosis Report.

Across the U.S., the number of reported TB cases significantly declined at the beginning of the pandemic in 2020 but increased again in 2021, according to a recent CDC study.

The Kansas Department of Health also reported an outbreak of TB cases in March, according to USA Today.

At the beginning of the pandemic, some people with TB may have been diagnosed with COVID-19 because both are infectious diseases that attack the lungs and have similar symptoms, the Washington Health Department said.

Like COVID-19, tuberculosis can spread through the air when an infected person coughs or sneezes. But unlike COVID-19, TB typically requires that you have prolonged exposure to become infected.

Symptoms of tuberculosis can include chest pain and coughing, with or without blood, as well as fever, night sweats, weight loss, and fatigue.

Tuberculosis is preventable, treatable, and curable, the Washington Health Department said. Those who travel to countries where TB is more common face higher risks for exposure, as well as those who live or work in settings where TB may spread, such as homeless shelters, prisons, jails, and nursing homes.

People can develop inactive TB, also called latent TB, which doesn’t have any symptoms and isn’t contagious. If people with inactive TB don’t get quick diagnosis or treatment, the infection can become active TB and cause symptoms. State health officials estimated that about 200,000 people in Washington have inactive TB.

Tuberculosis treatment can take a minimum of 6 months, and if it’s not followed carefully, symptoms can become more severe, the Health Department said. Incomplete treatment can also contribute to the spread of antibiotic-resistant strains of tuberculosis.

A version of this article first appeared on WebMD.com.

Tuberculosis cases are increasing in Washington, which has put public health officials on “heightened alert,” according to a recent announcement from the Washington State Department of Health.

Widespread disruptions in health care and missed tuberculosis diagnoses during the COVID-19 pandemic have likely added to the increase – both locally and globally.

“It’s been 20 years since we saw a cluster of TB cases like this,” Tao Sheng Kwan-Gett, MD, the state’s chief science officer, said in the announcement.

“The pandemic has likely contributed to the rise in cases and the outbreak in at least one correctional facility,” he said. “Increased access to TB testing and treatment in the community is going to be key to getting TB under control.”

Case numbers appeared to fall in Washington during the first year of the pandemic, possibly because of less reporting and missed diagnoses. But in 2021, cases rose quickly. The state reported 199 cases, marking a 22% increase from 2020.

So far this year, 70 cases have been reported, including 17 new cases that all have connections with each other and several state prisons.

The state’s Department of Corrections, Department of Health, and the Centers for Disease Control and Prevention are working together on testing and decreasing spread, MaryAnn Curl, MD, the chief medical officer for the Department of Corrections, said in the statement.

Tuberculosis cases are increasing worldwide. For the first time in more than a decade, TB deaths increased to about 1.5 million, according to the World Health Organization’s 2021 Global Tuberculosis Report.

Across the U.S., the number of reported TB cases significantly declined at the beginning of the pandemic in 2020 but increased again in 2021, according to a recent CDC study.

The Kansas Department of Health also reported an outbreak of TB cases in March, according to USA Today.

At the beginning of the pandemic, some people with TB may have been diagnosed with COVID-19 because both are infectious diseases that attack the lungs and have similar symptoms, the Washington Health Department said.

Like COVID-19, tuberculosis can spread through the air when an infected person coughs or sneezes. But unlike COVID-19, TB typically requires that you have prolonged exposure to become infected.

Symptoms of tuberculosis can include chest pain and coughing, with or without blood, as well as fever, night sweats, weight loss, and fatigue.

Tuberculosis is preventable, treatable, and curable, the Washington Health Department said. Those who travel to countries where TB is more common face higher risks for exposure, as well as those who live or work in settings where TB may spread, such as homeless shelters, prisons, jails, and nursing homes.

People can develop inactive TB, also called latent TB, which doesn’t have any symptoms and isn’t contagious. If people with inactive TB don’t get quick diagnosis or treatment, the infection can become active TB and cause symptoms. State health officials estimated that about 200,000 people in Washington have inactive TB.

Tuberculosis treatment can take a minimum of 6 months, and if it’s not followed carefully, symptoms can become more severe, the Health Department said. Incomplete treatment can also contribute to the spread of antibiotic-resistant strains of tuberculosis.

A version of this article first appeared on WebMD.com.

Upper airway hypoglossal nerve stimulation is safe and effective in adolescents with Down syndrome and severe persistent obstructive sleep apnea (OSA) occurring after adenotonsillectomy and who couldn’t tolerate positive airway pressure, early research suggests.

In a phase I study, 42 adolescents received a surgically implanted device that moves the tongue forward during sleep. Results at 1-year follow-up showed 66% “responded well” to treatment and showed a drop in apnea-hypopnea index (AHI) of at least 50%.

“Parents came back to us and said not only is the sleep better but my child seems to be doing better during the day,” lead investigator Christopher Hartnick, MD, director of the Division of Pediatric Otolaryngology and the Pediatric Airway, Voice, and Swallowing Center at Massachusetts Eye and Ear, Boston, told this news organization.

The findings were published online  in JAMA Otolaryngology – Head and Neck Surgery.
 

Limited options

Upper airway simulation has been shown previously to be effective for adults with OSA, but up until now, the process has not been evaluated in children.

The device used in the current study “stimulates the hypoglossal nerve to protrude the tongue and open the airway on inspiration during sleep,” the investigators note.

“Hypoglossal nerve stimulation may be a particularly suitable therapy for patients with Down syndrome because it can augment neuromuscular airway tone and reduce anatomical obstruction at the base of the tongue, a common site of residual obstruction in children with Down syndrome,” they add.

“This study was born out of the frustration of not having an effective treatment option for children with Down syndrome who struggle with sleep apnea,” Dr. Hartnick said in a news release.

A total of 42 adolescents (67% male; mean age, 15 years) with Down syndrome and persistent severe OSA after adenotonsillectomy were implanted with the hypoglossal nerve stimulator. All were followed for 12 months.

The surgery was safe, with the most common adverse event being temporary tongue discomfort in five patients (12%). This typically resolved in weeks, the researchers note.
 

High response, adherence rates

Results showed response rates and adherence to therapy was high. The mean duration of nightly therapy was 9 hours, with 40 children (95.2%) using the device at least 4 hours every night.

The implant was also effective, with a mean decrease in AHI of 12.9 events per hour (95% confidence interval, –17.0 to –8.7 events per hour).

Nearly two-thirds of the children had at least a 50% reduction in their AHI, while roughly three-fourths had a 12-month follow-up AHI of less than 10 events per hour.

There were also significant improvements in polysomnographic and parent-reported quality of life outcomes 12 months after the implant, including improvement in sleep and daily functioning, behavior, and language.

“Sleep apnea remains one of the most common conditions that I grapple with working with patients with Down syndrome and their families,” co-investigator Brian Skotko, MD, Emma Campbell endowed chair on Down syndrome at Massachusetts General Hospital, Boston, said in the release.

“Until now, so many of our patients had run out of treatment options, and their health and well-being were declining. Now, with the hypoglossal nerve stimulator treatment, we may have an effective and safe way to treat apnea and maximize brain health for people with Down syndrome,” Dr. Skotko added.

Dr. Hartnick and Dr. Skotko have received a $4 million, 5-year grant from the National Institutes of Health to assess whether upper airway stimulation might help cognition in children with Down syndrome.
 

Landmark investigation

Co-authors of an invited commentary said they “applaud” the researchers for their “landmark” investigation, which demonstrated a response to upper airway stimulation in children with Down syndrome and OSA that is on par with what has been achieved in adults with OSA.

“They have established the safety of the procedure; however, future research is necessary to optimize the results of implant,” write Norman Friedman, MD, and Katherine Green, MD, both from the department of otolaryngology – head and neck surgery, University of Colorado School of Medicine, Aurora.

“Further assessment regarding patient selection and the systematic preoperative identification of potential barriers that might affect successful use of therapy will be beneficial to improve longitudinal outcomes and success in this population that is uniquely different from the adult cohorts that have received implants to date,” they add.

The study was funded by Inspire Medical Systems, which provided eight devices for the study but otherwise did not have a role in its design and conduct. The LuMind IDSC Down Syndrome Foundation also provided funding for the study. Dr. Hartnick and the editorialists have disclosed no relevant financial relationships. A complete list of disclosures for the other investigators is available in the original article.

A version of this article first appeared on Medscape.com.

Upper airway hypoglossal nerve stimulation is safe and effective in adolescents with Down syndrome and severe persistent obstructive sleep apnea (OSA) occurring after adenotonsillectomy and who couldn’t tolerate positive airway pressure, early research suggests.

In a phase I study, 42 adolescents received a surgically implanted device that moves the tongue forward during sleep. Results at 1-year follow-up showed 66% “responded well” to treatment and showed a drop in apnea-hypopnea index (AHI) of at least 50%.

“Parents came back to us and said not only is the sleep better but my child seems to be doing better during the day,” lead investigator Christopher Hartnick, MD, director of the Division of Pediatric Otolaryngology and the Pediatric Airway, Voice, and Swallowing Center at Massachusetts Eye and Ear, Boston, told this news organization.

The findings were published online  in JAMA Otolaryngology – Head and Neck Surgery.
 

Limited options

Upper airway simulation has been shown previously to be effective for adults with OSA, but up until now, the process has not been evaluated in children.

The device used in the current study “stimulates the hypoglossal nerve to protrude the tongue and open the airway on inspiration during sleep,” the investigators note.

“Hypoglossal nerve stimulation may be a particularly suitable therapy for patients with Down syndrome because it can augment neuromuscular airway tone and reduce anatomical obstruction at the base of the tongue, a common site of residual obstruction in children with Down syndrome,” they add.

“This study was born out of the frustration of not having an effective treatment option for children with Down syndrome who struggle with sleep apnea,” Dr. Hartnick said in a news release.

A total of 42 adolescents (67% male; mean age, 15 years) with Down syndrome and persistent severe OSA after adenotonsillectomy were implanted with the hypoglossal nerve stimulator. All were followed for 12 months.

The surgery was safe, with the most common adverse event being temporary tongue discomfort in five patients (12%). This typically resolved in weeks, the researchers note.
 

High response, adherence rates

Results showed response rates and adherence to therapy was high. The mean duration of nightly therapy was 9 hours, with 40 children (95.2%) using the device at least 4 hours every night.

The implant was also effective, with a mean decrease in AHI of 12.9 events per hour (95% confidence interval, –17.0 to –8.7 events per hour).

Nearly two-thirds of the children had at least a 50% reduction in their AHI, while roughly three-fourths had a 12-month follow-up AHI of less than 10 events per hour.

There were also significant improvements in polysomnographic and parent-reported quality of life outcomes 12 months after the implant, including improvement in sleep and daily functioning, behavior, and language.

“Sleep apnea remains one of the most common conditions that I grapple with working with patients with Down syndrome and their families,” co-investigator Brian Skotko, MD, Emma Campbell endowed chair on Down syndrome at Massachusetts General Hospital, Boston, said in the release.

“Until now, so many of our patients had run out of treatment options, and their health and well-being were declining. Now, with the hypoglossal nerve stimulator treatment, we may have an effective and safe way to treat apnea and maximize brain health for people with Down syndrome,” Dr. Skotko added.

Dr. Hartnick and Dr. Skotko have received a $4 million, 5-year grant from the National Institutes of Health to assess whether upper airway stimulation might help cognition in children with Down syndrome.
 

Landmark investigation

Co-authors of an invited commentary said they “applaud” the researchers for their “landmark” investigation, which demonstrated a response to upper airway stimulation in children with Down syndrome and OSA that is on par with what has been achieved in adults with OSA.

“They have established the safety of the procedure; however, future research is necessary to optimize the results of implant,” write Norman Friedman, MD, and Katherine Green, MD, both from the department of otolaryngology – head and neck surgery, University of Colorado School of Medicine, Aurora.

“Further assessment regarding patient selection and the systematic preoperative identification of potential barriers that might affect successful use of therapy will be beneficial to improve longitudinal outcomes and success in this population that is uniquely different from the adult cohorts that have received implants to date,” they add.

The study was funded by Inspire Medical Systems, which provided eight devices for the study but otherwise did not have a role in its design and conduct. The LuMind IDSC Down Syndrome Foundation also provided funding for the study. Dr. Hartnick and the editorialists have disclosed no relevant financial relationships. A complete list of disclosures for the other investigators is available in the original article.

A version of this article first appeared on Medscape.com.

Upper airway hypoglossal nerve stimulation is safe and effective in adolescents with Down syndrome and severe persistent obstructive sleep apnea (OSA) occurring after adenotonsillectomy and who couldn’t tolerate positive airway pressure, early research suggests.

In a phase I study, 42 adolescents received a surgically implanted device that moves the tongue forward during sleep. Results at 1-year follow-up showed 66% “responded well” to treatment and showed a drop in apnea-hypopnea index (AHI) of at least 50%.

“Parents came back to us and said not only is the sleep better but my child seems to be doing better during the day,” lead investigator Christopher Hartnick, MD, director of the Division of Pediatric Otolaryngology and the Pediatric Airway, Voice, and Swallowing Center at Massachusetts Eye and Ear, Boston, told this news organization.

The findings were published online  in JAMA Otolaryngology – Head and Neck Surgery.
 

Limited options

Upper airway simulation has been shown previously to be effective for adults with OSA, but up until now, the process has not been evaluated in children.

The device used in the current study “stimulates the hypoglossal nerve to protrude the tongue and open the airway on inspiration during sleep,” the investigators note.

“Hypoglossal nerve stimulation may be a particularly suitable therapy for patients with Down syndrome because it can augment neuromuscular airway tone and reduce anatomical obstruction at the base of the tongue, a common site of residual obstruction in children with Down syndrome,” they add.

“This study was born out of the frustration of not having an effective treatment option for children with Down syndrome who struggle with sleep apnea,” Dr. Hartnick said in a news release.

A total of 42 adolescents (67% male; mean age, 15 years) with Down syndrome and persistent severe OSA after adenotonsillectomy were implanted with the hypoglossal nerve stimulator. All were followed for 12 months.

The surgery was safe, with the most common adverse event being temporary tongue discomfort in five patients (12%). This typically resolved in weeks, the researchers note.
 

High response, adherence rates

Results showed response rates and adherence to therapy was high. The mean duration of nightly therapy was 9 hours, with 40 children (95.2%) using the device at least 4 hours every night.

The implant was also effective, with a mean decrease in AHI of 12.9 events per hour (95% confidence interval, –17.0 to –8.7 events per hour).

Nearly two-thirds of the children had at least a 50% reduction in their AHI, while roughly three-fourths had a 12-month follow-up AHI of less than 10 events per hour.

There were also significant improvements in polysomnographic and parent-reported quality of life outcomes 12 months after the implant, including improvement in sleep and daily functioning, behavior, and language.

“Sleep apnea remains one of the most common conditions that I grapple with working with patients with Down syndrome and their families,” co-investigator Brian Skotko, MD, Emma Campbell endowed chair on Down syndrome at Massachusetts General Hospital, Boston, said in the release.

“Until now, so many of our patients had run out of treatment options, and their health and well-being were declining. Now, with the hypoglossal nerve stimulator treatment, we may have an effective and safe way to treat apnea and maximize brain health for people with Down syndrome,” Dr. Skotko added.

Dr. Hartnick and Dr. Skotko have received a $4 million, 5-year grant from the National Institutes of Health to assess whether upper airway stimulation might help cognition in children with Down syndrome.
 

Landmark investigation

Co-authors of an invited commentary said they “applaud” the researchers for their “landmark” investigation, which demonstrated a response to upper airway stimulation in children with Down syndrome and OSA that is on par with what has been achieved in adults with OSA.

“They have established the safety of the procedure; however, future research is necessary to optimize the results of implant,” write Norman Friedman, MD, and Katherine Green, MD, both from the department of otolaryngology – head and neck surgery, University of Colorado School of Medicine, Aurora.

“Further assessment regarding patient selection and the systematic preoperative identification of potential barriers that might affect successful use of therapy will be beneficial to improve longitudinal outcomes and success in this population that is uniquely different from the adult cohorts that have received implants to date,” they add.

The study was funded by Inspire Medical Systems, which provided eight devices for the study but otherwise did not have a role in its design and conduct. The LuMind IDSC Down Syndrome Foundation also provided funding for the study. Dr. Hartnick and the editorialists have disclosed no relevant financial relationships. A complete list of disclosures for the other investigators is available in the original article.

A version of this article first appeared on Medscape.com.

A medication used to reduce fluid retention can also safely be used to prevent a dangerous lung condition that affects newborns, particularly those born premature, according to a new study.

Furosemide (Lasix) – which can reduce excess fluid in the body caused by heart failure, liver disease, and kidney trouble – is commonly used off-label to prevent bronchopulmonary dysplasia (BPD), a disorder that causes irritation and poor development of lungs in premature infants. But until now, researchers have not studied its safety in this setting.

BPD often affects babies born more than 2 months early and can sometimes result in breathing difficulties into adolescence and young adulthood.

“There are so few drugs that have been tested for newborns, and there are very little data to help neonatologists decide if certain medications are safe and effective,” said Rachel Greenberg, MD, MHS, a neonatologist and member of the Duke Clinical Research Institute, Durham, N.C. “We found there was no greater risk of safety events for newborns given furosemide.”

Dr. Greenberg presented the findings at the 2022 Pediatric Academic Societies meeting in Denver.

For the 28-day randomized controlled trial, Dr. Greenberg and colleagues enrolled 80 preterm newborns, born at less than 29 weeks’ gestation, at 17 centers within the Eunice Kennedy Shriver National Institute of Child Health and Human Development Pediatric Trials Network. Of those, 61 received furosemide and 19 received a placebo.

Although babies given furosemide had more problems with electrolytes – an expected outcome from the use of diuretic medications – the researchers observed no greater risk for more serious issues, namely hearing loss or kidney stones, Dr. Greenberg told this news organization.

“The mechanism here is we know that extra fluid can damage the lungs and can cause you to have to use more respiratory support and more oxygen,” she said. “The thought from a physiological standpoint is using a diuretic can decrease fluid in the lungs and lead to improvements in lung outcomes.”

The researchers did not observe a reduction in BDP or death in babies who received furosemide, but Dr. Greenberg said the study was underpowered to detect such an effect.

“We were not powered to detect a difference in that outcome; the overall objective of this study was always to evaluate safety,” she said. “Of course, we wanted to capture variables that would measure effectiveness as well.

“Because this was a pragmatic trial, we did not limit the amount of fluids that the clinicians could give the participating infants. This could have impacted the effectiveness of furosemide. We would need a different design and larger study to truly determine effectiveness.” 

Dr. Greenberg said she hoped the new data will provide greater insight to neonatal providers and help bolster future, more large-scale trials using furosemide in premature infants.   

The drug has previously been associated with both kidney stones and ototoxicity, which occurs when medication causes a person to develop hearing or balance problems, said Nicolas Bamat, MD, MSCE, assistant professor of pediatrics at the Perelman School of Medicine, University of Pennsylvania, Philadelphia.

Although the number of children in the latest study was too small to generate any firm conclusions, he said, the trial provides the best data to date on furosemide in premature infants.

The medication is used frequently both on babies at risk of developing BPD and babies who have already reached BPD status. Among newborns with highest risk of dying, furosemide is indeed the “most frequently used pharmacotherapy,” Dr. Bamat said.

“What’s worth noting is that furosemide is an old medication that has been used extensively in the neonatal populations for 40 years, and that is occurring in the absence of data,” Dr. Bamat added. “This is a very important step forward.”

Dr. Greenberg and Dr. Bamat have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A medication used to reduce fluid retention can also safely be used to prevent a dangerous lung condition that affects newborns, particularly those born premature, according to a new study.

Furosemide (Lasix) – which can reduce excess fluid in the body caused by heart failure, liver disease, and kidney trouble – is commonly used off-label to prevent bronchopulmonary dysplasia (BPD), a disorder that causes irritation and poor development of lungs in premature infants. But until now, researchers have not studied its safety in this setting.

BPD often affects babies born more than 2 months early and can sometimes result in breathing difficulties into adolescence and young adulthood.

“There are so few drugs that have been tested for newborns, and there are very little data to help neonatologists decide if certain medications are safe and effective,” said Rachel Greenberg, MD, MHS, a neonatologist and member of the Duke Clinical Research Institute, Durham, N.C. “We found there was no greater risk of safety events for newborns given furosemide.”

Dr. Greenberg presented the findings at the 2022 Pediatric Academic Societies meeting in Denver.

For the 28-day randomized controlled trial, Dr. Greenberg and colleagues enrolled 80 preterm newborns, born at less than 29 weeks’ gestation, at 17 centers within the Eunice Kennedy Shriver National Institute of Child Health and Human Development Pediatric Trials Network. Of those, 61 received furosemide and 19 received a placebo.

Although babies given furosemide had more problems with electrolytes – an expected outcome from the use of diuretic medications – the researchers observed no greater risk for more serious issues, namely hearing loss or kidney stones, Dr. Greenberg told this news organization.

“The mechanism here is we know that extra fluid can damage the lungs and can cause you to have to use more respiratory support and more oxygen,” she said. “The thought from a physiological standpoint is using a diuretic can decrease fluid in the lungs and lead to improvements in lung outcomes.”

The researchers did not observe a reduction in BDP or death in babies who received furosemide, but Dr. Greenberg said the study was underpowered to detect such an effect.

“We were not powered to detect a difference in that outcome; the overall objective of this study was always to evaluate safety,” she said. “Of course, we wanted to capture variables that would measure effectiveness as well.

“Because this was a pragmatic trial, we did not limit the amount of fluids that the clinicians could give the participating infants. This could have impacted the effectiveness of furosemide. We would need a different design and larger study to truly determine effectiveness.” 

Dr. Greenberg said she hoped the new data will provide greater insight to neonatal providers and help bolster future, more large-scale trials using furosemide in premature infants.   

The drug has previously been associated with both kidney stones and ototoxicity, which occurs when medication causes a person to develop hearing or balance problems, said Nicolas Bamat, MD, MSCE, assistant professor of pediatrics at the Perelman School of Medicine, University of Pennsylvania, Philadelphia.

Although the number of children in the latest study was too small to generate any firm conclusions, he said, the trial provides the best data to date on furosemide in premature infants.

The medication is used frequently both on babies at risk of developing BPD and babies who have already reached BPD status. Among newborns with highest risk of dying, furosemide is indeed the “most frequently used pharmacotherapy,” Dr. Bamat said.

“What’s worth noting is that furosemide is an old medication that has been used extensively in the neonatal populations for 40 years, and that is occurring in the absence of data,” Dr. Bamat added. “This is a very important step forward.”

Dr. Greenberg and Dr. Bamat have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A medication used to reduce fluid retention can also safely be used to prevent a dangerous lung condition that affects newborns, particularly those born premature, according to a new study.

Furosemide (Lasix) – which can reduce excess fluid in the body caused by heart failure, liver disease, and kidney trouble – is commonly used off-label to prevent bronchopulmonary dysplasia (BPD), a disorder that causes irritation and poor development of lungs in premature infants. But until now, researchers have not studied its safety in this setting.

BPD often affects babies born more than 2 months early and can sometimes result in breathing difficulties into adolescence and young adulthood.

“There are so few drugs that have been tested for newborns, and there are very little data to help neonatologists decide if certain medications are safe and effective,” said Rachel Greenberg, MD, MHS, a neonatologist and member of the Duke Clinical Research Institute, Durham, N.C. “We found there was no greater risk of safety events for newborns given furosemide.”

Dr. Greenberg presented the findings at the 2022 Pediatric Academic Societies meeting in Denver.

For the 28-day randomized controlled trial, Dr. Greenberg and colleagues enrolled 80 preterm newborns, born at less than 29 weeks’ gestation, at 17 centers within the Eunice Kennedy Shriver National Institute of Child Health and Human Development Pediatric Trials Network. Of those, 61 received furosemide and 19 received a placebo.

Although babies given furosemide had more problems with electrolytes – an expected outcome from the use of diuretic medications – the researchers observed no greater risk for more serious issues, namely hearing loss or kidney stones, Dr. Greenberg told this news organization.

“The mechanism here is we know that extra fluid can damage the lungs and can cause you to have to use more respiratory support and more oxygen,” she said. “The thought from a physiological standpoint is using a diuretic can decrease fluid in the lungs and lead to improvements in lung outcomes.”

The researchers did not observe a reduction in BDP or death in babies who received furosemide, but Dr. Greenberg said the study was underpowered to detect such an effect.

“We were not powered to detect a difference in that outcome; the overall objective of this study was always to evaluate safety,” she said. “Of course, we wanted to capture variables that would measure effectiveness as well.

“Because this was a pragmatic trial, we did not limit the amount of fluids that the clinicians could give the participating infants. This could have impacted the effectiveness of furosemide. We would need a different design and larger study to truly determine effectiveness.” 

Dr. Greenberg said she hoped the new data will provide greater insight to neonatal providers and help bolster future, more large-scale trials using furosemide in premature infants.   

The drug has previously been associated with both kidney stones and ototoxicity, which occurs when medication causes a person to develop hearing or balance problems, said Nicolas Bamat, MD, MSCE, assistant professor of pediatrics at the Perelman School of Medicine, University of Pennsylvania, Philadelphia.

Although the number of children in the latest study was too small to generate any firm conclusions, he said, the trial provides the best data to date on furosemide in premature infants.

The medication is used frequently both on babies at risk of developing BPD and babies who have already reached BPD status. Among newborns with highest risk of dying, furosemide is indeed the “most frequently used pharmacotherapy,” Dr. Bamat said.

“What’s worth noting is that furosemide is an old medication that has been used extensively in the neonatal populations for 40 years, and that is occurring in the absence of data,” Dr. Bamat added. “This is a very important step forward.”

Dr. Greenberg and Dr. Bamat have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Most health care providers are comfortable recommending palliative care (PC) for their patients with interstitial lung disease (ILD), but most do so at the time of disease progression, rather than diagnosis, as indicated on survey data from 128 clinicians.

ILD is associated with a high mortality rate and profound symptoms that contribute to poor quality of life, Rebecca A. Gersen, MD, of Johns Hopkins University, Baltimore, and colleagues wrote.

“Nevertheless, there is often a lack of preparedness for death by both patients and providers, contributing to increased distress,” they said. Clinician perspectives on the use of PC for ILD patients have not been well studied, although PC is not limited to end-of-life care and is recommended for ILD patients by professional organizations, including the American Thoracic Society. “PC is successful in improving breathlessness in chronic lung disease and can increase survival.”

In a study published in the journal CHEST^®, the researchers surveyed health care providers at 68 Pulmonary Fibrosis Foundation centers across the United States. The survey was sent and collected by email and a restricted social media platform. A total of 128 providers from 34 states completed the survey between October 2020 and January 2021. Of these, 61% were physicians, and 67% identified as White.

Overall, 95% of the respondents agreed or strongly agreed that addressing advance directives is important, but only 66% agreed or strongly agreed that they themselves addressed advance directives in the outpatient ILD clinic setting. A greater number (91%) agreed or strongly agreed that they had a high level of comfort in discussing prognosis, while 88% agreed or strongly agreed that they felt comfortable assessing a patient’s readiness for and acceptance of PC. Approximately two-thirds (67%) agreed or strongly agreed that they use PC services for ILD patients. There were no significant differences in responses from clinicians who had more than 10 years of experience and those who had less.

Of the providers who referred patients to PC, 54% did so at objective disease progression, and 80% did so at objective and/or symptomatic progress; 2% referred patients to PC at initial ILD diagnosis.

Lack of resources

Health care providers who reported that they rarely referred patients to palliative care were significantly more likely to cite a lack of local PC options (P < .01). Those who rarely referred patients for PC also were significantly less likely to feel comfortable discussing prognoses or advance directives in the ILD clinic (P = .03 and P = .02, respectively).

Among the 23% of responders who reported that they rarely referred patients, 66% said they did not have PC at their institution.

“In addition to understanding and addressing barriers to care, educational resources may be key to improving PC delivery to the ILD population,” the researchers wrote.

The study findings were limited by several factors, including voluntary participation, lack of a validated questionnaire, and use of self-reports, which may not reflect physicians’ actual practice, the researchers noted. Other limitations include the use of U.S. data only, which may not generalize to countries with different health care models.

However, the results were strengthened by the use of data from providers at a range of institutions across the United States and by the high overall survey response rate, the researchers said.

“While ILD providers reassuringly demonstrate knowledge and interest in PC involvement, no current system exists to facilitate and monitor response to referral,” they noted. “Future research is desperately needed to address barriers to the provision of PC in order to enhance access to a critical service in the management and care of patients with ILD.”

The study was supported by the National Heart, Lung, and Blood Institute. The researchers disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Most health care providers are comfortable recommending palliative care (PC) for their patients with interstitial lung disease (ILD), but most do so at the time of disease progression, rather than diagnosis, as indicated on survey data from 128 clinicians.

ILD is associated with a high mortality rate and profound symptoms that contribute to poor quality of life, Rebecca A. Gersen, MD, of Johns Hopkins University, Baltimore, and colleagues wrote.

“Nevertheless, there is often a lack of preparedness for death by both patients and providers, contributing to increased distress,” they said. Clinician perspectives on the use of PC for ILD patients have not been well studied, although PC is not limited to end-of-life care and is recommended for ILD patients by professional organizations, including the American Thoracic Society. “PC is successful in improving breathlessness in chronic lung disease and can increase survival.”

In a study published in the journal CHEST^®, the researchers surveyed health care providers at 68 Pulmonary Fibrosis Foundation centers across the United States. The survey was sent and collected by email and a restricted social media platform. A total of 128 providers from 34 states completed the survey between October 2020 and January 2021. Of these, 61% were physicians, and 67% identified as White.

Overall, 95% of the respondents agreed or strongly agreed that addressing advance directives is important, but only 66% agreed or strongly agreed that they themselves addressed advance directives in the outpatient ILD clinic setting. A greater number (91%) agreed or strongly agreed that they had a high level of comfort in discussing prognosis, while 88% agreed or strongly agreed that they felt comfortable assessing a patient’s readiness for and acceptance of PC. Approximately two-thirds (67%) agreed or strongly agreed that they use PC services for ILD patients. There were no significant differences in responses from clinicians who had more than 10 years of experience and those who had less.

Of the providers who referred patients to PC, 54% did so at objective disease progression, and 80% did so at objective and/or symptomatic progress; 2% referred patients to PC at initial ILD diagnosis.

Lack of resources

Health care providers who reported that they rarely referred patients to palliative care were significantly more likely to cite a lack of local PC options (P < .01). Those who rarely referred patients for PC also were significantly less likely to feel comfortable discussing prognoses or advance directives in the ILD clinic (P = .03 and P = .02, respectively).

Among the 23% of responders who reported that they rarely referred patients, 66% said they did not have PC at their institution.

“In addition to understanding and addressing barriers to care, educational resources may be key to improving PC delivery to the ILD population,” the researchers wrote.

The study findings were limited by several factors, including voluntary participation, lack of a validated questionnaire, and use of self-reports, which may not reflect physicians’ actual practice, the researchers noted. Other limitations include the use of U.S. data only, which may not generalize to countries with different health care models.

However, the results were strengthened by the use of data from providers at a range of institutions across the United States and by the high overall survey response rate, the researchers said.

“While ILD providers reassuringly demonstrate knowledge and interest in PC involvement, no current system exists to facilitate and monitor response to referral,” they noted. “Future research is desperately needed to address barriers to the provision of PC in order to enhance access to a critical service in the management and care of patients with ILD.”

The study was supported by the National Heart, Lung, and Blood Institute. The researchers disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Most health care providers are comfortable recommending palliative care (PC) for their patients with interstitial lung disease (ILD), but most do so at the time of disease progression, rather than diagnosis, as indicated on survey data from 128 clinicians.

ILD is associated with a high mortality rate and profound symptoms that contribute to poor quality of life, Rebecca A. Gersen, MD, of Johns Hopkins University, Baltimore, and colleagues wrote.

“Nevertheless, there is often a lack of preparedness for death by both patients and providers, contributing to increased distress,” they said. Clinician perspectives on the use of PC for ILD patients have not been well studied, although PC is not limited to end-of-life care and is recommended for ILD patients by professional organizations, including the American Thoracic Society. “PC is successful in improving breathlessness in chronic lung disease and can increase survival.”

In a study published in the journal CHEST^®, the researchers surveyed health care providers at 68 Pulmonary Fibrosis Foundation centers across the United States. The survey was sent and collected by email and a restricted social media platform. A total of 128 providers from 34 states completed the survey between October 2020 and January 2021. Of these, 61% were physicians, and 67% identified as White.

Overall, 95% of the respondents agreed or strongly agreed that addressing advance directives is important, but only 66% agreed or strongly agreed that they themselves addressed advance directives in the outpatient ILD clinic setting. A greater number (91%) agreed or strongly agreed that they had a high level of comfort in discussing prognosis, while 88% agreed or strongly agreed that they felt comfortable assessing a patient’s readiness for and acceptance of PC. Approximately two-thirds (67%) agreed or strongly agreed that they use PC services for ILD patients. There were no significant differences in responses from clinicians who had more than 10 years of experience and those who had less.

Of the providers who referred patients to PC, 54% did so at objective disease progression, and 80% did so at objective and/or symptomatic progress; 2% referred patients to PC at initial ILD diagnosis.

Lack of resources

Health care providers who reported that they rarely referred patients to palliative care were significantly more likely to cite a lack of local PC options (P < .01). Those who rarely referred patients for PC also were significantly less likely to feel comfortable discussing prognoses or advance directives in the ILD clinic (P = .03 and P = .02, respectively).

Among the 23% of responders who reported that they rarely referred patients, 66% said they did not have PC at their institution.

“In addition to understanding and addressing barriers to care, educational resources may be key to improving PC delivery to the ILD population,” the researchers wrote.

The study findings were limited by several factors, including voluntary participation, lack of a validated questionnaire, and use of self-reports, which may not reflect physicians’ actual practice, the researchers noted. Other limitations include the use of U.S. data only, which may not generalize to countries with different health care models.

However, the results were strengthened by the use of data from providers at a range of institutions across the United States and by the high overall survey response rate, the researchers said.

“While ILD providers reassuringly demonstrate knowledge and interest in PC involvement, no current system exists to facilitate and monitor response to referral,” they noted. “Future research is desperately needed to address barriers to the provision of PC in order to enhance access to a critical service in the management and care of patients with ILD.”

The study was supported by the National Heart, Lung, and Blood Institute. The researchers disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Since November 2021, the Omicron variant of SARS-CoV-2 has quickly become the most dominant variant worldwide. Early sequencing of Omicron in South Africa alerted researchers to the possibility that Omicron could be a cause for concern because of extensive mutations of the spike protein. Omicron has 30 mutations of the spike protein, compared with the original Wuhan-Hu-1 variant, with 15 mutations of the receptor-binding domain (which are linked to a decrease in antibody binding), mutations at the furin S1/S2 site (which improves furin binding and increases infectiousness), and mutations of the amino terminal domain (which is the main binding site for some of the therapeutic antibodies used to treat COVID-19 infections).

Omicron’s functional characteristics

Non–peer-reviewed studies have shown a replication of Omicron in pulmonary epithelial cells, which was shown to be less efficient, when compared with Delta and Wuhan-Hu-1. The number of viral copies from an Omicron infection in pulmonary epithelial cells was significantly lower, compared with infection with the Delta or Wuhan-Hu-1 variants. The association of these characteristics found an increase in the number of viral copies in human epithelial cells (taken from the nasal airways) infected with Omicron. This supports the understanding that Omicron is more transmissible but results in a less severe manifestation of the disease.

As for the phenotypic expression of the infection, attention has been focused on Omicron’s reduced capacity to cause syncytia in pulmonary tissue cultures, information which is relevant to its clinical significance, if we consider that the formation of syncytia has been associated with a more severe manifestation of the disease. Furthermore, it has emerged that Omicron can use different cellular entry routes, with a preference for endosomal fusion over superficial cellular fusion. This characteristic allows Omicron to significantly increase the number of types of cells it can infect.
 

Omicron BA.2 evolves

Between November and December 2021, Omicron progressed, evolving into a variant with characteristics similar to those of its predecessors (that is, it underwent a gradual and progressive increase in transmissibility). Early studies on the Omicron variant were mainly based on the BA.1 subvariant. Since the start of January 2022, there has been an unexpected increase in BA.2 in Europe and Asia. Since then, continued surveillance on the evolution of Omicron has shown an increased prevalence of two subvariants: BA.1 with a R346K mutation (BA.1 + R346K) and B.1.1.529.2 (BA.2), with the latter containing eight unique spike mutations and 13 missing spike mutations, compared with those found in BA.1.

From these differences, we cannot presume that their antigenic properties are similar or different, but they seem to be antigenically equidistant from wild-type SARS-CoV-2, likely jeopardizing in equal measures the efficacy of current COVID-19 vaccines. Furthermore, BA.2 shows significant resistance to 17 out of 19 neutralizing monoclonal antibodies tested in this study, demonstrating that current monoclonal antibody therapy may have significant limitations in terms of adequate coverage for all subvariants of the Omicron variant.
 

Omicron BA.2 and reinfection

BA.2 initially represented only 13% of Omicron sequences at a global level, quickly becoming the dominant form in some countries, such as Denmark. At the end of 2021, BA.2 represented around 20% of all Danish cases of SARS-CoV-2. Halfway through January 2022, this had increased to around 45%, data that indicate that BA.2 carries an advantage over BA.1 within the highly vaccinated population of Denmark.

BA.2 is associated with an increased susceptibility of infection for unvaccinated individuals (odds ratio, 2.19; 95% confidence interval, 1.58-3.04), fully vaccinated individuals (OR, 2.45; 95% CI, 1.77-3.40), and booster-vaccinated individuals (OR, 2.99; 95% CI, 2.11-4.24), compared with BA.1. The pattern of increased transmissibility in BA.2 households was not observed for fully vaccinated and booster-vaccinated primary cases, where the OR of transmission was below 1 for BA.2, compared with BA.1. These data confirm the immune-evasive properties of BA.2 that further reduce the protective effect of vaccination against infection, but do not increase its transmissibility from vaccinated individuals with breakthrough infections.
 

Omicron, BA.2, and vaccination

The understanding of serum neutralizing activity, in correlation to the efficacy of a vaccine, is a priority of research because of the growing epidemiological significance of BA.2. There is evidence to support the claim that the immune-evasive nature of BA.2 doesn›t seem to be as severe as that of BA.1, and it is possible that there are other viral or host factors that are enabling the rapid diffusion of BA.2. A study published in Science Immunology investigated humoral and cellular immune responses to Omicron and other variants of concern (VOCs), looking to understand how, and to what degree, vaccinated individuals are protected against Omicron. From the results, a very low level of antibody cross-neutralization of Omicron, or a lack thereof, was seen when compared with wild type, Beta, and Delta variants, which could be partially restored by a third booster vaccination. Furthermore, T lymphocytes were shown to recognize Omicron with the same efficacy as seen for the other VOCs, suggesting that vaccinated individuals maintain T lymphocyte immunity, an element that is capable of providing protection in the absence of neutralizing antibodies, limiting the chance of serious disease.

These results are consistent with those available from a study performed in a population from Qatar made up of 2,239,193 people who had received at least two doses of a BNT162b2 or mRNA-1273 vaccine. The efficacy of the booster against a symptomatic Omicron infection, compared with that from the primary series, was 49.4% (95% CI, 47.1-51.6). The efficacy of the booster against hospitalization for COVID-19 and the death rate from Omicron infection, compared with the primary series, was 76.5% (95% CI, 55.9-87.5). The efficacy of the BNT162b2 booster against a symptomatic Delta variant infection (or B.1.617.2), compared with the primary series, was 86.1% (95% CI, 67.3-94.1).

To summarize, the constant increase in the prevalence of BA.2 in more countries over the world has confirmed the growth advantage that this variant has compared with others. BA.2 reduces the protective effect of vaccination against infection. Omicron antibody cross-neutralization can be partially restored by a third booster vaccination, an aspect that becomes problematic in the context of a low vaccination rate, where peaks of Omicron may increase the likelihood of infection in the elderly and in other groups at a higher risk of severe disease. Omicron BA.2 opens up new evolution channels, but what do the experts think will happen?

A version of this article was originally published in Italian on Univadis.

Since November 2021, the Omicron variant of SARS-CoV-2 has quickly become the most dominant variant worldwide. Early sequencing of Omicron in South Africa alerted researchers to the possibility that Omicron could be a cause for concern because of extensive mutations of the spike protein. Omicron has 30 mutations of the spike protein, compared with the original Wuhan-Hu-1 variant, with 15 mutations of the receptor-binding domain (which are linked to a decrease in antibody binding), mutations at the furin S1/S2 site (which improves furin binding and increases infectiousness), and mutations of the amino terminal domain (which is the main binding site for some of the therapeutic antibodies used to treat COVID-19 infections).

Omicron’s functional characteristics

Non–peer-reviewed studies have shown a replication of Omicron in pulmonary epithelial cells, which was shown to be less efficient, when compared with Delta and Wuhan-Hu-1. The number of viral copies from an Omicron infection in pulmonary epithelial cells was significantly lower, compared with infection with the Delta or Wuhan-Hu-1 variants. The association of these characteristics found an increase in the number of viral copies in human epithelial cells (taken from the nasal airways) infected with Omicron. This supports the understanding that Omicron is more transmissible but results in a less severe manifestation of the disease.

As for the phenotypic expression of the infection, attention has been focused on Omicron’s reduced capacity to cause syncytia in pulmonary tissue cultures, information which is relevant to its clinical significance, if we consider that the formation of syncytia has been associated with a more severe manifestation of the disease. Furthermore, it has emerged that Omicron can use different cellular entry routes, with a preference for endosomal fusion over superficial cellular fusion. This characteristic allows Omicron to significantly increase the number of types of cells it can infect.
 

Omicron BA.2 evolves

Between November and December 2021, Omicron progressed, evolving into a variant with characteristics similar to those of its predecessors (that is, it underwent a gradual and progressive increase in transmissibility). Early studies on the Omicron variant were mainly based on the BA.1 subvariant. Since the start of January 2022, there has been an unexpected increase in BA.2 in Europe and Asia. Since then, continued surveillance on the evolution of Omicron has shown an increased prevalence of two subvariants: BA.1 with a R346K mutation (BA.1 + R346K) and B.1.1.529.2 (BA.2), with the latter containing eight unique spike mutations and 13 missing spike mutations, compared with those found in BA.1.

From these differences, we cannot presume that their antigenic properties are similar or different, but they seem to be antigenically equidistant from wild-type SARS-CoV-2, likely jeopardizing in equal measures the efficacy of current COVID-19 vaccines. Furthermore, BA.2 shows significant resistance to 17 out of 19 neutralizing monoclonal antibodies tested in this study, demonstrating that current monoclonal antibody therapy may have significant limitations in terms of adequate coverage for all subvariants of the Omicron variant.
 

Omicron BA.2 and reinfection

BA.2 initially represented only 13% of Omicron sequences at a global level, quickly becoming the dominant form in some countries, such as Denmark. At the end of 2021, BA.2 represented around 20% of all Danish cases of SARS-CoV-2. Halfway through January 2022, this had increased to around 45%, data that indicate that BA.2 carries an advantage over BA.1 within the highly vaccinated population of Denmark.

BA.2 is associated with an increased susceptibility of infection for unvaccinated individuals (odds ratio, 2.19; 95% confidence interval, 1.58-3.04), fully vaccinated individuals (OR, 2.45; 95% CI, 1.77-3.40), and booster-vaccinated individuals (OR, 2.99; 95% CI, 2.11-4.24), compared with BA.1. The pattern of increased transmissibility in BA.2 households was not observed for fully vaccinated and booster-vaccinated primary cases, where the OR of transmission was below 1 for BA.2, compared with BA.1. These data confirm the immune-evasive properties of BA.2 that further reduce the protective effect of vaccination against infection, but do not increase its transmissibility from vaccinated individuals with breakthrough infections.
 

Omicron, BA.2, and vaccination

The understanding of serum neutralizing activity, in correlation to the efficacy of a vaccine, is a priority of research because of the growing epidemiological significance of BA.2. There is evidence to support the claim that the immune-evasive nature of BA.2 doesn›t seem to be as severe as that of BA.1, and it is possible that there are other viral or host factors that are enabling the rapid diffusion of BA.2. A study published in Science Immunology investigated humoral and cellular immune responses to Omicron and other variants of concern (VOCs), looking to understand how, and to what degree, vaccinated individuals are protected against Omicron. From the results, a very low level of antibody cross-neutralization of Omicron, or a lack thereof, was seen when compared with wild type, Beta, and Delta variants, which could be partially restored by a third booster vaccination. Furthermore, T lymphocytes were shown to recognize Omicron with the same efficacy as seen for the other VOCs, suggesting that vaccinated individuals maintain T lymphocyte immunity, an element that is capable of providing protection in the absence of neutralizing antibodies, limiting the chance of serious disease.

These results are consistent with those available from a study performed in a population from Qatar made up of 2,239,193 people who had received at least two doses of a BNT162b2 or mRNA-1273 vaccine. The efficacy of the booster against a symptomatic Omicron infection, compared with that from the primary series, was 49.4% (95% CI, 47.1-51.6). The efficacy of the booster against hospitalization for COVID-19 and the death rate from Omicron infection, compared with the primary series, was 76.5% (95% CI, 55.9-87.5). The efficacy of the BNT162b2 booster against a symptomatic Delta variant infection (or B.1.617.2), compared with the primary series, was 86.1% (95% CI, 67.3-94.1).

To summarize, the constant increase in the prevalence of BA.2 in more countries over the world has confirmed the growth advantage that this variant has compared with others. BA.2 reduces the protective effect of vaccination against infection. Omicron antibody cross-neutralization can be partially restored by a third booster vaccination, an aspect that becomes problematic in the context of a low vaccination rate, where peaks of Omicron may increase the likelihood of infection in the elderly and in other groups at a higher risk of severe disease. Omicron BA.2 opens up new evolution channels, but what do the experts think will happen?

A version of this article was originally published in Italian on Univadis.

Since November 2021, the Omicron variant of SARS-CoV-2 has quickly become the most dominant variant worldwide. Early sequencing of Omicron in South Africa alerted researchers to the possibility that Omicron could be a cause for concern because of extensive mutations of the spike protein. Omicron has 30 mutations of the spike protein, compared with the original Wuhan-Hu-1 variant, with 15 mutations of the receptor-binding domain (which are linked to a decrease in antibody binding), mutations at the furin S1/S2 site (which improves furin binding and increases infectiousness), and mutations of the amino terminal domain (which is the main binding site for some of the therapeutic antibodies used to treat COVID-19 infections).

Omicron’s functional characteristics

Non–peer-reviewed studies have shown a replication of Omicron in pulmonary epithelial cells, which was shown to be less efficient, when compared with Delta and Wuhan-Hu-1. The number of viral copies from an Omicron infection in pulmonary epithelial cells was significantly lower, compared with infection with the Delta or Wuhan-Hu-1 variants. The association of these characteristics found an increase in the number of viral copies in human epithelial cells (taken from the nasal airways) infected with Omicron. This supports the understanding that Omicron is more transmissible but results in a less severe manifestation of the disease.

As for the phenotypic expression of the infection, attention has been focused on Omicron’s reduced capacity to cause syncytia in pulmonary tissue cultures, information which is relevant to its clinical significance, if we consider that the formation of syncytia has been associated with a more severe manifestation of the disease. Furthermore, it has emerged that Omicron can use different cellular entry routes, with a preference for endosomal fusion over superficial cellular fusion. This characteristic allows Omicron to significantly increase the number of types of cells it can infect.
 

Omicron BA.2 evolves

Between November and December 2021, Omicron progressed, evolving into a variant with characteristics similar to those of its predecessors (that is, it underwent a gradual and progressive increase in transmissibility). Early studies on the Omicron variant were mainly based on the BA.1 subvariant. Since the start of January 2022, there has been an unexpected increase in BA.2 in Europe and Asia. Since then, continued surveillance on the evolution of Omicron has shown an increased prevalence of two subvariants: BA.1 with a R346K mutation (BA.1 + R346K) and B.1.1.529.2 (BA.2), with the latter containing eight unique spike mutations and 13 missing spike mutations, compared with those found in BA.1.

From these differences, we cannot presume that their antigenic properties are similar or different, but they seem to be antigenically equidistant from wild-type SARS-CoV-2, likely jeopardizing in equal measures the efficacy of current COVID-19 vaccines. Furthermore, BA.2 shows significant resistance to 17 out of 19 neutralizing monoclonal antibodies tested in this study, demonstrating that current monoclonal antibody therapy may have significant limitations in terms of adequate coverage for all subvariants of the Omicron variant.
 

Omicron BA.2 and reinfection

BA.2 initially represented only 13% of Omicron sequences at a global level, quickly becoming the dominant form in some countries, such as Denmark. At the end of 2021, BA.2 represented around 20% of all Danish cases of SARS-CoV-2. Halfway through January 2022, this had increased to around 45%, data that indicate that BA.2 carries an advantage over BA.1 within the highly vaccinated population of Denmark.

BA.2 is associated with an increased susceptibility of infection for unvaccinated individuals (odds ratio, 2.19; 95% confidence interval, 1.58-3.04), fully vaccinated individuals (OR, 2.45; 95% CI, 1.77-3.40), and booster-vaccinated individuals (OR, 2.99; 95% CI, 2.11-4.24), compared with BA.1. The pattern of increased transmissibility in BA.2 households was not observed for fully vaccinated and booster-vaccinated primary cases, where the OR of transmission was below 1 for BA.2, compared with BA.1. These data confirm the immune-evasive properties of BA.2 that further reduce the protective effect of vaccination against infection, but do not increase its transmissibility from vaccinated individuals with breakthrough infections.
 

Omicron, BA.2, and vaccination

The understanding of serum neutralizing activity, in correlation to the efficacy of a vaccine, is a priority of research because of the growing epidemiological significance of BA.2. There is evidence to support the claim that the immune-evasive nature of BA.2 doesn›t seem to be as severe as that of BA.1, and it is possible that there are other viral or host factors that are enabling the rapid diffusion of BA.2. A study published in Science Immunology investigated humoral and cellular immune responses to Omicron and other variants of concern (VOCs), looking to understand how, and to what degree, vaccinated individuals are protected against Omicron. From the results, a very low level of antibody cross-neutralization of Omicron, or a lack thereof, was seen when compared with wild type, Beta, and Delta variants, which could be partially restored by a third booster vaccination. Furthermore, T lymphocytes were shown to recognize Omicron with the same efficacy as seen for the other VOCs, suggesting that vaccinated individuals maintain T lymphocyte immunity, an element that is capable of providing protection in the absence of neutralizing antibodies, limiting the chance of serious disease.

These results are consistent with those available from a study performed in a population from Qatar made up of 2,239,193 people who had received at least two doses of a BNT162b2 or mRNA-1273 vaccine. The efficacy of the booster against a symptomatic Omicron infection, compared with that from the primary series, was 49.4% (95% CI, 47.1-51.6). The efficacy of the booster against hospitalization for COVID-19 and the death rate from Omicron infection, compared with the primary series, was 76.5% (95% CI, 55.9-87.5). The efficacy of the BNT162b2 booster against a symptomatic Delta variant infection (or B.1.617.2), compared with the primary series, was 86.1% (95% CI, 67.3-94.1).

To summarize, the constant increase in the prevalence of BA.2 in more countries over the world has confirmed the growth advantage that this variant has compared with others. BA.2 reduces the protective effect of vaccination against infection. Omicron antibody cross-neutralization can be partially restored by a third booster vaccination, an aspect that becomes problematic in the context of a low vaccination rate, where peaks of Omicron may increase the likelihood of infection in the elderly and in other groups at a higher risk of severe disease. Omicron BA.2 opens up new evolution channels, but what do the experts think will happen?

A version of this article was originally published in Italian on Univadis.

A recently published set of treatment flow diagrams uses simplified diagnosis and management pathways to help primary care providers (PCPs) in Europe, the United States, and elsewhere treat patients with allergies.

Most patients with allergy problems first see PCPs, not allergists, the authors write in Allergy. The new flow diagrams help PCPs treat anaphylaxis, asthma, drug allergy, food allergy, and urticaria.

“The European Academy of Allergy and Clinical Immunology established the Logogram Task Force to create a set of simple flow diagrams to assist allergy nonspecialist, generalist, and primary care teams in the diagnosis of five common allergic diseases encountered in primary care,” lead author Dermot Ryan, MB BCh, BAO, FRGCP, of the University of Edinburgh told this news organization.

“The source documents were mainstream guidelines coupled with ancillary literature,” he added in an email. “A multi-disciplinary taskforce ... distilled these guidelines into accessible, comprehensible, usable, and context-specific flow diagrams.”
 

The flow diagrams developed in Europe can be used by providers in the United States and elsewhere

“These diagrams are consistent with practices in the U.S.,” Christina E. Ciaccio, MD, an associate professor of pediatrics and the section chief of pediatric allergy and immunology at the University of Chicago Medicine, said in an email. “They will prove helpful to PCPs in the U.S. and elsewhere, particularly to young physicians new to practice.

“Treating allergies is part of the ‘bread-and-butter’ practice of primary care physicians in the U.S.,” Dr. Ciaccio, who was not involved in developing the flow diagrams, explained. “Up to 30% of Americans are atopic, and the vast majority seek treatment advice from their PCP first.”

The flow diagrams can help providers in developing countries, where allergic diseases are common, provide the best patient care possible, she said.
 

At some point, a PCP may need to think beyond flow diagrams and refer the patient to an allergist

“If the treatment plan for a patient falls outside first- or second-line medications, or if a diagnosis is unclear with preliminary testing, a PCP may reach out to an allergy/immunology specialist to assist in providing care,” Dr. Ciaccio advised. “Allergists may provide treatment options, such as immunotherapy, that the PCP does not offer. PCPs also often reach out to allergy team members for help with patients whose allergies are not ‘run-of-the-mill.’

“The flow diagrams are complex and may not be practical in the middle of a busy clinic,” she cautioned. “However, when a patient comes into a primary care clinic with an atypical presentation of an allergic disease, the diagrams are likely to help a physician feel confident that an allergist is the right physician for consultation.”

Patricia Lynne Lugar, MD, an associate professor of medicine in pulmonary, allergy, and critical care medicine at Duke University in Durham, N.C., noted that providers in the U.S. can use the flow diagrams because the definitions, differential diagnosis, and treatments for the conditions they cover are similar.

“The flow diagrams are comprehensive, and they attempt to condense a great deal of information into summary points. They are very useful in the U.S., and not just for generalists,” Dr. Lugar, who also was not involved in the project, said. “Even emergency rooms would benefit from these flow diagrams, especially regarding the recognition of symptoms and differential diagnosis.”

Asthma and seasonal and environmental allergies are often managed by PCPs, and the flow diagrams would help them decide when to refer their patients to an allergist, she added in an email.

Dr. Lugar advises PCPs to “recognize the symptoms of an allergic condition, offer treatment based on confidence the diagnosis is correct, and offer a referral for testing to confirm the allergy.

“Because 50% or more of asthmatics are allergic, all asthmatics should be offered an allergy evaluation to determine their allergies and avoid exacerbating the asthma,” she added. “I do not see the flow diagrams as comprehensive enough to manage chronic urticaria, asthma, venom allergy, and drug allergy.”

With food allergy, environmental allergy, venom allergy, or anaphylaxis, “allergists are experts at considering the differential diagnosis and providing the next steps in the diagnostic workup,” Dr. Lugar said. “Allergists can also provide special treatments, such as allergen-specific immunotherapy or desensitization.”

The flow diagrams guide nonspecialists in diagnosis and treatment of their patients with allergy, with supplementary information as needed. The diagrams recommend referral to a specialist when appropriate, as in cases of anaphylaxis, or chronic urticaria.

A version of this article first appeared on Medscape.com.

A recently published set of treatment flow diagrams uses simplified diagnosis and management pathways to help primary care providers (PCPs) in Europe, the United States, and elsewhere treat patients with allergies.

Most patients with allergy problems first see PCPs, not allergists, the authors write in Allergy. The new flow diagrams help PCPs treat anaphylaxis, asthma, drug allergy, food allergy, and urticaria.

“The European Academy of Allergy and Clinical Immunology established the Logogram Task Force to create a set of simple flow diagrams to assist allergy nonspecialist, generalist, and primary care teams in the diagnosis of five common allergic diseases encountered in primary care,” lead author Dermot Ryan, MB BCh, BAO, FRGCP, of the University of Edinburgh told this news organization.

“The source documents were mainstream guidelines coupled with ancillary literature,” he added in an email. “A multi-disciplinary taskforce ... distilled these guidelines into accessible, comprehensible, usable, and context-specific flow diagrams.”
 

The flow diagrams developed in Europe can be used by providers in the United States and elsewhere

“These diagrams are consistent with practices in the U.S.,” Christina E. Ciaccio, MD, an associate professor of pediatrics and the section chief of pediatric allergy and immunology at the University of Chicago Medicine, said in an email. “They will prove helpful to PCPs in the U.S. and elsewhere, particularly to young physicians new to practice.

“Treating allergies is part of the ‘bread-and-butter’ practice of primary care physicians in the U.S.,” Dr. Ciaccio, who was not involved in developing the flow diagrams, explained. “Up to 30% of Americans are atopic, and the vast majority seek treatment advice from their PCP first.”

The flow diagrams can help providers in developing countries, where allergic diseases are common, provide the best patient care possible, she said.
 

At some point, a PCP may need to think beyond flow diagrams and refer the patient to an allergist

“If the treatment plan for a patient falls outside first- or second-line medications, or if a diagnosis is unclear with preliminary testing, a PCP may reach out to an allergy/immunology specialist to assist in providing care,” Dr. Ciaccio advised. “Allergists may provide treatment options, such as immunotherapy, that the PCP does not offer. PCPs also often reach out to allergy team members for help with patients whose allergies are not ‘run-of-the-mill.’

“The flow diagrams are complex and may not be practical in the middle of a busy clinic,” she cautioned. “However, when a patient comes into a primary care clinic with an atypical presentation of an allergic disease, the diagrams are likely to help a physician feel confident that an allergist is the right physician for consultation.”

Patricia Lynne Lugar, MD, an associate professor of medicine in pulmonary, allergy, and critical care medicine at Duke University in Durham, N.C., noted that providers in the U.S. can use the flow diagrams because the definitions, differential diagnosis, and treatments for the conditions they cover are similar.

“The flow diagrams are comprehensive, and they attempt to condense a great deal of information into summary points. They are very useful in the U.S., and not just for generalists,” Dr. Lugar, who also was not involved in the project, said. “Even emergency rooms would benefit from these flow diagrams, especially regarding the recognition of symptoms and differential diagnosis.”

Asthma and seasonal and environmental allergies are often managed by PCPs, and the flow diagrams would help them decide when to refer their patients to an allergist, she added in an email.

Dr. Lugar advises PCPs to “recognize the symptoms of an allergic condition, offer treatment based on confidence the diagnosis is correct, and offer a referral for testing to confirm the allergy.

“Because 50% or more of asthmatics are allergic, all asthmatics should be offered an allergy evaluation to determine their allergies and avoid exacerbating the asthma,” she added. “I do not see the flow diagrams as comprehensive enough to manage chronic urticaria, asthma, venom allergy, and drug allergy.”

With food allergy, environmental allergy, venom allergy, or anaphylaxis, “allergists are experts at considering the differential diagnosis and providing the next steps in the diagnostic workup,” Dr. Lugar said. “Allergists can also provide special treatments, such as allergen-specific immunotherapy or desensitization.”

The flow diagrams guide nonspecialists in diagnosis and treatment of their patients with allergy, with supplementary information as needed. The diagrams recommend referral to a specialist when appropriate, as in cases of anaphylaxis, or chronic urticaria.

A version of this article first appeared on Medscape.com.

A recently published set of treatment flow diagrams uses simplified diagnosis and management pathways to help primary care providers (PCPs) in Europe, the United States, and elsewhere treat patients with allergies.

Most patients with allergy problems first see PCPs, not allergists, the authors write in Allergy. The new flow diagrams help PCPs treat anaphylaxis, asthma, drug allergy, food allergy, and urticaria.

“The European Academy of Allergy and Clinical Immunology established the Logogram Task Force to create a set of simple flow diagrams to assist allergy nonspecialist, generalist, and primary care teams in the diagnosis of five common allergic diseases encountered in primary care,” lead author Dermot Ryan, MB BCh, BAO, FRGCP, of the University of Edinburgh told this news organization.

“The source documents were mainstream guidelines coupled with ancillary literature,” he added in an email. “A multi-disciplinary taskforce ... distilled these guidelines into accessible, comprehensible, usable, and context-specific flow diagrams.”
 

The flow diagrams developed in Europe can be used by providers in the United States and elsewhere

“These diagrams are consistent with practices in the U.S.,” Christina E. Ciaccio, MD, an associate professor of pediatrics and the section chief of pediatric allergy and immunology at the University of Chicago Medicine, said in an email. “They will prove helpful to PCPs in the U.S. and elsewhere, particularly to young physicians new to practice.

“Treating allergies is part of the ‘bread-and-butter’ practice of primary care physicians in the U.S.,” Dr. Ciaccio, who was not involved in developing the flow diagrams, explained. “Up to 30% of Americans are atopic, and the vast majority seek treatment advice from their PCP first.”

The flow diagrams can help providers in developing countries, where allergic diseases are common, provide the best patient care possible, she said.
 

At some point, a PCP may need to think beyond flow diagrams and refer the patient to an allergist

“If the treatment plan for a patient falls outside first- or second-line medications, or if a diagnosis is unclear with preliminary testing, a PCP may reach out to an allergy/immunology specialist to assist in providing care,” Dr. Ciaccio advised. “Allergists may provide treatment options, such as immunotherapy, that the PCP does not offer. PCPs also often reach out to allergy team members for help with patients whose allergies are not ‘run-of-the-mill.’

“The flow diagrams are complex and may not be practical in the middle of a busy clinic,” she cautioned. “However, when a patient comes into a primary care clinic with an atypical presentation of an allergic disease, the diagrams are likely to help a physician feel confident that an allergist is the right physician for consultation.”

Patricia Lynne Lugar, MD, an associate professor of medicine in pulmonary, allergy, and critical care medicine at Duke University in Durham, N.C., noted that providers in the U.S. can use the flow diagrams because the definitions, differential diagnosis, and treatments for the conditions they cover are similar.

“The flow diagrams are comprehensive, and they attempt to condense a great deal of information into summary points. They are very useful in the U.S., and not just for generalists,” Dr. Lugar, who also was not involved in the project, said. “Even emergency rooms would benefit from these flow diagrams, especially regarding the recognition of symptoms and differential diagnosis.”

Asthma and seasonal and environmental allergies are often managed by PCPs, and the flow diagrams would help them decide when to refer their patients to an allergist, she added in an email.

Dr. Lugar advises PCPs to “recognize the symptoms of an allergic condition, offer treatment based on confidence the diagnosis is correct, and offer a referral for testing to confirm the allergy.

“Because 50% or more of asthmatics are allergic, all asthmatics should be offered an allergy evaluation to determine their allergies and avoid exacerbating the asthma,” she added. “I do not see the flow diagrams as comprehensive enough to manage chronic urticaria, asthma, venom allergy, and drug allergy.”

With food allergy, environmental allergy, venom allergy, or anaphylaxis, “allergists are experts at considering the differential diagnosis and providing the next steps in the diagnostic workup,” Dr. Lugar said. “Allergists can also provide special treatments, such as allergen-specific immunotherapy or desensitization.”

The flow diagrams guide nonspecialists in diagnosis and treatment of their patients with allergy, with supplementary information as needed. The diagrams recommend referral to a specialist when appropriate, as in cases of anaphylaxis, or chronic urticaria.

A version of this article first appeared on Medscape.com.

Jo Ward’s twin boys have been to the emergency department for respiratory problems about as many times as the dozen years they’ve been alive. Both have asthma and bronchopulmonary dysplasia, a form of chronic airway damage that can occur in children born premature, as the twins were. But each time Ms. Ward took them in for treatment during an acute bout of breathing distress, the staff told her to schedule a follow-up visit for the children with their physician only if they didn’t get better, not regardless of the outcome – as medical guidelines recommend.

“They asked questions, they did the exams, but they really didn’t give you a lot of information to help you at home,” Ms. Ward told this news organization. If they had, she doesn’t think she’d have needed to take them in for emergency care so often.

A new study, published in Academic Pediatrics, suggests she’s right.

Current clinical guidelines for asthma recommend that patients who visit the ED for an asthma-related problem should have a follow-up appointment within a month after the visit, independent of how well they have recovered once home, according to Naomi S. Bardach, MD, a professor of pediatrics and health policy at the University of California, San Francisco, who led the new study.

Her research found that children who have a follow-up appointment within 2 weeks of such a visit are less likely to come back again the next year. Yet the study also found that only about one in five youth had a follow-up visit within that 2-week window.

“The emergency department visit is probably a sign that they need some additional attention for their asthma,” Dr. Bardach said. “We know we can prevent emergency department visits if they get the right kind of medication or if they figure out how to avoid the things that are going to cause an asthma exacerbation or flare.”

For the study, Dr. Bardach and colleagues analyzed data from California, Vermont, and Massachusetts for all asthma-related emergency visits for patients aged 3-21 years between 2013 and 2016.

Out of the 90,267 such visits they identified, 22.6% of patients had a follow-up within 2 weeks, more often by patients who were younger, had commercial insurance, had evidence of prior asthma, or had complex chronic conditions.

Whereas 5.7% of patients who had follow-up visits returned to the ED within 60 days, 6.4% of those who didn’t came back – a 12% difference (P < .001). The gap was larger a year out, with 25% of those with follow-ups returning to the ED, compared with 28.3% of those without follow-ups returning (P < .001), according to the researchers.

Overall, Dr. Bardach’s group estimates that for every 30 children who have follow-up visits with a physician, one would avoid a return trip to the emergency department for asthma within a year.

But given the sheer number of asthma-related trips to the ED each year – 164,145 for kids age 1-17 years in the United States in 2016 alone – that translates into big numbers of kids not going back to the hospital: approximately 72,000 such trips avoided at a savings to the health care system of at least $8.6 million annually.
 

Missed opportunities

Had Ms. Ward’s boys been among the one in five to receive follow-up care earlier in their lives, she might have saved a significant amount of time, money, anxiety, and heartache. When the twins were 9 years old, she took them to a new pediatric pulmonologist. That changed everything. In that first visit, “they gave me way more information than I ever had in the first 9 years,” she said.

The doctor told Ms. Ward to keep steroids on hand, gave her a prescription for extra doses of the powerful medication, and explained that they needed to be used within 24 hours of the first sign of a breathing problem.

“She said if you give them the steroids right away, it keeps them out of the emergency room, and that’s actually worked,” Ms. Ward said. “She made sure we had care plans every visit and asked me each time if I still had it or we needed to rewrite it. They gave me signs to look for, for when to go to hospital visits. I think that when you go to the doctor, they should be telling you stuff like that.”

Dr. Bardach said visits with a primary care doctor or asthma specialist offer families a chance to receive information to keep the condition from becoming critical.

“Going to that follow-up visit, they can get access to education from the provider about how to avoid things that trigger asthma, and there’s medication that kids can take that keeps the lungs calm and less likely to have a big asthma reaction, so getting access to that medication can be really helpful,” she said.

That was the case for Amy Davenport, of Chapel Hill, N.C., whose 6-year-old son has been to the ED twice for his asthma.

The first time, when he was 3, he was having trouble breathing with a respiratory tract infection and received nebulizer treatment – although he received it in the ED since no beds were available in the ICU. The staff did tell Ms. Davenport to follow up with her primary care provider, but her son’s pediatrician was reluctant to diagnose him with asthma at such a young age and didn’t prescribe any maintenance medications.

A few months later, Ms. Davenport and her son found themselves back in the hospital, and an ICU bed was open this time. The critical care staff referred Davenport to a pediatric pulmonary specialist, and they haven’t been back to the hospital since. Ms. Davenport said she believes if they’d received a maintenance medication after the first visit, it likely would have prevented the second one.

“I’ve definitely seen now that, after the second admission, we got an asthma action plan and it said exactly what to do,” she said. “I felt like we had really good follow-up. We had that action plan on our refrigerator for a long time, and it helped us as parents with three small children to manage.”

Of course, follow-up care takes time – time away from work and school that not all families can spare, the researchers acknowledged. Telehealth may be an option, especially after its use expanded during the COVID-19 pandemic.

“We know that health systems have a hard time being flexible enough to actually have a kid be able to make an appointment within a short period of time, and we also know it’s hard for families sometimes to go back into a clinical setting within a certain period of time,” Dr. Bardach said. The urgency for the appointment may wane for those whose children seem to be doing better.

When the researchers adjusted their calculations for socioeconomic status, the results didn’t change much. But the study did find that patients with private insurance were about twice as likely to have follow-up visits as those on Medicaid (43.7% vs. 21.7%). And “the content and conduct” of the follow-up visit makes a difference as well.

Ms. Ward, whose boys are insured through Medicaid, recalled several visits to the ED where she had to push the staff to get the care her children needed. In one case, when one of her boys was a year old and struggling to breathe, the emergency doctor handed her a prescription and recommended she fill it at a neighborhood drugstore that would be cheaper than the hospital’s pharmacy. Then a nurse came in to begin the discharge process.

“I said no, ‘we’re not ready yet. Look at him,’” Ms. Ward said. The nurse took a pulse oximeter reading that showed the boy’s oxygen levels were at 84%, dangerously low. “If I wasn’t so knowledgeable and paid attention when they were born, since they were preemies, if it would have been somebody else, they probably would’ve went home and he’d have died.”

With the pediatric pulmonologist the boys have now, Ms. Ward said she feels more capable of managing their asthma and knowing how to reduce the likelihood that they’ll need to visit the ED.

“Part of what we’re seeing here is that having an existing and trusting relationship with a clinician can be helpful to kids with asthma,” Dr. Bardach said. “If we help establish and maintain those connections, and explain how important that connection can be, that can also help somebody with asthma overall.”

The research was funded by the Agency for Healthcare Research and Quality. The authors disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Jo Ward’s twin boys have been to the emergency department for respiratory problems about as many times as the dozen years they’ve been alive. Both have asthma and bronchopulmonary dysplasia, a form of chronic airway damage that can occur in children born premature, as the twins were. But each time Ms. Ward took them in for treatment during an acute bout of breathing distress, the staff told her to schedule a follow-up visit for the children with their physician only if they didn’t get better, not regardless of the outcome – as medical guidelines recommend.

“They asked questions, they did the exams, but they really didn’t give you a lot of information to help you at home,” Ms. Ward told this news organization. If they had, she doesn’t think she’d have needed to take them in for emergency care so often.

A new study, published in Academic Pediatrics, suggests she’s right.

Current clinical guidelines for asthma recommend that patients who visit the ED for an asthma-related problem should have a follow-up appointment within a month after the visit, independent of how well they have recovered once home, according to Naomi S. Bardach, MD, a professor of pediatrics and health policy at the University of California, San Francisco, who led the new study.

Her research found that children who have a follow-up appointment within 2 weeks of such a visit are less likely to come back again the next year. Yet the study also found that only about one in five youth had a follow-up visit within that 2-week window.

“The emergency department visit is probably a sign that they need some additional attention for their asthma,” Dr. Bardach said. “We know we can prevent emergency department visits if they get the right kind of medication or if they figure out how to avoid the things that are going to cause an asthma exacerbation or flare.”

For the study, Dr. Bardach and colleagues analyzed data from California, Vermont, and Massachusetts for all asthma-related emergency visits for patients aged 3-21 years between 2013 and 2016.

Out of the 90,267 such visits they identified, 22.6% of patients had a follow-up within 2 weeks, more often by patients who were younger, had commercial insurance, had evidence of prior asthma, or had complex chronic conditions.

Whereas 5.7% of patients who had follow-up visits returned to the ED within 60 days, 6.4% of those who didn’t came back – a 12% difference (P < .001). The gap was larger a year out, with 25% of those with follow-ups returning to the ED, compared with 28.3% of those without follow-ups returning (P < .001), according to the researchers.

Overall, Dr. Bardach’s group estimates that for every 30 children who have follow-up visits with a physician, one would avoid a return trip to the emergency department for asthma within a year.

But given the sheer number of asthma-related trips to the ED each year – 164,145 for kids age 1-17 years in the United States in 2016 alone – that translates into big numbers of kids not going back to the hospital: approximately 72,000 such trips avoided at a savings to the health care system of at least $8.6 million annually.
 

Missed opportunities

Had Ms. Ward’s boys been among the one in five to receive follow-up care earlier in their lives, she might have saved a significant amount of time, money, anxiety, and heartache. When the twins were 9 years old, she took them to a new pediatric pulmonologist. That changed everything. In that first visit, “they gave me way more information than I ever had in the first 9 years,” she said.

The doctor told Ms. Ward to keep steroids on hand, gave her a prescription for extra doses of the powerful medication, and explained that they needed to be used within 24 hours of the first sign of a breathing problem.

“She said if you give them the steroids right away, it keeps them out of the emergency room, and that’s actually worked,” Ms. Ward said. “She made sure we had care plans every visit and asked me each time if I still had it or we needed to rewrite it. They gave me signs to look for, for when to go to hospital visits. I think that when you go to the doctor, they should be telling you stuff like that.”

Dr. Bardach said visits with a primary care doctor or asthma specialist offer families a chance to receive information to keep the condition from becoming critical.

“Going to that follow-up visit, they can get access to education from the provider about how to avoid things that trigger asthma, and there’s medication that kids can take that keeps the lungs calm and less likely to have a big asthma reaction, so getting access to that medication can be really helpful,” she said.

That was the case for Amy Davenport, of Chapel Hill, N.C., whose 6-year-old son has been to the ED twice for his asthma.

The first time, when he was 3, he was having trouble breathing with a respiratory tract infection and received nebulizer treatment – although he received it in the ED since no beds were available in the ICU. The staff did tell Ms. Davenport to follow up with her primary care provider, but her son’s pediatrician was reluctant to diagnose him with asthma at such a young age and didn’t prescribe any maintenance medications.

A few months later, Ms. Davenport and her son found themselves back in the hospital, and an ICU bed was open this time. The critical care staff referred Davenport to a pediatric pulmonary specialist, and they haven’t been back to the hospital since. Ms. Davenport said she believes if they’d received a maintenance medication after the first visit, it likely would have prevented the second one.

“I’ve definitely seen now that, after the second admission, we got an asthma action plan and it said exactly what to do,” she said. “I felt like we had really good follow-up. We had that action plan on our refrigerator for a long time, and it helped us as parents with three small children to manage.”

Of course, follow-up care takes time – time away from work and school that not all families can spare, the researchers acknowledged. Telehealth may be an option, especially after its use expanded during the COVID-19 pandemic.

“We know that health systems have a hard time being flexible enough to actually have a kid be able to make an appointment within a short period of time, and we also know it’s hard for families sometimes to go back into a clinical setting within a certain period of time,” Dr. Bardach said. The urgency for the appointment may wane for those whose children seem to be doing better.

When the researchers adjusted their calculations for socioeconomic status, the results didn’t change much. But the study did find that patients with private insurance were about twice as likely to have follow-up visits as those on Medicaid (43.7% vs. 21.7%). And “the content and conduct” of the follow-up visit makes a difference as well.

Ms. Ward, whose boys are insured through Medicaid, recalled several visits to the ED where she had to push the staff to get the care her children needed. In one case, when one of her boys was a year old and struggling to breathe, the emergency doctor handed her a prescription and recommended she fill it at a neighborhood drugstore that would be cheaper than the hospital’s pharmacy. Then a nurse came in to begin the discharge process.

“I said no, ‘we’re not ready yet. Look at him,’” Ms. Ward said. The nurse took a pulse oximeter reading that showed the boy’s oxygen levels were at 84%, dangerously low. “If I wasn’t so knowledgeable and paid attention when they were born, since they were preemies, if it would have been somebody else, they probably would’ve went home and he’d have died.”

With the pediatric pulmonologist the boys have now, Ms. Ward said she feels more capable of managing their asthma and knowing how to reduce the likelihood that they’ll need to visit the ED.

“Part of what we’re seeing here is that having an existing and trusting relationship with a clinician can be helpful to kids with asthma,” Dr. Bardach said. “If we help establish and maintain those connections, and explain how important that connection can be, that can also help somebody with asthma overall.”

The research was funded by the Agency for Healthcare Research and Quality. The authors disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Jo Ward’s twin boys have been to the emergency department for respiratory problems about as many times as the dozen years they’ve been alive. Both have asthma and bronchopulmonary dysplasia, a form of chronic airway damage that can occur in children born premature, as the twins were. But each time Ms. Ward took them in for treatment during an acute bout of breathing distress, the staff told her to schedule a follow-up visit for the children with their physician only if they didn’t get better, not regardless of the outcome – as medical guidelines recommend.

“They asked questions, they did the exams, but they really didn’t give you a lot of information to help you at home,” Ms. Ward told this news organization. If they had, she doesn’t think she’d have needed to take them in for emergency care so often.

A new study, published in Academic Pediatrics, suggests she’s right.

Current clinical guidelines for asthma recommend that patients who visit the ED for an asthma-related problem should have a follow-up appointment within a month after the visit, independent of how well they have recovered once home, according to Naomi S. Bardach, MD, a professor of pediatrics and health policy at the University of California, San Francisco, who led the new study.

Her research found that children who have a follow-up appointment within 2 weeks of such a visit are less likely to come back again the next year. Yet the study also found that only about one in five youth had a follow-up visit within that 2-week window.

“The emergency department visit is probably a sign that they need some additional attention for their asthma,” Dr. Bardach said. “We know we can prevent emergency department visits if they get the right kind of medication or if they figure out how to avoid the things that are going to cause an asthma exacerbation or flare.”

For the study, Dr. Bardach and colleagues analyzed data from California, Vermont, and Massachusetts for all asthma-related emergency visits for patients aged 3-21 years between 2013 and 2016.

Out of the 90,267 such visits they identified, 22.6% of patients had a follow-up within 2 weeks, more often by patients who were younger, had commercial insurance, had evidence of prior asthma, or had complex chronic conditions.

Whereas 5.7% of patients who had follow-up visits returned to the ED within 60 days, 6.4% of those who didn’t came back – a 12% difference (P < .001). The gap was larger a year out, with 25% of those with follow-ups returning to the ED, compared with 28.3% of those without follow-ups returning (P < .001), according to the researchers.

Overall, Dr. Bardach’s group estimates that for every 30 children who have follow-up visits with a physician, one would avoid a return trip to the emergency department for asthma within a year.

But given the sheer number of asthma-related trips to the ED each year – 164,145 for kids age 1-17 years in the United States in 2016 alone – that translates into big numbers of kids not going back to the hospital: approximately 72,000 such trips avoided at a savings to the health care system of at least $8.6 million annually.
 

Missed opportunities

Had Ms. Ward’s boys been among the one in five to receive follow-up care earlier in their lives, she might have saved a significant amount of time, money, anxiety, and heartache. When the twins were 9 years old, she took them to a new pediatric pulmonologist. That changed everything. In that first visit, “they gave me way more information than I ever had in the first 9 years,” she said.

The doctor told Ms. Ward to keep steroids on hand, gave her a prescription for extra doses of the powerful medication, and explained that they needed to be used within 24 hours of the first sign of a breathing problem.

“She said if you give them the steroids right away, it keeps them out of the emergency room, and that’s actually worked,” Ms. Ward said. “She made sure we had care plans every visit and asked me each time if I still had it or we needed to rewrite it. They gave me signs to look for, for when to go to hospital visits. I think that when you go to the doctor, they should be telling you stuff like that.”

Dr. Bardach said visits with a primary care doctor or asthma specialist offer families a chance to receive information to keep the condition from becoming critical.

“Going to that follow-up visit, they can get access to education from the provider about how to avoid things that trigger asthma, and there’s medication that kids can take that keeps the lungs calm and less likely to have a big asthma reaction, so getting access to that medication can be really helpful,” she said.

That was the case for Amy Davenport, of Chapel Hill, N.C., whose 6-year-old son has been to the ED twice for his asthma.

The first time, when he was 3, he was having trouble breathing with a respiratory tract infection and received nebulizer treatment – although he received it in the ED since no beds were available in the ICU. The staff did tell Ms. Davenport to follow up with her primary care provider, but her son’s pediatrician was reluctant to diagnose him with asthma at such a young age and didn’t prescribe any maintenance medications.

A few months later, Ms. Davenport and her son found themselves back in the hospital, and an ICU bed was open this time. The critical care staff referred Davenport to a pediatric pulmonary specialist, and they haven’t been back to the hospital since. Ms. Davenport said she believes if they’d received a maintenance medication after the first visit, it likely would have prevented the second one.

“I’ve definitely seen now that, after the second admission, we got an asthma action plan and it said exactly what to do,” she said. “I felt like we had really good follow-up. We had that action plan on our refrigerator for a long time, and it helped us as parents with three small children to manage.”

Of course, follow-up care takes time – time away from work and school that not all families can spare, the researchers acknowledged. Telehealth may be an option, especially after its use expanded during the COVID-19 pandemic.

“We know that health systems have a hard time being flexible enough to actually have a kid be able to make an appointment within a short period of time, and we also know it’s hard for families sometimes to go back into a clinical setting within a certain period of time,” Dr. Bardach said. The urgency for the appointment may wane for those whose children seem to be doing better.

When the researchers adjusted their calculations for socioeconomic status, the results didn’t change much. But the study did find that patients with private insurance were about twice as likely to have follow-up visits as those on Medicaid (43.7% vs. 21.7%). And “the content and conduct” of the follow-up visit makes a difference as well.

Ms. Ward, whose boys are insured through Medicaid, recalled several visits to the ED where she had to push the staff to get the care her children needed. In one case, when one of her boys was a year old and struggling to breathe, the emergency doctor handed her a prescription and recommended she fill it at a neighborhood drugstore that would be cheaper than the hospital’s pharmacy. Then a nurse came in to begin the discharge process.

“I said no, ‘we’re not ready yet. Look at him,’” Ms. Ward said. The nurse took a pulse oximeter reading that showed the boy’s oxygen levels were at 84%, dangerously low. “If I wasn’t so knowledgeable and paid attention when they were born, since they were preemies, if it would have been somebody else, they probably would’ve went home and he’d have died.”

With the pediatric pulmonologist the boys have now, Ms. Ward said she feels more capable of managing their asthma and knowing how to reduce the likelihood that they’ll need to visit the ED.

“Part of what we’re seeing here is that having an existing and trusting relationship with a clinician can be helpful to kids with asthma,” Dr. Bardach said. “If we help establish and maintain those connections, and explain how important that connection can be, that can also help somebody with asthma overall.”

The research was funded by the Agency for Healthcare Research and Quality. The authors disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Living in coastal areas of Florida and California has great appeal for many, with the warm, sunny climate and nearby fresh water and salt water.

But, unknown to many, those balmy coasts also carry the risk of infection from nontuberculous (atypical) mycobacteria (NTM). Unlike its relative, tuberculosis, NTM is not transmitted from person to person, with one exception: patients with cystic fibrosis.

It is estimated that there were 181,000 people with NTM lung disease in the U.S. in 2015, and according to one study, the incidence is increasing by 8.2% annually among those aged 65 years and older. But NTM doesn’t only affect the elderly; it’s estimated that 31% of all NTM patients are younger than 65 years.

With the warm, moist soil and water, NTM is most commonly found in Florida, California, Hawaii, and the Gulf Coast states. The incidence is somewhat lower in states along the Great Lakes. Other states are not without risk – but NTM is perhaps even more likely to be overlooked in these states by physicians because of a lack of awareness of the disease.

Rebecca Prevots, PhD, MPH, chief of the epidemiology and population studies unit of the Division of Intramural Research at the National Institute of Allergy and Infectious Diseases, told this news organization that “why NTM is increasing is one of the most common questions” she gets, followed by whether it is due to climate change. “The short answer is, we don’t know.”

She suggests that the increase in diagnoses is due to a combination of increased awareness, host susceptibility, and perhaps environmental changes. One problem is that NTM is not a reportable disease. Also, public health resources have been decimated, both through funding cuts and loss of personnel. Dr. Prevots said, “It’s not just NTM surveillance that is important, but you can’t just make a certain condition reportable and expect to have good data without putting resources to it. ... Diseases are made reportable at the state level. There’s no mandated reporting up to CDC. So CDC is piloting reporting events through their emerging infectious program.”

Anthony Cannella, MD, assistant professor of infectious diseases at the University of South Florida (USF), is in the midst of NTM. He told this news organization that “there’s a huge circle with big old dots right over the center of the state.” He is adamant that “a soil-water survey has to occur. We need to know what the devil is happening.”

Florida legislators agreed to allocate $519,000 for NTM testing and surveillance in 2019. But Florida Governor Ron DeSantis vetoed that line item in the budget. WUSF (a National Public Radio affiliate on the USF campus) was unable to get a response to their query about this from the governor’s office.
 

Who gets NTM?

Mycobacterium avium complex primarily causes lung disease, which presents as two clinical syndromes.

“These infections don’t affect everyone,” Kenneth Olivier, MD, MPH, chief of pulmonary clinical medicine, Cardiovascular Pulmonary Branch of the National Heart, Lung, and Blood Institute, said in an interview. They affect “patients that have underlying genetic conditions that cause abnormalities in the airway clearance mechanisms, particularly cystic fibrosis and primary ciliary dyskinesia [and], to some extent, patients with COPD.”

The second group is “comprised mainly of postmenopausal women, many of whom have had no predisposing medical problems prior to onset of generally frequent throat clearing or chronic cough, which is what brings them to medical attention.” Dr. Olivier added that “many of these patients have a fairly unique appearance. They tend to have a high prevalence of curvature of the spine, scoliosis, indentation of the chest wall (pectus excavatum), and physical characteristics that overlap heritable connective tissue disorders like Marfan syndrome or Ehlers-Danlos syndrome.”

Dr. Olivier pointed out a major problem in NTM diagnosis and treatment: “The guidelines-based approach to chronic cough generally calls for treating postnasal drip, airway reactivity, asthma type symptoms first empirically, before doing different diagnostic studies. That generally causes a delay in obtaining things like CT scan, where you can see the characteristic changes.”

Dr. Cannella added, “People are starting to become more aware of it. It’s kind of like pneumocystis back in the 80s. ... We’ve had patients who have had long periods of febrile neutropenia, and NTM wasn’t on the radar. Now we’ve picked up at least seven or eight.”

In addition to pulmonary infections, nosocomial outbreaks have occurred, owing to contaminated heater-cooler units, catheter infections, nail salons, or to medical tourism. These more commonly involve rapidly growing species, such as M abscessus, M chelonae, and M fortuitum. Clinicians should also be aware of skin infections from M marinum, which come from wounds from aquariums, fish, or shellfish. Incubation can occur over months, highlighting the importance of a detailed history and special cultures.
 

Diagnostics

The diagnosis of NTM is delayed for several reasons. One is the lack of awareness among clinicians about NTM and its risk factors, including hobbies such as gardening or working in places where dirt is aerosolized, such as on road crews, or even from hot tubs. A thorough history is critical.

Another is not recognizing the need for an acid-fast bacilli (AFB) culture, which requires specialized media. Fortunately, NTM can be picked up on fungal cultures, Dr. Cannella noted. Clinicians are sometimes discouraged from culturing AFB because doing so may not be cost-effective. And many hospital laboratories are increasingly sending cultures to outside labs, and it can take days – sometimes even more than a week – to receive a report of results.

Charles Daley, MD, chief of the Division of Mycobacterial and Respiratory Infections at National Jewish Health, expressed his frustration about labs in an interview, saying diagnostics is “an important hole in the U.S., as our laboratories do not provide clinicians with the results that they need to make good decisions. Most laboratories in the U.S. just don’t speciate the organisms or subspeciate in the setting of abscesses. They don’t tell the clinician enough about the susceptibility, particularly whether there’s inducible resistance. As a clinician, you just don’t have the information to make the right decisions. ... We need to improve diagnostics in NTM. Everything is there and available. They just don’t want to do it because it increases the costs.”

Men tend to have fibrocavitary disease, which shows on ordinary chest x-rays, but CT scans are essential for women because women tend to have either nodular disease or bronchiectasis, which does not show on a plain film.
 

Treatment

A standard treatment for NTM lung disease includes three or four medications – clarithromycin or azithromycin, rifampin or rifabutin, ethambutol, and streptomycin or amikacin. In vitro resistance is important in predicting the clinical response to a macrolide or amikacin.

For bronchiectatic disease, National Jewish Hospital recommends treatment three times per week rather than daily therapy, as it is better tolerated. Azithromycin is preferred over clarithromycin. Amikacin should be added if there is cavitary or severe disease, and the macrolide is then given daily.

Dr. Olivier suggested that physicians stagger the initiation of those drugs to improve the tolerability of the difficult regimen. Generally, treatment is for 18 months – a year after sputum cultures become negative.

If therapy fails – that is, sputum is persistently positive at 6 months – amikacin liposomal inhalation solution (Arikayce) is likely to be added. Patients should be monitored with monthly safety labs, sputum cultures, and an audiogram (if receiving amikacin). Every 3 months, vestibular tests, eye exams, and spirometry should be conducted, and every 6 months, physicians should order a CT, an audiogram, and an electrocardiogram.

Despite completing such a rigorous regimen, about half of patients experience reinfection because of their underlying host susceptibility. Genomic sequencing shows that these are new infections, not relapses, Dr. Prevots said. She also noted that gastroesophageal reflux disease is a significant risk factor because of chronic aspiration.

Dr. Daley outlined the newer treatments being studied. They include Arikayce, omadocycline, and bedaquiline. He added, “There’s a neutrophil elastase inhibitor trial that’s ongoing, a huge trial. There’s another one looking at basically eosinophilic inflammation.”

Other trials are in the offing, he said, all focusing on the inflammatory response – a development he described as exciting, because for the longest time, there were few if any NTM trials.

Dr. Cannella is also buoyed by the potential synergy of dual beta-lactam therapy with ceftaroline and a carbapenem for M abscessus infections, which are notoriously difficult to treat.

There are unique problems facing drug development for NTM because, for approval, the U.S. Food and Drug Administration requires the drug to “improve how a patient feels, functions, or survives.” NTM is associated with low mortality, so that “is off the table,” Dr. Daley explained. It’s hard to quantify improvement in function. The top two symptoms to measure are coughing and fatigue, he said. But both are difficult to measure, and some of the medicines worsen cough. Some research groups are now trying to validate patient-reported outcome instruments to satisfy the FDA’s requirements.
 

Tips for patients and physicians

The experts this news organization spoke to had very consistent recommendations for patients:

• NTM is resistant to chlorine and bromine, so tap water is a major source of infection. Patients should consider to greater than 130° F and using metal showerheads or bathing rather than showering.
• Good bathroom ventilation helps.
• Patients should consider using a water filter that filters entities less than 5 mcm in size – but not carbon filters, which concentrate the organisms.
• Humidifiers and hot tubs should be avoided.
• A good face mask, such as an N95, should be worn when gardening or repotting plants.

Dr. Olivier stressed that clinicians should familiarize themselves with the guidelines for diagnosing and treating NTM. In particular, clinicians should be aware that using azithromycin for bronchitis might cause resistance in NTM. “Macrolide resistance turns what may be a slowly progressive or bothersome infection into a lethal infection with a 1-year mortality of 35%.”

He concluded, “I would just urge that if the patient’s on their second or third Z-Pak within a year, it’s probably time to look for other causes of what might be happening.”

Dr. Cannella, Dr. Prevots, and Dr. Olivier reported no relevant financial relationships. Dr. Cannella adds, “My views are not those of my employers, the U.S. Dept of VA, or the University of South Florida Morsani College of Medicine.” Dr. Daley reports research grants/contracts with AN2, Beyond Air, Bugworks, Insmed, and Paratek and service on advisory boards or as a consultant for AN2, AstraZeneca, Genentech, Insmed, Matinas, Paratek, Pfizer, and Spero.

A version of this article first appeared on Medscape.com.

Living in coastal areas of Florida and California has great appeal for many, with the warm, sunny climate and nearby fresh water and salt water.

But, unknown to many, those balmy coasts also carry the risk of infection from nontuberculous (atypical) mycobacteria (NTM). Unlike its relative, tuberculosis, NTM is not transmitted from person to person, with one exception: patients with cystic fibrosis.

It is estimated that there were 181,000 people with NTM lung disease in the U.S. in 2015, and according to one study, the incidence is increasing by 8.2% annually among those aged 65 years and older. But NTM doesn’t only affect the elderly; it’s estimated that 31% of all NTM patients are younger than 65 years.

With the warm, moist soil and water, NTM is most commonly found in Florida, California, Hawaii, and the Gulf Coast states. The incidence is somewhat lower in states along the Great Lakes. Other states are not without risk – but NTM is perhaps even more likely to be overlooked in these states by physicians because of a lack of awareness of the disease.

Rebecca Prevots, PhD, MPH, chief of the epidemiology and population studies unit of the Division of Intramural Research at the National Institute of Allergy and Infectious Diseases, told this news organization that “why NTM is increasing is one of the most common questions” she gets, followed by whether it is due to climate change. “The short answer is, we don’t know.”

She suggests that the increase in diagnoses is due to a combination of increased awareness, host susceptibility, and perhaps environmental changes. One problem is that NTM is not a reportable disease. Also, public health resources have been decimated, both through funding cuts and loss of personnel. Dr. Prevots said, “It’s not just NTM surveillance that is important, but you can’t just make a certain condition reportable and expect to have good data without putting resources to it. ... Diseases are made reportable at the state level. There’s no mandated reporting up to CDC. So CDC is piloting reporting events through their emerging infectious program.”

Anthony Cannella, MD, assistant professor of infectious diseases at the University of South Florida (USF), is in the midst of NTM. He told this news organization that “there’s a huge circle with big old dots right over the center of the state.” He is adamant that “a soil-water survey has to occur. We need to know what the devil is happening.”

Florida legislators agreed to allocate $519,000 for NTM testing and surveillance in 2019. But Florida Governor Ron DeSantis vetoed that line item in the budget. WUSF (a National Public Radio affiliate on the USF campus) was unable to get a response to their query about this from the governor’s office.
 

Who gets NTM?

Mycobacterium avium complex primarily causes lung disease, which presents as two clinical syndromes.

“These infections don’t affect everyone,” Kenneth Olivier, MD, MPH, chief of pulmonary clinical medicine, Cardiovascular Pulmonary Branch of the National Heart, Lung, and Blood Institute, said in an interview. They affect “patients that have underlying genetic conditions that cause abnormalities in the airway clearance mechanisms, particularly cystic fibrosis and primary ciliary dyskinesia [and], to some extent, patients with COPD.”

The second group is “comprised mainly of postmenopausal women, many of whom have had no predisposing medical problems prior to onset of generally frequent throat clearing or chronic cough, which is what brings them to medical attention.” Dr. Olivier added that “many of these patients have a fairly unique appearance. They tend to have a high prevalence of curvature of the spine, scoliosis, indentation of the chest wall (pectus excavatum), and physical characteristics that overlap heritable connective tissue disorders like Marfan syndrome or Ehlers-Danlos syndrome.”

Dr. Olivier pointed out a major problem in NTM diagnosis and treatment: “The guidelines-based approach to chronic cough generally calls for treating postnasal drip, airway reactivity, asthma type symptoms first empirically, before doing different diagnostic studies. That generally causes a delay in obtaining things like CT scan, where you can see the characteristic changes.”

Dr. Cannella added, “People are starting to become more aware of it. It’s kind of like pneumocystis back in the 80s. ... We’ve had patients who have had long periods of febrile neutropenia, and NTM wasn’t on the radar. Now we’ve picked up at least seven or eight.”

In addition to pulmonary infections, nosocomial outbreaks have occurred, owing to contaminated heater-cooler units, catheter infections, nail salons, or to medical tourism. These more commonly involve rapidly growing species, such as M abscessus, M chelonae, and M fortuitum. Clinicians should also be aware of skin infections from M marinum, which come from wounds from aquariums, fish, or shellfish. Incubation can occur over months, highlighting the importance of a detailed history and special cultures.
 

Diagnostics

The diagnosis of NTM is delayed for several reasons. One is the lack of awareness among clinicians about NTM and its risk factors, including hobbies such as gardening or working in places where dirt is aerosolized, such as on road crews, or even from hot tubs. A thorough history is critical.

Another is not recognizing the need for an acid-fast bacilli (AFB) culture, which requires specialized media. Fortunately, NTM can be picked up on fungal cultures, Dr. Cannella noted. Clinicians are sometimes discouraged from culturing AFB because doing so may not be cost-effective. And many hospital laboratories are increasingly sending cultures to outside labs, and it can take days – sometimes even more than a week – to receive a report of results.

Charles Daley, MD, chief of the Division of Mycobacterial and Respiratory Infections at National Jewish Health, expressed his frustration about labs in an interview, saying diagnostics is “an important hole in the U.S., as our laboratories do not provide clinicians with the results that they need to make good decisions. Most laboratories in the U.S. just don’t speciate the organisms or subspeciate in the setting of abscesses. They don’t tell the clinician enough about the susceptibility, particularly whether there’s inducible resistance. As a clinician, you just don’t have the information to make the right decisions. ... We need to improve diagnostics in NTM. Everything is there and available. They just don’t want to do it because it increases the costs.”

Men tend to have fibrocavitary disease, which shows on ordinary chest x-rays, but CT scans are essential for women because women tend to have either nodular disease or bronchiectasis, which does not show on a plain film.
 

Treatment

A standard treatment for NTM lung disease includes three or four medications – clarithromycin or azithromycin, rifampin or rifabutin, ethambutol, and streptomycin or amikacin. In vitro resistance is important in predicting the clinical response to a macrolide or amikacin.

For bronchiectatic disease, National Jewish Hospital recommends treatment three times per week rather than daily therapy, as it is better tolerated. Azithromycin is preferred over clarithromycin. Amikacin should be added if there is cavitary or severe disease, and the macrolide is then given daily.

Dr. Olivier suggested that physicians stagger the initiation of those drugs to improve the tolerability of the difficult regimen. Generally, treatment is for 18 months – a year after sputum cultures become negative.

If therapy fails – that is, sputum is persistently positive at 6 months – amikacin liposomal inhalation solution (Arikayce) is likely to be added. Patients should be monitored with monthly safety labs, sputum cultures, and an audiogram (if receiving amikacin). Every 3 months, vestibular tests, eye exams, and spirometry should be conducted, and every 6 months, physicians should order a CT, an audiogram, and an electrocardiogram.

Despite completing such a rigorous regimen, about half of patients experience reinfection because of their underlying host susceptibility. Genomic sequencing shows that these are new infections, not relapses, Dr. Prevots said. She also noted that gastroesophageal reflux disease is a significant risk factor because of chronic aspiration.

Dr. Daley outlined the newer treatments being studied. They include Arikayce, omadocycline, and bedaquiline. He added, “There’s a neutrophil elastase inhibitor trial that’s ongoing, a huge trial. There’s another one looking at basically eosinophilic inflammation.”

Other trials are in the offing, he said, all focusing on the inflammatory response – a development he described as exciting, because for the longest time, there were few if any NTM trials.

Dr. Cannella is also buoyed by the potential synergy of dual beta-lactam therapy with ceftaroline and a carbapenem for M abscessus infections, which are notoriously difficult to treat.

There are unique problems facing drug development for NTM because, for approval, the U.S. Food and Drug Administration requires the drug to “improve how a patient feels, functions, or survives.” NTM is associated with low mortality, so that “is off the table,” Dr. Daley explained. It’s hard to quantify improvement in function. The top two symptoms to measure are coughing and fatigue, he said. But both are difficult to measure, and some of the medicines worsen cough. Some research groups are now trying to validate patient-reported outcome instruments to satisfy the FDA’s requirements.
 

Tips for patients and physicians

The experts this news organization spoke to had very consistent recommendations for patients:

• NTM is resistant to chlorine and bromine, so tap water is a major source of infection. Patients should consider to greater than 130° F and using metal showerheads or bathing rather than showering.
• Good bathroom ventilation helps.
• Patients should consider using a water filter that filters entities less than 5 mcm in size – but not carbon filters, which concentrate the organisms.
• Humidifiers and hot tubs should be avoided.
• A good face mask, such as an N95, should be worn when gardening or repotting plants.

Dr. Olivier stressed that clinicians should familiarize themselves with the guidelines for diagnosing and treating NTM. In particular, clinicians should be aware that using azithromycin for bronchitis might cause resistance in NTM. “Macrolide resistance turns what may be a slowly progressive or bothersome infection into a lethal infection with a 1-year mortality of 35%.”

He concluded, “I would just urge that if the patient’s on their second or third Z-Pak within a year, it’s probably time to look for other causes of what might be happening.”

Dr. Cannella, Dr. Prevots, and Dr. Olivier reported no relevant financial relationships. Dr. Cannella adds, “My views are not those of my employers, the U.S. Dept of VA, or the University of South Florida Morsani College of Medicine.” Dr. Daley reports research grants/contracts with AN2, Beyond Air, Bugworks, Insmed, and Paratek and service on advisory boards or as a consultant for AN2, AstraZeneca, Genentech, Insmed, Matinas, Paratek, Pfizer, and Spero.

A version of this article first appeared on Medscape.com.

Living in coastal areas of Florida and California has great appeal for many, with the warm, sunny climate and nearby fresh water and salt water.

But, unknown to many, those balmy coasts also carry the risk of infection from nontuberculous (atypical) mycobacteria (NTM). Unlike its relative, tuberculosis, NTM is not transmitted from person to person, with one exception: patients with cystic fibrosis.

It is estimated that there were 181,000 people with NTM lung disease in the U.S. in 2015, and according to one study, the incidence is increasing by 8.2% annually among those aged 65 years and older. But NTM doesn’t only affect the elderly; it’s estimated that 31% of all NTM patients are younger than 65 years.

With the warm, moist soil and water, NTM is most commonly found in Florida, California, Hawaii, and the Gulf Coast states. The incidence is somewhat lower in states along the Great Lakes. Other states are not without risk – but NTM is perhaps even more likely to be overlooked in these states by physicians because of a lack of awareness of the disease.

Rebecca Prevots, PhD, MPH, chief of the epidemiology and population studies unit of the Division of Intramural Research at the National Institute of Allergy and Infectious Diseases, told this news organization that “why NTM is increasing is one of the most common questions” she gets, followed by whether it is due to climate change. “The short answer is, we don’t know.”

She suggests that the increase in diagnoses is due to a combination of increased awareness, host susceptibility, and perhaps environmental changes. One problem is that NTM is not a reportable disease. Also, public health resources have been decimated, both through funding cuts and loss of personnel. Dr. Prevots said, “It’s not just NTM surveillance that is important, but you can’t just make a certain condition reportable and expect to have good data without putting resources to it. ... Diseases are made reportable at the state level. There’s no mandated reporting up to CDC. So CDC is piloting reporting events through their emerging infectious program.”

Anthony Cannella, MD, assistant professor of infectious diseases at the University of South Florida (USF), is in the midst of NTM. He told this news organization that “there’s a huge circle with big old dots right over the center of the state.” He is adamant that “a soil-water survey has to occur. We need to know what the devil is happening.”

Florida legislators agreed to allocate $519,000 for NTM testing and surveillance in 2019. But Florida Governor Ron DeSantis vetoed that line item in the budget. WUSF (a National Public Radio affiliate on the USF campus) was unable to get a response to their query about this from the governor’s office.
 

Who gets NTM?

Mycobacterium avium complex primarily causes lung disease, which presents as two clinical syndromes.

“These infections don’t affect everyone,” Kenneth Olivier, MD, MPH, chief of pulmonary clinical medicine, Cardiovascular Pulmonary Branch of the National Heart, Lung, and Blood Institute, said in an interview. They affect “patients that have underlying genetic conditions that cause abnormalities in the airway clearance mechanisms, particularly cystic fibrosis and primary ciliary dyskinesia [and], to some extent, patients with COPD.”

The second group is “comprised mainly of postmenopausal women, many of whom have had no predisposing medical problems prior to onset of generally frequent throat clearing or chronic cough, which is what brings them to medical attention.” Dr. Olivier added that “many of these patients have a fairly unique appearance. They tend to have a high prevalence of curvature of the spine, scoliosis, indentation of the chest wall (pectus excavatum), and physical characteristics that overlap heritable connective tissue disorders like Marfan syndrome or Ehlers-Danlos syndrome.”

Dr. Olivier pointed out a major problem in NTM diagnosis and treatment: “The guidelines-based approach to chronic cough generally calls for treating postnasal drip, airway reactivity, asthma type symptoms first empirically, before doing different diagnostic studies. That generally causes a delay in obtaining things like CT scan, where you can see the characteristic changes.”

Dr. Cannella added, “People are starting to become more aware of it. It’s kind of like pneumocystis back in the 80s. ... We’ve had patients who have had long periods of febrile neutropenia, and NTM wasn’t on the radar. Now we’ve picked up at least seven or eight.”

In addition to pulmonary infections, nosocomial outbreaks have occurred, owing to contaminated heater-cooler units, catheter infections, nail salons, or to medical tourism. These more commonly involve rapidly growing species, such as M abscessus, M chelonae, and M fortuitum. Clinicians should also be aware of skin infections from M marinum, which come from wounds from aquariums, fish, or shellfish. Incubation can occur over months, highlighting the importance of a detailed history and special cultures.
 

Diagnostics

The diagnosis of NTM is delayed for several reasons. One is the lack of awareness among clinicians about NTM and its risk factors, including hobbies such as gardening or working in places where dirt is aerosolized, such as on road crews, or even from hot tubs. A thorough history is critical.

Another is not recognizing the need for an acid-fast bacilli (AFB) culture, which requires specialized media. Fortunately, NTM can be picked up on fungal cultures, Dr. Cannella noted. Clinicians are sometimes discouraged from culturing AFB because doing so may not be cost-effective. And many hospital laboratories are increasingly sending cultures to outside labs, and it can take days – sometimes even more than a week – to receive a report of results.

Charles Daley, MD, chief of the Division of Mycobacterial and Respiratory Infections at National Jewish Health, expressed his frustration about labs in an interview, saying diagnostics is “an important hole in the U.S., as our laboratories do not provide clinicians with the results that they need to make good decisions. Most laboratories in the U.S. just don’t speciate the organisms or subspeciate in the setting of abscesses. They don’t tell the clinician enough about the susceptibility, particularly whether there’s inducible resistance. As a clinician, you just don’t have the information to make the right decisions. ... We need to improve diagnostics in NTM. Everything is there and available. They just don’t want to do it because it increases the costs.”

Men tend to have fibrocavitary disease, which shows on ordinary chest x-rays, but CT scans are essential for women because women tend to have either nodular disease or bronchiectasis, which does not show on a plain film.
 

Treatment

A standard treatment for NTM lung disease includes three or four medications – clarithromycin or azithromycin, rifampin or rifabutin, ethambutol, and streptomycin or amikacin. In vitro resistance is important in predicting the clinical response to a macrolide or amikacin.

For bronchiectatic disease, National Jewish Hospital recommends treatment three times per week rather than daily therapy, as it is better tolerated. Azithromycin is preferred over clarithromycin. Amikacin should be added if there is cavitary or severe disease, and the macrolide is then given daily.

Dr. Olivier suggested that physicians stagger the initiation of those drugs to improve the tolerability of the difficult regimen. Generally, treatment is for 18 months – a year after sputum cultures become negative.

If therapy fails – that is, sputum is persistently positive at 6 months – amikacin liposomal inhalation solution (Arikayce) is likely to be added. Patients should be monitored with monthly safety labs, sputum cultures, and an audiogram (if receiving amikacin). Every 3 months, vestibular tests, eye exams, and spirometry should be conducted, and every 6 months, physicians should order a CT, an audiogram, and an electrocardiogram.

Despite completing such a rigorous regimen, about half of patients experience reinfection because of their underlying host susceptibility. Genomic sequencing shows that these are new infections, not relapses, Dr. Prevots said. She also noted that gastroesophageal reflux disease is a significant risk factor because of chronic aspiration.

Dr. Daley outlined the newer treatments being studied. They include Arikayce, omadocycline, and bedaquiline. He added, “There’s a neutrophil elastase inhibitor trial that’s ongoing, a huge trial. There’s another one looking at basically eosinophilic inflammation.”

Other trials are in the offing, he said, all focusing on the inflammatory response – a development he described as exciting, because for the longest time, there were few if any NTM trials.

Dr. Cannella is also buoyed by the potential synergy of dual beta-lactam therapy with ceftaroline and a carbapenem for M abscessus infections, which are notoriously difficult to treat.

There are unique problems facing drug development for NTM because, for approval, the U.S. Food and Drug Administration requires the drug to “improve how a patient feels, functions, or survives.” NTM is associated with low mortality, so that “is off the table,” Dr. Daley explained. It’s hard to quantify improvement in function. The top two symptoms to measure are coughing and fatigue, he said. But both are difficult to measure, and some of the medicines worsen cough. Some research groups are now trying to validate patient-reported outcome instruments to satisfy the FDA’s requirements.
 

Tips for patients and physicians

The experts this news organization spoke to had very consistent recommendations for patients:

• NTM is resistant to chlorine and bromine, so tap water is a major source of infection. Patients should consider to greater than 130° F and using metal showerheads or bathing rather than showering.
• Good bathroom ventilation helps.
• Patients should consider using a water filter that filters entities less than 5 mcm in size – but not carbon filters, which concentrate the organisms.
• Humidifiers and hot tubs should be avoided.
• A good face mask, such as an N95, should be worn when gardening or repotting plants.

Dr. Olivier stressed that clinicians should familiarize themselves with the guidelines for diagnosing and treating NTM. In particular, clinicians should be aware that using azithromycin for bronchitis might cause resistance in NTM. “Macrolide resistance turns what may be a slowly progressive or bothersome infection into a lethal infection with a 1-year mortality of 35%.”

He concluded, “I would just urge that if the patient’s on their second or third Z-Pak within a year, it’s probably time to look for other causes of what might be happening.”

Dr. Cannella, Dr. Prevots, and Dr. Olivier reported no relevant financial relationships. Dr. Cannella adds, “My views are not those of my employers, the U.S. Dept of VA, or the University of South Florida Morsani College of Medicine.” Dr. Daley reports research grants/contracts with AN2, Beyond Air, Bugworks, Insmed, and Paratek and service on advisory boards or as a consultant for AN2, AstraZeneca, Genentech, Insmed, Matinas, Paratek, Pfizer, and Spero.

A version of this article first appeared on Medscape.com.

U.K. scientists said microplastics may pose even more of a threat than previously thought after confirming their presence in lung tissue taken from living people.

Microplastics were identified in all lung regions, but significantly higher levels were found in the lower lung.

The results supported inhalation as an exposure risk, according to the team from the University of Hull and Hull York Medical School (England), who said their findings could support further investigations into the effects of airborne microplastics on respiratory health.

The study, published in Science of the Total Environment, used lung tissue collected from surgical procedures on patients during routine medical care at Castle Hill Hospital in East Yorkshire.
 

Polypropylene and polyethylene

It found 39 microplastics in 11 of the 13 lung tissue samples tested using micro-Fourier-transform infrared (μFTIR) analysis, which the scientists said was considerably higher than results from previous laboratory tests.

Of microplastics detected, 12 polymer types were identified, of which the most common were polypropylene, (23%) polyethylene terephthalate (18%), and resin (15%). The fibers are commonly found in packaging, bottles, clothing, rope and twine manufacture, and other industries, the scientists said.

Microplastics with dimensions as small as 4 μm were found, but the scientists said they were surprised to discover samples as large as greater than 2 mm within all lung region samples, with the majority being fibrous and fragmented.

The study identified 11 microplastics in the upper part of the lung, seven in the mid part, and 21 in the lower part of the lung.

Laura Sadofsky, the study’s lead author, said: “Microplastics have previously been found in human cadaver autopsy samples. This is the first robust study to show microplastics in lungs from live people. It also shows that they are in the lower parts of the lung. Lung airways are very narrow, so no one thought they could possibly get there, but they clearly have.”

There were also considerably higher levels of microplastics found in male patients, compared with female patients.
 

Future investigations into health implications

“The characterization of types and levels of microplastics we have found can now inform realistic conditions for laboratory exposure experiments with the aim of determining health impacts,” said Laura Sadofsky, who is a senior lecturer in respiratory medicine in the Centre for Atherothrombotic and Metabolic Research at Hull York Medical School.

The latest investigation followed previous research by the medical school and the University of Hull, which found high levels of atmospheric microplastics within the Humber region.

That study, published in Atmosphere, identified resins, which could have originated from degraded roads, paint marking, or tire rubber, as well as polyethylene fibers.

A version of this article first appeared on Medscape UK.

U.K. scientists said microplastics may pose even more of a threat than previously thought after confirming their presence in lung tissue taken from living people.

Microplastics were identified in all lung regions, but significantly higher levels were found in the lower lung.

The results supported inhalation as an exposure risk, according to the team from the University of Hull and Hull York Medical School (England), who said their findings could support further investigations into the effects of airborne microplastics on respiratory health.

The study, published in Science of the Total Environment, used lung tissue collected from surgical procedures on patients during routine medical care at Castle Hill Hospital in East Yorkshire.
 

Polypropylene and polyethylene

It found 39 microplastics in 11 of the 13 lung tissue samples tested using micro-Fourier-transform infrared (μFTIR) analysis, which the scientists said was considerably higher than results from previous laboratory tests.

Of microplastics detected, 12 polymer types were identified, of which the most common were polypropylene, (23%) polyethylene terephthalate (18%), and resin (15%). The fibers are commonly found in packaging, bottles, clothing, rope and twine manufacture, and other industries, the scientists said.

Microplastics with dimensions as small as 4 μm were found, but the scientists said they were surprised to discover samples as large as greater than 2 mm within all lung region samples, with the majority being fibrous and fragmented.

The study identified 11 microplastics in the upper part of the lung, seven in the mid part, and 21 in the lower part of the lung.

Laura Sadofsky, the study’s lead author, said: “Microplastics have previously been found in human cadaver autopsy samples. This is the first robust study to show microplastics in lungs from live people. It also shows that they are in the lower parts of the lung. Lung airways are very narrow, so no one thought they could possibly get there, but they clearly have.”

There were also considerably higher levels of microplastics found in male patients, compared with female patients.
 

Future investigations into health implications

“The characterization of types and levels of microplastics we have found can now inform realistic conditions for laboratory exposure experiments with the aim of determining health impacts,” said Laura Sadofsky, who is a senior lecturer in respiratory medicine in the Centre for Atherothrombotic and Metabolic Research at Hull York Medical School.

The latest investigation followed previous research by the medical school and the University of Hull, which found high levels of atmospheric microplastics within the Humber region.

That study, published in Atmosphere, identified resins, which could have originated from degraded roads, paint marking, or tire rubber, as well as polyethylene fibers.

A version of this article first appeared on Medscape UK.

U.K. scientists said microplastics may pose even more of a threat than previously thought after confirming their presence in lung tissue taken from living people.

Microplastics were identified in all lung regions, but significantly higher levels were found in the lower lung.

The results supported inhalation as an exposure risk, according to the team from the University of Hull and Hull York Medical School (England), who said their findings could support further investigations into the effects of airborne microplastics on respiratory health.

The study, published in Science of the Total Environment, used lung tissue collected from surgical procedures on patients during routine medical care at Castle Hill Hospital in East Yorkshire.
 

Polypropylene and polyethylene

It found 39 microplastics in 11 of the 13 lung tissue samples tested using micro-Fourier-transform infrared (μFTIR) analysis, which the scientists said was considerably higher than results from previous laboratory tests.

Of microplastics detected, 12 polymer types were identified, of which the most common were polypropylene, (23%) polyethylene terephthalate (18%), and resin (15%). The fibers are commonly found in packaging, bottles, clothing, rope and twine manufacture, and other industries, the scientists said.

Microplastics with dimensions as small as 4 μm were found, but the scientists said they were surprised to discover samples as large as greater than 2 mm within all lung region samples, with the majority being fibrous and fragmented.

The study identified 11 microplastics in the upper part of the lung, seven in the mid part, and 21 in the lower part of the lung.

Laura Sadofsky, the study’s lead author, said: “Microplastics have previously been found in human cadaver autopsy samples. This is the first robust study to show microplastics in lungs from live people. It also shows that they are in the lower parts of the lung. Lung airways are very narrow, so no one thought they could possibly get there, but they clearly have.”

There were also considerably higher levels of microplastics found in male patients, compared with female patients.
 

Future investigations into health implications

“The characterization of types and levels of microplastics we have found can now inform realistic conditions for laboratory exposure experiments with the aim of determining health impacts,” said Laura Sadofsky, who is a senior lecturer in respiratory medicine in the Centre for Atherothrombotic and Metabolic Research at Hull York Medical School.

The latest investigation followed previous research by the medical school and the University of Hull, which found high levels of atmospheric microplastics within the Humber region.

That study, published in Atmosphere, identified resins, which could have originated from degraded roads, paint marking, or tire rubber, as well as polyethylene fibers.

A version of this article first appeared on Medscape UK.

When Sigmund Freud claimed that “anatomy is destiny” he was referring to anatomical sex as a determinant of personality traits. Expert consensus statements have previously offered some recommendations for managing these syndromes, but clinical data are scarce, so the present review “is intended to establish a starting point for future research,”

That notion has been widely discredited, but Freud appears to be inadvertently right in one respect: When it comes to chronic obstructive pulmonary disease (COPD), anatomy really is destiny, and sex may be as well, pulmonary researchers say.

There is a growing body of evidence to indicate that COPD affects men and women differently, and that men and women patients with COPD require different clinical management. Yet women are often underdiagnosed or misdiagnosed, partly because of poorly understood sex differences, but also because of cultural biases.

But plunging any farther into the weeds, it’s important to define terms. Although various investigators have used the terms “sex” and “gender” interchangeably, sex is the preferred term when referring to biological attributes of individual patients, while gender refers to personal identity.

These distinctions are important, contended Amik Sodhi, MBBS, MPH, from the division of allergy, pulmonology, and critical care medicine at the University of Wisconsin–Madison.

“Sex is essentially a biologic construct, so it’s got to do with the sex chromosomes, the genetics of that person, and it refers to the anatomic variations that can change susceptibility to different diseases,” she said in an interview.

An example of sex differences or “sexual dimorphism” can be found in a recent meta-analysis of sex-based genetic associations by Megan Hardin, MD, MPH from Brigham & Women’s Hospital in Boston and colleagues.

They reported that CELSR1, a gene involved in fetal lung development, was expressed more among women than among men and that a single nucleotide polymorphism in the gene was associated with COPD among women smokers, but not among men smokers.

The finding points to a potential risk locus for COPD in women, and could help shed light on sexual dimorphism in COPD, Dr. Hardin and colleagues said.

In contrast to sex, “gender is more of a psychosocial construct which can impact how diseases manifest themselves, how they are potentially managed, and what outcomes might occur for that particular disease,” Dr. Sodhi said.

She and her colleagues recently published a review of sex and gender in common lung disorders and sleep in the journal CHEST, where they wrote that the “influence of sex and gender is portrayed in epidemiological data, disease pathogenesis and pathophysiology, clinical manifestations, response to treatment, access to care, and health outcomes. Hence, sex and gender should be considered in all types of research, clinical practice and educational curricula.”

For example, as previously reported at the 2021 annual meeting of the American Thoracic Society, sex-specific differences in the severity of symptoms and prevalence of comorbidities in patients with COPD may point to different criteria for diagnosing cardiac comorbidities in women and men.

Those conclusions came from a retrospective analysis of data on 795 women and 1,251 men with GOLD (Global Initiative for Chronic Obstructive Lung Disease) class 1-3 disease.

The investigators looked at the patients’ clinical history, comorbidities, lung function, COPD Assessment Test scores, and modified Medical Research Council (mMRC) dyspnea score, and found significant differences between men and women for most functional parameters and comorbidities, and for CAT items of cough, phlegm, and energy.

In logistic regression analysis, predictors for cardiac disease in men were energy, mMRC score, smoking status, body mass index, age, and spirometric lung function, but in women only age was significantly predictive for cardiac disease.

An example of gender effects on COPD differences in men and women is the increase in cigarette advertising aimed at women in the 1960s and the advent of women-targeted brands such as Virginia Slims, which in turn lead to increased smoking rates among women. In addition, in the developing world, where the sex/gender gap in COPD is narrowing, women tend to have greater exposure to wood smoke and cooking fuels in unventilated or poorly ventilated spaces, compared with men.
 

Increasing incidence among women

According to the Centers for Disease Control and Prevention, chronic lower respiratory diseases, primarily COPD, were the fourth-leading cause of death in women in the United States in 2018, following only heart disease, cancer, and accidents/injuries.

And as a CDC analysis of data from the 2013 Behavioral Risk Factor Surveillance System showed, women were more likely to report being told by a physician that they had COPD than did men (6.6%, compared with 5.4%).

Dr. Sodhi and colleagues noted that, at all time points examined from 2005 to 2014, women had a higher proportion than men of COPD hospitalizations and in-hospital deaths. They also noted that female sex is associated with a threefold risk for severe early-onset COPD, and that women with COPD have lower diffusion capacity of lungs for carbon monoxide, despite having higher predicted forced expiratory volume in 1 second, compared with men.

“Historically, COPD wasn’t a disease that was so prevalent in women. It’s been in the past 20 years that the trends have changed,” said Patricia Silveyra, MSc, PhD, ATSF, associate professor of environmental and occupational health at Indiana University, Bloomington.

The increasing prevalence of COPD among women cannot be explained by smoking alone, she said in an interview.

“It used to be thought that it was because more women smoked, but actually a lot of women who don’t smoke can develop COPD, so it appears to be probably something environmental, but because it used to be a disease of older men, in the clinic there was also a bias to diagnose men with COPD, and women with asthma, so a lot of women went underdiagnosed,” Dr. Silveyra said.

In their review, Dr. Sodhi and colleagues noted that women with COPD “may be underdiagnosed as a result of having different symptoms from those classically recognized. Reasons for underdiagnosis or a delay in diagnosis may also be due to lack of a formal evaluation with spirometry, women seeking care later in the course of disease, physician bias, or associated fatigue or depression misdirecting diagnostic strategies. Underdiagnosis may be associated with psychological distress and worse health-related quality of life.”

Although the evidence is mixed, women tend to present more frequently with the chronic bronchitis phenotype of COPD, compared with the emphysema phenotype, and women tend to have greater degrees of pulmonary function impairment when exposed to tobacco smoke, even after controlling for differences in height and weight.

“For the same amount of exposure to tobacco smoke, females are likely to develop more severe airflow limitation at an earlier age than males, and have more exacerbation,” Dr. Sodhi and colleagues wrote.

Both Dr. Silveyra and Dr. Sodhi said that reason why men and women differ in their physiological reactions to smoke are still unknown.
 

Sex differences in drug responses

There is only limited evidence to indicate that women and men respond differently to various therapeutic agents, but what is clear is that more research into this area is needed, Dr. Sodhi and Dr. Silveyra said.

For example, among the few studies that have documented sex differences, one showed no sex differences in the efficacy of salmeterol/fluticasone combination therapy for reducing exacerbations or improving quality of life, whereas another showed that women were more likely than men to experience COPD symptoms or exacerbations after stopping inhaled corticosteroids, Dr. Sodhi and colleagues noted.

Both Dr. Sodhi and Dr. Silveyra emphasized the need for clinical trials that study the effects of sex on treatment outcomes in COPD, which could lead to better, more personalized therapeutic regimens that take sex and gender into account.

Dr. Sodhi and colleagues offered the following advice to clinicians: “Interaction with female patients should take into account that their symptoms may not conform to traditionally accepted presentations. Challenges exist for female patients at all levels of health care interaction and as clinicians we need to acknowledge the bias and willfully work toward recognition and elimination of unconscious and conscious bias. Empowering our patients to have frank discussions with their health care team when they perceive bias is another step to help promote equity.”

The review by Dr. Sodhi and colleagues was supported by grants from the National Institutes of Health. Dr. Sodhi and Dr. Silveyra reported having no conflicts of interest to disclose.

When Sigmund Freud claimed that “anatomy is destiny” he was referring to anatomical sex as a determinant of personality traits. Expert consensus statements have previously offered some recommendations for managing these syndromes, but clinical data are scarce, so the present review “is intended to establish a starting point for future research,”

That notion has been widely discredited, but Freud appears to be inadvertently right in one respect: When it comes to chronic obstructive pulmonary disease (COPD), anatomy really is destiny, and sex may be as well, pulmonary researchers say.

There is a growing body of evidence to indicate that COPD affects men and women differently, and that men and women patients with COPD require different clinical management. Yet women are often underdiagnosed or misdiagnosed, partly because of poorly understood sex differences, but also because of cultural biases.

But plunging any farther into the weeds, it’s important to define terms. Although various investigators have used the terms “sex” and “gender” interchangeably, sex is the preferred term when referring to biological attributes of individual patients, while gender refers to personal identity.

These distinctions are important, contended Amik Sodhi, MBBS, MPH, from the division of allergy, pulmonology, and critical care medicine at the University of Wisconsin–Madison.

“Sex is essentially a biologic construct, so it’s got to do with the sex chromosomes, the genetics of that person, and it refers to the anatomic variations that can change susceptibility to different diseases,” she said in an interview.

An example of sex differences or “sexual dimorphism” can be found in a recent meta-analysis of sex-based genetic associations by Megan Hardin, MD, MPH from Brigham & Women’s Hospital in Boston and colleagues.

They reported that CELSR1, a gene involved in fetal lung development, was expressed more among women than among men and that a single nucleotide polymorphism in the gene was associated with COPD among women smokers, but not among men smokers.

The finding points to a potential risk locus for COPD in women, and could help shed light on sexual dimorphism in COPD, Dr. Hardin and colleagues said.

In contrast to sex, “gender is more of a psychosocial construct which can impact how diseases manifest themselves, how they are potentially managed, and what outcomes might occur for that particular disease,” Dr. Sodhi said.

She and her colleagues recently published a review of sex and gender in common lung disorders and sleep in the journal CHEST, where they wrote that the “influence of sex and gender is portrayed in epidemiological data, disease pathogenesis and pathophysiology, clinical manifestations, response to treatment, access to care, and health outcomes. Hence, sex and gender should be considered in all types of research, clinical practice and educational curricula.”

For example, as previously reported at the 2021 annual meeting of the American Thoracic Society, sex-specific differences in the severity of symptoms and prevalence of comorbidities in patients with COPD may point to different criteria for diagnosing cardiac comorbidities in women and men.

Those conclusions came from a retrospective analysis of data on 795 women and 1,251 men with GOLD (Global Initiative for Chronic Obstructive Lung Disease) class 1-3 disease.

The investigators looked at the patients’ clinical history, comorbidities, lung function, COPD Assessment Test scores, and modified Medical Research Council (mMRC) dyspnea score, and found significant differences between men and women for most functional parameters and comorbidities, and for CAT items of cough, phlegm, and energy.

In logistic regression analysis, predictors for cardiac disease in men were energy, mMRC score, smoking status, body mass index, age, and spirometric lung function, but in women only age was significantly predictive for cardiac disease.

An example of gender effects on COPD differences in men and women is the increase in cigarette advertising aimed at women in the 1960s and the advent of women-targeted brands such as Virginia Slims, which in turn lead to increased smoking rates among women. In addition, in the developing world, where the sex/gender gap in COPD is narrowing, women tend to have greater exposure to wood smoke and cooking fuels in unventilated or poorly ventilated spaces, compared with men.
 

Increasing incidence among women

According to the Centers for Disease Control and Prevention, chronic lower respiratory diseases, primarily COPD, were the fourth-leading cause of death in women in the United States in 2018, following only heart disease, cancer, and accidents/injuries.

And as a CDC analysis of data from the 2013 Behavioral Risk Factor Surveillance System showed, women were more likely to report being told by a physician that they had COPD than did men (6.6%, compared with 5.4%).

Dr. Sodhi and colleagues noted that, at all time points examined from 2005 to 2014, women had a higher proportion than men of COPD hospitalizations and in-hospital deaths. They also noted that female sex is associated with a threefold risk for severe early-onset COPD, and that women with COPD have lower diffusion capacity of lungs for carbon monoxide, despite having higher predicted forced expiratory volume in 1 second, compared with men.

“Historically, COPD wasn’t a disease that was so prevalent in women. It’s been in the past 20 years that the trends have changed,” said Patricia Silveyra, MSc, PhD, ATSF, associate professor of environmental and occupational health at Indiana University, Bloomington.

The increasing prevalence of COPD among women cannot be explained by smoking alone, she said in an interview.

“It used to be thought that it was because more women smoked, but actually a lot of women who don’t smoke can develop COPD, so it appears to be probably something environmental, but because it used to be a disease of older men, in the clinic there was also a bias to diagnose men with COPD, and women with asthma, so a lot of women went underdiagnosed,” Dr. Silveyra said.

In their review, Dr. Sodhi and colleagues noted that women with COPD “may be underdiagnosed as a result of having different symptoms from those classically recognized. Reasons for underdiagnosis or a delay in diagnosis may also be due to lack of a formal evaluation with spirometry, women seeking care later in the course of disease, physician bias, or associated fatigue or depression misdirecting diagnostic strategies. Underdiagnosis may be associated with psychological distress and worse health-related quality of life.”

Although the evidence is mixed, women tend to present more frequently with the chronic bronchitis phenotype of COPD, compared with the emphysema phenotype, and women tend to have greater degrees of pulmonary function impairment when exposed to tobacco smoke, even after controlling for differences in height and weight.

“For the same amount of exposure to tobacco smoke, females are likely to develop more severe airflow limitation at an earlier age than males, and have more exacerbation,” Dr. Sodhi and colleagues wrote.

Both Dr. Silveyra and Dr. Sodhi said that reason why men and women differ in their physiological reactions to smoke are still unknown.
 

Sex differences in drug responses

There is only limited evidence to indicate that women and men respond differently to various therapeutic agents, but what is clear is that more research into this area is needed, Dr. Sodhi and Dr. Silveyra said.

For example, among the few studies that have documented sex differences, one showed no sex differences in the efficacy of salmeterol/fluticasone combination therapy for reducing exacerbations or improving quality of life, whereas another showed that women were more likely than men to experience COPD symptoms or exacerbations after stopping inhaled corticosteroids, Dr. Sodhi and colleagues noted.

Both Dr. Sodhi and Dr. Silveyra emphasized the need for clinical trials that study the effects of sex on treatment outcomes in COPD, which could lead to better, more personalized therapeutic regimens that take sex and gender into account.

Dr. Sodhi and colleagues offered the following advice to clinicians: “Interaction with female patients should take into account that their symptoms may not conform to traditionally accepted presentations. Challenges exist for female patients at all levels of health care interaction and as clinicians we need to acknowledge the bias and willfully work toward recognition and elimination of unconscious and conscious bias. Empowering our patients to have frank discussions with their health care team when they perceive bias is another step to help promote equity.”

The review by Dr. Sodhi and colleagues was supported by grants from the National Institutes of Health. Dr. Sodhi and Dr. Silveyra reported having no conflicts of interest to disclose.

When Sigmund Freud claimed that “anatomy is destiny” he was referring to anatomical sex as a determinant of personality traits. Expert consensus statements have previously offered some recommendations for managing these syndromes, but clinical data are scarce, so the present review “is intended to establish a starting point for future research,”

That notion has been widely discredited, but Freud appears to be inadvertently right in one respect: When it comes to chronic obstructive pulmonary disease (COPD), anatomy really is destiny, and sex may be as well, pulmonary researchers say.

There is a growing body of evidence to indicate that COPD affects men and women differently, and that men and women patients with COPD require different clinical management. Yet women are often underdiagnosed or misdiagnosed, partly because of poorly understood sex differences, but also because of cultural biases.

But plunging any farther into the weeds, it’s important to define terms. Although various investigators have used the terms “sex” and “gender” interchangeably, sex is the preferred term when referring to biological attributes of individual patients, while gender refers to personal identity.

These distinctions are important, contended Amik Sodhi, MBBS, MPH, from the division of allergy, pulmonology, and critical care medicine at the University of Wisconsin–Madison.

“Sex is essentially a biologic construct, so it’s got to do with the sex chromosomes, the genetics of that person, and it refers to the anatomic variations that can change susceptibility to different diseases,” she said in an interview.

An example of sex differences or “sexual dimorphism” can be found in a recent meta-analysis of sex-based genetic associations by Megan Hardin, MD, MPH from Brigham & Women’s Hospital in Boston and colleagues.

They reported that CELSR1, a gene involved in fetal lung development, was expressed more among women than among men and that a single nucleotide polymorphism in the gene was associated with COPD among women smokers, but not among men smokers.

The finding points to a potential risk locus for COPD in women, and could help shed light on sexual dimorphism in COPD, Dr. Hardin and colleagues said.

In contrast to sex, “gender is more of a psychosocial construct which can impact how diseases manifest themselves, how they are potentially managed, and what outcomes might occur for that particular disease,” Dr. Sodhi said.

She and her colleagues recently published a review of sex and gender in common lung disorders and sleep in the journal CHEST, where they wrote that the “influence of sex and gender is portrayed in epidemiological data, disease pathogenesis and pathophysiology, clinical manifestations, response to treatment, access to care, and health outcomes. Hence, sex and gender should be considered in all types of research, clinical practice and educational curricula.”

For example, as previously reported at the 2021 annual meeting of the American Thoracic Society, sex-specific differences in the severity of symptoms and prevalence of comorbidities in patients with COPD may point to different criteria for diagnosing cardiac comorbidities in women and men.

Those conclusions came from a retrospective analysis of data on 795 women and 1,251 men with GOLD (Global Initiative for Chronic Obstructive Lung Disease) class 1-3 disease.

The investigators looked at the patients’ clinical history, comorbidities, lung function, COPD Assessment Test scores, and modified Medical Research Council (mMRC) dyspnea score, and found significant differences between men and women for most functional parameters and comorbidities, and for CAT items of cough, phlegm, and energy.

In logistic regression analysis, predictors for cardiac disease in men were energy, mMRC score, smoking status, body mass index, age, and spirometric lung function, but in women only age was significantly predictive for cardiac disease.

An example of gender effects on COPD differences in men and women is the increase in cigarette advertising aimed at women in the 1960s and the advent of women-targeted brands such as Virginia Slims, which in turn lead to increased smoking rates among women. In addition, in the developing world, where the sex/gender gap in COPD is narrowing, women tend to have greater exposure to wood smoke and cooking fuels in unventilated or poorly ventilated spaces, compared with men.
 

Increasing incidence among women

According to the Centers for Disease Control and Prevention, chronic lower respiratory diseases, primarily COPD, were the fourth-leading cause of death in women in the United States in 2018, following only heart disease, cancer, and accidents/injuries.

And as a CDC analysis of data from the 2013 Behavioral Risk Factor Surveillance System showed, women were more likely to report being told by a physician that they had COPD than did men (6.6%, compared with 5.4%).

Dr. Sodhi and colleagues noted that, at all time points examined from 2005 to 2014, women had a higher proportion than men of COPD hospitalizations and in-hospital deaths. They also noted that female sex is associated with a threefold risk for severe early-onset COPD, and that women with COPD have lower diffusion capacity of lungs for carbon monoxide, despite having higher predicted forced expiratory volume in 1 second, compared with men.

“Historically, COPD wasn’t a disease that was so prevalent in women. It’s been in the past 20 years that the trends have changed,” said Patricia Silveyra, MSc, PhD, ATSF, associate professor of environmental and occupational health at Indiana University, Bloomington.

The increasing prevalence of COPD among women cannot be explained by smoking alone, she said in an interview.

“It used to be thought that it was because more women smoked, but actually a lot of women who don’t smoke can develop COPD, so it appears to be probably something environmental, but because it used to be a disease of older men, in the clinic there was also a bias to diagnose men with COPD, and women with asthma, so a lot of women went underdiagnosed,” Dr. Silveyra said.

In their review, Dr. Sodhi and colleagues noted that women with COPD “may be underdiagnosed as a result of having different symptoms from those classically recognized. Reasons for underdiagnosis or a delay in diagnosis may also be due to lack of a formal evaluation with spirometry, women seeking care later in the course of disease, physician bias, or associated fatigue or depression misdirecting diagnostic strategies. Underdiagnosis may be associated with psychological distress and worse health-related quality of life.”

Although the evidence is mixed, women tend to present more frequently with the chronic bronchitis phenotype of COPD, compared with the emphysema phenotype, and women tend to have greater degrees of pulmonary function impairment when exposed to tobacco smoke, even after controlling for differences in height and weight.

“For the same amount of exposure to tobacco smoke, females are likely to develop more severe airflow limitation at an earlier age than males, and have more exacerbation,” Dr. Sodhi and colleagues wrote.

Both Dr. Silveyra and Dr. Sodhi said that reason why men and women differ in their physiological reactions to smoke are still unknown.
 

Sex differences in drug responses

There is only limited evidence to indicate that women and men respond differently to various therapeutic agents, but what is clear is that more research into this area is needed, Dr. Sodhi and Dr. Silveyra said.

For example, among the few studies that have documented sex differences, one showed no sex differences in the efficacy of salmeterol/fluticasone combination therapy for reducing exacerbations or improving quality of life, whereas another showed that women were more likely than men to experience COPD symptoms or exacerbations after stopping inhaled corticosteroids, Dr. Sodhi and colleagues noted.

Both Dr. Sodhi and Dr. Silveyra emphasized the need for clinical trials that study the effects of sex on treatment outcomes in COPD, which could lead to better, more personalized therapeutic regimens that take sex and gender into account.

Dr. Sodhi and colleagues offered the following advice to clinicians: “Interaction with female patients should take into account that their symptoms may not conform to traditionally accepted presentations. Challenges exist for female patients at all levels of health care interaction and as clinicians we need to acknowledge the bias and willfully work toward recognition and elimination of unconscious and conscious bias. Empowering our patients to have frank discussions with their health care team when they perceive bias is another step to help promote equity.”

The review by Dr. Sodhi and colleagues was supported by grants from the National Institutes of Health. Dr. Sodhi and Dr. Silveyra reported having no conflicts of interest to disclose.