Pulmonology

While lung cancer is generally on the decline among both sexes, men have a ways to go to catch up with women, according to the Centers for Disease Control and Prevention.

From 2007 to 2016, rates dropped among both sexes in metropolitan and nonmetropolitan areas, according to Mary Elizabeth O’Neil, MPH, and colleagues. Their report is in Morbidity and Mortality Weekly Report (MMWR Morb Mortal Wkly Rep. 2019 Nov 8;68[44];993-8). But lung cancer incidence in 2016 was still 40% higher among men than among women, said Ms. O’Neil, an epidemiologist at the CDC.

Rather than narrowly focusing on the “just stop smoking” message, “a comprehensive approach to lung cancer prevention and control includes such population-based strategies as screening for tobacco dependence, promoting tobacco cessation, implementing comprehensive smoke-free laws, testing all homes for radon and using proven methods to lower high radon levels, and reducing exposure to lung carcinogens such as asbestos.” According to the authors of the report, “increasing the implementation of these strategies, particularly among persons living in nonmetropolitan counties, might help to reduce disparities in the decline of lung cancer incidence.”

The recommendation is based on data extracted from the U.S. Cancer Statistics Database for 2007-2016. The data cover 97% of the population.

In nonmetropolitan counties in 2007, incidence rates among men were 60% higher (99 vs. 61 per 100,000). Although rates decreased in both sexes, they were still elevated compared with women in 2016 (82 vs. 58 per 100,000; 40%).

Over the 10-year period, the rate declined more among men than among women (–2.9% vs. –1.5%) in metropolitan areas. The pattern repeated in nonmetropolitan areas (–2.1% and –0.5%, respectively).

There were different declines in different age groups by region, the authors noted.

Men aged 45-54 years in metropolitan areas experienced the largest decline (–5.2%).

Among women, the largest decline occurred in metropolitan areas among those aged 35-44 years (–5%). In nonmetropolitan areas, women in this age group experienced a 3.6% decline and women aged 65-74 years, a 1.3% decline.

Among persons aged 35-54 years, incidence rates in nonmetropolitan and metropolitan counties did not differ by sex but were higher in nonmetropolitan counties than in metropolitan counties.

There were also overall changes in smoking patterns. According to 2017 data from the National Health Interview Survey data, more adults in metropolitan areas than nonmetropolitan areas smoked (23% versus 13%) but fewer had tried to quit (50% vs. 56%). Successful quitting attempts also were lower (5% vs. 9%).

Although it is a large contributing factor, smoking is not the only risk factor for lung cancer, the authors wrote. About 10%-15% of lung cancer patients have never smoked tobacco. Nonsmoked tobacco products and second-hand exposure to cigarette smoke are risks, as are indoor radon and asbestos exposure.

Clinicians can help improve this scenario by screening at each office visit, the authors said. The recommendation is based on U.S. Preventive Services Task Force guidance.

“Lung cancer screening is recommended for adults at high risk for developing lung cancer because of their age and cigarette smoking history. Screening efforts can identify lung cancer in its early stages and provide an important opportunity to promote tobacco smoking cessation.”

However, lack of insurance among residents of nonmetropolitan areas may hamper access to these services, they said. In those regions, “a higher percentage of residents aged less than 65 years report being uninsured compared with those in metropolitan areas.”

msullivan@mdedge.com

SOURCE: O’Neil ME et al. MMWR Morb Mortal Wkly Rep. 2019 Nov 8: 68(44);993-8.

While lung cancer is generally on the decline among both sexes, men have a ways to go to catch up with women, according to the Centers for Disease Control and Prevention.

From 2007 to 2016, rates dropped among both sexes in metropolitan and nonmetropolitan areas, according to Mary Elizabeth O’Neil, MPH, and colleagues. Their report is in Morbidity and Mortality Weekly Report (MMWR Morb Mortal Wkly Rep. 2019 Nov 8;68[44];993-8). But lung cancer incidence in 2016 was still 40% higher among men than among women, said Ms. O’Neil, an epidemiologist at the CDC.

Rather than narrowly focusing on the “just stop smoking” message, “a comprehensive approach to lung cancer prevention and control includes such population-based strategies as screening for tobacco dependence, promoting tobacco cessation, implementing comprehensive smoke-free laws, testing all homes for radon and using proven methods to lower high radon levels, and reducing exposure to lung carcinogens such as asbestos.” According to the authors of the report, “increasing the implementation of these strategies, particularly among persons living in nonmetropolitan counties, might help to reduce disparities in the decline of lung cancer incidence.”

The recommendation is based on data extracted from the U.S. Cancer Statistics Database for 2007-2016. The data cover 97% of the population.

In nonmetropolitan counties in 2007, incidence rates among men were 60% higher (99 vs. 61 per 100,000). Although rates decreased in both sexes, they were still elevated compared with women in 2016 (82 vs. 58 per 100,000; 40%).

Over the 10-year period, the rate declined more among men than among women (–2.9% vs. –1.5%) in metropolitan areas. The pattern repeated in nonmetropolitan areas (–2.1% and –0.5%, respectively).

There were different declines in different age groups by region, the authors noted.

Men aged 45-54 years in metropolitan areas experienced the largest decline (–5.2%).

Among women, the largest decline occurred in metropolitan areas among those aged 35-44 years (–5%). In nonmetropolitan areas, women in this age group experienced a 3.6% decline and women aged 65-74 years, a 1.3% decline.

Among persons aged 35-54 years, incidence rates in nonmetropolitan and metropolitan counties did not differ by sex but were higher in nonmetropolitan counties than in metropolitan counties.

There were also overall changes in smoking patterns. According to 2017 data from the National Health Interview Survey data, more adults in metropolitan areas than nonmetropolitan areas smoked (23% versus 13%) but fewer had tried to quit (50% vs. 56%). Successful quitting attempts also were lower (5% vs. 9%).

Although it is a large contributing factor, smoking is not the only risk factor for lung cancer, the authors wrote. About 10%-15% of lung cancer patients have never smoked tobacco. Nonsmoked tobacco products and second-hand exposure to cigarette smoke are risks, as are indoor radon and asbestos exposure.

Clinicians can help improve this scenario by screening at each office visit, the authors said. The recommendation is based on U.S. Preventive Services Task Force guidance.

“Lung cancer screening is recommended for adults at high risk for developing lung cancer because of their age and cigarette smoking history. Screening efforts can identify lung cancer in its early stages and provide an important opportunity to promote tobacco smoking cessation.”

However, lack of insurance among residents of nonmetropolitan areas may hamper access to these services, they said. In those regions, “a higher percentage of residents aged less than 65 years report being uninsured compared with those in metropolitan areas.”

msullivan@mdedge.com

SOURCE: O’Neil ME et al. MMWR Morb Mortal Wkly Rep. 2019 Nov 8: 68(44);993-8.

While lung cancer is generally on the decline among both sexes, men have a ways to go to catch up with women, according to the Centers for Disease Control and Prevention.

From 2007 to 2016, rates dropped among both sexes in metropolitan and nonmetropolitan areas, according to Mary Elizabeth O’Neil, MPH, and colleagues. Their report is in Morbidity and Mortality Weekly Report (MMWR Morb Mortal Wkly Rep. 2019 Nov 8;68[44];993-8). But lung cancer incidence in 2016 was still 40% higher among men than among women, said Ms. O’Neil, an epidemiologist at the CDC.

Rather than narrowly focusing on the “just stop smoking” message, “a comprehensive approach to lung cancer prevention and control includes such population-based strategies as screening for tobacco dependence, promoting tobacco cessation, implementing comprehensive smoke-free laws, testing all homes for radon and using proven methods to lower high radon levels, and reducing exposure to lung carcinogens such as asbestos.” According to the authors of the report, “increasing the implementation of these strategies, particularly among persons living in nonmetropolitan counties, might help to reduce disparities in the decline of lung cancer incidence.”

The recommendation is based on data extracted from the U.S. Cancer Statistics Database for 2007-2016. The data cover 97% of the population.

In nonmetropolitan counties in 2007, incidence rates among men were 60% higher (99 vs. 61 per 100,000). Although rates decreased in both sexes, they were still elevated compared with women in 2016 (82 vs. 58 per 100,000; 40%).

Over the 10-year period, the rate declined more among men than among women (–2.9% vs. –1.5%) in metropolitan areas. The pattern repeated in nonmetropolitan areas (–2.1% and –0.5%, respectively).

There were different declines in different age groups by region, the authors noted.

Men aged 45-54 years in metropolitan areas experienced the largest decline (–5.2%).

Among women, the largest decline occurred in metropolitan areas among those aged 35-44 years (–5%). In nonmetropolitan areas, women in this age group experienced a 3.6% decline and women aged 65-74 years, a 1.3% decline.

Among persons aged 35-54 years, incidence rates in nonmetropolitan and metropolitan counties did not differ by sex but were higher in nonmetropolitan counties than in metropolitan counties.

There were also overall changes in smoking patterns. According to 2017 data from the National Health Interview Survey data, more adults in metropolitan areas than nonmetropolitan areas smoked (23% versus 13%) but fewer had tried to quit (50% vs. 56%). Successful quitting attempts also were lower (5% vs. 9%).

Although it is a large contributing factor, smoking is not the only risk factor for lung cancer, the authors wrote. About 10%-15% of lung cancer patients have never smoked tobacco. Nonsmoked tobacco products and second-hand exposure to cigarette smoke are risks, as are indoor radon and asbestos exposure.

Clinicians can help improve this scenario by screening at each office visit, the authors said. The recommendation is based on U.S. Preventive Services Task Force guidance.

“Lung cancer screening is recommended for adults at high risk for developing lung cancer because of their age and cigarette smoking history. Screening efforts can identify lung cancer in its early stages and provide an important opportunity to promote tobacco smoking cessation.”

However, lack of insurance among residents of nonmetropolitan areas may hamper access to these services, they said. In those regions, “a higher percentage of residents aged less than 65 years report being uninsured compared with those in metropolitan areas.”

msullivan@mdedge.com

SOURCE: O’Neil ME et al. MMWR Morb Mortal Wkly Rep. 2019 Nov 8: 68(44);993-8.

The most rural counties in the United States had higher percentages of potentially preventable deaths from the five leading causes of mortality, compared with the most urban counties during 2010-2017, according to study published in CDC’s Morbidity and Mortality Weekly Report.

These leading causes of death comprised heart disease, cancer, unintentional injury, chronic lower respiratory disease, and stroke and accounted for approximately 1.7 million deaths or 61% of all deaths in 2017.

The study presents estimates, percentages, and annual percent changes for potentially excess deaths by urban-rural classification from heart disease, cancer, unintentional injury, chronic lower respiratory disease, and stroke. Urban-rural categories were identified using the National Center for Health Statistics 2013 urban-rural classification scheme for counties.

The report’s main findings include the following statistics:

• In 2010, 28.7% of deaths from cancer in the most rural counties were potentially preventable, compared with 17.9% in the most urban counties. By 2017, 21.7% of cancer deaths in the most rural counties were potentially preventable, compared with 3.2% in the most urban counties.
• In 2010, 45.1% of deaths from heart disease in the most rural counties were potentially preventable, compared with 33.5% in the most urban counties. By 2017, 44.9% of deaths from heart disease in the most rural counties were potentially preventable, compared with 28.0% in the most urban counties.
• In 2010, 60.9% of deaths from unintentional injury in the most rural counties were potentially preventable, compared with 25.4% in the most urban counties. By 2017, 64.1% of deaths from unintentional injury in the most rural counties were potentially preventable, compared with 47.8% in the most urban counties.
• In 2010, 54.3% of deaths from chronic lower respiratory disease (such as COPD) in the most rural counties were potentially preventable, compared with 23.4% in the most urban counties. By 2017, 57.1% of deaths from chronic lower respiratory disease in the most rural counties were potentially preventable, compared with 13% in the most urban counties.
• In 2010, 41.6% of deaths from stroke in the most rural counties were potentially preventable, compared with 31.7% in most urban areas. By 2017, 37.8% of deaths from stroke in the most rural counties were potentially preventable, compared with 27.4% most urban counties.

“This report demonstrates the value of analyzing potentially excess deaths according to the six 2013 [National Center for Health Statistics] urban-rural county classifications. Reporting trends in potentially excess deaths over an 8-year period highlights differences over time, independent of traditional underlying structural, environmental, and genetic factors,” wrote Macarena C. Garcia, DrPH, and coauthors.

“Because of increasing percentages of potentially excess deaths in recent years for certain causes of death and certain demographic groups, these data can be used, with traditional rate comparisons, by public health practitioners who are involved in planning interventions. Comparing the findings in this report with data from tools such as the CDC Interactive Atlas of Heart Disease and Stroke might help identify the social determinants, health care infrastructures, and public policies that could increase or decrease numbers of deaths in specific nonmetropolitan areas,” they added.

The study authors did not disclose any potential conflicts of interest.
 

klennon@mdedge.com

SOURCE: Garcia MC et al. MMWR Morb Mortal Wkly Rep. 2019 Nov 8: 68(10);1-11.

The most rural counties in the United States had higher percentages of potentially preventable deaths from the five leading causes of mortality, compared with the most urban counties during 2010-2017, according to study published in CDC’s Morbidity and Mortality Weekly Report.

These leading causes of death comprised heart disease, cancer, unintentional injury, chronic lower respiratory disease, and stroke and accounted for approximately 1.7 million deaths or 61% of all deaths in 2017.

The study presents estimates, percentages, and annual percent changes for potentially excess deaths by urban-rural classification from heart disease, cancer, unintentional injury, chronic lower respiratory disease, and stroke. Urban-rural categories were identified using the National Center for Health Statistics 2013 urban-rural classification scheme for counties.

The report’s main findings include the following statistics:

• In 2010, 28.7% of deaths from cancer in the most rural counties were potentially preventable, compared with 17.9% in the most urban counties. By 2017, 21.7% of cancer deaths in the most rural counties were potentially preventable, compared with 3.2% in the most urban counties.
• In 2010, 45.1% of deaths from heart disease in the most rural counties were potentially preventable, compared with 33.5% in the most urban counties. By 2017, 44.9% of deaths from heart disease in the most rural counties were potentially preventable, compared with 28.0% in the most urban counties.
• In 2010, 60.9% of deaths from unintentional injury in the most rural counties were potentially preventable, compared with 25.4% in the most urban counties. By 2017, 64.1% of deaths from unintentional injury in the most rural counties were potentially preventable, compared with 47.8% in the most urban counties.
• In 2010, 54.3% of deaths from chronic lower respiratory disease (such as COPD) in the most rural counties were potentially preventable, compared with 23.4% in the most urban counties. By 2017, 57.1% of deaths from chronic lower respiratory disease in the most rural counties were potentially preventable, compared with 13% in the most urban counties.
• In 2010, 41.6% of deaths from stroke in the most rural counties were potentially preventable, compared with 31.7% in most urban areas. By 2017, 37.8% of deaths from stroke in the most rural counties were potentially preventable, compared with 27.4% most urban counties.

“This report demonstrates the value of analyzing potentially excess deaths according to the six 2013 [National Center for Health Statistics] urban-rural county classifications. Reporting trends in potentially excess deaths over an 8-year period highlights differences over time, independent of traditional underlying structural, environmental, and genetic factors,” wrote Macarena C. Garcia, DrPH, and coauthors.

“Because of increasing percentages of potentially excess deaths in recent years for certain causes of death and certain demographic groups, these data can be used, with traditional rate comparisons, by public health practitioners who are involved in planning interventions. Comparing the findings in this report with data from tools such as the CDC Interactive Atlas of Heart Disease and Stroke might help identify the social determinants, health care infrastructures, and public policies that could increase or decrease numbers of deaths in specific nonmetropolitan areas,” they added.

The study authors did not disclose any potential conflicts of interest.
 

klennon@mdedge.com

SOURCE: Garcia MC et al. MMWR Morb Mortal Wkly Rep. 2019 Nov 8: 68(10);1-11.

The most rural counties in the United States had higher percentages of potentially preventable deaths from the five leading causes of mortality, compared with the most urban counties during 2010-2017, according to study published in CDC’s Morbidity and Mortality Weekly Report.

These leading causes of death comprised heart disease, cancer, unintentional injury, chronic lower respiratory disease, and stroke and accounted for approximately 1.7 million deaths or 61% of all deaths in 2017.

The study presents estimates, percentages, and annual percent changes for potentially excess deaths by urban-rural classification from heart disease, cancer, unintentional injury, chronic lower respiratory disease, and stroke. Urban-rural categories were identified using the National Center for Health Statistics 2013 urban-rural classification scheme for counties.

The report’s main findings include the following statistics:

• In 2010, 28.7% of deaths from cancer in the most rural counties were potentially preventable, compared with 17.9% in the most urban counties. By 2017, 21.7% of cancer deaths in the most rural counties were potentially preventable, compared with 3.2% in the most urban counties.
• In 2010, 45.1% of deaths from heart disease in the most rural counties were potentially preventable, compared with 33.5% in the most urban counties. By 2017, 44.9% of deaths from heart disease in the most rural counties were potentially preventable, compared with 28.0% in the most urban counties.
• In 2010, 60.9% of deaths from unintentional injury in the most rural counties were potentially preventable, compared with 25.4% in the most urban counties. By 2017, 64.1% of deaths from unintentional injury in the most rural counties were potentially preventable, compared with 47.8% in the most urban counties.
• In 2010, 54.3% of deaths from chronic lower respiratory disease (such as COPD) in the most rural counties were potentially preventable, compared with 23.4% in the most urban counties. By 2017, 57.1% of deaths from chronic lower respiratory disease in the most rural counties were potentially preventable, compared with 13% in the most urban counties.
• In 2010, 41.6% of deaths from stroke in the most rural counties were potentially preventable, compared with 31.7% in most urban areas. By 2017, 37.8% of deaths from stroke in the most rural counties were potentially preventable, compared with 27.4% most urban counties.

“This report demonstrates the value of analyzing potentially excess deaths according to the six 2013 [National Center for Health Statistics] urban-rural county classifications. Reporting trends in potentially excess deaths over an 8-year period highlights differences over time, independent of traditional underlying structural, environmental, and genetic factors,” wrote Macarena C. Garcia, DrPH, and coauthors.

“Because of increasing percentages of potentially excess deaths in recent years for certain causes of death and certain demographic groups, these data can be used, with traditional rate comparisons, by public health practitioners who are involved in planning interventions. Comparing the findings in this report with data from tools such as the CDC Interactive Atlas of Heart Disease and Stroke might help identify the social determinants, health care infrastructures, and public policies that could increase or decrease numbers of deaths in specific nonmetropolitan areas,” they added.

The study authors did not disclose any potential conflicts of interest.
 

klennon@mdedge.com

SOURCE: Garcia MC et al. MMWR Morb Mortal Wkly Rep. 2019 Nov 8: 68(10);1-11.

ILLUSTRATIVE CASE

A 60-year-old woman who is generally healthy except for a history of recurrent urinary tract infections presents to the emergency department with fever, hypotension, and altered mental status, meeting criteria for septic shock. During her resuscitation, supplemental oxygen is administered. Standard treatment calls for a minimum SpO₂ (saturation of peripheral oxygen) > 90%. What should your SpO₂ goal be?

Use of supplemental oxygen in the acute care of the critically ill adult is a common practice in pre-hospital, emergency department (ED), and hospitalized settings.^2,3 Despite their prevalence, guidelines about appropriate oxygen concentration and target SpO₂ levels are often conflicting or vague.^3-5

Excessive oxygen supplementation in acute illness may be harmful and cause increased risk of hypercapnic respiratory failure, delayed recognition of clinical deterioration, and oxygen toxicity.^2,6 The perception of oxygen safety persists despite these findings, and it likely contributes to the ongoing practice of liberal oxygen supplementation in the acutely ill adult.^2,7,8

STUDY SUMMARY

Liberal supplemental O₂ linked to increased mortality

The Improving Oxygen Therapy in Acute illness (IOTA) study was a systematic review and meta-analysis of 25 randomized controlled trials (RCTs) that compared liberal vs conservative oxygen strategies for acutely ill adults (N = 16,037; median age = 64 years; range = 28-76 years). Patients with sepsis, critical illness, stroke, trauma, myocardial infarction, or cardiac arrest, and patients who had emergency surgery were included. Studies were excluded if they involved patients who had chronic respiratory illness or psychiatric diseases, were receiving extracorporeal membrane oxygenation, were undergoing elective surgeries, were being treated with hyperbaric oxygen therapy, or were pregnant.

The outcomes studied were mortality (in-hospital, at 30 days, and at the longest ­follow-up) and morbidity (disability measured by the modified Rankin Scale at longest follow-up, risk of hospital-acquired pneumonia, risk of any hospital-acquired infection, and hospital length of stay).

Liberal supplemental oxygen, above an SpO₂ range of 94% to 96%, increased mortality during inpatient stays (relative risk [RR] = 1.21; 95% confidence interval [CI], 1.03-1.43; N = 15,071), at 30 days (RR = 1.14; 95% CI, 1.01-1.29; N = 15,053), and at longest follow-up (RR = 1.10; 95% CI, 1.00-1.20; N = 15,754; median = 90 days; range = 14,365 days). There was no difference in morbidity outcomes between groups.

While it’s difficult to define a specific target SpO₂ range, the number needed to harm when using a liberal oxygen approach (SpO₂ > 96%) resulting in 1 death was 71 (95% CI, 37-1000).

Continue to: WHAT'S NEW

 

 

WHAT’S NEW

High-quality evidence points to the dangers of liberal O₂ therapy

This comprehensive meta-analysis is the first high-quality evidence to suggest that liberal use of oxygen in acutely ill adults above a specific SpO₂ level increases all-cause mortality. Previous small RCTs and observational studies have examined the effect of liberal oxygen only on specific presenting conditions, thus making more generalizable conclusions challenging.^9-12

CAVEATS

Varied definitions of “liberal” and “conservative”

This review included studies with variable ranges of SpO₂ defined as liberal vs conservative supplementation. However, in all of these, SpO₂ above 96% was correlated with unfavorable outcomes.

This meta-analysis is the first high-quality evidence to suggest that liberal use of oxygen in acutely ill adults above a specific SpO₂ level increases all-cause mortality.

The study excluded 2 potentially important patient groups: patients with chronic respiratory diseases and pregnant patients. Increased oxygen supplementation in patients with chronic respiratory diseases in noncritical settings has been shown to be deleterious.^13-15 While this study does not address the issue of oxygen supplementation in acutely ill patients with chronic respiratory disease, use should be considered with caution. The results from this study may not be generalizable to women who are pregnant.

CHALLENGES TO IMPLEMENTATION

Reversing the tide

Liberal oxygen administration continues to be practiced in many health care settings. The main challenges to implementing the conclusions of this study are these pervasive practices.

ACKNOWLEDGMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

ILLUSTRATIVE CASE

A 60-year-old woman who is generally healthy except for a history of recurrent urinary tract infections presents to the emergency department with fever, hypotension, and altered mental status, meeting criteria for septic shock. During her resuscitation, supplemental oxygen is administered. Standard treatment calls for a minimum SpO₂ (saturation of peripheral oxygen) > 90%. What should your SpO₂ goal be?

Use of supplemental oxygen in the acute care of the critically ill adult is a common practice in pre-hospital, emergency department (ED), and hospitalized settings.^2,3 Despite their prevalence, guidelines about appropriate oxygen concentration and target SpO₂ levels are often conflicting or vague.^3-5

Excessive oxygen supplementation in acute illness may be harmful and cause increased risk of hypercapnic respiratory failure, delayed recognition of clinical deterioration, and oxygen toxicity.^2,6 The perception of oxygen safety persists despite these findings, and it likely contributes to the ongoing practice of liberal oxygen supplementation in the acutely ill adult.^2,7,8

STUDY SUMMARY

Liberal supplemental O₂ linked to increased mortality

The Improving Oxygen Therapy in Acute illness (IOTA) study was a systematic review and meta-analysis of 25 randomized controlled trials (RCTs) that compared liberal vs conservative oxygen strategies for acutely ill adults (N = 16,037; median age = 64 years; range = 28-76 years). Patients with sepsis, critical illness, stroke, trauma, myocardial infarction, or cardiac arrest, and patients who had emergency surgery were included. Studies were excluded if they involved patients who had chronic respiratory illness or psychiatric diseases, were receiving extracorporeal membrane oxygenation, were undergoing elective surgeries, were being treated with hyperbaric oxygen therapy, or were pregnant.

The outcomes studied were mortality (in-hospital, at 30 days, and at the longest ­follow-up) and morbidity (disability measured by the modified Rankin Scale at longest follow-up, risk of hospital-acquired pneumonia, risk of any hospital-acquired infection, and hospital length of stay).

Liberal supplemental oxygen, above an SpO₂ range of 94% to 96%, increased mortality during inpatient stays (relative risk [RR] = 1.21; 95% confidence interval [CI], 1.03-1.43; N = 15,071), at 30 days (RR = 1.14; 95% CI, 1.01-1.29; N = 15,053), and at longest follow-up (RR = 1.10; 95% CI, 1.00-1.20; N = 15,754; median = 90 days; range = 14,365 days). There was no difference in morbidity outcomes between groups.

While it’s difficult to define a specific target SpO₂ range, the number needed to harm when using a liberal oxygen approach (SpO₂ > 96%) resulting in 1 death was 71 (95% CI, 37-1000).

Continue to: WHAT'S NEW

 

 

WHAT’S NEW

High-quality evidence points to the dangers of liberal O₂ therapy

This comprehensive meta-analysis is the first high-quality evidence to suggest that liberal use of oxygen in acutely ill adults above a specific SpO₂ level increases all-cause mortality. Previous small RCTs and observational studies have examined the effect of liberal oxygen only on specific presenting conditions, thus making more generalizable conclusions challenging.^9-12

CAVEATS

Varied definitions of “liberal” and “conservative”

This review included studies with variable ranges of SpO₂ defined as liberal vs conservative supplementation. However, in all of these, SpO₂ above 96% was correlated with unfavorable outcomes.

This meta-analysis is the first high-quality evidence to suggest that liberal use of oxygen in acutely ill adults above a specific SpO₂ level increases all-cause mortality.

The study excluded 2 potentially important patient groups: patients with chronic respiratory diseases and pregnant patients. Increased oxygen supplementation in patients with chronic respiratory diseases in noncritical settings has been shown to be deleterious.^13-15 While this study does not address the issue of oxygen supplementation in acutely ill patients with chronic respiratory disease, use should be considered with caution. The results from this study may not be generalizable to women who are pregnant.

CHALLENGES TO IMPLEMENTATION

Reversing the tide

Liberal oxygen administration continues to be practiced in many health care settings. The main challenges to implementing the conclusions of this study are these pervasive practices.

ACKNOWLEDGMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

ILLUSTRATIVE CASE

A 60-year-old woman who is generally healthy except for a history of recurrent urinary tract infections presents to the emergency department with fever, hypotension, and altered mental status, meeting criteria for septic shock. During her resuscitation, supplemental oxygen is administered. Standard treatment calls for a minimum SpO₂ (saturation of peripheral oxygen) > 90%. What should your SpO₂ goal be?

Use of supplemental oxygen in the acute care of the critically ill adult is a common practice in pre-hospital, emergency department (ED), and hospitalized settings.^2,3 Despite their prevalence, guidelines about appropriate oxygen concentration and target SpO₂ levels are often conflicting or vague.^3-5

Excessive oxygen supplementation in acute illness may be harmful and cause increased risk of hypercapnic respiratory failure, delayed recognition of clinical deterioration, and oxygen toxicity.^2,6 The perception of oxygen safety persists despite these findings, and it likely contributes to the ongoing practice of liberal oxygen supplementation in the acutely ill adult.^2,7,8

STUDY SUMMARY

Liberal supplemental O₂ linked to increased mortality

The Improving Oxygen Therapy in Acute illness (IOTA) study was a systematic review and meta-analysis of 25 randomized controlled trials (RCTs) that compared liberal vs conservative oxygen strategies for acutely ill adults (N = 16,037; median age = 64 years; range = 28-76 years). Patients with sepsis, critical illness, stroke, trauma, myocardial infarction, or cardiac arrest, and patients who had emergency surgery were included. Studies were excluded if they involved patients who had chronic respiratory illness or psychiatric diseases, were receiving extracorporeal membrane oxygenation, were undergoing elective surgeries, were being treated with hyperbaric oxygen therapy, or were pregnant.

The outcomes studied were mortality (in-hospital, at 30 days, and at the longest ­follow-up) and morbidity (disability measured by the modified Rankin Scale at longest follow-up, risk of hospital-acquired pneumonia, risk of any hospital-acquired infection, and hospital length of stay).

Liberal supplemental oxygen, above an SpO₂ range of 94% to 96%, increased mortality during inpatient stays (relative risk [RR] = 1.21; 95% confidence interval [CI], 1.03-1.43; N = 15,071), at 30 days (RR = 1.14; 95% CI, 1.01-1.29; N = 15,053), and at longest follow-up (RR = 1.10; 95% CI, 1.00-1.20; N = 15,754; median = 90 days; range = 14,365 days). There was no difference in morbidity outcomes between groups.

While it’s difficult to define a specific target SpO₂ range, the number needed to harm when using a liberal oxygen approach (SpO₂ > 96%) resulting in 1 death was 71 (95% CI, 37-1000).

Continue to: WHAT'S NEW

 

 

WHAT’S NEW

High-quality evidence points to the dangers of liberal O₂ therapy

This comprehensive meta-analysis is the first high-quality evidence to suggest that liberal use of oxygen in acutely ill adults above a specific SpO₂ level increases all-cause mortality. Previous small RCTs and observational studies have examined the effect of liberal oxygen only on specific presenting conditions, thus making more generalizable conclusions challenging.^9-12

CAVEATS

Varied definitions of “liberal” and “conservative”

This review included studies with variable ranges of SpO₂ defined as liberal vs conservative supplementation. However, in all of these, SpO₂ above 96% was correlated with unfavorable outcomes.

This meta-analysis is the first high-quality evidence to suggest that liberal use of oxygen in acutely ill adults above a specific SpO₂ level increases all-cause mortality.

The study excluded 2 potentially important patient groups: patients with chronic respiratory diseases and pregnant patients. Increased oxygen supplementation in patients with chronic respiratory diseases in noncritical settings has been shown to be deleterious.^13-15 While this study does not address the issue of oxygen supplementation in acutely ill patients with chronic respiratory disease, use should be considered with caution. The results from this study may not be generalizable to women who are pregnant.

CHALLENGES TO IMPLEMENTATION

Reversing the tide

Liberal oxygen administration continues to be practiced in many health care settings. The main challenges to implementing the conclusions of this study are these pervasive practices.

ACKNOWLEDGMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

Infection with the measles virus appears to reduce immunity to other pathogens, according to a paper published in Science.

CDC/Molly Kurnit, M.P.H.

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

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

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

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

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

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

The study did find increases in measles virus–specific antigens in children both after measles infection and MMR vaccination. However the authors did not detect any changes in total IgG, IgA, or IgM levels.

“These results suggest that, rather than a simple loss of total IgG, there is a restructuring of the antibody repertoire after measles,” Dr. Mina and associates wrote.

They also noted that controls who received the MMR vaccine showed a marked increase in overall antibody repertoire.

In a separate investigation reported in Science Immunology, Velislava N. Petrova, PhD, of the Wellcome Sanger Institute in Cambridge, England, and coauthors investigated genetic changes in 26 unvaccinated children from the Netherlands who previously had measles to determine if B-cell impairment can lead to measles-associated immunosuppression. Their antibody genes were sequenced before any symptoms of measles developed and roughly 40 days after rash. Two control groups also were sequenced accordingly: vaccinated adults and three unvaccinated children from the same community who were not infected with measles.

Naive B cells from individuals in the vaccinated and uninfected control groups showed high correlation of immunoglobulin heavy chain (IgVH-J) gene frequencies across time periods (R2 = 0.96 and 0.92, respectively) but no significant differences in gene expression (P greater than .05). At the same time, although B-cell frequencies in measles patients recovered to levels before infection, they had significant changes in IgVH-J gene frequencies (P = .01) and decreased correlation in gene expression (R2 = 0.78).

In addition, individuals in the control groups had “a stable genetic composition of B memory cells” but no significant changes in the third complementarity-determining region (CDR3) lengths or mutational frequency of IgVH-J genes (P greater than .05). B memory cells in measles patients, however, showed increases in mutational frequency (P = .0008) and a reduction in CDR3 length (P = .017) of IgVH genes, Dr. Petrova and associates reported.

The study by Mina et al. was supported by grants from various U.S., European, and Finnish foundations and national organizations. Some of the coauthors had relationships with biotechnology and pharmaceutical companies, and three reported a patent holding related to technology used in the study. The study by Petrova et al. was funded by grants to the investigators from various Indonesian and German organizations and the Wellcome Trust. The authors reported no conflicts of interest.
 

SOURCES: Mina M et al. Science. 2019 Nov 1;366:599-606; Petrova VN et al. Sci Immunol. 2019 Nov 1. doi: 10.1126/sciimmunol.aay6125.

Infection with the measles virus appears to reduce immunity to other pathogens, according to a paper published in Science.

CDC/Molly Kurnit, M.P.H.

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

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

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

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

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

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

The study did find increases in measles virus–specific antigens in children both after measles infection and MMR vaccination. However the authors did not detect any changes in total IgG, IgA, or IgM levels.

“These results suggest that, rather than a simple loss of total IgG, there is a restructuring of the antibody repertoire after measles,” Dr. Mina and associates wrote.

They also noted that controls who received the MMR vaccine showed a marked increase in overall antibody repertoire.

In a separate investigation reported in Science Immunology, Velislava N. Petrova, PhD, of the Wellcome Sanger Institute in Cambridge, England, and coauthors investigated genetic changes in 26 unvaccinated children from the Netherlands who previously had measles to determine if B-cell impairment can lead to measles-associated immunosuppression. Their antibody genes were sequenced before any symptoms of measles developed and roughly 40 days after rash. Two control groups also were sequenced accordingly: vaccinated adults and three unvaccinated children from the same community who were not infected with measles.

Naive B cells from individuals in the vaccinated and uninfected control groups showed high correlation of immunoglobulin heavy chain (IgVH-J) gene frequencies across time periods (R2 = 0.96 and 0.92, respectively) but no significant differences in gene expression (P greater than .05). At the same time, although B-cell frequencies in measles patients recovered to levels before infection, they had significant changes in IgVH-J gene frequencies (P = .01) and decreased correlation in gene expression (R2 = 0.78).

In addition, individuals in the control groups had “a stable genetic composition of B memory cells” but no significant changes in the third complementarity-determining region (CDR3) lengths or mutational frequency of IgVH-J genes (P greater than .05). B memory cells in measles patients, however, showed increases in mutational frequency (P = .0008) and a reduction in CDR3 length (P = .017) of IgVH genes, Dr. Petrova and associates reported.

The study by Mina et al. was supported by grants from various U.S., European, and Finnish foundations and national organizations. Some of the coauthors had relationships with biotechnology and pharmaceutical companies, and three reported a patent holding related to technology used in the study. The study by Petrova et al. was funded by grants to the investigators from various Indonesian and German organizations and the Wellcome Trust. The authors reported no conflicts of interest.
 

SOURCES: Mina M et al. Science. 2019 Nov 1;366:599-606; Petrova VN et al. Sci Immunol. 2019 Nov 1. doi: 10.1126/sciimmunol.aay6125.

Infection with the measles virus appears to reduce immunity to other pathogens, according to a paper published in Science.

CDC/Molly Kurnit, M.P.H.

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

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

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

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

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

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

The study did find increases in measles virus–specific antigens in children both after measles infection and MMR vaccination. However the authors did not detect any changes in total IgG, IgA, or IgM levels.

“These results suggest that, rather than a simple loss of total IgG, there is a restructuring of the antibody repertoire after measles,” Dr. Mina and associates wrote.

They also noted that controls who received the MMR vaccine showed a marked increase in overall antibody repertoire.

In a separate investigation reported in Science Immunology, Velislava N. Petrova, PhD, of the Wellcome Sanger Institute in Cambridge, England, and coauthors investigated genetic changes in 26 unvaccinated children from the Netherlands who previously had measles to determine if B-cell impairment can lead to measles-associated immunosuppression. Their antibody genes were sequenced before any symptoms of measles developed and roughly 40 days after rash. Two control groups also were sequenced accordingly: vaccinated adults and three unvaccinated children from the same community who were not infected with measles.

Naive B cells from individuals in the vaccinated and uninfected control groups showed high correlation of immunoglobulin heavy chain (IgVH-J) gene frequencies across time periods (R2 = 0.96 and 0.92, respectively) but no significant differences in gene expression (P greater than .05). At the same time, although B-cell frequencies in measles patients recovered to levels before infection, they had significant changes in IgVH-J gene frequencies (P = .01) and decreased correlation in gene expression (R2 = 0.78).

In addition, individuals in the control groups had “a stable genetic composition of B memory cells” but no significant changes in the third complementarity-determining region (CDR3) lengths or mutational frequency of IgVH-J genes (P greater than .05). B memory cells in measles patients, however, showed increases in mutational frequency (P = .0008) and a reduction in CDR3 length (P = .017) of IgVH genes, Dr. Petrova and associates reported.

The study by Mina et al. was supported by grants from various U.S., European, and Finnish foundations and national organizations. Some of the coauthors had relationships with biotechnology and pharmaceutical companies, and three reported a patent holding related to technology used in the study. The study by Petrova et al. was funded by grants to the investigators from various Indonesian and German organizations and the Wellcome Trust. The authors reported no conflicts of interest.
 

SOURCES: Mina M et al. Science. 2019 Nov 1;366:599-606; Petrova VN et al. Sci Immunol. 2019 Nov 1. doi: 10.1126/sciimmunol.aay6125.

References

1. Lewis N, McCaffrey K, Sage K, et al. E-cigarette use, or vaping, practices and characteristics among persons with associated lung injury — Utah, April–October 2019. MMWR Morb Mortal Wkly Rep. 2019;68. https://www.cdc.gov/mmwr/volumes/68/wr/mm6842e1.htm?s_cid=mm6842e1_w. Published October 22, 2019. Accessed October 24, 2019.
2. Siegal DA, Jatlaoui TC, Koumans EH, et al. Update: interim guidance for health care providers evaluating and caring for patients with suspected e-cigarette, or vaping, product use associated lung injury – United States, October 2019. MMWR Morb Mortal Wkly Rep. 2019;68:919-927.
3. Centers for Disease Control and Prevention. Outbreak of lung injury associated with e-cigarette use, or vaping. https://www.cdc.gov/tobacco/basic_information/e-cigarettes/severe-lung-disease.html. Updated October 17, 2019. Accessed October 24, 2019.

References

1. Lewis N, McCaffrey K, Sage K, et al. E-cigarette use, or vaping, practices and characteristics among persons with associated lung injury — Utah, April–October 2019. MMWR Morb Mortal Wkly Rep. 2019;68. https://www.cdc.gov/mmwr/volumes/68/wr/mm6842e1.htm?s_cid=mm6842e1_w. Published October 22, 2019. Accessed October 24, 2019.
2. Siegal DA, Jatlaoui TC, Koumans EH, et al. Update: interim guidance for health care providers evaluating and caring for patients with suspected e-cigarette, or vaping, product use associated lung injury – United States, October 2019. MMWR Morb Mortal Wkly Rep. 2019;68:919-927.
3. Centers for Disease Control and Prevention. Outbreak of lung injury associated with e-cigarette use, or vaping. https://www.cdc.gov/tobacco/basic_information/e-cigarettes/severe-lung-disease.html. Updated October 17, 2019. Accessed October 24, 2019.

References

1. Lewis N, McCaffrey K, Sage K, et al. E-cigarette use, or vaping, practices and characteristics among persons with associated lung injury — Utah, April–October 2019. MMWR Morb Mortal Wkly Rep. 2019;68. https://www.cdc.gov/mmwr/volumes/68/wr/mm6842e1.htm?s_cid=mm6842e1_w. Published October 22, 2019. Accessed October 24, 2019.
2. Siegal DA, Jatlaoui TC, Koumans EH, et al. Update: interim guidance for health care providers evaluating and caring for patients with suspected e-cigarette, or vaping, product use associated lung injury – United States, October 2019. MMWR Morb Mortal Wkly Rep. 2019;68:919-927.
3. Centers for Disease Control and Prevention. Outbreak of lung injury associated with e-cigarette use, or vaping. https://www.cdc.gov/tobacco/basic_information/e-cigarettes/severe-lung-disease.html. Updated October 17, 2019. Accessed October 24, 2019.

Mint is the most popular flavor among school students who use Juul e-cigarettes, according to data from the 2019 Monitoring the Future study.

Almost half (47.1%) of the 12th graders who had used Juul e-cigarettes in the past 30 days reported that mint was the flavor they most often used, compared with 23.8% for mango and 8.6% for fruit, which is a combination of flavors, Adam M. Leventhal, PhD, of the University of Southern California, Los Angeles, and associates wrote in JAMA.

Mint was also the flavor most often used by 10th graders (43.5%), with mango again second at 27.3%, and fruit third at 10.8%. Eighth-grade students switched mango (33.5%) and mint (29.2%) but had fruit third again at 16.0%, the investigators reported, based on data for 1,739 respondents to the Monitoring the Future survey who had used a vaping product within the past 30 days.

Juul has suspended sales of four – mango, fruit, creme, and cucumber – of its original eight flavors, Dr. Leventhal and associates noted, and e-cigarette flavors other than tobacco, menthol, and mint have been prohibited by some local municipalities.

“The current findings raise uncertainty whether regulations or sales suspensions that exempt mint flavors are optimal strategies for reducing youth e-cigarette use,” they wrote.

As this article was being written, the Wall Street Journal had just reported that the Food and Drug Administration will ban mint and all other e-cigarette flavors except tobacco and menthol.

rfranki@mdedge.com

SOURCE: Leventhal AM et al. JAMA. 2019 Nov 5. doi: 10.1001/jama.2019.17968.

Mint is the most popular flavor among school students who use Juul e-cigarettes, according to data from the 2019 Monitoring the Future study.

Almost half (47.1%) of the 12th graders who had used Juul e-cigarettes in the past 30 days reported that mint was the flavor they most often used, compared with 23.8% for mango and 8.6% for fruit, which is a combination of flavors, Adam M. Leventhal, PhD, of the University of Southern California, Los Angeles, and associates wrote in JAMA.

Mint was also the flavor most often used by 10th graders (43.5%), with mango again second at 27.3%, and fruit third at 10.8%. Eighth-grade students switched mango (33.5%) and mint (29.2%) but had fruit third again at 16.0%, the investigators reported, based on data for 1,739 respondents to the Monitoring the Future survey who had used a vaping product within the past 30 days.

Juul has suspended sales of four – mango, fruit, creme, and cucumber – of its original eight flavors, Dr. Leventhal and associates noted, and e-cigarette flavors other than tobacco, menthol, and mint have been prohibited by some local municipalities.

“The current findings raise uncertainty whether regulations or sales suspensions that exempt mint flavors are optimal strategies for reducing youth e-cigarette use,” they wrote.

As this article was being written, the Wall Street Journal had just reported that the Food and Drug Administration will ban mint and all other e-cigarette flavors except tobacco and menthol.

rfranki@mdedge.com

SOURCE: Leventhal AM et al. JAMA. 2019 Nov 5. doi: 10.1001/jama.2019.17968.

Mint is the most popular flavor among school students who use Juul e-cigarettes, according to data from the 2019 Monitoring the Future study.

Almost half (47.1%) of the 12th graders who had used Juul e-cigarettes in the past 30 days reported that mint was the flavor they most often used, compared with 23.8% for mango and 8.6% for fruit, which is a combination of flavors, Adam M. Leventhal, PhD, of the University of Southern California, Los Angeles, and associates wrote in JAMA.

Mint was also the flavor most often used by 10th graders (43.5%), with mango again second at 27.3%, and fruit third at 10.8%. Eighth-grade students switched mango (33.5%) and mint (29.2%) but had fruit third again at 16.0%, the investigators reported, based on data for 1,739 respondents to the Monitoring the Future survey who had used a vaping product within the past 30 days.

Juul has suspended sales of four – mango, fruit, creme, and cucumber – of its original eight flavors, Dr. Leventhal and associates noted, and e-cigarette flavors other than tobacco, menthol, and mint have been prohibited by some local municipalities.

“The current findings raise uncertainty whether regulations or sales suspensions that exempt mint flavors are optimal strategies for reducing youth e-cigarette use,” they wrote.

As this article was being written, the Wall Street Journal had just reported that the Food and Drug Administration will ban mint and all other e-cigarette flavors except tobacco and menthol.

rfranki@mdedge.com

SOURCE: Leventhal AM et al. JAMA. 2019 Nov 5. doi: 10.1001/jama.2019.17968.

NEW ORLEANS – Robotic bronchoscopy with shape-sensing technology performed more effectively in comparison with standard techniques for localizing and puncturing nodules in the periphery of the lung.

A prospective study in a cadaver model showed that robotic bronchoscopy targeted nodules more effectively than electromagnetic navigation or an ultrathin bronchoscope with radial endobronchial ultrasound (UTB-rEBUS).

“This is really the first study to randomize, blind, and compare procedural outcomes between existing technologies in advanced bronchoscopy,” said Lonny Yarmus, DO, of Johns Hopkins Medicine in Baltimore.

Dr. Yarmus described this study, PRECISION-1, at the annual meeting of the American Society of Chest Physicians. The study was designed to compare the following:

• UTB-rEBUS (3.0 mm outer diameter and 1.7 mm working channel).
• Electromagnetic navigation bronchoscopy (Superdimension version 7.1).
• Robotic bronchoscopy (3.5 mm outer diameter and 2.0-mm working channel).

With all methods, a 21-gauge needle was used. For each nodule, UTB-rEBUS was done first to eliminate potential localization bias. The subsequent order of electromagnetic navigation and robotic bronchoscopy was determined based on block randomization.

Eight bronchoscopists performed a total of 60 procedures using each of the methods to target 20 nodules implanted in cadavers. The nodules were distributed across all lobes, 80% were in the outer third of the lung, and 50% had a positive bronchus sign on computed tomography (CT). The mean nodule size was 16.5 plus or minus 1.5 mm.

The study’s primary endpoint was the ability to localize and puncture target nodules within a maximum of three attempts per method. This includes center, peripheral, and distal punctures of nodules. Cone-beam CT was used to confirm that needles punctured the target lesions. The bronchoscopists were blinded to cone-beam CT results, and a blinded, independent investigator assessed whether nodule punctures were successful. The primary endpoint was met in 25% of UTB-rEBUS procedures, 45% of electromagnetic navigation procedures, and 80% of robotic bronchoscopy procedures.

The study’s secondary endpoint was localization success, which was defined as navigation to within needle biopsy distance of the nodule. This includes center, peripheral, and distal punctures of nodules, as well as adjacent punctures (touching the nodule but not within it). The secondary endpoint was met in 35% of UTB-rEBUS procedures, 65% of electromagnetic navigation procedures, and 90% of robotic bronchoscopy procedures.

The researchers also assessed successful navigation, which was defined as the provider localizing with software or radial ultrasound and passing the needle to make a biopsy attempt. Navigation was successful in 65% of UTB-rEBUS procedures, 85% of electromagnetic navigation procedures, and 100% of robotic bronchoscopy procedures.

“Utilization of robotic bronchoscopy with shape-sensing technology can significantly increase the ability to localize and puncture lesions when compared with standard existing technologies,” Dr. Yarmus said in closing.

He did note that this research was done in a cadaveric model, so “prospective, randomized, and comparative in vivo studies are needed.”

This study was funded by the Association of Interventional Pulmonary Program Directors. Dr. Yarmus disclosed government and societal funding and relationships with Boston Scientific, Veran, Medtronic, Intuitive, Auris, Erbe, Olympus, BD, Rocket, Ambu, Inspire Medical, and AstraZeneca.

jensmith@mdedge.com

SOURCE: Yarmus L et al. CHEST 2019. Abstract, doi: 10.1016/j.chest.2019.08.311.

NEW ORLEANS – Robotic bronchoscopy with shape-sensing technology performed more effectively in comparison with standard techniques for localizing and puncturing nodules in the periphery of the lung.

A prospective study in a cadaver model showed that robotic bronchoscopy targeted nodules more effectively than electromagnetic navigation or an ultrathin bronchoscope with radial endobronchial ultrasound (UTB-rEBUS).

“This is really the first study to randomize, blind, and compare procedural outcomes between existing technologies in advanced bronchoscopy,” said Lonny Yarmus, DO, of Johns Hopkins Medicine in Baltimore.

Dr. Yarmus described this study, PRECISION-1, at the annual meeting of the American Society of Chest Physicians. The study was designed to compare the following:

• UTB-rEBUS (3.0 mm outer diameter and 1.7 mm working channel).
• Electromagnetic navigation bronchoscopy (Superdimension version 7.1).
• Robotic bronchoscopy (3.5 mm outer diameter and 2.0-mm working channel).

With all methods, a 21-gauge needle was used. For each nodule, UTB-rEBUS was done first to eliminate potential localization bias. The subsequent order of electromagnetic navigation and robotic bronchoscopy was determined based on block randomization.

Eight bronchoscopists performed a total of 60 procedures using each of the methods to target 20 nodules implanted in cadavers. The nodules were distributed across all lobes, 80% were in the outer third of the lung, and 50% had a positive bronchus sign on computed tomography (CT). The mean nodule size was 16.5 plus or minus 1.5 mm.

The study’s primary endpoint was the ability to localize and puncture target nodules within a maximum of three attempts per method. This includes center, peripheral, and distal punctures of nodules. Cone-beam CT was used to confirm that needles punctured the target lesions. The bronchoscopists were blinded to cone-beam CT results, and a blinded, independent investigator assessed whether nodule punctures were successful. The primary endpoint was met in 25% of UTB-rEBUS procedures, 45% of electromagnetic navigation procedures, and 80% of robotic bronchoscopy procedures.

The study’s secondary endpoint was localization success, which was defined as navigation to within needle biopsy distance of the nodule. This includes center, peripheral, and distal punctures of nodules, as well as adjacent punctures (touching the nodule but not within it). The secondary endpoint was met in 35% of UTB-rEBUS procedures, 65% of electromagnetic navigation procedures, and 90% of robotic bronchoscopy procedures.

The researchers also assessed successful navigation, which was defined as the provider localizing with software or radial ultrasound and passing the needle to make a biopsy attempt. Navigation was successful in 65% of UTB-rEBUS procedures, 85% of electromagnetic navigation procedures, and 100% of robotic bronchoscopy procedures.

“Utilization of robotic bronchoscopy with shape-sensing technology can significantly increase the ability to localize and puncture lesions when compared with standard existing technologies,” Dr. Yarmus said in closing.

He did note that this research was done in a cadaveric model, so “prospective, randomized, and comparative in vivo studies are needed.”

This study was funded by the Association of Interventional Pulmonary Program Directors. Dr. Yarmus disclosed government and societal funding and relationships with Boston Scientific, Veran, Medtronic, Intuitive, Auris, Erbe, Olympus, BD, Rocket, Ambu, Inspire Medical, and AstraZeneca.

jensmith@mdedge.com

SOURCE: Yarmus L et al. CHEST 2019. Abstract, doi: 10.1016/j.chest.2019.08.311.

NEW ORLEANS – Robotic bronchoscopy with shape-sensing technology performed more effectively in comparison with standard techniques for localizing and puncturing nodules in the periphery of the lung.

A prospective study in a cadaver model showed that robotic bronchoscopy targeted nodules more effectively than electromagnetic navigation or an ultrathin bronchoscope with radial endobronchial ultrasound (UTB-rEBUS).

“This is really the first study to randomize, blind, and compare procedural outcomes between existing technologies in advanced bronchoscopy,” said Lonny Yarmus, DO, of Johns Hopkins Medicine in Baltimore.

Dr. Yarmus described this study, PRECISION-1, at the annual meeting of the American Society of Chest Physicians. The study was designed to compare the following:

• UTB-rEBUS (3.0 mm outer diameter and 1.7 mm working channel).
• Electromagnetic navigation bronchoscopy (Superdimension version 7.1).
• Robotic bronchoscopy (3.5 mm outer diameter and 2.0-mm working channel).

With all methods, a 21-gauge needle was used. For each nodule, UTB-rEBUS was done first to eliminate potential localization bias. The subsequent order of electromagnetic navigation and robotic bronchoscopy was determined based on block randomization.

Eight bronchoscopists performed a total of 60 procedures using each of the methods to target 20 nodules implanted in cadavers. The nodules were distributed across all lobes, 80% were in the outer third of the lung, and 50% had a positive bronchus sign on computed tomography (CT). The mean nodule size was 16.5 plus or minus 1.5 mm.

The study’s primary endpoint was the ability to localize and puncture target nodules within a maximum of three attempts per method. This includes center, peripheral, and distal punctures of nodules. Cone-beam CT was used to confirm that needles punctured the target lesions. The bronchoscopists were blinded to cone-beam CT results, and a blinded, independent investigator assessed whether nodule punctures were successful. The primary endpoint was met in 25% of UTB-rEBUS procedures, 45% of electromagnetic navigation procedures, and 80% of robotic bronchoscopy procedures.

The study’s secondary endpoint was localization success, which was defined as navigation to within needle biopsy distance of the nodule. This includes center, peripheral, and distal punctures of nodules, as well as adjacent punctures (touching the nodule but not within it). The secondary endpoint was met in 35% of UTB-rEBUS procedures, 65% of electromagnetic navigation procedures, and 90% of robotic bronchoscopy procedures.

The researchers also assessed successful navigation, which was defined as the provider localizing with software or radial ultrasound and passing the needle to make a biopsy attempt. Navigation was successful in 65% of UTB-rEBUS procedures, 85% of electromagnetic navigation procedures, and 100% of robotic bronchoscopy procedures.

“Utilization of robotic bronchoscopy with shape-sensing technology can significantly increase the ability to localize and puncture lesions when compared with standard existing technologies,” Dr. Yarmus said in closing.

He did note that this research was done in a cadaveric model, so “prospective, randomized, and comparative in vivo studies are needed.”

This study was funded by the Association of Interventional Pulmonary Program Directors. Dr. Yarmus disclosed government and societal funding and relationships with Boston Scientific, Veran, Medtronic, Intuitive, Auris, Erbe, Olympus, BD, Rocket, Ambu, Inspire Medical, and AstraZeneca.

jensmith@mdedge.com

SOURCE: Yarmus L et al. CHEST 2019. Abstract, doi: 10.1016/j.chest.2019.08.311.

NEW ORLEANS – In patients with interstitial lung diseases at risk of pulmonary hypertension, inhaled nitric oxide produced meaningful improvements in activity that have been maintained over the long term, an investigator reported here.

Inhaled nitric oxide, which improved moderate to vigorous physical activity by 34% versus placebo in an 8-week controlled trial, has demonstrated long-term maintenance of activity parameters in open-label extension data, presented at the annual meeting of the American College of Chest Physicians.

SOURCE: Nathan SD et al. CHEST 2019. Abstract, doi: 10.1016/j.chest.2019.08.308.

NEW ORLEANS – In patients with interstitial lung diseases at risk of pulmonary hypertension, inhaled nitric oxide produced meaningful improvements in activity that have been maintained over the long term, an investigator reported here.

Inhaled nitric oxide, which improved moderate to vigorous physical activity by 34% versus placebo in an 8-week controlled trial, has demonstrated long-term maintenance of activity parameters in open-label extension data, presented at the annual meeting of the American College of Chest Physicians.

SOURCE: Nathan SD et al. CHEST 2019. Abstract, doi: 10.1016/j.chest.2019.08.308.

NEW ORLEANS – In patients with interstitial lung diseases at risk of pulmonary hypertension, inhaled nitric oxide produced meaningful improvements in activity that have been maintained over the long term, an investigator reported here.

Inhaled nitric oxide, which improved moderate to vigorous physical activity by 34% versus placebo in an 8-week controlled trial, has demonstrated long-term maintenance of activity parameters in open-label extension data, presented at the annual meeting of the American College of Chest Physicians.

SOURCE: Nathan SD et al. CHEST 2019. Abstract, doi: 10.1016/j.chest.2019.08.308.

NEW ORLEANS – A novel electromagnetic navigation bronchoscopy system can improve targeting of peripheral lung lesions, according to an industry-sponsored, prospective study.

The system, which incorporates fluoroscopic navigation, increased the percentage of cases in which the target overlapped with the lesion, from 60% to 83%. The percentage of cases without any target overlap decreased from 32% to 5%.

“Tomosynthesis-based fluoroscopic navigation … improves the three-dimensional convergence between the virtual target and the actual target,” said Krish Bhadra, MD, of CHI Memorial Medical Group in Chattanooga, Tenn.

Dr. Bhadra presented results with this system at the annual meeting of the American College of Chest Physicians.

He and his colleagues conducted a study of Medtronic’s superDimension navigation system (version 7.2), which provides real-time imaging with three-dimensional fluoroscopy. The system has a “local registration” feature, which uses fluoroscopy and an algorithm to update the virtual target location during the procedure. This allows the user to reposition the catheter based on the location of the lesion.

The researchers tested the system in 50 patients from two centers (NCT03585959). Patients’ lesions had to be larger than 10 mm, not visible endobronchially, and not reachable by convex endobronchial ultrasound. Lesions within 10 mm of the diaphragm were excluded.

The median lesion size was 17.0 mm, 61.2% were smaller than 20 mm, 65.3% were in the upper lobe, and 53.1% had a bronchus sign present. The median distance from lesion to pleura was 5.9 mm.

Dr. Bhadra said the system performed as designed in all cases, and the protocol-defined technical success rate was 95.9% (47/49). Local registration was attempted in 49 patients and was successful in 47 patients (95.9%). In the unsuccessful cases, local registration was not completed based on the system design because the correction distance was greater than 3.0 cm.

The study’s primary endpoint was three-dimensional overlap of the virtual target and the actual lesion, as confirmed by cone-beam computed tomography. Success was defined as greater than 0% overlap after location correction. Target overlap was achieved in 59.6% (28/47) of cases before local registration and 83.0% (39/47) of cases after.

There were six cases in which local registration was successful, but these subjects weren’t evaluable because of failed procedure recording. When those subjects were excluded, target overlap was achieved in 95.1% (39/41) of cases after local registration.

The median percent overlap between the virtual target and the actual lesion was 11.4% before local registration and 32.8% after. The percentage of cases without any target overlap decreased from 31.7% (13/41) before local registration to 4.9% (2/41) after.

Focusing on the two cases without target overlap, Dr. Bhadra noted that he was able to get a biopsy that proved a malignancy in one of those patients. In the other patient, Dr. Bhadra was able to identify features of organizing pneumonia.

“Even though we did not have overlap, we must have been close enough that we were able to get malignant tissue in one [patient] and features of organizing pneumonia in a patient who’s got no history of organizing pneumonia,” Dr. Bhadra said.

He and his colleagues did not evaluate diagnostic yield in this study, but they did assess complications up to 7 days after the procedure.

The team reported one case of pneumothorax, but the patient didn’t require a chest tube. Additionally, there were two cases of bronchopulmonary hemorrhage, but the patients didn’t require any interventions.

This study was sponsored by Medtronic. Dr. Bhadra disclosed relationships with Medtronic, Boston Scientific, BodyVision, Auris Surgical Robotics, Intuitive Surgical, Veracyte, Biodesix, Merit Medical Endotek, and Johnson & Johnson.

jensmith@mdedge.com

SOURCE: Bhadra K et al. CHEST 2019. doi: 10.1016/j.chest.2019.08.314.

NEW ORLEANS – A novel electromagnetic navigation bronchoscopy system can improve targeting of peripheral lung lesions, according to an industry-sponsored, prospective study.

The system, which incorporates fluoroscopic navigation, increased the percentage of cases in which the target overlapped with the lesion, from 60% to 83%. The percentage of cases without any target overlap decreased from 32% to 5%.

“Tomosynthesis-based fluoroscopic navigation … improves the three-dimensional convergence between the virtual target and the actual target,” said Krish Bhadra, MD, of CHI Memorial Medical Group in Chattanooga, Tenn.

Dr. Bhadra presented results with this system at the annual meeting of the American College of Chest Physicians.

He and his colleagues conducted a study of Medtronic’s superDimension navigation system (version 7.2), which provides real-time imaging with three-dimensional fluoroscopy. The system has a “local registration” feature, which uses fluoroscopy and an algorithm to update the virtual target location during the procedure. This allows the user to reposition the catheter based on the location of the lesion.

The researchers tested the system in 50 patients from two centers (NCT03585959). Patients’ lesions had to be larger than 10 mm, not visible endobronchially, and not reachable by convex endobronchial ultrasound. Lesions within 10 mm of the diaphragm were excluded.

The median lesion size was 17.0 mm, 61.2% were smaller than 20 mm, 65.3% were in the upper lobe, and 53.1% had a bronchus sign present. The median distance from lesion to pleura was 5.9 mm.

Dr. Bhadra said the system performed as designed in all cases, and the protocol-defined technical success rate was 95.9% (47/49). Local registration was attempted in 49 patients and was successful in 47 patients (95.9%). In the unsuccessful cases, local registration was not completed based on the system design because the correction distance was greater than 3.0 cm.

The study’s primary endpoint was three-dimensional overlap of the virtual target and the actual lesion, as confirmed by cone-beam computed tomography. Success was defined as greater than 0% overlap after location correction. Target overlap was achieved in 59.6% (28/47) of cases before local registration and 83.0% (39/47) of cases after.

There were six cases in which local registration was successful, but these subjects weren’t evaluable because of failed procedure recording. When those subjects were excluded, target overlap was achieved in 95.1% (39/41) of cases after local registration.

The median percent overlap between the virtual target and the actual lesion was 11.4% before local registration and 32.8% after. The percentage of cases without any target overlap decreased from 31.7% (13/41) before local registration to 4.9% (2/41) after.

Focusing on the two cases without target overlap, Dr. Bhadra noted that he was able to get a biopsy that proved a malignancy in one of those patients. In the other patient, Dr. Bhadra was able to identify features of organizing pneumonia.

“Even though we did not have overlap, we must have been close enough that we were able to get malignant tissue in one [patient] and features of organizing pneumonia in a patient who’s got no history of organizing pneumonia,” Dr. Bhadra said.

He and his colleagues did not evaluate diagnostic yield in this study, but they did assess complications up to 7 days after the procedure.

The team reported one case of pneumothorax, but the patient didn’t require a chest tube. Additionally, there were two cases of bronchopulmonary hemorrhage, but the patients didn’t require any interventions.

This study was sponsored by Medtronic. Dr. Bhadra disclosed relationships with Medtronic, Boston Scientific, BodyVision, Auris Surgical Robotics, Intuitive Surgical, Veracyte, Biodesix, Merit Medical Endotek, and Johnson & Johnson.

jensmith@mdedge.com

SOURCE: Bhadra K et al. CHEST 2019. doi: 10.1016/j.chest.2019.08.314.

NEW ORLEANS – A novel electromagnetic navigation bronchoscopy system can improve targeting of peripheral lung lesions, according to an industry-sponsored, prospective study.

The system, which incorporates fluoroscopic navigation, increased the percentage of cases in which the target overlapped with the lesion, from 60% to 83%. The percentage of cases without any target overlap decreased from 32% to 5%.

“Tomosynthesis-based fluoroscopic navigation … improves the three-dimensional convergence between the virtual target and the actual target,” said Krish Bhadra, MD, of CHI Memorial Medical Group in Chattanooga, Tenn.

Dr. Bhadra presented results with this system at the annual meeting of the American College of Chest Physicians.

He and his colleagues conducted a study of Medtronic’s superDimension navigation system (version 7.2), which provides real-time imaging with three-dimensional fluoroscopy. The system has a “local registration” feature, which uses fluoroscopy and an algorithm to update the virtual target location during the procedure. This allows the user to reposition the catheter based on the location of the lesion.

The researchers tested the system in 50 patients from two centers (NCT03585959). Patients’ lesions had to be larger than 10 mm, not visible endobronchially, and not reachable by convex endobronchial ultrasound. Lesions within 10 mm of the diaphragm were excluded.

The median lesion size was 17.0 mm, 61.2% were smaller than 20 mm, 65.3% were in the upper lobe, and 53.1% had a bronchus sign present. The median distance from lesion to pleura was 5.9 mm.

Dr. Bhadra said the system performed as designed in all cases, and the protocol-defined technical success rate was 95.9% (47/49). Local registration was attempted in 49 patients and was successful in 47 patients (95.9%). In the unsuccessful cases, local registration was not completed based on the system design because the correction distance was greater than 3.0 cm.

The study’s primary endpoint was three-dimensional overlap of the virtual target and the actual lesion, as confirmed by cone-beam computed tomography. Success was defined as greater than 0% overlap after location correction. Target overlap was achieved in 59.6% (28/47) of cases before local registration and 83.0% (39/47) of cases after.

There were six cases in which local registration was successful, but these subjects weren’t evaluable because of failed procedure recording. When those subjects were excluded, target overlap was achieved in 95.1% (39/41) of cases after local registration.

The median percent overlap between the virtual target and the actual lesion was 11.4% before local registration and 32.8% after. The percentage of cases without any target overlap decreased from 31.7% (13/41) before local registration to 4.9% (2/41) after.

Focusing on the two cases without target overlap, Dr. Bhadra noted that he was able to get a biopsy that proved a malignancy in one of those patients. In the other patient, Dr. Bhadra was able to identify features of organizing pneumonia.

“Even though we did not have overlap, we must have been close enough that we were able to get malignant tissue in one [patient] and features of organizing pneumonia in a patient who’s got no history of organizing pneumonia,” Dr. Bhadra said.

He and his colleagues did not evaluate diagnostic yield in this study, but they did assess complications up to 7 days after the procedure.

The team reported one case of pneumothorax, but the patient didn’t require a chest tube. Additionally, there were two cases of bronchopulmonary hemorrhage, but the patients didn’t require any interventions.

This study was sponsored by Medtronic. Dr. Bhadra disclosed relationships with Medtronic, Boston Scientific, BodyVision, Auris Surgical Robotics, Intuitive Surgical, Veracyte, Biodesix, Merit Medical Endotek, and Johnson & Johnson.

jensmith@mdedge.com

SOURCE: Bhadra K et al. CHEST 2019. doi: 10.1016/j.chest.2019.08.314.

A new study has uncovered how the measles virus (MeV) can induce immunosuppression by delaying the reconstitution of B cells.

CDC/ Cynthia S. Goldsmith; William Bellini, Ph.D.

“Our findings provide a biological explanation for the observed increase in childhood mortality and secondary infections several years after an episode of measles,” said Velislava N. Petrova, PhD, of the Wellcome Sanger Institute in Cambridge, England, and coauthors. The study was published in Science Immunology.

To determine if B-cell impairment can lead to measles-associated immunosuppression, the researchers investigated genetic changes in 26 unvaccinated children from the Netherlands who previously had measles. Their antibody genes were sequenced before any symptoms of measles developed and roughly 40 days after rash. Two control groups also were sequenced accordingly: vaccinated adults and three unvaccinated children from the same community who were not infected with measles.

Naive B cells from individuals in the vaccinated and uninfected control groups showed high correlation of immunoglobulin heavy chain (IGHV-J) gene frequencies across time periods (R² = 0.96 and 0.92, respectively) but no significant differences in gene expression (P greater than .05). At the same time, although B cell frequencies in measles patients recovered to levels before infection, they had significant changes in IGHV-J gene frequencies (P = .01) and decreased correlation in gene expression (R² = 0.78).

In addition, individuals in the control groups had “a stable genetic composition of B memory cells” but no significant changes in the third complementarity-determining region (CDR3) lengths or mutational frequency of IGHV genes (P greater than .05). B memory cells in measles patients, however, showed increases in mutational frequency (P = .0008) and a reduction in CDR3 length (P = .017) of IGHV genes, Dr. Petrova and associates said.

Finally, the researchers confirmed a hypothesis about the depletion of B memory cell clones during measles and a repopulation of new cells with less clonal expansion. The frequency of individual IGHV-J gene combinations before infection was correlated with a reduction after infection, “with the most frequent combinations undergoing the most marked depletion” and the result being an increase in genetic diversity.

To further test their findings, the researchers vaccinated two groups of four ferrets with live-attenuated influenza vaccine (LAIV) and at 4 weeks infected one of the groups with canine distemper virus (CDV), a surrogate for MeV. At 14 weeks after vaccination, the uninfected group maintained high levels of influenza-specific neutralizing antibodies while the infected group saw impaired B cells and a subsequent reduction in neutralizing antibodies.
 

Understanding the impact of measles on the immune system

“How measles infection has such a long-lasting deleterious effect on the immune system while allowing robust immunity against itself has been a burning immunological question,” Duane R. Wesemann, MD, PhD, of Brigham and Women’s Hospital in Boston, said in an accompanying editorial. The research from Petrova et al. begins to answer that question.

Among the observations he found most interesting was how “post-measles memory cells were more diverse than the pre-measles memory pool,” despite expectations that measles immunity would be dominant. He speculated that the void in memory cells is filled by a set of clones binding to unidentified or nonnative antigens, which may bring polyclonal diversity into B memory cells.

More research is needed to determine just what these findings mean, including looking beyond memory cell depletion and focusing on the impact of immature immunoglobulin repertoires in naive cells. But his broad takeaway is that measles remains both a public health concern and an opportunity to understand how the human body counters disease.

“The unique relationship measles has with the human immune system,” he said, “can illuminate aspects of its inner workings.”

The study was funded by grants to the investigators the Indonesian Endowment Fund for Education, the Wellcome Trust, the German Centre for Infection Research, the Collaborative Research Centre of the German Research Foundation, the German Ministry of Health, and the Royal Society. The authors declared no conflicts of interest. Dr. Wesemann reported receiving support from National Institutes of Health grants and an award from the Burroughs Wellcome Fund; he also reports being a consultant for OpenBiome.

SOURCE: Petrova VN et al. Sci Immunol. 2019 Nov 1. doi: 10.1126/sciimmunol.aay6125; Wesemann DR. Sci Immunol. 2019 Nov 1. doi: 10.1126/sciimmunol.aaz4195.

A new study has uncovered how the measles virus (MeV) can induce immunosuppression by delaying the reconstitution of B cells.

CDC/ Cynthia S. Goldsmith; William Bellini, Ph.D.

“Our findings provide a biological explanation for the observed increase in childhood mortality and secondary infections several years after an episode of measles,” said Velislava N. Petrova, PhD, of the Wellcome Sanger Institute in Cambridge, England, and coauthors. The study was published in Science Immunology.

To determine if B-cell impairment can lead to measles-associated immunosuppression, the researchers investigated genetic changes in 26 unvaccinated children from the Netherlands who previously had measles. Their antibody genes were sequenced before any symptoms of measles developed and roughly 40 days after rash. Two control groups also were sequenced accordingly: vaccinated adults and three unvaccinated children from the same community who were not infected with measles.

Naive B cells from individuals in the vaccinated and uninfected control groups showed high correlation of immunoglobulin heavy chain (IGHV-J) gene frequencies across time periods (R² = 0.96 and 0.92, respectively) but no significant differences in gene expression (P greater than .05). At the same time, although B cell frequencies in measles patients recovered to levels before infection, they had significant changes in IGHV-J gene frequencies (P = .01) and decreased correlation in gene expression (R² = 0.78).

In addition, individuals in the control groups had “a stable genetic composition of B memory cells” but no significant changes in the third complementarity-determining region (CDR3) lengths or mutational frequency of IGHV genes (P greater than .05). B memory cells in measles patients, however, showed increases in mutational frequency (P = .0008) and a reduction in CDR3 length (P = .017) of IGHV genes, Dr. Petrova and associates said.

Finally, the researchers confirmed a hypothesis about the depletion of B memory cell clones during measles and a repopulation of new cells with less clonal expansion. The frequency of individual IGHV-J gene combinations before infection was correlated with a reduction after infection, “with the most frequent combinations undergoing the most marked depletion” and the result being an increase in genetic diversity.

To further test their findings, the researchers vaccinated two groups of four ferrets with live-attenuated influenza vaccine (LAIV) and at 4 weeks infected one of the groups with canine distemper virus (CDV), a surrogate for MeV. At 14 weeks after vaccination, the uninfected group maintained high levels of influenza-specific neutralizing antibodies while the infected group saw impaired B cells and a subsequent reduction in neutralizing antibodies.
 

Understanding the impact of measles on the immune system

“How measles infection has such a long-lasting deleterious effect on the immune system while allowing robust immunity against itself has been a burning immunological question,” Duane R. Wesemann, MD, PhD, of Brigham and Women’s Hospital in Boston, said in an accompanying editorial. The research from Petrova et al. begins to answer that question.

Among the observations he found most interesting was how “post-measles memory cells were more diverse than the pre-measles memory pool,” despite expectations that measles immunity would be dominant. He speculated that the void in memory cells is filled by a set of clones binding to unidentified or nonnative antigens, which may bring polyclonal diversity into B memory cells.

More research is needed to determine just what these findings mean, including looking beyond memory cell depletion and focusing on the impact of immature immunoglobulin repertoires in naive cells. But his broad takeaway is that measles remains both a public health concern and an opportunity to understand how the human body counters disease.

“The unique relationship measles has with the human immune system,” he said, “can illuminate aspects of its inner workings.”

The study was funded by grants to the investigators the Indonesian Endowment Fund for Education, the Wellcome Trust, the German Centre for Infection Research, the Collaborative Research Centre of the German Research Foundation, the German Ministry of Health, and the Royal Society. The authors declared no conflicts of interest. Dr. Wesemann reported receiving support from National Institutes of Health grants and an award from the Burroughs Wellcome Fund; he also reports being a consultant for OpenBiome.

SOURCE: Petrova VN et al. Sci Immunol. 2019 Nov 1. doi: 10.1126/sciimmunol.aay6125; Wesemann DR. Sci Immunol. 2019 Nov 1. doi: 10.1126/sciimmunol.aaz4195.

A new study has uncovered how the measles virus (MeV) can induce immunosuppression by delaying the reconstitution of B cells.

CDC/ Cynthia S. Goldsmith; William Bellini, Ph.D.

“Our findings provide a biological explanation for the observed increase in childhood mortality and secondary infections several years after an episode of measles,” said Velislava N. Petrova, PhD, of the Wellcome Sanger Institute in Cambridge, England, and coauthors. The study was published in Science Immunology.

To determine if B-cell impairment can lead to measles-associated immunosuppression, the researchers investigated genetic changes in 26 unvaccinated children from the Netherlands who previously had measles. Their antibody genes were sequenced before any symptoms of measles developed and roughly 40 days after rash. Two control groups also were sequenced accordingly: vaccinated adults and three unvaccinated children from the same community who were not infected with measles.

Naive B cells from individuals in the vaccinated and uninfected control groups showed high correlation of immunoglobulin heavy chain (IGHV-J) gene frequencies across time periods (R² = 0.96 and 0.92, respectively) but no significant differences in gene expression (P greater than .05). At the same time, although B cell frequencies in measles patients recovered to levels before infection, they had significant changes in IGHV-J gene frequencies (P = .01) and decreased correlation in gene expression (R² = 0.78).

In addition, individuals in the control groups had “a stable genetic composition of B memory cells” but no significant changes in the third complementarity-determining region (CDR3) lengths or mutational frequency of IGHV genes (P greater than .05). B memory cells in measles patients, however, showed increases in mutational frequency (P = .0008) and a reduction in CDR3 length (P = .017) of IGHV genes, Dr. Petrova and associates said.

Finally, the researchers confirmed a hypothesis about the depletion of B memory cell clones during measles and a repopulation of new cells with less clonal expansion. The frequency of individual IGHV-J gene combinations before infection was correlated with a reduction after infection, “with the most frequent combinations undergoing the most marked depletion” and the result being an increase in genetic diversity.

To further test their findings, the researchers vaccinated two groups of four ferrets with live-attenuated influenza vaccine (LAIV) and at 4 weeks infected one of the groups with canine distemper virus (CDV), a surrogate for MeV. At 14 weeks after vaccination, the uninfected group maintained high levels of influenza-specific neutralizing antibodies while the infected group saw impaired B cells and a subsequent reduction in neutralizing antibodies.
 

Understanding the impact of measles on the immune system

“How measles infection has such a long-lasting deleterious effect on the immune system while allowing robust immunity against itself has been a burning immunological question,” Duane R. Wesemann, MD, PhD, of Brigham and Women’s Hospital in Boston, said in an accompanying editorial. The research from Petrova et al. begins to answer that question.

Among the observations he found most interesting was how “post-measles memory cells were more diverse than the pre-measles memory pool,” despite expectations that measles immunity would be dominant. He speculated that the void in memory cells is filled by a set of clones binding to unidentified or nonnative antigens, which may bring polyclonal diversity into B memory cells.

More research is needed to determine just what these findings mean, including looking beyond memory cell depletion and focusing on the impact of immature immunoglobulin repertoires in naive cells. But his broad takeaway is that measles remains both a public health concern and an opportunity to understand how the human body counters disease.

“The unique relationship measles has with the human immune system,” he said, “can illuminate aspects of its inner workings.”

The study was funded by grants to the investigators the Indonesian Endowment Fund for Education, the Wellcome Trust, the German Centre for Infection Research, the Collaborative Research Centre of the German Research Foundation, the German Ministry of Health, and the Royal Society. The authors declared no conflicts of interest. Dr. Wesemann reported receiving support from National Institutes of Health grants and an award from the Burroughs Wellcome Fund; he also reports being a consultant for OpenBiome.

SOURCE: Petrova VN et al. Sci Immunol. 2019 Nov 1. doi: 10.1126/sciimmunol.aay6125; Wesemann DR. Sci Immunol. 2019 Nov 1. doi: 10.1126/sciimmunol.aaz4195.