Pulmonology

SAN ANTONIO – Chronic liver disease increased mortality risk by up to about 80% in patients with pneumonia, according to an investigator who presented results of a large retrospective analysis.

Andrew Bowser/MDedge News

Liver disease increased the risk of intubation by 39% and increased length of stay by 1 day in the study, presented at the annual meeting of the American College of Chest Physicians.

These findings have implications for clinicians and the scoring systems they use to evaluate patients with pneumonia, according to investigator Zin Mar Htun, MD, internal medicine resident at Louis A. Weiss Memorial Hospital and Presence Saint Joseph Hospital, Chicago.

“We should recognize the importance of chronic liver disease as an independent risk factor for worse outcomes in pneumonia, regardless of the clinical findings or other coexisting comorbidities,” Dr. Htun said in a podium presentation.

Traditional scoring systems for evaluating pneumonia severity do not incorporate hepatic function status, she said.

“We need to come up with a better scoring system that recognizes comorbidities better than the Patient Safety Indicator scoring,” she told attendees at the meeting.

In their study, Dr. Htun and coinvestigator Muhammad Gul, MD, used the 2014 Nationwide Inpatient Sample database to look at pneumonia patients with or without a liver disease diagnosis.

Intubation was done in 14.2% of pneumonia patients with chronic liver disease present, compared with 10.6% of patients with no chronic liver disease (odds ratio [OR], 1.39; 95% confidence interval, 1.30-1.48) in one of their analyses, which included 17,528 pneumonia patients with a liver disease diagnosis and 17,528 pneumonia patients with no such diagnosis, propensity score-matched for age, gender, and Charlson comorbidities.

Length of stay was 8.76 and 7.83 days, respectively, for pneumonia patients with and without chronic liver disease (P less than .001), the propensity score-matched analysis further showed. In-hospital mortality was 10.5% and 6.9% for the liver disease and no liver disease groups in this analysis (OR, 1.57; 95% CI, 1.46-1.70).

In a regression analysis looking at 1.5 million pneumonia patients, of whom about 51,000 had chronic liver disease, the odds ratio for mortality was 1.82 (95% CI, 1.76-1.88; P less than .001), Dr. Htun further reported.

The pathogens causing pneumonia in patients with chronic liver disease were about the same as those in other hospitalized patients, she said in her presentation.

These are “compelling” results that suggest liver disease should considered as a factor in the development of future pneumonia scoring systems, according to Zachary Q. Morris, MD, of Henry Ford Hospital.

Creators of scoring systems may err on the side of making them “simplistic” so they are accessible and easy to analyze, Dr. Morris said in an interview.

“There comes a point in time that maybe you do need to have another layer of complexity to it,” added Dr. Morris, who moderated the original research session where Dr. Htun presented her results.

Both Dr. Htun and Dr. Gul reported that they had no relationships relevant to their study.

SOURCE: Htun ZM, et al. CHEST 2018. doi: 10.1016/j.chest.2018.08.862.

SAN ANTONIO – Chronic liver disease increased mortality risk by up to about 80% in patients with pneumonia, according to an investigator who presented results of a large retrospective analysis.

Andrew Bowser/MDedge News

Liver disease increased the risk of intubation by 39% and increased length of stay by 1 day in the study, presented at the annual meeting of the American College of Chest Physicians.

These findings have implications for clinicians and the scoring systems they use to evaluate patients with pneumonia, according to investigator Zin Mar Htun, MD, internal medicine resident at Louis A. Weiss Memorial Hospital and Presence Saint Joseph Hospital, Chicago.

“We should recognize the importance of chronic liver disease as an independent risk factor for worse outcomes in pneumonia, regardless of the clinical findings or other coexisting comorbidities,” Dr. Htun said in a podium presentation.

Traditional scoring systems for evaluating pneumonia severity do not incorporate hepatic function status, she said.

“We need to come up with a better scoring system that recognizes comorbidities better than the Patient Safety Indicator scoring,” she told attendees at the meeting.

In their study, Dr. Htun and coinvestigator Muhammad Gul, MD, used the 2014 Nationwide Inpatient Sample database to look at pneumonia patients with or without a liver disease diagnosis.

Intubation was done in 14.2% of pneumonia patients with chronic liver disease present, compared with 10.6% of patients with no chronic liver disease (odds ratio [OR], 1.39; 95% confidence interval, 1.30-1.48) in one of their analyses, which included 17,528 pneumonia patients with a liver disease diagnosis and 17,528 pneumonia patients with no such diagnosis, propensity score-matched for age, gender, and Charlson comorbidities.

Length of stay was 8.76 and 7.83 days, respectively, for pneumonia patients with and without chronic liver disease (P less than .001), the propensity score-matched analysis further showed. In-hospital mortality was 10.5% and 6.9% for the liver disease and no liver disease groups in this analysis (OR, 1.57; 95% CI, 1.46-1.70).

In a regression analysis looking at 1.5 million pneumonia patients, of whom about 51,000 had chronic liver disease, the odds ratio for mortality was 1.82 (95% CI, 1.76-1.88; P less than .001), Dr. Htun further reported.

The pathogens causing pneumonia in patients with chronic liver disease were about the same as those in other hospitalized patients, she said in her presentation.

These are “compelling” results that suggest liver disease should considered as a factor in the development of future pneumonia scoring systems, according to Zachary Q. Morris, MD, of Henry Ford Hospital.

Creators of scoring systems may err on the side of making them “simplistic” so they are accessible and easy to analyze, Dr. Morris said in an interview.

“There comes a point in time that maybe you do need to have another layer of complexity to it,” added Dr. Morris, who moderated the original research session where Dr. Htun presented her results.

Both Dr. Htun and Dr. Gul reported that they had no relationships relevant to their study.

SOURCE: Htun ZM, et al. CHEST 2018. doi: 10.1016/j.chest.2018.08.862.

SAN ANTONIO – Chronic liver disease increased mortality risk by up to about 80% in patients with pneumonia, according to an investigator who presented results of a large retrospective analysis.

Andrew Bowser/MDedge News

Liver disease increased the risk of intubation by 39% and increased length of stay by 1 day in the study, presented at the annual meeting of the American College of Chest Physicians.

These findings have implications for clinicians and the scoring systems they use to evaluate patients with pneumonia, according to investigator Zin Mar Htun, MD, internal medicine resident at Louis A. Weiss Memorial Hospital and Presence Saint Joseph Hospital, Chicago.

“We should recognize the importance of chronic liver disease as an independent risk factor for worse outcomes in pneumonia, regardless of the clinical findings or other coexisting comorbidities,” Dr. Htun said in a podium presentation.

Traditional scoring systems for evaluating pneumonia severity do not incorporate hepatic function status, she said.

“We need to come up with a better scoring system that recognizes comorbidities better than the Patient Safety Indicator scoring,” she told attendees at the meeting.

In their study, Dr. Htun and coinvestigator Muhammad Gul, MD, used the 2014 Nationwide Inpatient Sample database to look at pneumonia patients with or without a liver disease diagnosis.

Intubation was done in 14.2% of pneumonia patients with chronic liver disease present, compared with 10.6% of patients with no chronic liver disease (odds ratio [OR], 1.39; 95% confidence interval, 1.30-1.48) in one of their analyses, which included 17,528 pneumonia patients with a liver disease diagnosis and 17,528 pneumonia patients with no such diagnosis, propensity score-matched for age, gender, and Charlson comorbidities.

Length of stay was 8.76 and 7.83 days, respectively, for pneumonia patients with and without chronic liver disease (P less than .001), the propensity score-matched analysis further showed. In-hospital mortality was 10.5% and 6.9% for the liver disease and no liver disease groups in this analysis (OR, 1.57; 95% CI, 1.46-1.70).

In a regression analysis looking at 1.5 million pneumonia patients, of whom about 51,000 had chronic liver disease, the odds ratio for mortality was 1.82 (95% CI, 1.76-1.88; P less than .001), Dr. Htun further reported.

The pathogens causing pneumonia in patients with chronic liver disease were about the same as those in other hospitalized patients, she said in her presentation.

These are “compelling” results that suggest liver disease should considered as a factor in the development of future pneumonia scoring systems, according to Zachary Q. Morris, MD, of Henry Ford Hospital.

Creators of scoring systems may err on the side of making them “simplistic” so they are accessible and easy to analyze, Dr. Morris said in an interview.

“There comes a point in time that maybe you do need to have another layer of complexity to it,” added Dr. Morris, who moderated the original research session where Dr. Htun presented her results.

Both Dr. Htun and Dr. Gul reported that they had no relationships relevant to their study.

SOURCE: Htun ZM, et al. CHEST 2018. doi: 10.1016/j.chest.2018.08.862.

SAN FRANCISCO – Influenza season is upon us, and Helen Chu, MD, MPH, is here at ID Week 2018 to talk vaccines, especially for pregnant women.

They are at greater risk for more severe illness, and influenza can lead to adverse outcomes in infants. The good news is that recent studies have shown that flu vaccines are safe and effective in pregnant women.

The bad news is that many women are hesitant to be vaccinated out of concerns over safety, in a trend that reflects broader societal worries over vaccination, said Dr. Chu, of the University of Washington, Seattle. In a video interview at an annual scientific meeting on infectious diseases, Dr. Chu advised steps to ensure that pregnant women are aware of the safety and efficacy of flu vaccines, and the benefits to the infant who acquires immunity through the mother. It’s also a good idea to have vaccine on hand to be able to offer it immediately during an office visit.

SAN FRANCISCO – Influenza season is upon us, and Helen Chu, MD, MPH, is here at ID Week 2018 to talk vaccines, especially for pregnant women.

They are at greater risk for more severe illness, and influenza can lead to adverse outcomes in infants. The good news is that recent studies have shown that flu vaccines are safe and effective in pregnant women.

The bad news is that many women are hesitant to be vaccinated out of concerns over safety, in a trend that reflects broader societal worries over vaccination, said Dr. Chu, of the University of Washington, Seattle. In a video interview at an annual scientific meeting on infectious diseases, Dr. Chu advised steps to ensure that pregnant women are aware of the safety and efficacy of flu vaccines, and the benefits to the infant who acquires immunity through the mother. It’s also a good idea to have vaccine on hand to be able to offer it immediately during an office visit.

SAN FRANCISCO – Influenza season is upon us, and Helen Chu, MD, MPH, is here at ID Week 2018 to talk vaccines, especially for pregnant women.

They are at greater risk for more severe illness, and influenza can lead to adverse outcomes in infants. The good news is that recent studies have shown that flu vaccines are safe and effective in pregnant women.

The bad news is that many women are hesitant to be vaccinated out of concerns over safety, in a trend that reflects broader societal worries over vaccination, said Dr. Chu, of the University of Washington, Seattle. In a video interview at an annual scientific meeting on infectious diseases, Dr. Chu advised steps to ensure that pregnant women are aware of the safety and efficacy of flu vaccines, and the benefits to the infant who acquires immunity through the mother. It’s also a good idea to have vaccine on hand to be able to offer it immediately during an office visit.

Clinical question: Can a procalcitonin (PCT)–guided strategy safely reduce antibiotic exposure in patients admitted to the ICU with severe acute exacerbations of chronic obstructive pulmonary disease (COPD) with or without pneumonia?

Background: Studies have demonstrated PCT-based strategies can safely reduce antibiotic use in patients without severe lower respiratory tract infections, community-acquired pneumonia, or acute exacerbations of COPD. The data on safety of PCT-based strategies in critically ill patients is limited.

Study design: Prospective, multicenter, randomized, controlled trial.

Setting: ICUs of 11 hospitals in France, including 7 tertiary care hospitals.

Synopsis: In this study 302 patients admitted to the ICU with severe exacerbations of COPD with or without pneumonia were randomly assigned to groups with antibiotic therapy guided by a PCT protocol or standard guidelines. Overall, the study failed to demonstrate noninferiority of a PCT-based strategy to reduce exposure to antibiotics. Specifically, the adjusted difference in mortality was 6.6% higher (90% confidence interval, 0.3%-13.5%) in the intervention group with no significant reduction in antibiotic exposure.

One limitation of this study was that it was an open trial in which clinicians were aware that their management was being observed.

Bottom line: A PCT-based algorithm was not effective in safely reducing antibiotic exposure in patients with acute exacerbations of COPD admitted to the ICU.

Citation: Daubin C et al. Procalcitonin algorithm to guide initial antibiotic therapy in acute exacerbations of COPD admitted to the ICU: A randomized multicenter study. Intensive Care Med. 2018 Apr;44(4):428-37.

Dr. Agith is a hospitalist in the division of hospital medicine in the department of medicine at Loyola University Chicago, Maywood, Ill.

Clinical question: Can a procalcitonin (PCT)–guided strategy safely reduce antibiotic exposure in patients admitted to the ICU with severe acute exacerbations of chronic obstructive pulmonary disease (COPD) with or without pneumonia?

Background: Studies have demonstrated PCT-based strategies can safely reduce antibiotic use in patients without severe lower respiratory tract infections, community-acquired pneumonia, or acute exacerbations of COPD. The data on safety of PCT-based strategies in critically ill patients is limited.

Study design: Prospective, multicenter, randomized, controlled trial.

Setting: ICUs of 11 hospitals in France, including 7 tertiary care hospitals.

Synopsis: In this study 302 patients admitted to the ICU with severe exacerbations of COPD with or without pneumonia were randomly assigned to groups with antibiotic therapy guided by a PCT protocol or standard guidelines. Overall, the study failed to demonstrate noninferiority of a PCT-based strategy to reduce exposure to antibiotics. Specifically, the adjusted difference in mortality was 6.6% higher (90% confidence interval, 0.3%-13.5%) in the intervention group with no significant reduction in antibiotic exposure.

One limitation of this study was that it was an open trial in which clinicians were aware that their management was being observed.

Bottom line: A PCT-based algorithm was not effective in safely reducing antibiotic exposure in patients with acute exacerbations of COPD admitted to the ICU.

Citation: Daubin C et al. Procalcitonin algorithm to guide initial antibiotic therapy in acute exacerbations of COPD admitted to the ICU: A randomized multicenter study. Intensive Care Med. 2018 Apr;44(4):428-37.

Dr. Agith is a hospitalist in the division of hospital medicine in the department of medicine at Loyola University Chicago, Maywood, Ill.

Clinical question: Can a procalcitonin (PCT)–guided strategy safely reduce antibiotic exposure in patients admitted to the ICU with severe acute exacerbations of chronic obstructive pulmonary disease (COPD) with or without pneumonia?

Background: Studies have demonstrated PCT-based strategies can safely reduce antibiotic use in patients without severe lower respiratory tract infections, community-acquired pneumonia, or acute exacerbations of COPD. The data on safety of PCT-based strategies in critically ill patients is limited.

Study design: Prospective, multicenter, randomized, controlled trial.

Setting: ICUs of 11 hospitals in France, including 7 tertiary care hospitals.

Synopsis: In this study 302 patients admitted to the ICU with severe exacerbations of COPD with or without pneumonia were randomly assigned to groups with antibiotic therapy guided by a PCT protocol or standard guidelines. Overall, the study failed to demonstrate noninferiority of a PCT-based strategy to reduce exposure to antibiotics. Specifically, the adjusted difference in mortality was 6.6% higher (90% confidence interval, 0.3%-13.5%) in the intervention group with no significant reduction in antibiotic exposure.

One limitation of this study was that it was an open trial in which clinicians were aware that their management was being observed.

Bottom line: A PCT-based algorithm was not effective in safely reducing antibiotic exposure in patients with acute exacerbations of COPD admitted to the ICU.

Citation: Daubin C et al. Procalcitonin algorithm to guide initial antibiotic therapy in acute exacerbations of COPD admitted to the ICU: A randomized multicenter study. Intensive Care Med. 2018 Apr;44(4):428-37.

Dr. Agith is a hospitalist in the division of hospital medicine in the department of medicine at Loyola University Chicago, Maywood, Ill.

Influenza outbreaks in the United States tend to be concentrated and intense in small cities and more evenly spread throughout the season in large cities, results of a recent study show.

Swings in humidity further intensified the influenza spikes in small cities, but didn’t seem to have as much of an effect in large cities, the results suggest.

These findings help explain differences in influenza transmission patterns between cities that have similar climates and virus epidemiology, according to researcher Benjamin D. Dalziel, PhD, of the departments of integrative biology and mathematics at Oregon State University in Corvallis.

“City size and structure can play a role in determining how other factors such as climate affect and influence transmission,” Dr. Dalziel said in a press conference.

“Our results show how metropolises play a disproportionately important role in this process, as epidemic foci, and as potential sentinel hubs, where epidemiological observatories could integrate local strain dynamics to predict larger-scale patterns. As the growth and form of cities affect their function as climate-driven incubators of infectious disease, it may be possible to design smarter cities that better control epidemics in the face of accelerating global change,” the researchers wrote in their study.

Dr. Dalziel and his coauthors analyzed the weekly incidence of influenza-like illness across 603 U.S. ZIP codes using data obtained from medical claims from 2002 to 2008. They used epidemic intensity as a summary statistic to compare cities. By this variable, low epidemic intensity indicated a diffuse spread evenly across weeks of the flu season, whereas high epidemic intensity indicated intensively focused outbreaks on particular weeks.

In small cities, epidemics were more intensely focused on shorter periods at the peak of flu season, they found. In large cities, incidence was more diffuse, according to results published in Science.

Patterns of where people live and work in a city may account for the more diffuse and prolonged outbreaks seen in large cities, the authors wrote. Large cities have organized population movement patterns and crowding. In more highly established work locations, for example, the population density is pronounced during the day.

“We found the structure makes a difference for how the flu spreads at different times of year,” Dr. Dalziel said of the study, which used U.S. Census data to evaluate spatial population distributions. “In large cities with more highly organized patterns, conditions play a relatively smaller role in flu transmission.”

Humidity’s lower impact on outbreaks in large cities might also be explained by population effects: “If an infected person is sitting beside you, it matters less what the specific humidity is,” Dr. Dalziel said, adding that the proximity helps the virus find hosts even when climatic conditions are not at their most favorable.

The study findings may have implications for health care resources in small cities, which could be strained by intense outbreaks, said coinvestigator Cecile Viboud, PhD, of the Division of International Epidemiology and Population Studies, Fogarty International Center, National Institutes of Health, Bethesda, Md.

Intense outbreaks could overload the health care system, making it challenging to respond, especially around the peak of the epidemic. Pressure on the health care system may be less intense in cities such as Miami or New York, where flu epidemics are more diffuse and spread out during the year, she said.

Variations in vaccination coverage were not associated with variations in epidemic intensity at the state level. However, the data period that was analyzed ended in 2008, a time when flu vaccination rates were much lower than they are today, according to Dr. Viboud.

“It would be important to revisit the effect of city structure and humidity on flu transmission in a high vaccination regime in more recent years, especially if there is a lot of interest in developing broadly cross-protective flu vaccines, which might become available in the market in the future,” she said.

The researchers declared no competing interests related to their research, which was supported by a grant from the Bill & Melinda Gates Foundation, the RAPIDD program of the Science and Technology Directorate Department of Homeland Security, and the Fogarty International Center, National Institutes of Health.

SOURCE: Dalziel BD et al. Science. 2018 Oct 5;362(6410):75-9.

Influenza outbreaks in the United States tend to be concentrated and intense in small cities and more evenly spread throughout the season in large cities, results of a recent study show.

Swings in humidity further intensified the influenza spikes in small cities, but didn’t seem to have as much of an effect in large cities, the results suggest.

These findings help explain differences in influenza transmission patterns between cities that have similar climates and virus epidemiology, according to researcher Benjamin D. Dalziel, PhD, of the departments of integrative biology and mathematics at Oregon State University in Corvallis.

“City size and structure can play a role in determining how other factors such as climate affect and influence transmission,” Dr. Dalziel said in a press conference.

“Our results show how metropolises play a disproportionately important role in this process, as epidemic foci, and as potential sentinel hubs, where epidemiological observatories could integrate local strain dynamics to predict larger-scale patterns. As the growth and form of cities affect their function as climate-driven incubators of infectious disease, it may be possible to design smarter cities that better control epidemics in the face of accelerating global change,” the researchers wrote in their study.

Dr. Dalziel and his coauthors analyzed the weekly incidence of influenza-like illness across 603 U.S. ZIP codes using data obtained from medical claims from 2002 to 2008. They used epidemic intensity as a summary statistic to compare cities. By this variable, low epidemic intensity indicated a diffuse spread evenly across weeks of the flu season, whereas high epidemic intensity indicated intensively focused outbreaks on particular weeks.

In small cities, epidemics were more intensely focused on shorter periods at the peak of flu season, they found. In large cities, incidence was more diffuse, according to results published in Science.

Patterns of where people live and work in a city may account for the more diffuse and prolonged outbreaks seen in large cities, the authors wrote. Large cities have organized population movement patterns and crowding. In more highly established work locations, for example, the population density is pronounced during the day.

“We found the structure makes a difference for how the flu spreads at different times of year,” Dr. Dalziel said of the study, which used U.S. Census data to evaluate spatial population distributions. “In large cities with more highly organized patterns, conditions play a relatively smaller role in flu transmission.”

Humidity’s lower impact on outbreaks in large cities might also be explained by population effects: “If an infected person is sitting beside you, it matters less what the specific humidity is,” Dr. Dalziel said, adding that the proximity helps the virus find hosts even when climatic conditions are not at their most favorable.

The study findings may have implications for health care resources in small cities, which could be strained by intense outbreaks, said coinvestigator Cecile Viboud, PhD, of the Division of International Epidemiology and Population Studies, Fogarty International Center, National Institutes of Health, Bethesda, Md.

Intense outbreaks could overload the health care system, making it challenging to respond, especially around the peak of the epidemic. Pressure on the health care system may be less intense in cities such as Miami or New York, where flu epidemics are more diffuse and spread out during the year, she said.

Variations in vaccination coverage were not associated with variations in epidemic intensity at the state level. However, the data period that was analyzed ended in 2008, a time when flu vaccination rates were much lower than they are today, according to Dr. Viboud.

“It would be important to revisit the effect of city structure and humidity on flu transmission in a high vaccination regime in more recent years, especially if there is a lot of interest in developing broadly cross-protective flu vaccines, which might become available in the market in the future,” she said.

The researchers declared no competing interests related to their research, which was supported by a grant from the Bill & Melinda Gates Foundation, the RAPIDD program of the Science and Technology Directorate Department of Homeland Security, and the Fogarty International Center, National Institutes of Health.

SOURCE: Dalziel BD et al. Science. 2018 Oct 5;362(6410):75-9.

Influenza outbreaks in the United States tend to be concentrated and intense in small cities and more evenly spread throughout the season in large cities, results of a recent study show.

Swings in humidity further intensified the influenza spikes in small cities, but didn’t seem to have as much of an effect in large cities, the results suggest.

These findings help explain differences in influenza transmission patterns between cities that have similar climates and virus epidemiology, according to researcher Benjamin D. Dalziel, PhD, of the departments of integrative biology and mathematics at Oregon State University in Corvallis.

“City size and structure can play a role in determining how other factors such as climate affect and influence transmission,” Dr. Dalziel said in a press conference.

“Our results show how metropolises play a disproportionately important role in this process, as epidemic foci, and as potential sentinel hubs, where epidemiological observatories could integrate local strain dynamics to predict larger-scale patterns. As the growth and form of cities affect their function as climate-driven incubators of infectious disease, it may be possible to design smarter cities that better control epidemics in the face of accelerating global change,” the researchers wrote in their study.

Dr. Dalziel and his coauthors analyzed the weekly incidence of influenza-like illness across 603 U.S. ZIP codes using data obtained from medical claims from 2002 to 2008. They used epidemic intensity as a summary statistic to compare cities. By this variable, low epidemic intensity indicated a diffuse spread evenly across weeks of the flu season, whereas high epidemic intensity indicated intensively focused outbreaks on particular weeks.

In small cities, epidemics were more intensely focused on shorter periods at the peak of flu season, they found. In large cities, incidence was more diffuse, according to results published in Science.

Patterns of where people live and work in a city may account for the more diffuse and prolonged outbreaks seen in large cities, the authors wrote. Large cities have organized population movement patterns and crowding. In more highly established work locations, for example, the population density is pronounced during the day.

“We found the structure makes a difference for how the flu spreads at different times of year,” Dr. Dalziel said of the study, which used U.S. Census data to evaluate spatial population distributions. “In large cities with more highly organized patterns, conditions play a relatively smaller role in flu transmission.”

Humidity’s lower impact on outbreaks in large cities might also be explained by population effects: “If an infected person is sitting beside you, it matters less what the specific humidity is,” Dr. Dalziel said, adding that the proximity helps the virus find hosts even when climatic conditions are not at their most favorable.

The study findings may have implications for health care resources in small cities, which could be strained by intense outbreaks, said coinvestigator Cecile Viboud, PhD, of the Division of International Epidemiology and Population Studies, Fogarty International Center, National Institutes of Health, Bethesda, Md.

Intense outbreaks could overload the health care system, making it challenging to respond, especially around the peak of the epidemic. Pressure on the health care system may be less intense in cities such as Miami or New York, where flu epidemics are more diffuse and spread out during the year, she said.

Variations in vaccination coverage were not associated with variations in epidemic intensity at the state level. However, the data period that was analyzed ended in 2008, a time when flu vaccination rates were much lower than they are today, according to Dr. Viboud.

“It would be important to revisit the effect of city structure and humidity on flu transmission in a high vaccination regime in more recent years, especially if there is a lot of interest in developing broadly cross-protective flu vaccines, which might become available in the market in the future,” she said.

The researchers declared no competing interests related to their research, which was supported by a grant from the Bill & Melinda Gates Foundation, the RAPIDD program of the Science and Technology Directorate Department of Homeland Security, and the Fogarty International Center, National Institutes of Health.

SOURCE: Dalziel BD et al. Science. 2018 Oct 5;362(6410):75-9.

The Food and Drug Administration has approved omadacycline (Nuzyra), a tetracycline antibiotic, for treating community-acquired bacterial pneumonia (CABP) and acute bacterial skin and skin structure infections (ABSSSI) in adults, the manufacturer, Paratek, announced in a press release.

The company expects that omadacycline will be available in the first quarter of 2019. Administered once-daily in either oral or IV formulations, the antibiotic was effective and well tolerated across multiple trials, which altogether included almost 2,000 patients, according to Paratek. As part of the approval, the company has agreed to conduct postmarketing studies, specifically, more studies in CABP and in pediatric populations. “To reduce the development of drug-resistant bacteria and maintain the effectiveness of Nuzyra and other antibacterial drugs, Nuzyra should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria,” according to a statement in the indications section of the prescribing information.

Omadacycline is contraindicated for patients with a known hypersensitivity to the drug or any members of the tetracycline class of antibacterial drugs; hypersensitivity reactions have been observed, so use should be discontinued if one is suspected. Use of this drug during later stages of pregnancy can lead to irreversible discoloration of the infant’s teeth and inhibition of bone growth; it should also not be used during breastfeeding.

Because omadacycline is structurally similar to tetracycline class drugs, some adverse reactions to those drugs may be seen with this one, such as photosensitivity, pseudotumor cerebri, and antianabolic action. Adverse reactions known to have an association with omadacycline include nausea, vomiting, hypertension, insomnia, diarrhea, constipation, and increases of alanine aminotransferase, aspartate aminotransferase, and/or gamma-glutamyl transferase.

Drug interactions may occur with anticoagulants, so dosage of those drugs may need to be reduced while treating with omadacycline. Antacids also are believed to have a drug interaction – specifically, impairing absorption of omadacycline

cpalmer@mdedge.com

The Food and Drug Administration has approved omadacycline (Nuzyra), a tetracycline antibiotic, for treating community-acquired bacterial pneumonia (CABP) and acute bacterial skin and skin structure infections (ABSSSI) in adults, the manufacturer, Paratek, announced in a press release.

The company expects that omadacycline will be available in the first quarter of 2019. Administered once-daily in either oral or IV formulations, the antibiotic was effective and well tolerated across multiple trials, which altogether included almost 2,000 patients, according to Paratek. As part of the approval, the company has agreed to conduct postmarketing studies, specifically, more studies in CABP and in pediatric populations. “To reduce the development of drug-resistant bacteria and maintain the effectiveness of Nuzyra and other antibacterial drugs, Nuzyra should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria,” according to a statement in the indications section of the prescribing information.

Omadacycline is contraindicated for patients with a known hypersensitivity to the drug or any members of the tetracycline class of antibacterial drugs; hypersensitivity reactions have been observed, so use should be discontinued if one is suspected. Use of this drug during later stages of pregnancy can lead to irreversible discoloration of the infant’s teeth and inhibition of bone growth; it should also not be used during breastfeeding.

Because omadacycline is structurally similar to tetracycline class drugs, some adverse reactions to those drugs may be seen with this one, such as photosensitivity, pseudotumor cerebri, and antianabolic action. Adverse reactions known to have an association with omadacycline include nausea, vomiting, hypertension, insomnia, diarrhea, constipation, and increases of alanine aminotransferase, aspartate aminotransferase, and/or gamma-glutamyl transferase.

Drug interactions may occur with anticoagulants, so dosage of those drugs may need to be reduced while treating with omadacycline. Antacids also are believed to have a drug interaction – specifically, impairing absorption of omadacycline

cpalmer@mdedge.com

The Food and Drug Administration has approved omadacycline (Nuzyra), a tetracycline antibiotic, for treating community-acquired bacterial pneumonia (CABP) and acute bacterial skin and skin structure infections (ABSSSI) in adults, the manufacturer, Paratek, announced in a press release.

The company expects that omadacycline will be available in the first quarter of 2019. Administered once-daily in either oral or IV formulations, the antibiotic was effective and well tolerated across multiple trials, which altogether included almost 2,000 patients, according to Paratek. As part of the approval, the company has agreed to conduct postmarketing studies, specifically, more studies in CABP and in pediatric populations. “To reduce the development of drug-resistant bacteria and maintain the effectiveness of Nuzyra and other antibacterial drugs, Nuzyra should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria,” according to a statement in the indications section of the prescribing information.

Omadacycline is contraindicated for patients with a known hypersensitivity to the drug or any members of the tetracycline class of antibacterial drugs; hypersensitivity reactions have been observed, so use should be discontinued if one is suspected. Use of this drug during later stages of pregnancy can lead to irreversible discoloration of the infant’s teeth and inhibition of bone growth; it should also not be used during breastfeeding.

Because omadacycline is structurally similar to tetracycline class drugs, some adverse reactions to those drugs may be seen with this one, such as photosensitivity, pseudotumor cerebri, and antianabolic action. Adverse reactions known to have an association with omadacycline include nausea, vomiting, hypertension, insomnia, diarrhea, constipation, and increases of alanine aminotransferase, aspartate aminotransferase, and/or gamma-glutamyl transferase.

Drug interactions may occur with anticoagulants, so dosage of those drugs may need to be reduced while treating with omadacycline. Antacids also are believed to have a drug interaction – specifically, impairing absorption of omadacycline

cpalmer@mdedge.com

Cases

Case 1

It’s a busy shift on an unusually chilly and rainy July night. Emergency medical services (EMS) brings in a 9-month-old boy who woke up with a “squeaking” noise. His parents reported that he has had a fever, cough, rhinorrhea, and difficulty breathing for the past 2 days; however, they did not hear the noisy breathing until the night of presentation. When the patient is examined, it is noted that he has inspiratory stridor at rest, moderate subcostal retractions, and an occasional deep cough. Upper airway transmitted noises were present, but otherwise the patient had clear lungs.

The patient’s vital signs at presentation were: blood pressure (BP), 85/55 mm Hg; heart rate (HR), 163 beats/min; respiratory rate (RR), 55 breaths/min; and temperature (T), 101.8°F. Oxygen saturation was 90% on room air. The patient’s mother wants to know how the respiratory distress will be fixed and is inquiring if they will have to stay in the hospital overnight.

Case 2

As work begins on the child described above, EMS brings in a 3-year-old girl who appears to be in moderate-severe respiratory distress. Her parents report that she started to drool earlier in the day followed by coughing and occasional gagging. Her parents relay that they thought the symptoms were because of post-nasal drip due to her cold, but the respiratory distress seems to be getting worse, and she now has very noisy breathing and is reluctant to lay down. Upon examination, both inspiratory and expiratory stridor is heard, and it is noted that moderate subcostal retractions are present when the patient is supine.

The patient’s vital signs at presentation were: BP, 89/58 mm Hg; HR, 144 beats/min; RR, 52 breaths/min; and T, 99.5°F. Oxygen saturation was 88% on room air. The nursing staff asked what to do next and why the 2 stridor cases are being managed so differently.

Stridor

Stridor is a high-pitched, harsh sound heard during respiration, predominantly during inspiration, as a result of turbulent air passage.^1-3 Stridor is not a diagnosis in itself, but rather a sign of underlying acute or chronic etiology, which needs to be classified based on elicited history and examination.^1,4 While the etiology of obstruction may be infectious, congenital, mechanical, or traumatic, the distinct features of the pediatric airway make respiratory failure an important concern independent of the underlying cause.

Anatomy

There are several anatomical differences unique to the pediatric airway that make children, especially infants under 1 year of age, more susceptible to airway obstruction.^5,6The pediatric larynx is more anterior and superior and less fibrous than adults, thereby more compliant.^6,7 The pediatric epiglottis is longer, omega-shaped, and softer, and the tongue is larger in comparison to the size of the oral cavity, resulting in obstructed airflow.^6,7 Children also have a larger and more prominent occiput, causing mechanical obstruction by flexion of the neck when supine.⁶ While the cricoid cartilage was previously believed to be the narrowest portion of the airway, more recent measurement techniques have challenged this and shown that the glottic and subglottic areas may be narrower in children.^7,8

Worsening obstruction resulting in a decreased airway radius leads to increased turbulence to air flow, which is explained by Poiseuille’s law.^1,2,7 The resistance to airflow becomes inversely related to the fourth power of the radius, so even a small change in an already narrow pediatric airway can make a huge difference.⁵ In practice, this means 1 mm of mucosal edema will decrease the cross-sectional area of the airway by 75% and increase the resistance of airflow by a magnitude of 16 to 32 times depending on the level of turbulence.⁷The airway can be divided into extrathoracic and intrathoracic regions, separated by the vocal cords.¹³ Inspiratory stridor is typically due to extrathoracic obstruction and expiratory stridor is due to intrathoracic obstruction below the level of the cords. Biphasic stridor, however, may indicate a fixed obstruction at the level of the cords.^2,3,5,9

Acute Differentials

The pediatric patient is at high risk for respiratory decompensation when the upper airway is acutely compromised. The history, physical examination, and phases of stridor can help determine the underlying diagnosis and definitive treatment plan.

Acute Croup

Acute croup (laryngotracheitis) is a clinical diagnosis based on acute onset of barky cough and inspiratory stridor.¹ It is usually secondary to an infection, most commonly viral (parainfluenza virus), resulting in edema and increased secretions of the subglottic mucosa.⁷ The onset is typically preceded by upper respiratory illness (URI) symptoms, and is often worse at night or after waking from a nap.¹ The peak incidence is between ages 6 months to 3 years. While croup is a clinical diagnosis, an anteroposterior X-ray will often show a steeple sign.^7,10

Spasmodic Croup

Spasmodic croup is an atypical presentation usually seen in children 8 years or older without a preceding URI. Patients will wake up overnight with a harsh brass-like cough, stridor, and hoarse voice. The etiology is unclear, but often these patients have a history of atopy and respond in part to treatment with antihistamines.

Foreign Body Aspiration

All that is acutely stridulous is not croup. Stridor from foreign body aspiration is sudden in onset and children do not always present with a history suggestive of foreign body aspiration. Diagnosis requires a high index of suspicion because the event is often unwitnessed and typical patients are pre-verbal. The physical examination may reveal diminished air entry along with stridor. Diagnosis is made by obtaining an X-ray (lateral neck [Figure 1], lateral decubitus, or inspiratory/expiratory chest X-ray) or by bronchoscopy which is both diagnostic and therapeutic.^7,10 Remember to always think of foreign body aspiration in children with acute stridor who have neither fever nor antecedent URI symptoms.

Bacterial Tracheitis

Bacterial tracheitis should be suspected in toxic appearing children who present with respiratory distress and stridor but who have a poor response to nebulized epinephrine. It is typically seen in toddlers and school-aged children, and like a viral tracheitis, presentation can be preceded by either URI or fever.¹⁰ Stridor is caused by subglottic edema and mucopurulent secretions in the airway.^7,10 Infection is most commonly by S. aureus but initial antibiotic choice should be broad spectrum, and include a third-generation cephalosporin or beta-lactamase resistant penicillin.

Epiglottitis

Epiglottitis is edema of the epiglottis, most commonly secondary to bacterial infection. The epidemiology of epiglottitis has changed dramatically since widespread immunization for H. influenza with a significantly decreased incidence and change in the average age of presentation to 14.6 years (previously 5.6 years).⁷ The clinical course begins with sore throat, dysphonia, refusal to eat and progressive difficulty handling secretions with eventual drooling, stridor, tripoding, and toxic appearance. Epiglottitis can be differentiated from croup and bacterial tracheitis because presentation typically lacks a cough.^7,10,11 Diagnosis is made either by direct visualization of the epiglottis or a lateral neck X-ray showing a ‘thumb print’ sign (Figure 2).¹² Emergency department treatment is similar to the management of the child with a partial foreign body occlusion and focuses on maintaining the airway and minimizing anything that agitates the patient. Intravenous (IV) antibiotic coverage is similar to bacterial tracheitis (third-generation cephalosporin or a beta-lactamase resistant penicillin).

Retropharyngeal Abscess

The most common chief complaint of retropharyngeal abscess (RPA) is neck pain (38%) with fever. As such, it can clinically be mistaken for meningitis on initial presentation. Retropharyngeal abscess will present rarely with either stridor or associated respiratory distress, and it can also mimic croup on initial presentation. Physical examination findings which differentiate this entity include limited or painful neck extension (45%), torticollis (36.5%), and to a lesser extent limitation of neck flexion (12.5%).¹³ The median age at diagnosis is 36 months with 75% of patients less than 5 years. Typical presentation is insidious with fever and URI symptoms preceding onset. Diagnosis can be made with a lateral neck X-ray showing widening of the prevertebral space (Figure 3), but the gold standard diagnostic study is a computed tomography with contrast.¹⁴ Management is IV antibiotics covering aerobic and anaerobic bacteria (eg, ampicillin-sulbactam) ± surgical intervention.

Caustic Ingestion

Caustic ingestion is most commonly accidental and seen in children aged 12 months to 2 years. However, with recent fads, such as the “Tide Pod challenge” teenagers are also at risk. Airway compromise and stridor are secondary to mucosal injury and edema. Oral injury is not always a useful marker for significant distal injury. A complete evaluation of the upper airway and digestive tract within 48 hours after known/suspected caustic ingestion is recommended to assess full extent of damage.¹⁵

Chronic Differentials

Laryngomalacia

Laryngomalacia is a congenital weakness of laryngeal tissues, and it is the most common cause of both chronic stridor and neonatal stridor. It is characterized by progressive worsening of symptoms with crying/feeding and supine positioning. Diagnosis is made by bronchoscopy and management is conservative unless there are life threatening apneic or cyanotic events.⁷

Rings/Slings

There are many anatomic structures with the potential to cause extrinsic airway compression which present with stridor. This type of stridor is often biphasic. Examples include innominate artery compression, double aortic arch, aberrant subclavian artery, and pulmonary artery sling.⁷

Stridor presenting in children with a history of prematurity or prolonged intubation should raise concern for subglottic and tracheal stenosis.¹⁶

Evaluation

Regardless of the etiology of stridor, efforts should be made to keep the patient calm (ie, allow the parent to keep holding a young child, limit any examination not absolutely necessary). Much of the examination can be completed from a distance without disturbing the child.¹⁷ Observation of the inspiratory:expiratory (I:E) ratio can localize the level of airway obstruction. For example, an I:E ratio weighted toward a longer inspiration indicates an extrathoracic airway obstruction. Whereas an I:E with a prolonged expiratory phase is consistent with intrathoracic obstruction (eg, terminal bronchial obstruction).¹⁷

Another way to localize the level of obstruction is to look for changes in the voice; patients who present with a change in their voice have a subglottic partial obstruction such as croup. However, patients with a muffled voice or drooling have a supraglottic obstruction such as epiglottitis or RPA.¹⁷

Management

Management of stridor focuses on reducing airway obstruction, which is usually secondary to edema in the acute setting.

Viral Laryngotracheitis

Oral steroids are the mainstay of treatment. Research has shown dexamethasone is preferred over prednisolone.^18-20 Steroids are not only useful in moderate to severe laryngotracheitis but also have a therapeutic role in children with mild laryngotracheitis.¹⁸ In hospital settings the parenteral formulation of dexamethasone can be safely given orally with good effect. There is no therapeutic advantage in acute laryngotracheitis to giving dexamethasone via either the IV or intramuscular route vs oral.²¹ In the outpatient setting, decadron tablets can be crushed and mixed in with a young child’s favorite soft food (eg, mashed potatoes or apple sauce). The authors recommend this strategy in lieu of prescribing dexamethasone suspension as its dilute concentration (1 mg/10 ml) results in a need for a child to receive a relatively large volume of a distasteful liquid. There is a wide therapeutic range of dexamethasone with studies documenting efficacy for laryngotracheitis in doses ranging from 0.15 mg/kg to 0.6 mg/kg. To date there are no large studies which demonstrate routine therapeutic utility of subsequent doses of dexamethasone. Nebulized budesonide (2.5 mg) can be given if oral steroids are not tolerated, however it is significantly more expensive.

Racemic epinephrine is the agent of choice for rapid onset of action in children who demonstrate stridor at rest. It causes vasoconstriction in the laryngeal mucosa, promotes bronchial smooth muscle relaxation, and thinning of bronchial secretions. It offers short-term relief of symptoms until steroids start to work. There is no rebound effect or worsening of symptoms once the epinephrine wears off, but children who receive this drug should be observed in the ED for a period of time (2-3 hours is standard of care in many hospitals) for return of symptoms.^10,22 Patients who are persistently symptomatic 4 hours after administration of steroids or who require repeat doses of racemic epinephrine should be admitted for observation.¹⁰There are no contraindications to adjuvant treatments, such as antipyretics and non-sedating analgesics. Clinicians should maintain a high index of suspicion for anatomic airway anomalies that may need further evaluation/direct visualization in pediatric patients who present with repeated episodes of croup.¹⁰

Case Conclusions

Case 1

The 9-month-old boy with stridor was noted to have increased stridor while fussy, but even at rest some inspiratory stridor was present. A barky cough was noted in the examination room. The patient was placed on a monitor and a nebulized racemic epinephrine treatment was started. A single dose of oral dexamethasone was given shortly after presentation to the ED. Since the patient had inspiratory stridor at rest with associated tachypnea and hypoxia on initial presentation, a neck X-ray was obtained (Figure 4). Subglottic narrowing was identified on the imaging, but both the epiglottis and the prevertebral space were normal in appearance and no foreign bodies were visualized. The inspiratory stridor at rest, tachypnea, and mild hypoxia all improved after treatment, the patient was observed for 2 hours in the ED without recurrence of respiratory distress and was able to be discharged home with a diagnosis of acute croup.

Case 2

The 3-year-old girl was noted to be in significant positional respiratory distress, so the physician asked her parents to keep her calm in her position of comfort. She was calmly and quickly placed on a monitor with age-appropriate distraction techniques in place and advanced airway equipment at the bedside. A portable chest X-ray was obtained and revealed a coin was partially obstructing the trachea. Care was taken in the ED to avoid all interventions such as IV access that might upset the child so as not to inadvertently convert this partial airway obstruction to a complete obstruction. The otolaryngology team was called urgently, and the patient was transported to the operating room for foreign body removal in a controlled environment.

Cases

Case 1

It’s a busy shift on an unusually chilly and rainy July night. Emergency medical services (EMS) brings in a 9-month-old boy who woke up with a “squeaking” noise. His parents reported that he has had a fever, cough, rhinorrhea, and difficulty breathing for the past 2 days; however, they did not hear the noisy breathing until the night of presentation. When the patient is examined, it is noted that he has inspiratory stridor at rest, moderate subcostal retractions, and an occasional deep cough. Upper airway transmitted noises were present, but otherwise the patient had clear lungs.

The patient’s vital signs at presentation were: blood pressure (BP), 85/55 mm Hg; heart rate (HR), 163 beats/min; respiratory rate (RR), 55 breaths/min; and temperature (T), 101.8°F. Oxygen saturation was 90% on room air. The patient’s mother wants to know how the respiratory distress will be fixed and is inquiring if they will have to stay in the hospital overnight.

Case 2

As work begins on the child described above, EMS brings in a 3-year-old girl who appears to be in moderate-severe respiratory distress. Her parents report that she started to drool earlier in the day followed by coughing and occasional gagging. Her parents relay that they thought the symptoms were because of post-nasal drip due to her cold, but the respiratory distress seems to be getting worse, and she now has very noisy breathing and is reluctant to lay down. Upon examination, both inspiratory and expiratory stridor is heard, and it is noted that moderate subcostal retractions are present when the patient is supine.

The patient’s vital signs at presentation were: BP, 89/58 mm Hg; HR, 144 beats/min; RR, 52 breaths/min; and T, 99.5°F. Oxygen saturation was 88% on room air. The nursing staff asked what to do next and why the 2 stridor cases are being managed so differently.

Stridor

Stridor is a high-pitched, harsh sound heard during respiration, predominantly during inspiration, as a result of turbulent air passage.^1-3 Stridor is not a diagnosis in itself, but rather a sign of underlying acute or chronic etiology, which needs to be classified based on elicited history and examination.^1,4 While the etiology of obstruction may be infectious, congenital, mechanical, or traumatic, the distinct features of the pediatric airway make respiratory failure an important concern independent of the underlying cause.

Anatomy

There are several anatomical differences unique to the pediatric airway that make children, especially infants under 1 year of age, more susceptible to airway obstruction.^5,6The pediatric larynx is more anterior and superior and less fibrous than adults, thereby more compliant.^6,7 The pediatric epiglottis is longer, omega-shaped, and softer, and the tongue is larger in comparison to the size of the oral cavity, resulting in obstructed airflow.^6,7 Children also have a larger and more prominent occiput, causing mechanical obstruction by flexion of the neck when supine.⁶ While the cricoid cartilage was previously believed to be the narrowest portion of the airway, more recent measurement techniques have challenged this and shown that the glottic and subglottic areas may be narrower in children.^7,8

Worsening obstruction resulting in a decreased airway radius leads to increased turbulence to air flow, which is explained by Poiseuille’s law.^1,2,7 The resistance to airflow becomes inversely related to the fourth power of the radius, so even a small change in an already narrow pediatric airway can make a huge difference.⁵ In practice, this means 1 mm of mucosal edema will decrease the cross-sectional area of the airway by 75% and increase the resistance of airflow by a magnitude of 16 to 32 times depending on the level of turbulence.⁷The airway can be divided into extrathoracic and intrathoracic regions, separated by the vocal cords.¹³ Inspiratory stridor is typically due to extrathoracic obstruction and expiratory stridor is due to intrathoracic obstruction below the level of the cords. Biphasic stridor, however, may indicate a fixed obstruction at the level of the cords.^2,3,5,9

Acute Differentials

The pediatric patient is at high risk for respiratory decompensation when the upper airway is acutely compromised. The history, physical examination, and phases of stridor can help determine the underlying diagnosis and definitive treatment plan.

Acute Croup

Acute croup (laryngotracheitis) is a clinical diagnosis based on acute onset of barky cough and inspiratory stridor.¹ It is usually secondary to an infection, most commonly viral (parainfluenza virus), resulting in edema and increased secretions of the subglottic mucosa.⁷ The onset is typically preceded by upper respiratory illness (URI) symptoms, and is often worse at night or after waking from a nap.¹ The peak incidence is between ages 6 months to 3 years. While croup is a clinical diagnosis, an anteroposterior X-ray will often show a steeple sign.^7,10

Spasmodic Croup

Spasmodic croup is an atypical presentation usually seen in children 8 years or older without a preceding URI. Patients will wake up overnight with a harsh brass-like cough, stridor, and hoarse voice. The etiology is unclear, but often these patients have a history of atopy and respond in part to treatment with antihistamines.

Foreign Body Aspiration

All that is acutely stridulous is not croup. Stridor from foreign body aspiration is sudden in onset and children do not always present with a history suggestive of foreign body aspiration. Diagnosis requires a high index of suspicion because the event is often unwitnessed and typical patients are pre-verbal. The physical examination may reveal diminished air entry along with stridor. Diagnosis is made by obtaining an X-ray (lateral neck [Figure 1], lateral decubitus, or inspiratory/expiratory chest X-ray) or by bronchoscopy which is both diagnostic and therapeutic.^7,10 Remember to always think of foreign body aspiration in children with acute stridor who have neither fever nor antecedent URI symptoms.

Bacterial Tracheitis

Bacterial tracheitis should be suspected in toxic appearing children who present with respiratory distress and stridor but who have a poor response to nebulized epinephrine. It is typically seen in toddlers and school-aged children, and like a viral tracheitis, presentation can be preceded by either URI or fever.¹⁰ Stridor is caused by subglottic edema and mucopurulent secretions in the airway.^7,10 Infection is most commonly by S. aureus but initial antibiotic choice should be broad spectrum, and include a third-generation cephalosporin or beta-lactamase resistant penicillin.

Epiglottitis

Epiglottitis is edema of the epiglottis, most commonly secondary to bacterial infection. The epidemiology of epiglottitis has changed dramatically since widespread immunization for H. influenza with a significantly decreased incidence and change in the average age of presentation to 14.6 years (previously 5.6 years).⁷ The clinical course begins with sore throat, dysphonia, refusal to eat and progressive difficulty handling secretions with eventual drooling, stridor, tripoding, and toxic appearance. Epiglottitis can be differentiated from croup and bacterial tracheitis because presentation typically lacks a cough.^7,10,11 Diagnosis is made either by direct visualization of the epiglottis or a lateral neck X-ray showing a ‘thumb print’ sign (Figure 2).¹² Emergency department treatment is similar to the management of the child with a partial foreign body occlusion and focuses on maintaining the airway and minimizing anything that agitates the patient. Intravenous (IV) antibiotic coverage is similar to bacterial tracheitis (third-generation cephalosporin or a beta-lactamase resistant penicillin).

Retropharyngeal Abscess

The most common chief complaint of retropharyngeal abscess (RPA) is neck pain (38%) with fever. As such, it can clinically be mistaken for meningitis on initial presentation. Retropharyngeal abscess will present rarely with either stridor or associated respiratory distress, and it can also mimic croup on initial presentation. Physical examination findings which differentiate this entity include limited or painful neck extension (45%), torticollis (36.5%), and to a lesser extent limitation of neck flexion (12.5%).¹³ The median age at diagnosis is 36 months with 75% of patients less than 5 years. Typical presentation is insidious with fever and URI symptoms preceding onset. Diagnosis can be made with a lateral neck X-ray showing widening of the prevertebral space (Figure 3), but the gold standard diagnostic study is a computed tomography with contrast.¹⁴ Management is IV antibiotics covering aerobic and anaerobic bacteria (eg, ampicillin-sulbactam) ± surgical intervention.

Caustic Ingestion

Caustic ingestion is most commonly accidental and seen in children aged 12 months to 2 years. However, with recent fads, such as the “Tide Pod challenge” teenagers are also at risk. Airway compromise and stridor are secondary to mucosal injury and edema. Oral injury is not always a useful marker for significant distal injury. A complete evaluation of the upper airway and digestive tract within 48 hours after known/suspected caustic ingestion is recommended to assess full extent of damage.¹⁵

Chronic Differentials

Laryngomalacia

Laryngomalacia is a congenital weakness of laryngeal tissues, and it is the most common cause of both chronic stridor and neonatal stridor. It is characterized by progressive worsening of symptoms with crying/feeding and supine positioning. Diagnosis is made by bronchoscopy and management is conservative unless there are life threatening apneic or cyanotic events.⁷

Rings/Slings

There are many anatomic structures with the potential to cause extrinsic airway compression which present with stridor. This type of stridor is often biphasic. Examples include innominate artery compression, double aortic arch, aberrant subclavian artery, and pulmonary artery sling.⁷

Stridor presenting in children with a history of prematurity or prolonged intubation should raise concern for subglottic and tracheal stenosis.¹⁶

Evaluation

Regardless of the etiology of stridor, efforts should be made to keep the patient calm (ie, allow the parent to keep holding a young child, limit any examination not absolutely necessary). Much of the examination can be completed from a distance without disturbing the child.¹⁷ Observation of the inspiratory:expiratory (I:E) ratio can localize the level of airway obstruction. For example, an I:E ratio weighted toward a longer inspiration indicates an extrathoracic airway obstruction. Whereas an I:E with a prolonged expiratory phase is consistent with intrathoracic obstruction (eg, terminal bronchial obstruction).¹⁷

Another way to localize the level of obstruction is to look for changes in the voice; patients who present with a change in their voice have a subglottic partial obstruction such as croup. However, patients with a muffled voice or drooling have a supraglottic obstruction such as epiglottitis or RPA.¹⁷

Management

Management of stridor focuses on reducing airway obstruction, which is usually secondary to edema in the acute setting.

Viral Laryngotracheitis

Oral steroids are the mainstay of treatment. Research has shown dexamethasone is preferred over prednisolone.^18-20 Steroids are not only useful in moderate to severe laryngotracheitis but also have a therapeutic role in children with mild laryngotracheitis.¹⁸ In hospital settings the parenteral formulation of dexamethasone can be safely given orally with good effect. There is no therapeutic advantage in acute laryngotracheitis to giving dexamethasone via either the IV or intramuscular route vs oral.²¹ In the outpatient setting, decadron tablets can be crushed and mixed in with a young child’s favorite soft food (eg, mashed potatoes or apple sauce). The authors recommend this strategy in lieu of prescribing dexamethasone suspension as its dilute concentration (1 mg/10 ml) results in a need for a child to receive a relatively large volume of a distasteful liquid. There is a wide therapeutic range of dexamethasone with studies documenting efficacy for laryngotracheitis in doses ranging from 0.15 mg/kg to 0.6 mg/kg. To date there are no large studies which demonstrate routine therapeutic utility of subsequent doses of dexamethasone. Nebulized budesonide (2.5 mg) can be given if oral steroids are not tolerated, however it is significantly more expensive.

Racemic epinephrine is the agent of choice for rapid onset of action in children who demonstrate stridor at rest. It causes vasoconstriction in the laryngeal mucosa, promotes bronchial smooth muscle relaxation, and thinning of bronchial secretions. It offers short-term relief of symptoms until steroids start to work. There is no rebound effect or worsening of symptoms once the epinephrine wears off, but children who receive this drug should be observed in the ED for a period of time (2-3 hours is standard of care in many hospitals) for return of symptoms.^10,22 Patients who are persistently symptomatic 4 hours after administration of steroids or who require repeat doses of racemic epinephrine should be admitted for observation.¹⁰There are no contraindications to adjuvant treatments, such as antipyretics and non-sedating analgesics. Clinicians should maintain a high index of suspicion for anatomic airway anomalies that may need further evaluation/direct visualization in pediatric patients who present with repeated episodes of croup.¹⁰

Case Conclusions

Case 1

The 9-month-old boy with stridor was noted to have increased stridor while fussy, but even at rest some inspiratory stridor was present. A barky cough was noted in the examination room. The patient was placed on a monitor and a nebulized racemic epinephrine treatment was started. A single dose of oral dexamethasone was given shortly after presentation to the ED. Since the patient had inspiratory stridor at rest with associated tachypnea and hypoxia on initial presentation, a neck X-ray was obtained (Figure 4). Subglottic narrowing was identified on the imaging, but both the epiglottis and the prevertebral space were normal in appearance and no foreign bodies were visualized. The inspiratory stridor at rest, tachypnea, and mild hypoxia all improved after treatment, the patient was observed for 2 hours in the ED without recurrence of respiratory distress and was able to be discharged home with a diagnosis of acute croup.

Case 2

The 3-year-old girl was noted to be in significant positional respiratory distress, so the physician asked her parents to keep her calm in her position of comfort. She was calmly and quickly placed on a monitor with age-appropriate distraction techniques in place and advanced airway equipment at the bedside. A portable chest X-ray was obtained and revealed a coin was partially obstructing the trachea. Care was taken in the ED to avoid all interventions such as IV access that might upset the child so as not to inadvertently convert this partial airway obstruction to a complete obstruction. The otolaryngology team was called urgently, and the patient was transported to the operating room for foreign body removal in a controlled environment.

Cases

Case 1

It’s a busy shift on an unusually chilly and rainy July night. Emergency medical services (EMS) brings in a 9-month-old boy who woke up with a “squeaking” noise. His parents reported that he has had a fever, cough, rhinorrhea, and difficulty breathing for the past 2 days; however, they did not hear the noisy breathing until the night of presentation. When the patient is examined, it is noted that he has inspiratory stridor at rest, moderate subcostal retractions, and an occasional deep cough. Upper airway transmitted noises were present, but otherwise the patient had clear lungs.

The patient’s vital signs at presentation were: blood pressure (BP), 85/55 mm Hg; heart rate (HR), 163 beats/min; respiratory rate (RR), 55 breaths/min; and temperature (T), 101.8°F. Oxygen saturation was 90% on room air. The patient’s mother wants to know how the respiratory distress will be fixed and is inquiring if they will have to stay in the hospital overnight.

Case 2

As work begins on the child described above, EMS brings in a 3-year-old girl who appears to be in moderate-severe respiratory distress. Her parents report that she started to drool earlier in the day followed by coughing and occasional gagging. Her parents relay that they thought the symptoms were because of post-nasal drip due to her cold, but the respiratory distress seems to be getting worse, and she now has very noisy breathing and is reluctant to lay down. Upon examination, both inspiratory and expiratory stridor is heard, and it is noted that moderate subcostal retractions are present when the patient is supine.

The patient’s vital signs at presentation were: BP, 89/58 mm Hg; HR, 144 beats/min; RR, 52 breaths/min; and T, 99.5°F. Oxygen saturation was 88% on room air. The nursing staff asked what to do next and why the 2 stridor cases are being managed so differently.

Stridor

Stridor is a high-pitched, harsh sound heard during respiration, predominantly during inspiration, as a result of turbulent air passage.^1-3 Stridor is not a diagnosis in itself, but rather a sign of underlying acute or chronic etiology, which needs to be classified based on elicited history and examination.^1,4 While the etiology of obstruction may be infectious, congenital, mechanical, or traumatic, the distinct features of the pediatric airway make respiratory failure an important concern independent of the underlying cause.

Anatomy

There are several anatomical differences unique to the pediatric airway that make children, especially infants under 1 year of age, more susceptible to airway obstruction.^5,6The pediatric larynx is more anterior and superior and less fibrous than adults, thereby more compliant.^6,7 The pediatric epiglottis is longer, omega-shaped, and softer, and the tongue is larger in comparison to the size of the oral cavity, resulting in obstructed airflow.^6,7 Children also have a larger and more prominent occiput, causing mechanical obstruction by flexion of the neck when supine.⁶ While the cricoid cartilage was previously believed to be the narrowest portion of the airway, more recent measurement techniques have challenged this and shown that the glottic and subglottic areas may be narrower in children.^7,8

Worsening obstruction resulting in a decreased airway radius leads to increased turbulence to air flow, which is explained by Poiseuille’s law.^1,2,7 The resistance to airflow becomes inversely related to the fourth power of the radius, so even a small change in an already narrow pediatric airway can make a huge difference.⁵ In practice, this means 1 mm of mucosal edema will decrease the cross-sectional area of the airway by 75% and increase the resistance of airflow by a magnitude of 16 to 32 times depending on the level of turbulence.⁷The airway can be divided into extrathoracic and intrathoracic regions, separated by the vocal cords.¹³ Inspiratory stridor is typically due to extrathoracic obstruction and expiratory stridor is due to intrathoracic obstruction below the level of the cords. Biphasic stridor, however, may indicate a fixed obstruction at the level of the cords.^2,3,5,9

Acute Differentials

The pediatric patient is at high risk for respiratory decompensation when the upper airway is acutely compromised. The history, physical examination, and phases of stridor can help determine the underlying diagnosis and definitive treatment plan.

Acute Croup

Acute croup (laryngotracheitis) is a clinical diagnosis based on acute onset of barky cough and inspiratory stridor.¹ It is usually secondary to an infection, most commonly viral (parainfluenza virus), resulting in edema and increased secretions of the subglottic mucosa.⁷ The onset is typically preceded by upper respiratory illness (URI) symptoms, and is often worse at night or after waking from a nap.¹ The peak incidence is between ages 6 months to 3 years. While croup is a clinical diagnosis, an anteroposterior X-ray will often show a steeple sign.^7,10

Spasmodic Croup

Spasmodic croup is an atypical presentation usually seen in children 8 years or older without a preceding URI. Patients will wake up overnight with a harsh brass-like cough, stridor, and hoarse voice. The etiology is unclear, but often these patients have a history of atopy and respond in part to treatment with antihistamines.

Foreign Body Aspiration

All that is acutely stridulous is not croup. Stridor from foreign body aspiration is sudden in onset and children do not always present with a history suggestive of foreign body aspiration. Diagnosis requires a high index of suspicion because the event is often unwitnessed and typical patients are pre-verbal. The physical examination may reveal diminished air entry along with stridor. Diagnosis is made by obtaining an X-ray (lateral neck [Figure 1], lateral decubitus, or inspiratory/expiratory chest X-ray) or by bronchoscopy which is both diagnostic and therapeutic.^7,10 Remember to always think of foreign body aspiration in children with acute stridor who have neither fever nor antecedent URI symptoms.

Bacterial Tracheitis

Bacterial tracheitis should be suspected in toxic appearing children who present with respiratory distress and stridor but who have a poor response to nebulized epinephrine. It is typically seen in toddlers and school-aged children, and like a viral tracheitis, presentation can be preceded by either URI or fever.¹⁰ Stridor is caused by subglottic edema and mucopurulent secretions in the airway.^7,10 Infection is most commonly by S. aureus but initial antibiotic choice should be broad spectrum, and include a third-generation cephalosporin or beta-lactamase resistant penicillin.

Epiglottitis

Epiglottitis is edema of the epiglottis, most commonly secondary to bacterial infection. The epidemiology of epiglottitis has changed dramatically since widespread immunization for H. influenza with a significantly decreased incidence and change in the average age of presentation to 14.6 years (previously 5.6 years).⁷ The clinical course begins with sore throat, dysphonia, refusal to eat and progressive difficulty handling secretions with eventual drooling, stridor, tripoding, and toxic appearance. Epiglottitis can be differentiated from croup and bacterial tracheitis because presentation typically lacks a cough.^7,10,11 Diagnosis is made either by direct visualization of the epiglottis or a lateral neck X-ray showing a ‘thumb print’ sign (Figure 2).¹² Emergency department treatment is similar to the management of the child with a partial foreign body occlusion and focuses on maintaining the airway and minimizing anything that agitates the patient. Intravenous (IV) antibiotic coverage is similar to bacterial tracheitis (third-generation cephalosporin or a beta-lactamase resistant penicillin).

Retropharyngeal Abscess

The most common chief complaint of retropharyngeal abscess (RPA) is neck pain (38%) with fever. As such, it can clinically be mistaken for meningitis on initial presentation. Retropharyngeal abscess will present rarely with either stridor or associated respiratory distress, and it can also mimic croup on initial presentation. Physical examination findings which differentiate this entity include limited or painful neck extension (45%), torticollis (36.5%), and to a lesser extent limitation of neck flexion (12.5%).¹³ The median age at diagnosis is 36 months with 75% of patients less than 5 years. Typical presentation is insidious with fever and URI symptoms preceding onset. Diagnosis can be made with a lateral neck X-ray showing widening of the prevertebral space (Figure 3), but the gold standard diagnostic study is a computed tomography with contrast.¹⁴ Management is IV antibiotics covering aerobic and anaerobic bacteria (eg, ampicillin-sulbactam) ± surgical intervention.

Caustic Ingestion

Caustic ingestion is most commonly accidental and seen in children aged 12 months to 2 years. However, with recent fads, such as the “Tide Pod challenge” teenagers are also at risk. Airway compromise and stridor are secondary to mucosal injury and edema. Oral injury is not always a useful marker for significant distal injury. A complete evaluation of the upper airway and digestive tract within 48 hours after known/suspected caustic ingestion is recommended to assess full extent of damage.¹⁵

Chronic Differentials

Laryngomalacia

Laryngomalacia is a congenital weakness of laryngeal tissues, and it is the most common cause of both chronic stridor and neonatal stridor. It is characterized by progressive worsening of symptoms with crying/feeding and supine positioning. Diagnosis is made by bronchoscopy and management is conservative unless there are life threatening apneic or cyanotic events.⁷

Rings/Slings

There are many anatomic structures with the potential to cause extrinsic airway compression which present with stridor. This type of stridor is often biphasic. Examples include innominate artery compression, double aortic arch, aberrant subclavian artery, and pulmonary artery sling.⁷

Stridor presenting in children with a history of prematurity or prolonged intubation should raise concern for subglottic and tracheal stenosis.¹⁶

Evaluation

Regardless of the etiology of stridor, efforts should be made to keep the patient calm (ie, allow the parent to keep holding a young child, limit any examination not absolutely necessary). Much of the examination can be completed from a distance without disturbing the child.¹⁷ Observation of the inspiratory:expiratory (I:E) ratio can localize the level of airway obstruction. For example, an I:E ratio weighted toward a longer inspiration indicates an extrathoracic airway obstruction. Whereas an I:E with a prolonged expiratory phase is consistent with intrathoracic obstruction (eg, terminal bronchial obstruction).¹⁷

Another way to localize the level of obstruction is to look for changes in the voice; patients who present with a change in their voice have a subglottic partial obstruction such as croup. However, patients with a muffled voice or drooling have a supraglottic obstruction such as epiglottitis or RPA.¹⁷

Management

Management of stridor focuses on reducing airway obstruction, which is usually secondary to edema in the acute setting.

Viral Laryngotracheitis

Oral steroids are the mainstay of treatment. Research has shown dexamethasone is preferred over prednisolone.^18-20 Steroids are not only useful in moderate to severe laryngotracheitis but also have a therapeutic role in children with mild laryngotracheitis.¹⁸ In hospital settings the parenteral formulation of dexamethasone can be safely given orally with good effect. There is no therapeutic advantage in acute laryngotracheitis to giving dexamethasone via either the IV or intramuscular route vs oral.²¹ In the outpatient setting, decadron tablets can be crushed and mixed in with a young child’s favorite soft food (eg, mashed potatoes or apple sauce). The authors recommend this strategy in lieu of prescribing dexamethasone suspension as its dilute concentration (1 mg/10 ml) results in a need for a child to receive a relatively large volume of a distasteful liquid. There is a wide therapeutic range of dexamethasone with studies documenting efficacy for laryngotracheitis in doses ranging from 0.15 mg/kg to 0.6 mg/kg. To date there are no large studies which demonstrate routine therapeutic utility of subsequent doses of dexamethasone. Nebulized budesonide (2.5 mg) can be given if oral steroids are not tolerated, however it is significantly more expensive.

Racemic epinephrine is the agent of choice for rapid onset of action in children who demonstrate stridor at rest. It causes vasoconstriction in the laryngeal mucosa, promotes bronchial smooth muscle relaxation, and thinning of bronchial secretions. It offers short-term relief of symptoms until steroids start to work. There is no rebound effect or worsening of symptoms once the epinephrine wears off, but children who receive this drug should be observed in the ED for a period of time (2-3 hours is standard of care in many hospitals) for return of symptoms.^10,22 Patients who are persistently symptomatic 4 hours after administration of steroids or who require repeat doses of racemic epinephrine should be admitted for observation.¹⁰There are no contraindications to adjuvant treatments, such as antipyretics and non-sedating analgesics. Clinicians should maintain a high index of suspicion for anatomic airway anomalies that may need further evaluation/direct visualization in pediatric patients who present with repeated episodes of croup.¹⁰

Case Conclusions

Case 1

The 9-month-old boy with stridor was noted to have increased stridor while fussy, but even at rest some inspiratory stridor was present. A barky cough was noted in the examination room. The patient was placed on a monitor and a nebulized racemic epinephrine treatment was started. A single dose of oral dexamethasone was given shortly after presentation to the ED. Since the patient had inspiratory stridor at rest with associated tachypnea and hypoxia on initial presentation, a neck X-ray was obtained (Figure 4). Subglottic narrowing was identified on the imaging, but both the epiglottis and the prevertebral space were normal in appearance and no foreign bodies were visualized. The inspiratory stridor at rest, tachypnea, and mild hypoxia all improved after treatment, the patient was observed for 2 hours in the ED without recurrence of respiratory distress and was able to be discharged home with a diagnosis of acute croup.

Case 2

The 3-year-old girl was noted to be in significant positional respiratory distress, so the physician asked her parents to keep her calm in her position of comfort. She was calmly and quickly placed on a monitor with age-appropriate distraction techniques in place and advanced airway equipment at the bedside. A portable chest X-ray was obtained and revealed a coin was partially obstructing the trachea. Care was taken in the ED to avoid all interventions such as IV access that might upset the child so as not to inadvertently convert this partial airway obstruction to a complete obstruction. The otolaryngology team was called urgently, and the patient was transported to the operating room for foreign body removal in a controlled environment.

PARIS – A one-way endobronchial valve placed in the lungs of emphysema patients with hyperinflation provides acceptable safety and clinically significant improvement in lung function at 12 months, according to results from a multicenter trial presented as a late-breaker at the annual congress of the European Respiratory Society.

Ted Bosworth/MDedge News

Six-month results have been presented previously, but the 12-month results suggest that lung volume reduction associated with placement of the valves provides “durable effectiveness in appropriately selected hyperinflated emphysema patients,” according to Gerard Criner, MD, chair of the thoracic medicine department at Temple University, Philadelphia.

In this randomized controlled trial, called EMPROVE, 172 emphysema patients with severe dyspnea were randomized in a 2:1 fashion to receive a proprietary endobronchial valve or medical therapy alone. The valve, marketed under the brand name Spiration Valve System (SVS), is currently indicated for the treatment of air leaks after lung surgery.

“The valve serves to block airflow from edematous lungs with the objective of blocking hyperinflation and improving lung function,” Dr. Criner explained. The valves are retrievable, if necessary, with bronchoscopy.

High resolution computed tomography (HRCT) was used to identify emphysema obstruction and target valve placement to the most diseased lobes. The average number of valves placed per patient was slightly less than four. Most of the valves (70%) were placed in an upper lobe.

When reported at 6 months, the responder rate, defined as at least 15% improvement in forced expiratory volume in 1 second (FEV₁) was 36.8% and 10% in the SVS and control groups, respectively, a difference of 25.7% that Dr. Criner reported as statistically significant although he did not provide P values. At 12 months, the rates were 37.2% and 5.1%, respectively, demonstrating a persistent effect.

Thoracic adverse events were higher at both 6 months (31% vs. 11.9%) and 12 months (21.4% vs. 10.6%) in the treatment group relative to the control group. At 6 months, pneumothorax, which Dr. Criner characterized as “a recognized marker of target lobe volume reduction,” was the only event that occurred significantly more commonly (14.2% vs. 0%) in the SVS group.

Between 6 and 12 months, there were no pneumothorax events in either arm. The higher numerical rates of thoracic adverse events in the treatment arm were acute exacerbations (13.6% vs. 8.5%) and pneumonia in nontreated lobes (7.8% vs. 2.1%), but these rates were not statistically different.

At 6 months, there was a numerically higher rate of all-cause mortality in the treatment group (5.3% vs. 1.7%) but the rate was numerically lower between 6 and 12 months (2.9% vs. 6.4%). The differences were not significantly different at either time point or overall.

A significant reduction in hyperinflation favoring valve placement was accompanied by improvement in objective measures of lung function, such as FEV₁, and dyspnea, as measured with the Modified Medical Research Council (mMRC) Dyspnea Scale, at 6 and 12 months. These improvements translated into persistent quality of life benefits as measured with the St. George Respiratory Questionnaire (SGRQ). At 12 months, the SGRQ changes from baseline were a 5.5-point reduction and a four-point gain in the treatment and control groups, respectively. This absolute difference of 9.5 points is slightly more modest than the 13-point difference at 6 months (–8 vs. +5 points), but demonstrates a durable effect, Dr. Criner reported.

According to Dr. Criner, EMPROVE reinforces the principle that HRCT is effective “for selecting the lobe for therapy and which patients may benefit,” but the most important message from the 12-month results is persistent clinical benefit.

The endobronchial values “provide statistically and clinically meaningful improvements in FEV₁, reductions in lobe volume and dyspnea, and improvements in quality of life with an acceptable safety profile,” Dr. Criner reported.

On June 29, 2018, the Food and Drug Administration approved the first endobronchial valve for treatment of emphysema. This valve, marketed under the name Zephyr, was approved on the basis of the pivotal LIBERATE trial, also led by Dr. Criner and published earlier this year (Am J Respir Crit Care Med. 2018 May 22. doi: 10.1164/rccm.201803-0590OC.). The results of EMPROVE are consistent with previous evidence that a one-way valve, by preventing air from entering diseased lobes of patients with emphysema to exacerbate hyperinflation, improves lung function and reduces clinical symptoms.

Dr. Criner reports financial relationships with Olympus, the sponsor of this trial.

PARIS – A one-way endobronchial valve placed in the lungs of emphysema patients with hyperinflation provides acceptable safety and clinically significant improvement in lung function at 12 months, according to results from a multicenter trial presented as a late-breaker at the annual congress of the European Respiratory Society.

Ted Bosworth/MDedge News

Six-month results have been presented previously, but the 12-month results suggest that lung volume reduction associated with placement of the valves provides “durable effectiveness in appropriately selected hyperinflated emphysema patients,” according to Gerard Criner, MD, chair of the thoracic medicine department at Temple University, Philadelphia.

In this randomized controlled trial, called EMPROVE, 172 emphysema patients with severe dyspnea were randomized in a 2:1 fashion to receive a proprietary endobronchial valve or medical therapy alone. The valve, marketed under the brand name Spiration Valve System (SVS), is currently indicated for the treatment of air leaks after lung surgery.

“The valve serves to block airflow from edematous lungs with the objective of blocking hyperinflation and improving lung function,” Dr. Criner explained. The valves are retrievable, if necessary, with bronchoscopy.

High resolution computed tomography (HRCT) was used to identify emphysema obstruction and target valve placement to the most diseased lobes. The average number of valves placed per patient was slightly less than four. Most of the valves (70%) were placed in an upper lobe.

When reported at 6 months, the responder rate, defined as at least 15% improvement in forced expiratory volume in 1 second (FEV₁) was 36.8% and 10% in the SVS and control groups, respectively, a difference of 25.7% that Dr. Criner reported as statistically significant although he did not provide P values. At 12 months, the rates were 37.2% and 5.1%, respectively, demonstrating a persistent effect.

Thoracic adverse events were higher at both 6 months (31% vs. 11.9%) and 12 months (21.4% vs. 10.6%) in the treatment group relative to the control group. At 6 months, pneumothorax, which Dr. Criner characterized as “a recognized marker of target lobe volume reduction,” was the only event that occurred significantly more commonly (14.2% vs. 0%) in the SVS group.

Between 6 and 12 months, there were no pneumothorax events in either arm. The higher numerical rates of thoracic adverse events in the treatment arm were acute exacerbations (13.6% vs. 8.5%) and pneumonia in nontreated lobes (7.8% vs. 2.1%), but these rates were not statistically different.

At 6 months, there was a numerically higher rate of all-cause mortality in the treatment group (5.3% vs. 1.7%) but the rate was numerically lower between 6 and 12 months (2.9% vs. 6.4%). The differences were not significantly different at either time point or overall.

A significant reduction in hyperinflation favoring valve placement was accompanied by improvement in objective measures of lung function, such as FEV₁, and dyspnea, as measured with the Modified Medical Research Council (mMRC) Dyspnea Scale, at 6 and 12 months. These improvements translated into persistent quality of life benefits as measured with the St. George Respiratory Questionnaire (SGRQ). At 12 months, the SGRQ changes from baseline were a 5.5-point reduction and a four-point gain in the treatment and control groups, respectively. This absolute difference of 9.5 points is slightly more modest than the 13-point difference at 6 months (–8 vs. +5 points), but demonstrates a durable effect, Dr. Criner reported.

According to Dr. Criner, EMPROVE reinforces the principle that HRCT is effective “for selecting the lobe for therapy and which patients may benefit,” but the most important message from the 12-month results is persistent clinical benefit.

The endobronchial values “provide statistically and clinically meaningful improvements in FEV₁, reductions in lobe volume and dyspnea, and improvements in quality of life with an acceptable safety profile,” Dr. Criner reported.

On June 29, 2018, the Food and Drug Administration approved the first endobronchial valve for treatment of emphysema. This valve, marketed under the name Zephyr, was approved on the basis of the pivotal LIBERATE trial, also led by Dr. Criner and published earlier this year (Am J Respir Crit Care Med. 2018 May 22. doi: 10.1164/rccm.201803-0590OC.). The results of EMPROVE are consistent with previous evidence that a one-way valve, by preventing air from entering diseased lobes of patients with emphysema to exacerbate hyperinflation, improves lung function and reduces clinical symptoms.

Dr. Criner reports financial relationships with Olympus, the sponsor of this trial.

PARIS – A one-way endobronchial valve placed in the lungs of emphysema patients with hyperinflation provides acceptable safety and clinically significant improvement in lung function at 12 months, according to results from a multicenter trial presented as a late-breaker at the annual congress of the European Respiratory Society.

Ted Bosworth/MDedge News

Six-month results have been presented previously, but the 12-month results suggest that lung volume reduction associated with placement of the valves provides “durable effectiveness in appropriately selected hyperinflated emphysema patients,” according to Gerard Criner, MD, chair of the thoracic medicine department at Temple University, Philadelphia.

In this randomized controlled trial, called EMPROVE, 172 emphysema patients with severe dyspnea were randomized in a 2:1 fashion to receive a proprietary endobronchial valve or medical therapy alone. The valve, marketed under the brand name Spiration Valve System (SVS), is currently indicated for the treatment of air leaks after lung surgery.

“The valve serves to block airflow from edematous lungs with the objective of blocking hyperinflation and improving lung function,” Dr. Criner explained. The valves are retrievable, if necessary, with bronchoscopy.

High resolution computed tomography (HRCT) was used to identify emphysema obstruction and target valve placement to the most diseased lobes. The average number of valves placed per patient was slightly less than four. Most of the valves (70%) were placed in an upper lobe.

When reported at 6 months, the responder rate, defined as at least 15% improvement in forced expiratory volume in 1 second (FEV₁) was 36.8% and 10% in the SVS and control groups, respectively, a difference of 25.7% that Dr. Criner reported as statistically significant although he did not provide P values. At 12 months, the rates were 37.2% and 5.1%, respectively, demonstrating a persistent effect.

Thoracic adverse events were higher at both 6 months (31% vs. 11.9%) and 12 months (21.4% vs. 10.6%) in the treatment group relative to the control group. At 6 months, pneumothorax, which Dr. Criner characterized as “a recognized marker of target lobe volume reduction,” was the only event that occurred significantly more commonly (14.2% vs. 0%) in the SVS group.

Between 6 and 12 months, there were no pneumothorax events in either arm. The higher numerical rates of thoracic adverse events in the treatment arm were acute exacerbations (13.6% vs. 8.5%) and pneumonia in nontreated lobes (7.8% vs. 2.1%), but these rates were not statistically different.

At 6 months, there was a numerically higher rate of all-cause mortality in the treatment group (5.3% vs. 1.7%) but the rate was numerically lower between 6 and 12 months (2.9% vs. 6.4%). The differences were not significantly different at either time point or overall.

A significant reduction in hyperinflation favoring valve placement was accompanied by improvement in objective measures of lung function, such as FEV₁, and dyspnea, as measured with the Modified Medical Research Council (mMRC) Dyspnea Scale, at 6 and 12 months. These improvements translated into persistent quality of life benefits as measured with the St. George Respiratory Questionnaire (SGRQ). At 12 months, the SGRQ changes from baseline were a 5.5-point reduction and a four-point gain in the treatment and control groups, respectively. This absolute difference of 9.5 points is slightly more modest than the 13-point difference at 6 months (–8 vs. +5 points), but demonstrates a durable effect, Dr. Criner reported.

According to Dr. Criner, EMPROVE reinforces the principle that HRCT is effective “for selecting the lobe for therapy and which patients may benefit,” but the most important message from the 12-month results is persistent clinical benefit.

The endobronchial values “provide statistically and clinically meaningful improvements in FEV₁, reductions in lobe volume and dyspnea, and improvements in quality of life with an acceptable safety profile,” Dr. Criner reported.

On June 29, 2018, the Food and Drug Administration approved the first endobronchial valve for treatment of emphysema. This valve, marketed under the name Zephyr, was approved on the basis of the pivotal LIBERATE trial, also led by Dr. Criner and published earlier this year (Am J Respir Crit Care Med. 2018 May 22. doi: 10.1164/rccm.201803-0590OC.). The results of EMPROVE are consistent with previous evidence that a one-way valve, by preventing air from entering diseased lobes of patients with emphysema to exacerbate hyperinflation, improves lung function and reduces clinical symptoms.

Dr. Criner reports financial relationships with Olympus, the sponsor of this trial.

SAN DIEGO – In the ICU, ultrasound has been shown to reduce the need for CT to evaluate potential pulmonary embolism. But in the ED, this strategy hasn’t worked out so far, according to Joseph Brown, MD, of the department of emergency medicine at the University of California, San Francisco.

Vidyard Video

Based on the data so far, the ED patients were less likely than the ICU patients to have another etiology identified on ultrasound that explained their symptoms. Further, ultrasound alone missed small subsegmental pulmonary emboli that were detected on subsequent CT scans in 2 of 11 patients.

The study is continuing, and Dr. Brown explains in this interview how ultrasound might be combined with other risk stratification measures to safely achieve reductions in CT scans.

SAN DIEGO – In the ICU, ultrasound has been shown to reduce the need for CT to evaluate potential pulmonary embolism. But in the ED, this strategy hasn’t worked out so far, according to Joseph Brown, MD, of the department of emergency medicine at the University of California, San Francisco.

Vidyard Video

Based on the data so far, the ED patients were less likely than the ICU patients to have another etiology identified on ultrasound that explained their symptoms. Further, ultrasound alone missed small subsegmental pulmonary emboli that were detected on subsequent CT scans in 2 of 11 patients.

The study is continuing, and Dr. Brown explains in this interview how ultrasound might be combined with other risk stratification measures to safely achieve reductions in CT scans.

SAN DIEGO – In the ICU, ultrasound has been shown to reduce the need for CT to evaluate potential pulmonary embolism. But in the ED, this strategy hasn’t worked out so far, according to Joseph Brown, MD, of the department of emergency medicine at the University of California, San Francisco.

Vidyard Video

Based on the data so far, the ED patients were less likely than the ICU patients to have another etiology identified on ultrasound that explained their symptoms. Further, ultrasound alone missed small subsegmental pulmonary emboli that were detected on subsequent CT scans in 2 of 11 patients.

The study is continuing, and Dr. Brown explains in this interview how ultrasound might be combined with other risk stratification measures to safely achieve reductions in CT scans.

Extracorporeal membrane oxygenation (ECMO) has become increasingly accepted as a rescue therapy for severe respiratory failure from a variety of conditions, though most commonly, the acute respiratory distress syndrome (ARDS) (Thiagarajan R, et al. ASAIO. 2017;63[1]:60). ECMO can provide respiratory or cardiorespiratory support for failing lungs, heart, or both. The most common ECMO configuration used in ARDS is venovenous ECMO, in which blood is withdrawn from a catheter placed in a central vein, pumped through a gas exchange device known as an oxygenator, and returned to the venous system via another catheter. The blood flowing through the oxygenator is separated from a continuous supply of oxygen-rich sweep gas by a semipermeable membrane, across which diffusion-mediated gas exchange occurs, so that the blood exiting it is rich in oxygen and low in carbon dioxide. As venovenous ECMO functions in series with the native circulation, the well-oxygenated blood exiting the ECMO circuit mixes with poorly oxygenated blood flowing through the lungs. Therefore, oxygenation is dependent on native cardiac output to achieve systemic oxygen delivery (Figure 1).

ECMO been used successfully in adults with ARDS since the early 1970s (Hill JD, et al. N Engl J Med. 1972;286[12]:629-34) but, until recently, was limited to small numbers of patients at select global centers and associated with a high-risk profile. In the last decade, however, driven by improvements in ECMO circuit components making the device safer and easier to use, encouraging worldwide experience during the 2009 influenza A (H1N1) pandemic (Davies A, et al. JAMA. 2009;302[17]1888-95), and publication of the Efficacy and Economic Assessment of Conventional Ventilatory Support versus Extracorporeal Membrane Oxygenation for Severe Adult Respiratory Failure (CESAR) trial (Peek GJ, et al. Lancet. 2009;374[9698]:1351-63), ECMO use has markedly increased.

Despite its rapid growth, however, rigorous evidence supporting the use of ECMO has been lacking. The CESAR trial, while impressive in execution, had methodological issues that limited the strength of its conclusions. CESAR was a pragmatic trial that randomized 180 adults with severe respiratory failure from multiple etiologies to conventional management or transfer to an experienced, ECMO-capable center. CESAR met its primary outcome of improved survival without disability in the ECMO-referred group (63% vs 47%, relative risk [RR] 0.69; 95% confidence interval [CI] 0.05 to 0.97, P=.03), but not all patients in that group ultimately received ECMO. In addition, the use of lung protective ventilation was significantly higher in the ECMO-referred group, making it difficult to separate its benefit from that of ECMO. A conservative interpretation is that CESAR showed the clinical benefit of treatment at an ECMO-capable center, experienced in the management of patients with severe respiratory failure.

Not until the release of the Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome (EOLIA) trial earlier this year (Combes A, et al. N Engl J Med. 2018;378[21]:1965-75), did a modern, randomized controlled trial evaluating the use of ECMO itself exist. The EOLIA trial addressed the limitations of CESAR and randomized adult patients with early, severe ARDS to conventional, standard of care management that included a protocolized lung protective strategy in the control group vs immediate initiation of ECMO combined with an ultra-lung protective strategy (targeting end-inspiratory plateau pressure ≤24 cmH2O) in the intervention group. The primary outcome was all-cause mortality at 60 days. Of note, patients enrolled in EOLIA met entry criteria despite greater than 90% of patients receiving neuromuscular blockade and around 60% treated with prone positioning at the time of randomization (importantly, 90% of control group patients ultimately underwent prone positioning).

EOLIA was powered to detect a 20% decrease in mortality in the ECMO group. Based on trial design and the results of the fourth interim analysis, the trial was stopped for futility to reach that endpoint after enrollment of 249 of a maximum 331 patients. Although a 20% mortality reduction was not achieved, 60-day mortality was notably lower in the ECMO-treated group (35% vs 46%, RR 0.76, 95% CI 0.55 to 1.04, P=.09). The key secondary outcome of risk of treatment failure (defined as death in the ECMO group and death or crossover to ECMO in the control group) favored the ECMO group with a RR for mortality of 0.62 (95% CI, 0.47 to 0.82; P<.001), as did other secondary endpoints such as days free of renal and other organ failure.

A major limitation of the trial was that 35 (28%) of control group patients ultimately crossed over to ECMO, which diluted the effect of ECMO observed in the intention-to-treat analysis. Crossover occurred at clinician discretion an average of 6.5 days after randomization and after stringent criteria for crossover was met. These patients were incredibly ill, with a median oxygen saturation of 77%, rapidly worsening inotropic scores, and lactic acidosis; nine individuals had already suffered cardiac arrest, and six had received ECMO as part of extracorporeal cardiopulmonary resuscitation (ECPR), the initiation of venoarterial ECMO during cardiac arrest in attempt to restore spontaneous circulation. Mortality was considerably worse in the crossover group than in conventionally managed cohort overall, and, notably, 33% of patients crossed over to ECMO still survived.

In order to estimate the effect of ECMO on survival times if crossover had not occurred, the authors performed a post-hoc, rank-preserving structural failure time analysis. Though this relies on some assessment regarding the effect of the treatment itself, it showed a hazard ratio for mortality in the ECMO group of 0.51 (95% CI 0.24 to 1.02, P=.055). Although the EOLIA trial was not positive by traditional interpretation, all three major analyses and all secondary endpoints suggest some degree of benefit in patients with severe ARDS managed with ECMO.

Importantly, ECMO was well tolerated (at least when performed at expert centers, as done in this trial). There were significantly more bleeding events and cases of severe thrombocytopenia in the ECMO-treated group, but massive hemorrhage, ischemic and hemorrhagic stroke, arrhythmias, and other complications were similar.

Where do we go from here? Based on the totality of information, it is reasonable to consider ECMO for cases of severe ARDS not responsive to conventional measures, such as a lung protective ventilator strategy, neuromuscular blockade, and prone positioning. Initiation of ECMO may be reasonable prior to implementation of standard of care therapies, in order to permit safe transfer to an experienced center from a center not able to provide them.

Two take-away points: First, it is important to recognize that much of the clinical benefit derived from ECMO may be beyond its ability to normalize gas exchange and be due, at least in part, to the fact that ECMO allows the enhancement of proven lung protective ventilatory strategies. Initiation of ECMO and the “lung rest” it permits reduce the mechanical power applied to the injured alveoli and may attenuate ventilator-induced lung injury, cytokine release, and multiorgan failure that portend poor clinical outcomes in ARDS. Second, ECMO in EOLIA was conducted at expert centers with relatively low rates of complications.

It is too early to know how the critical care community will view ECMO for ARDS in light of EOLIA as well as a growing body of global ECMO experience, or how its wider application may impact the distribution and organization of ECMO centers. Regardless, of paramount importance in using ECMO as a treatment modality is optimizing patient management both prior to and after its initiation.

Dr. Agerstrand is Assistant Professor of Medicine, Director of the Medical ECMO Program, Columbia University College of Physicians and Surgeons, New York-Presbyterian Hospital.


 

Extracorporeal membrane oxygenation (ECMO) has become increasingly accepted as a rescue therapy for severe respiratory failure from a variety of conditions, though most commonly, the acute respiratory distress syndrome (ARDS) (Thiagarajan R, et al. ASAIO. 2017;63[1]:60). ECMO can provide respiratory or cardiorespiratory support for failing lungs, heart, or both. The most common ECMO configuration used in ARDS is venovenous ECMO, in which blood is withdrawn from a catheter placed in a central vein, pumped through a gas exchange device known as an oxygenator, and returned to the venous system via another catheter. The blood flowing through the oxygenator is separated from a continuous supply of oxygen-rich sweep gas by a semipermeable membrane, across which diffusion-mediated gas exchange occurs, so that the blood exiting it is rich in oxygen and low in carbon dioxide. As venovenous ECMO functions in series with the native circulation, the well-oxygenated blood exiting the ECMO circuit mixes with poorly oxygenated blood flowing through the lungs. Therefore, oxygenation is dependent on native cardiac output to achieve systemic oxygen delivery (Figure 1).

ECMO been used successfully in adults with ARDS since the early 1970s (Hill JD, et al. N Engl J Med. 1972;286[12]:629-34) but, until recently, was limited to small numbers of patients at select global centers and associated with a high-risk profile. In the last decade, however, driven by improvements in ECMO circuit components making the device safer and easier to use, encouraging worldwide experience during the 2009 influenza A (H1N1) pandemic (Davies A, et al. JAMA. 2009;302[17]1888-95), and publication of the Efficacy and Economic Assessment of Conventional Ventilatory Support versus Extracorporeal Membrane Oxygenation for Severe Adult Respiratory Failure (CESAR) trial (Peek GJ, et al. Lancet. 2009;374[9698]:1351-63), ECMO use has markedly increased.

Despite its rapid growth, however, rigorous evidence supporting the use of ECMO has been lacking. The CESAR trial, while impressive in execution, had methodological issues that limited the strength of its conclusions. CESAR was a pragmatic trial that randomized 180 adults with severe respiratory failure from multiple etiologies to conventional management or transfer to an experienced, ECMO-capable center. CESAR met its primary outcome of improved survival without disability in the ECMO-referred group (63% vs 47%, relative risk [RR] 0.69; 95% confidence interval [CI] 0.05 to 0.97, P=.03), but not all patients in that group ultimately received ECMO. In addition, the use of lung protective ventilation was significantly higher in the ECMO-referred group, making it difficult to separate its benefit from that of ECMO. A conservative interpretation is that CESAR showed the clinical benefit of treatment at an ECMO-capable center, experienced in the management of patients with severe respiratory failure.

Not until the release of the Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome (EOLIA) trial earlier this year (Combes A, et al. N Engl J Med. 2018;378[21]:1965-75), did a modern, randomized controlled trial evaluating the use of ECMO itself exist. The EOLIA trial addressed the limitations of CESAR and randomized adult patients with early, severe ARDS to conventional, standard of care management that included a protocolized lung protective strategy in the control group vs immediate initiation of ECMO combined with an ultra-lung protective strategy (targeting end-inspiratory plateau pressure ≤24 cmH2O) in the intervention group. The primary outcome was all-cause mortality at 60 days. Of note, patients enrolled in EOLIA met entry criteria despite greater than 90% of patients receiving neuromuscular blockade and around 60% treated with prone positioning at the time of randomization (importantly, 90% of control group patients ultimately underwent prone positioning).

EOLIA was powered to detect a 20% decrease in mortality in the ECMO group. Based on trial design and the results of the fourth interim analysis, the trial was stopped for futility to reach that endpoint after enrollment of 249 of a maximum 331 patients. Although a 20% mortality reduction was not achieved, 60-day mortality was notably lower in the ECMO-treated group (35% vs 46%, RR 0.76, 95% CI 0.55 to 1.04, P=.09). The key secondary outcome of risk of treatment failure (defined as death in the ECMO group and death or crossover to ECMO in the control group) favored the ECMO group with a RR for mortality of 0.62 (95% CI, 0.47 to 0.82; P<.001), as did other secondary endpoints such as days free of renal and other organ failure.

A major limitation of the trial was that 35 (28%) of control group patients ultimately crossed over to ECMO, which diluted the effect of ECMO observed in the intention-to-treat analysis. Crossover occurred at clinician discretion an average of 6.5 days after randomization and after stringent criteria for crossover was met. These patients were incredibly ill, with a median oxygen saturation of 77%, rapidly worsening inotropic scores, and lactic acidosis; nine individuals had already suffered cardiac arrest, and six had received ECMO as part of extracorporeal cardiopulmonary resuscitation (ECPR), the initiation of venoarterial ECMO during cardiac arrest in attempt to restore spontaneous circulation. Mortality was considerably worse in the crossover group than in conventionally managed cohort overall, and, notably, 33% of patients crossed over to ECMO still survived.

In order to estimate the effect of ECMO on survival times if crossover had not occurred, the authors performed a post-hoc, rank-preserving structural failure time analysis. Though this relies on some assessment regarding the effect of the treatment itself, it showed a hazard ratio for mortality in the ECMO group of 0.51 (95% CI 0.24 to 1.02, P=.055). Although the EOLIA trial was not positive by traditional interpretation, all three major analyses and all secondary endpoints suggest some degree of benefit in patients with severe ARDS managed with ECMO.

Importantly, ECMO was well tolerated (at least when performed at expert centers, as done in this trial). There were significantly more bleeding events and cases of severe thrombocytopenia in the ECMO-treated group, but massive hemorrhage, ischemic and hemorrhagic stroke, arrhythmias, and other complications were similar.

Where do we go from here? Based on the totality of information, it is reasonable to consider ECMO for cases of severe ARDS not responsive to conventional measures, such as a lung protective ventilator strategy, neuromuscular blockade, and prone positioning. Initiation of ECMO may be reasonable prior to implementation of standard of care therapies, in order to permit safe transfer to an experienced center from a center not able to provide them.

Two take-away points: First, it is important to recognize that much of the clinical benefit derived from ECMO may be beyond its ability to normalize gas exchange and be due, at least in part, to the fact that ECMO allows the enhancement of proven lung protective ventilatory strategies. Initiation of ECMO and the “lung rest” it permits reduce the mechanical power applied to the injured alveoli and may attenuate ventilator-induced lung injury, cytokine release, and multiorgan failure that portend poor clinical outcomes in ARDS. Second, ECMO in EOLIA was conducted at expert centers with relatively low rates of complications.

It is too early to know how the critical care community will view ECMO for ARDS in light of EOLIA as well as a growing body of global ECMO experience, or how its wider application may impact the distribution and organization of ECMO centers. Regardless, of paramount importance in using ECMO as a treatment modality is optimizing patient management both prior to and after its initiation.

Dr. Agerstrand is Assistant Professor of Medicine, Director of the Medical ECMO Program, Columbia University College of Physicians and Surgeons, New York-Presbyterian Hospital.


 

Extracorporeal membrane oxygenation (ECMO) has become increasingly accepted as a rescue therapy for severe respiratory failure from a variety of conditions, though most commonly, the acute respiratory distress syndrome (ARDS) (Thiagarajan R, et al. ASAIO. 2017;63[1]:60). ECMO can provide respiratory or cardiorespiratory support for failing lungs, heart, or both. The most common ECMO configuration used in ARDS is venovenous ECMO, in which blood is withdrawn from a catheter placed in a central vein, pumped through a gas exchange device known as an oxygenator, and returned to the venous system via another catheter. The blood flowing through the oxygenator is separated from a continuous supply of oxygen-rich sweep gas by a semipermeable membrane, across which diffusion-mediated gas exchange occurs, so that the blood exiting it is rich in oxygen and low in carbon dioxide. As venovenous ECMO functions in series with the native circulation, the well-oxygenated blood exiting the ECMO circuit mixes with poorly oxygenated blood flowing through the lungs. Therefore, oxygenation is dependent on native cardiac output to achieve systemic oxygen delivery (Figure 1).

ECMO been used successfully in adults with ARDS since the early 1970s (Hill JD, et al. N Engl J Med. 1972;286[12]:629-34) but, until recently, was limited to small numbers of patients at select global centers and associated with a high-risk profile. In the last decade, however, driven by improvements in ECMO circuit components making the device safer and easier to use, encouraging worldwide experience during the 2009 influenza A (H1N1) pandemic (Davies A, et al. JAMA. 2009;302[17]1888-95), and publication of the Efficacy and Economic Assessment of Conventional Ventilatory Support versus Extracorporeal Membrane Oxygenation for Severe Adult Respiratory Failure (CESAR) trial (Peek GJ, et al. Lancet. 2009;374[9698]:1351-63), ECMO use has markedly increased.

Despite its rapid growth, however, rigorous evidence supporting the use of ECMO has been lacking. The CESAR trial, while impressive in execution, had methodological issues that limited the strength of its conclusions. CESAR was a pragmatic trial that randomized 180 adults with severe respiratory failure from multiple etiologies to conventional management or transfer to an experienced, ECMO-capable center. CESAR met its primary outcome of improved survival without disability in the ECMO-referred group (63% vs 47%, relative risk [RR] 0.69; 95% confidence interval [CI] 0.05 to 0.97, P=.03), but not all patients in that group ultimately received ECMO. In addition, the use of lung protective ventilation was significantly higher in the ECMO-referred group, making it difficult to separate its benefit from that of ECMO. A conservative interpretation is that CESAR showed the clinical benefit of treatment at an ECMO-capable center, experienced in the management of patients with severe respiratory failure.

Not until the release of the Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome (EOLIA) trial earlier this year (Combes A, et al. N Engl J Med. 2018;378[21]:1965-75), did a modern, randomized controlled trial evaluating the use of ECMO itself exist. The EOLIA trial addressed the limitations of CESAR and randomized adult patients with early, severe ARDS to conventional, standard of care management that included a protocolized lung protective strategy in the control group vs immediate initiation of ECMO combined with an ultra-lung protective strategy (targeting end-inspiratory plateau pressure ≤24 cmH2O) in the intervention group. The primary outcome was all-cause mortality at 60 days. Of note, patients enrolled in EOLIA met entry criteria despite greater than 90% of patients receiving neuromuscular blockade and around 60% treated with prone positioning at the time of randomization (importantly, 90% of control group patients ultimately underwent prone positioning).

EOLIA was powered to detect a 20% decrease in mortality in the ECMO group. Based on trial design and the results of the fourth interim analysis, the trial was stopped for futility to reach that endpoint after enrollment of 249 of a maximum 331 patients. Although a 20% mortality reduction was not achieved, 60-day mortality was notably lower in the ECMO-treated group (35% vs 46%, RR 0.76, 95% CI 0.55 to 1.04, P=.09). The key secondary outcome of risk of treatment failure (defined as death in the ECMO group and death or crossover to ECMO in the control group) favored the ECMO group with a RR for mortality of 0.62 (95% CI, 0.47 to 0.82; P<.001), as did other secondary endpoints such as days free of renal and other organ failure.

A major limitation of the trial was that 35 (28%) of control group patients ultimately crossed over to ECMO, which diluted the effect of ECMO observed in the intention-to-treat analysis. Crossover occurred at clinician discretion an average of 6.5 days after randomization and after stringent criteria for crossover was met. These patients were incredibly ill, with a median oxygen saturation of 77%, rapidly worsening inotropic scores, and lactic acidosis; nine individuals had already suffered cardiac arrest, and six had received ECMO as part of extracorporeal cardiopulmonary resuscitation (ECPR), the initiation of venoarterial ECMO during cardiac arrest in attempt to restore spontaneous circulation. Mortality was considerably worse in the crossover group than in conventionally managed cohort overall, and, notably, 33% of patients crossed over to ECMO still survived.

In order to estimate the effect of ECMO on survival times if crossover had not occurred, the authors performed a post-hoc, rank-preserving structural failure time analysis. Though this relies on some assessment regarding the effect of the treatment itself, it showed a hazard ratio for mortality in the ECMO group of 0.51 (95% CI 0.24 to 1.02, P=.055). Although the EOLIA trial was not positive by traditional interpretation, all three major analyses and all secondary endpoints suggest some degree of benefit in patients with severe ARDS managed with ECMO.

Importantly, ECMO was well tolerated (at least when performed at expert centers, as done in this trial). There were significantly more bleeding events and cases of severe thrombocytopenia in the ECMO-treated group, but massive hemorrhage, ischemic and hemorrhagic stroke, arrhythmias, and other complications were similar.

Where do we go from here? Based on the totality of information, it is reasonable to consider ECMO for cases of severe ARDS not responsive to conventional measures, such as a lung protective ventilator strategy, neuromuscular blockade, and prone positioning. Initiation of ECMO may be reasonable prior to implementation of standard of care therapies, in order to permit safe transfer to an experienced center from a center not able to provide them.

Two take-away points: First, it is important to recognize that much of the clinical benefit derived from ECMO may be beyond its ability to normalize gas exchange and be due, at least in part, to the fact that ECMO allows the enhancement of proven lung protective ventilatory strategies. Initiation of ECMO and the “lung rest” it permits reduce the mechanical power applied to the injured alveoli and may attenuate ventilator-induced lung injury, cytokine release, and multiorgan failure that portend poor clinical outcomes in ARDS. Second, ECMO in EOLIA was conducted at expert centers with relatively low rates of complications.

It is too early to know how the critical care community will view ECMO for ARDS in light of EOLIA as well as a growing body of global ECMO experience, or how its wider application may impact the distribution and organization of ECMO centers. Regardless, of paramount importance in using ECMO as a treatment modality is optimizing patient management both prior to and after its initiation.

Dr. Agerstrand is Assistant Professor of Medicine, Director of the Medical ECMO Program, Columbia University College of Physicians and Surgeons, New York-Presbyterian Hospital.


 

Diversity

There is growing appreciation for diversity and inclusion (DI) as drivers of excellence in medicine. CHEST also promotes excellence in medicine. Therefore, it is intuitive that CHEST promote DI. Diversity encompasses differences in gender, race/ethnicity, vocational training, age, sexual orientation, thought processes, etc.

Academic medicine is rich with examples of how diversity is critical to the health of our nation:

– Diverse student populations have been shown to improve our learners’ satisfaction with their educational experience.

– Diverse teams have been shown to be more capable of solving complex problems than homogenous teams.

– Health care is moving toward a team-based, interprofessional model that values the contributions of a range of providers’ perspectives in improving patient outcomes.

– In biomedical research, investigators ask different research questions based on their own background and experiences. This implies that finding solutions to diseases that affect specific populations will require a diverse pool of biomedical researchers.

– Faculty diversity as a key component of excellence for medical education and research has been documented.

Diversity alone doesn’t drive inclusion. Noted diversity advocate, Verna Myers, stated, “Diversity is being invited to the party. Inclusion is being asked to dance.” In my opinion, diversity is the commencement of work, but inclusion helps complete the task.
 

Inclusion

An inclusive environment values the unique contributions all members bring. Teams with diversity of thought are more innovative as individual members with different backgrounds and points of view bring an extensive range of ideas and creativity to scientific discovery and decision-making processes. Inclusion leverages the power of our unique differences to accomplish our mutual goals. By valuing everyone’s perspective, we demonstrate excellence.

I recommend an article from the Harvard Business Review (HBR Feb 2017). The authors suggest several ways to promote inclusiveness: (1) ensuring team members speak up and are heard; (2) making it safe to propose novel ideas; (3) empowering team members to make decisions; (4) taking advice and implementing feedback; (5) giving actionable feedback; and ( 6) sharing credit for team success. If the team leader possesses at least three of these traits, 87% of team members say they feel welcome and included in their team; 87% say they feel free to express their views and opinions; and 74% say they feel that their ideas are heard and recognized. If the team leader possessed none of these traits, those percentages dropped to 51%, 46%, and 37%, respectively. I believe this concept is applicable in medicine also.

Sponsors

What can we do to advance diversity and inclusion individually and in our individual institutions? A sponsor is a senior level leader who advocates for key assignments, promotes for and puts his or her reputation on the line for the protégé’s advancement. This invigorates and drives engagement. One key to rising above the playing field for women and people of color is sponsorship. Being a sponsor does not mean one would recommend someone who is not qualified. It means one recommends or supports those who are capable of doing the job but would not otherwise be given the opportunity.

Ask yourself: Have I served as a sponsor? What would prevent me from being a sponsor? Do I believe in this concept?
 

Cause for Alarm

Numerous publications have recently discussed the crisis of the decline of black men entering medicine. In 1978, there were 1,410 black male applicants to medical school, and in 2014, there were 1,337. Additionally, the number of black male matriculants to medical school over more than 35 years has not surpassed the 1978 numbers. In 1978, there were 542 black male matriculants, and in 2014, there were 515 (J of Racial and Ethnic Health Disparities. 2017, 4:317-321). This report is thorough and insightful and illustrates the work that we must do to help improve this situation.

Dr. Marc Nivet, Association of American Medical Colleges (AAMC) Chief Diversity Officer, stated “No other minority group has experienced such declines. The inability to find, engage, and develop candidates for careers in medicine from all members of our society limits our ability to improve health care for all.” I recommend you read the 2015 AAMC publication entitled: Altering the Course: Black Males in Medicine.
 

Health-care Disparities

Research suggests that the overall health of Americans has improved; however, disparities continue to persist among many populations within the United States. Racial and ethnic minority populations have poorer access to care and worse outcomes than their white counterparts. Approximately 20% of the nation living in rural areas is less likely than those living in urban areas to receive preventive care and more likely to experience language barriers.

Individuals identifying as lesbian, gay, bisexual, or transgender are likely to experience discrimination in health-care settings. These individuals often face insurance-based barriers and are less likely to have a usual source of care than patients who identify as straight.

A 2002 report by the Institute of Medicine entitled: Unequal Treatment: What Healthcare Providers Need to Know about Racial and Ethnic Disparities in Healthcare is revealing. Salient information reported is: It is generally accepted that a diverse workforce is a key component in the delivery of quality, competent care throughout the nation. Physicians from racial and ethnic backgrounds typically underrepresented in medicine are significantly more likely to practice primary care than white physicians and are more likely to practice in impoverished and medically underserved areas. Diversity in the physician workforce impacts the quality of care received by patients. Race concordance between patient and physician results in longer visits and increased patient satisfaction, and language concordance is positively associated with adherence to treatment among certain racial or ethnic groups.

Improving the patient experience or quality of care received also requires attention to education and training on cultural competence. By weaving together a diverse and culturally responsive pool of physicians working collaboratively with other health-care professionals, access and quality of care can improve throughout the nation.

CHEST cannot attain more racial diversity in our organization if we don’t have this diversity in medical education and training. This is why CHEST must be actively involved in addressing these issues.
 

Unconscious Bias

Despite many examples of how diversity enriches the quality of health care and health research, there is still much work to be done to address the human biases that impede our ability to benefit from diversity in medicine. While academic medicine has made progress toward addressing overt discrimination, unconscious bias (implicit bias) represents another threat. Unconscious bias describes the prejudices we don’t know we have. While unconscious biases vary from person to person, we all possess them. The existence of unconscious bias in academic medicine, while uncomfortable and unsettling, is a reality. The AAMC developed an unconscious bias learning lab for the health professions and produced an oft-cited video about addressing unconscious bias in the faculty advancement, promotion, and tenure process. We must consider this and other ways in which we can help promote the acknowledgment of unconscious bias. The CHEST staff have undergone unconscious bias training, and I recommend it for all faculty in academic medicine.
 

Summary

Diversity and inclusion in medicine is of paramount importance. It leads to better patient care and better trainee education and will decrease health-care disparities. Progress has been made, but there is more work to be done.

CHEST is supportive of these efforts and has worked on this previously and with a renewed push in the past 2 years with the DI Task Force initially and, now, the DI Roundtable, which has representatives from each of the standing committees, including the Board of Regents. This roundtable group will help advance the DI initiatives of the organization. I ask that each person reading this article consider what we as individuals can do in helping make DI in medicine a priority.



Dr. Haynes is Professor of Medicine at The University of Mississippi Medical Center in Jackson, MS. He is also the Executive Vice Chair of the Department of Medicine. At CHEST, he is a member of the training and transitions committee, executive scientific program committee, former chair of the diversity and inclusion task force, and is the current chair of the diversity and inclusion roundtable.
 

Diversity

There is growing appreciation for diversity and inclusion (DI) as drivers of excellence in medicine. CHEST also promotes excellence in medicine. Therefore, it is intuitive that CHEST promote DI. Diversity encompasses differences in gender, race/ethnicity, vocational training, age, sexual orientation, thought processes, etc.

Academic medicine is rich with examples of how diversity is critical to the health of our nation:

– Diverse student populations have been shown to improve our learners’ satisfaction with their educational experience.

– Diverse teams have been shown to be more capable of solving complex problems than homogenous teams.

– Health care is moving toward a team-based, interprofessional model that values the contributions of a range of providers’ perspectives in improving patient outcomes.

– In biomedical research, investigators ask different research questions based on their own background and experiences. This implies that finding solutions to diseases that affect specific populations will require a diverse pool of biomedical researchers.

– Faculty diversity as a key component of excellence for medical education and research has been documented.

Diversity alone doesn’t drive inclusion. Noted diversity advocate, Verna Myers, stated, “Diversity is being invited to the party. Inclusion is being asked to dance.” In my opinion, diversity is the commencement of work, but inclusion helps complete the task.
 

Inclusion

An inclusive environment values the unique contributions all members bring. Teams with diversity of thought are more innovative as individual members with different backgrounds and points of view bring an extensive range of ideas and creativity to scientific discovery and decision-making processes. Inclusion leverages the power of our unique differences to accomplish our mutual goals. By valuing everyone’s perspective, we demonstrate excellence.

I recommend an article from the Harvard Business Review (HBR Feb 2017). The authors suggest several ways to promote inclusiveness: (1) ensuring team members speak up and are heard; (2) making it safe to propose novel ideas; (3) empowering team members to make decisions; (4) taking advice and implementing feedback; (5) giving actionable feedback; and ( 6) sharing credit for team success. If the team leader possesses at least three of these traits, 87% of team members say they feel welcome and included in their team; 87% say they feel free to express their views and opinions; and 74% say they feel that their ideas are heard and recognized. If the team leader possessed none of these traits, those percentages dropped to 51%, 46%, and 37%, respectively. I believe this concept is applicable in medicine also.

Sponsors

What can we do to advance diversity and inclusion individually and in our individual institutions? A sponsor is a senior level leader who advocates for key assignments, promotes for and puts his or her reputation on the line for the protégé’s advancement. This invigorates and drives engagement. One key to rising above the playing field for women and people of color is sponsorship. Being a sponsor does not mean one would recommend someone who is not qualified. It means one recommends or supports those who are capable of doing the job but would not otherwise be given the opportunity.

Ask yourself: Have I served as a sponsor? What would prevent me from being a sponsor? Do I believe in this concept?
 

Cause for Alarm

Numerous publications have recently discussed the crisis of the decline of black men entering medicine. In 1978, there were 1,410 black male applicants to medical school, and in 2014, there were 1,337. Additionally, the number of black male matriculants to medical school over more than 35 years has not surpassed the 1978 numbers. In 1978, there were 542 black male matriculants, and in 2014, there were 515 (J of Racial and Ethnic Health Disparities. 2017, 4:317-321). This report is thorough and insightful and illustrates the work that we must do to help improve this situation.

Dr. Marc Nivet, Association of American Medical Colleges (AAMC) Chief Diversity Officer, stated “No other minority group has experienced such declines. The inability to find, engage, and develop candidates for careers in medicine from all members of our society limits our ability to improve health care for all.” I recommend you read the 2015 AAMC publication entitled: Altering the Course: Black Males in Medicine.
 

Health-care Disparities

Research suggests that the overall health of Americans has improved; however, disparities continue to persist among many populations within the United States. Racial and ethnic minority populations have poorer access to care and worse outcomes than their white counterparts. Approximately 20% of the nation living in rural areas is less likely than those living in urban areas to receive preventive care and more likely to experience language barriers.

Individuals identifying as lesbian, gay, bisexual, or transgender are likely to experience discrimination in health-care settings. These individuals often face insurance-based barriers and are less likely to have a usual source of care than patients who identify as straight.

A 2002 report by the Institute of Medicine entitled: Unequal Treatment: What Healthcare Providers Need to Know about Racial and Ethnic Disparities in Healthcare is revealing. Salient information reported is: It is generally accepted that a diverse workforce is a key component in the delivery of quality, competent care throughout the nation. Physicians from racial and ethnic backgrounds typically underrepresented in medicine are significantly more likely to practice primary care than white physicians and are more likely to practice in impoverished and medically underserved areas. Diversity in the physician workforce impacts the quality of care received by patients. Race concordance between patient and physician results in longer visits and increased patient satisfaction, and language concordance is positively associated with adherence to treatment among certain racial or ethnic groups.

Improving the patient experience or quality of care received also requires attention to education and training on cultural competence. By weaving together a diverse and culturally responsive pool of physicians working collaboratively with other health-care professionals, access and quality of care can improve throughout the nation.

CHEST cannot attain more racial diversity in our organization if we don’t have this diversity in medical education and training. This is why CHEST must be actively involved in addressing these issues.
 

Unconscious Bias

Despite many examples of how diversity enriches the quality of health care and health research, there is still much work to be done to address the human biases that impede our ability to benefit from diversity in medicine. While academic medicine has made progress toward addressing overt discrimination, unconscious bias (implicit bias) represents another threat. Unconscious bias describes the prejudices we don’t know we have. While unconscious biases vary from person to person, we all possess them. The existence of unconscious bias in academic medicine, while uncomfortable and unsettling, is a reality. The AAMC developed an unconscious bias learning lab for the health professions and produced an oft-cited video about addressing unconscious bias in the faculty advancement, promotion, and tenure process. We must consider this and other ways in which we can help promote the acknowledgment of unconscious bias. The CHEST staff have undergone unconscious bias training, and I recommend it for all faculty in academic medicine.
 

Summary

Diversity and inclusion in medicine is of paramount importance. It leads to better patient care and better trainee education and will decrease health-care disparities. Progress has been made, but there is more work to be done.

CHEST is supportive of these efforts and has worked on this previously and with a renewed push in the past 2 years with the DI Task Force initially and, now, the DI Roundtable, which has representatives from each of the standing committees, including the Board of Regents. This roundtable group will help advance the DI initiatives of the organization. I ask that each person reading this article consider what we as individuals can do in helping make DI in medicine a priority.



Dr. Haynes is Professor of Medicine at The University of Mississippi Medical Center in Jackson, MS. He is also the Executive Vice Chair of the Department of Medicine. At CHEST, he is a member of the training and transitions committee, executive scientific program committee, former chair of the diversity and inclusion task force, and is the current chair of the diversity and inclusion roundtable.
 

Diversity

There is growing appreciation for diversity and inclusion (DI) as drivers of excellence in medicine. CHEST also promotes excellence in medicine. Therefore, it is intuitive that CHEST promote DI. Diversity encompasses differences in gender, race/ethnicity, vocational training, age, sexual orientation, thought processes, etc.

Academic medicine is rich with examples of how diversity is critical to the health of our nation:

– Diverse student populations have been shown to improve our learners’ satisfaction with their educational experience.

– Diverse teams have been shown to be more capable of solving complex problems than homogenous teams.

– Health care is moving toward a team-based, interprofessional model that values the contributions of a range of providers’ perspectives in improving patient outcomes.

– In biomedical research, investigators ask different research questions based on their own background and experiences. This implies that finding solutions to diseases that affect specific populations will require a diverse pool of biomedical researchers.

– Faculty diversity as a key component of excellence for medical education and research has been documented.

Diversity alone doesn’t drive inclusion. Noted diversity advocate, Verna Myers, stated, “Diversity is being invited to the party. Inclusion is being asked to dance.” In my opinion, diversity is the commencement of work, but inclusion helps complete the task.
 

Inclusion

An inclusive environment values the unique contributions all members bring. Teams with diversity of thought are more innovative as individual members with different backgrounds and points of view bring an extensive range of ideas and creativity to scientific discovery and decision-making processes. Inclusion leverages the power of our unique differences to accomplish our mutual goals. By valuing everyone’s perspective, we demonstrate excellence.

I recommend an article from the Harvard Business Review (HBR Feb 2017). The authors suggest several ways to promote inclusiveness: (1) ensuring team members speak up and are heard; (2) making it safe to propose novel ideas; (3) empowering team members to make decisions; (4) taking advice and implementing feedback; (5) giving actionable feedback; and ( 6) sharing credit for team success. If the team leader possesses at least three of these traits, 87% of team members say they feel welcome and included in their team; 87% say they feel free to express their views and opinions; and 74% say they feel that their ideas are heard and recognized. If the team leader possessed none of these traits, those percentages dropped to 51%, 46%, and 37%, respectively. I believe this concept is applicable in medicine also.

Sponsors

What can we do to advance diversity and inclusion individually and in our individual institutions? A sponsor is a senior level leader who advocates for key assignments, promotes for and puts his or her reputation on the line for the protégé’s advancement. This invigorates and drives engagement. One key to rising above the playing field for women and people of color is sponsorship. Being a sponsor does not mean one would recommend someone who is not qualified. It means one recommends or supports those who are capable of doing the job but would not otherwise be given the opportunity.

Ask yourself: Have I served as a sponsor? What would prevent me from being a sponsor? Do I believe in this concept?
 

Cause for Alarm

Numerous publications have recently discussed the crisis of the decline of black men entering medicine. In 1978, there were 1,410 black male applicants to medical school, and in 2014, there were 1,337. Additionally, the number of black male matriculants to medical school over more than 35 years has not surpassed the 1978 numbers. In 1978, there were 542 black male matriculants, and in 2014, there were 515 (J of Racial and Ethnic Health Disparities. 2017, 4:317-321). This report is thorough and insightful and illustrates the work that we must do to help improve this situation.

Dr. Marc Nivet, Association of American Medical Colleges (AAMC) Chief Diversity Officer, stated “No other minority group has experienced such declines. The inability to find, engage, and develop candidates for careers in medicine from all members of our society limits our ability to improve health care for all.” I recommend you read the 2015 AAMC publication entitled: Altering the Course: Black Males in Medicine.
 

Health-care Disparities

Research suggests that the overall health of Americans has improved; however, disparities continue to persist among many populations within the United States. Racial and ethnic minority populations have poorer access to care and worse outcomes than their white counterparts. Approximately 20% of the nation living in rural areas is less likely than those living in urban areas to receive preventive care and more likely to experience language barriers.

Individuals identifying as lesbian, gay, bisexual, or transgender are likely to experience discrimination in health-care settings. These individuals often face insurance-based barriers and are less likely to have a usual source of care than patients who identify as straight.

A 2002 report by the Institute of Medicine entitled: Unequal Treatment: What Healthcare Providers Need to Know about Racial and Ethnic Disparities in Healthcare is revealing. Salient information reported is: It is generally accepted that a diverse workforce is a key component in the delivery of quality, competent care throughout the nation. Physicians from racial and ethnic backgrounds typically underrepresented in medicine are significantly more likely to practice primary care than white physicians and are more likely to practice in impoverished and medically underserved areas. Diversity in the physician workforce impacts the quality of care received by patients. Race concordance between patient and physician results in longer visits and increased patient satisfaction, and language concordance is positively associated with adherence to treatment among certain racial or ethnic groups.

Improving the patient experience or quality of care received also requires attention to education and training on cultural competence. By weaving together a diverse and culturally responsive pool of physicians working collaboratively with other health-care professionals, access and quality of care can improve throughout the nation.

CHEST cannot attain more racial diversity in our organization if we don’t have this diversity in medical education and training. This is why CHEST must be actively involved in addressing these issues.
 

Unconscious Bias

Despite many examples of how diversity enriches the quality of health care and health research, there is still much work to be done to address the human biases that impede our ability to benefit from diversity in medicine. While academic medicine has made progress toward addressing overt discrimination, unconscious bias (implicit bias) represents another threat. Unconscious bias describes the prejudices we don’t know we have. While unconscious biases vary from person to person, we all possess them. The existence of unconscious bias in academic medicine, while uncomfortable and unsettling, is a reality. The AAMC developed an unconscious bias learning lab for the health professions and produced an oft-cited video about addressing unconscious bias in the faculty advancement, promotion, and tenure process. We must consider this and other ways in which we can help promote the acknowledgment of unconscious bias. The CHEST staff have undergone unconscious bias training, and I recommend it for all faculty in academic medicine.
 

Summary

Diversity and inclusion in medicine is of paramount importance. It leads to better patient care and better trainee education and will decrease health-care disparities. Progress has been made, but there is more work to be done.

CHEST is supportive of these efforts and has worked on this previously and with a renewed push in the past 2 years with the DI Task Force initially and, now, the DI Roundtable, which has representatives from each of the standing committees, including the Board of Regents. This roundtable group will help advance the DI initiatives of the organization. I ask that each person reading this article consider what we as individuals can do in helping make DI in medicine a priority.



Dr. Haynes is Professor of Medicine at The University of Mississippi Medical Center in Jackson, MS. He is also the Executive Vice Chair of the Department of Medicine. At CHEST, he is a member of the training and transitions committee, executive scientific program committee, former chair of the diversity and inclusion task force, and is the current chair of the diversity and inclusion roundtable.