CHEST Physician

The combination of methylprednisolone and intravenous immunoglobulins works better than intravenous immunoglobulins alone for multisystem inflammatory syndrome in children (MIS-C), researchers say.

“I’m not sure it’s the best treatment because we have not studied every possible treatment,” François Angoulvant, MD, PhD, told this news organization, “but right now, it’s the standard of care.”

Dr. Angoulvant, a professor of pediatrics at University of Paris, and colleagues published a comparison of the two treatments in the Journal of the American Medical Association.

A small percentage of children infected with SARS-CoV-2 develop MIS-C about 2 to 4 weeks later. It is considered a separate disease entity from COVID-19 and is associated with persistent fever, digestive symptoms, rash, bilateral nonpurulent conjunctivitis, mucocutaneous inflammation signs, and frequent cardiovascular involvement. In more than 60% of cases, it leads to hemodynamic failure, with acute cardiac dysfunction.

Because MIS-C resembles Kawasaki disease, clinicians modeled their treatment on that condition and started with immunoglobulins alone, Dr. Angoulvant said.

Based on expert opinion, the National Health Service in the United Kingdom published a consensus statement in Sept. listing immunoglobulins alone as the first-line treatment.

But anecdotal reports have emerged that combining the immunoglobulins with a corticosteroid worked better. To investigate this possibility, Dr. Angoulvant and colleagues analyzed records of MIS-C cases in France, where physicians are required to report all suspected cases of MIS-C to the French National Public Health Agency.

Among the 181 cases they scrutinized, 111 fulfilled the World Health Organization criteria for MIS-C. Of these, the researchers were able to match 64 patients who had received immunoglobulins alone with 32 who had received the combined therapy and could be matched using propensity scores.

The researchers defined treatment failure as persistence of fever for 2 days after the start of therapy or recurrence of fever within a week. By this measure, the combination treatment failed in only 9% of cases while immunoglobulins alone failed in 38% of cases. The difference was statistically significant (P = .008). Most of those for whom these treatments failed received second-line treatments such as steroids or biological agents.

Patients treated with the combination therapy also had a lower risk of secondary acute left ventricular dysfunction (odds ratio, 0.20; 95% confidence interval, 0.06-0.66) and a lower risk of needing hemodynamic support (OR, 0.21; 95% CI, 0.06-0.76).

Those receiving the combination therapy spent a mean of 4 days in the pediatric intensive care unit compared with 6 days for those receiving immunoglobulins alone. (Difference in days, −2.4; 95% CI, −4.0 to −0.7; P = .005).

There are few drawbacks to the combination approach, Dr. Angoulvant said, as the side effects of corticosteroids are generally not severe and they can be anticipated because this class of medications has been used for many years.

The study raises the question of whether corticosteroids might work as well by themselves, but it could not be answered with this database as no one is using that approach in France, Dr. Angoulvant said. “I hope other teams around the world could bring us the answer.”

In the United States, most physicians appear to already be using the combination therapy, said David Teachey, MD, an associate professor of pediatrics at the Children’s Hospital of Philadelphia and the University of Pennsylvania, Philadelphia.

The reduction in time in pediatric intensive care and the reduced risk of cardiac dysfunction are important findings, he said.

This retrospective study falls short of the evidence provided by a randomized clinical trial, Dr. Teachey noted. But he acknowledged that few families would agree to participate in such a trial as they would have to take a chance that the sick children would receive a less effective therapy than what they would otherwise get. “It’s hard to [talk] about a therapy reduction,” he told this news organization.

Given that impediment, he agreed with Dr. Angoulvant that the current study and others like it may provide the best data available pointing to a treatment approach for MIS-C.

The study received an unrestricted grant from Pfizer. The French COVID-19 Paediatric Inflammation Consortium received an unrestricted grant from the Square Foundation (Grandir–Fonds de Solidarité pour L’Enfance). Dr. Angoulvant and Dr. Teachey have disclosed no relevant financial relationships.

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

The combination of methylprednisolone and intravenous immunoglobulins works better than intravenous immunoglobulins alone for multisystem inflammatory syndrome in children (MIS-C), researchers say.

“I’m not sure it’s the best treatment because we have not studied every possible treatment,” François Angoulvant, MD, PhD, told this news organization, “but right now, it’s the standard of care.”

Dr. Angoulvant, a professor of pediatrics at University of Paris, and colleagues published a comparison of the two treatments in the Journal of the American Medical Association.

A small percentage of children infected with SARS-CoV-2 develop MIS-C about 2 to 4 weeks later. It is considered a separate disease entity from COVID-19 and is associated with persistent fever, digestive symptoms, rash, bilateral nonpurulent conjunctivitis, mucocutaneous inflammation signs, and frequent cardiovascular involvement. In more than 60% of cases, it leads to hemodynamic failure, with acute cardiac dysfunction.

Because MIS-C resembles Kawasaki disease, clinicians modeled their treatment on that condition and started with immunoglobulins alone, Dr. Angoulvant said.

Based on expert opinion, the National Health Service in the United Kingdom published a consensus statement in Sept. listing immunoglobulins alone as the first-line treatment.

But anecdotal reports have emerged that combining the immunoglobulins with a corticosteroid worked better. To investigate this possibility, Dr. Angoulvant and colleagues analyzed records of MIS-C cases in France, where physicians are required to report all suspected cases of MIS-C to the French National Public Health Agency.

Among the 181 cases they scrutinized, 111 fulfilled the World Health Organization criteria for MIS-C. Of these, the researchers were able to match 64 patients who had received immunoglobulins alone with 32 who had received the combined therapy and could be matched using propensity scores.

The researchers defined treatment failure as persistence of fever for 2 days after the start of therapy or recurrence of fever within a week. By this measure, the combination treatment failed in only 9% of cases while immunoglobulins alone failed in 38% of cases. The difference was statistically significant (P = .008). Most of those for whom these treatments failed received second-line treatments such as steroids or biological agents.

Patients treated with the combination therapy also had a lower risk of secondary acute left ventricular dysfunction (odds ratio, 0.20; 95% confidence interval, 0.06-0.66) and a lower risk of needing hemodynamic support (OR, 0.21; 95% CI, 0.06-0.76).

Those receiving the combination therapy spent a mean of 4 days in the pediatric intensive care unit compared with 6 days for those receiving immunoglobulins alone. (Difference in days, −2.4; 95% CI, −4.0 to −0.7; P = .005).

There are few drawbacks to the combination approach, Dr. Angoulvant said, as the side effects of corticosteroids are generally not severe and they can be anticipated because this class of medications has been used for many years.

The study raises the question of whether corticosteroids might work as well by themselves, but it could not be answered with this database as no one is using that approach in France, Dr. Angoulvant said. “I hope other teams around the world could bring us the answer.”

In the United States, most physicians appear to already be using the combination therapy, said David Teachey, MD, an associate professor of pediatrics at the Children’s Hospital of Philadelphia and the University of Pennsylvania, Philadelphia.

The reduction in time in pediatric intensive care and the reduced risk of cardiac dysfunction are important findings, he said.

This retrospective study falls short of the evidence provided by a randomized clinical trial, Dr. Teachey noted. But he acknowledged that few families would agree to participate in such a trial as they would have to take a chance that the sick children would receive a less effective therapy than what they would otherwise get. “It’s hard to [talk] about a therapy reduction,” he told this news organization.

Given that impediment, he agreed with Dr. Angoulvant that the current study and others like it may provide the best data available pointing to a treatment approach for MIS-C.

The study received an unrestricted grant from Pfizer. The French COVID-19 Paediatric Inflammation Consortium received an unrestricted grant from the Square Foundation (Grandir–Fonds de Solidarité pour L’Enfance). Dr. Angoulvant and Dr. Teachey have disclosed no relevant financial relationships.

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

The combination of methylprednisolone and intravenous immunoglobulins works better than intravenous immunoglobulins alone for multisystem inflammatory syndrome in children (MIS-C), researchers say.

“I’m not sure it’s the best treatment because we have not studied every possible treatment,” François Angoulvant, MD, PhD, told this news organization, “but right now, it’s the standard of care.”

Dr. Angoulvant, a professor of pediatrics at University of Paris, and colleagues published a comparison of the two treatments in the Journal of the American Medical Association.

A small percentage of children infected with SARS-CoV-2 develop MIS-C about 2 to 4 weeks later. It is considered a separate disease entity from COVID-19 and is associated with persistent fever, digestive symptoms, rash, bilateral nonpurulent conjunctivitis, mucocutaneous inflammation signs, and frequent cardiovascular involvement. In more than 60% of cases, it leads to hemodynamic failure, with acute cardiac dysfunction.

Because MIS-C resembles Kawasaki disease, clinicians modeled their treatment on that condition and started with immunoglobulins alone, Dr. Angoulvant said.

Based on expert opinion, the National Health Service in the United Kingdom published a consensus statement in Sept. listing immunoglobulins alone as the first-line treatment.

But anecdotal reports have emerged that combining the immunoglobulins with a corticosteroid worked better. To investigate this possibility, Dr. Angoulvant and colleagues analyzed records of MIS-C cases in France, where physicians are required to report all suspected cases of MIS-C to the French National Public Health Agency.

Among the 181 cases they scrutinized, 111 fulfilled the World Health Organization criteria for MIS-C. Of these, the researchers were able to match 64 patients who had received immunoglobulins alone with 32 who had received the combined therapy and could be matched using propensity scores.

The researchers defined treatment failure as persistence of fever for 2 days after the start of therapy or recurrence of fever within a week. By this measure, the combination treatment failed in only 9% of cases while immunoglobulins alone failed in 38% of cases. The difference was statistically significant (P = .008). Most of those for whom these treatments failed received second-line treatments such as steroids or biological agents.

Patients treated with the combination therapy also had a lower risk of secondary acute left ventricular dysfunction (odds ratio, 0.20; 95% confidence interval, 0.06-0.66) and a lower risk of needing hemodynamic support (OR, 0.21; 95% CI, 0.06-0.76).

Those receiving the combination therapy spent a mean of 4 days in the pediatric intensive care unit compared with 6 days for those receiving immunoglobulins alone. (Difference in days, −2.4; 95% CI, −4.0 to −0.7; P = .005).

There are few drawbacks to the combination approach, Dr. Angoulvant said, as the side effects of corticosteroids are generally not severe and they can be anticipated because this class of medications has been used for many years.

The study raises the question of whether corticosteroids might work as well by themselves, but it could not be answered with this database as no one is using that approach in France, Dr. Angoulvant said. “I hope other teams around the world could bring us the answer.”

In the United States, most physicians appear to already be using the combination therapy, said David Teachey, MD, an associate professor of pediatrics at the Children’s Hospital of Philadelphia and the University of Pennsylvania, Philadelphia.

The reduction in time in pediatric intensive care and the reduced risk of cardiac dysfunction are important findings, he said.

This retrospective study falls short of the evidence provided by a randomized clinical trial, Dr. Teachey noted. But he acknowledged that few families would agree to participate in such a trial as they would have to take a chance that the sick children would receive a less effective therapy than what they would otherwise get. “It’s hard to [talk] about a therapy reduction,” he told this news organization.

Given that impediment, he agreed with Dr. Angoulvant that the current study and others like it may provide the best data available pointing to a treatment approach for MIS-C.

The study received an unrestricted grant from Pfizer. The French COVID-19 Paediatric Inflammation Consortium received an unrestricted grant from the Square Foundation (Grandir–Fonds de Solidarité pour L’Enfance). Dr. Angoulvant and Dr. Teachey have disclosed no relevant financial relationships.

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

The Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention has updated its recommended immunization schedule for adults for 2021.

A summary of the annual update was published online Feb. 11 in the CDC’s Morbidity and Mortality Weekly Report and is available in Annals of Internal Medicine and on the CDC website.

It features a special section on vaccination during the pandemic as well as interim recommendations on administering the Pfizer-BioNtech and Moderna COVID-19 vaccines.

The authors, led by Mark S. Freedman, DVM, MPH, DACVPM, of the CDC’s National Center for Immunization and Respiratory Diseases, in Atlanta, note that this year’s recommendations for adults – persons aged 19 years and older – are largely the same as last year’s. “There have been very few changes,” Dr. Freedman said in an interview. “Changes to the schedule tables and notes were made to harmonize to the greatest extent possible the adult and child/adolescent schedules.”

Changes in the schedule include new or updated ACIP recommendations for influenza, hepatitis A, hepatitis B (Hep B), and human papillomavirus (HPV) as well as for meningococcal serogroups A, C, W, and Y (MenACYW) vaccines, meningococcal B (MenB) vaccines, and the zoster vaccine.

Vaccine-specific changes

Influenza

The schedule highlights updates to the composition of several influenza vaccines, which apply to components in both trivalent and quadrivalent formulations.

The cover page abbreviation for live attenuated influenza vaccine (LAIV) was changed to LAIV4. The abbreviation for live recombinant influenza vaccine (RIV) was changed to RIV4.

For individuals with a history of egg allergy who experience reactions other than hives, the following procedural warning has been added: “If using an influenza vaccine other than RIV4 or ccIIV4, administer in medical setting under supervision of health care provider who can recognize and manage severe allergic reactions.”

Zoster

The zoster vaccine live (Zostavax) has been removed from the schedule because it is no longer available in the United States. The recombinant zoster vaccine Shingrix remains available as a 2-dose regimen for adults aged 50 years or older.

HPV

As in previous years, HPV vaccination is routinely recommended for persons aged 11-12 years, with catch-up vaccination for those aged 26 or younger. Catch-up vaccination can be considered with shared decision making for those aged 27 through 45. In this year’s schedule, in the pregnancy column, the color pink, which formerly indicated “delay until after pregnancy,” has been replaced with red and an asterisk, indicating “vaccinate after pregnancy.”

HepB

ACIP continues to recommend vaccination of adults at risk for HepB; however, the text overlay has been changed to read, “2, 3, or 4 doses, depending on vaccine or condition.” Additionally, HepB vaccination is now routinely recommended for adults younger than 60 years with diabetes. For those with diabetes who are older than 60, shared decision making is recommended.

Meningococcal vaccine

ACIP continues to recommend routine vaccination with a quadrivalent meningococcal conjugate vaccine (MenACWY) for persons at increased risk for meningococcal disease caused by serogroups A, C, W, or Y. The MenQuadfi (MenACWY-TT) vaccine, which was first licensed in 2020, has been added to all relevant sections of MenACWY vaccines. For MenACWY booster doses, new text addresses special situations, including outbreaks.

Improvements have been made to text and layout, Dr. Freedman said. An example is the minimizing of specialized text. Other changes were made to ensure more consistent text structure and language. Various fine-tunings of color and positioning were made to the cover page and tables, and the wording of the notes sections was improved.

Vaccination in the pandemic

The updated schedule outlines guidance on the use of COVID-19 vaccines approved by the Food and Drug Administration under emergency use authorization, with interim recommendations for the Pfizer-BioNTech COVID-19 vaccine for people aged 16 and older and the Moderna COVID-19 vaccine for people aged 18 and older.

The authors stress the importance of receiving the recommended routine and catch-up immunizations notwithstanding widespread anxiety about visiting medical offices. Last spring, the CDC reported a dramatic drop in child vaccinations after the declaration of the national emergency in mid-March, a drop attributed to fear of COVID-19 exposure.

“ACIP continued to meet and make recommendations during the pandemic,” Dr. Freedman said. “Our recommendation remains that despite challenges caused by the COVID-19 pandemic, adults and their healthcare providers should follow the recommended vaccine schedule to protect against serious and sometimes deadly diseases.”

Regular vaccines can be safely administered even as COVID-19 retains its grasp on the United States. “Healthcare providers should follow the CDC’s interim guidance for the safe delivery of vaccines during the pandemic, which includes the use of personal protective equipment and physical distancing,” Dr. Freedman said.

Dr. Freedman has disclosed no relevant financial relationships. Coauthor Henry Bernstein, DO, is the editor of the Current Opinion in Pediatrics Office Pediatrics Series, is a Harvard School of Public Health faculty member, and is a member of the data safety and monitoring board for a Takeda study on intrathecal enzymes for Hunter and San Filippo syndromes. Coauthor Kevin Ault, MD, has served on the data safety and monitoring committee for ACI Clinical.
 

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

The Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention has updated its recommended immunization schedule for adults for 2021.

A summary of the annual update was published online Feb. 11 in the CDC’s Morbidity and Mortality Weekly Report and is available in Annals of Internal Medicine and on the CDC website.

It features a special section on vaccination during the pandemic as well as interim recommendations on administering the Pfizer-BioNtech and Moderna COVID-19 vaccines.

The authors, led by Mark S. Freedman, DVM, MPH, DACVPM, of the CDC’s National Center for Immunization and Respiratory Diseases, in Atlanta, note that this year’s recommendations for adults – persons aged 19 years and older – are largely the same as last year’s. “There have been very few changes,” Dr. Freedman said in an interview. “Changes to the schedule tables and notes were made to harmonize to the greatest extent possible the adult and child/adolescent schedules.”

Changes in the schedule include new or updated ACIP recommendations for influenza, hepatitis A, hepatitis B (Hep B), and human papillomavirus (HPV) as well as for meningococcal serogroups A, C, W, and Y (MenACYW) vaccines, meningococcal B (MenB) vaccines, and the zoster vaccine.

Vaccine-specific changes

Influenza

The schedule highlights updates to the composition of several influenza vaccines, which apply to components in both trivalent and quadrivalent formulations.

The cover page abbreviation for live attenuated influenza vaccine (LAIV) was changed to LAIV4. The abbreviation for live recombinant influenza vaccine (RIV) was changed to RIV4.

For individuals with a history of egg allergy who experience reactions other than hives, the following procedural warning has been added: “If using an influenza vaccine other than RIV4 or ccIIV4, administer in medical setting under supervision of health care provider who can recognize and manage severe allergic reactions.”

Zoster

The zoster vaccine live (Zostavax) has been removed from the schedule because it is no longer available in the United States. The recombinant zoster vaccine Shingrix remains available as a 2-dose regimen for adults aged 50 years or older.

HPV

As in previous years, HPV vaccination is routinely recommended for persons aged 11-12 years, with catch-up vaccination for those aged 26 or younger. Catch-up vaccination can be considered with shared decision making for those aged 27 through 45. In this year’s schedule, in the pregnancy column, the color pink, which formerly indicated “delay until after pregnancy,” has been replaced with red and an asterisk, indicating “vaccinate after pregnancy.”

HepB

ACIP continues to recommend vaccination of adults at risk for HepB; however, the text overlay has been changed to read, “2, 3, or 4 doses, depending on vaccine or condition.” Additionally, HepB vaccination is now routinely recommended for adults younger than 60 years with diabetes. For those with diabetes who are older than 60, shared decision making is recommended.

Meningococcal vaccine

ACIP continues to recommend routine vaccination with a quadrivalent meningococcal conjugate vaccine (MenACWY) for persons at increased risk for meningococcal disease caused by serogroups A, C, W, or Y. The MenQuadfi (MenACWY-TT) vaccine, which was first licensed in 2020, has been added to all relevant sections of MenACWY vaccines. For MenACWY booster doses, new text addresses special situations, including outbreaks.

Improvements have been made to text and layout, Dr. Freedman said. An example is the minimizing of specialized text. Other changes were made to ensure more consistent text structure and language. Various fine-tunings of color and positioning were made to the cover page and tables, and the wording of the notes sections was improved.

Vaccination in the pandemic

The updated schedule outlines guidance on the use of COVID-19 vaccines approved by the Food and Drug Administration under emergency use authorization, with interim recommendations for the Pfizer-BioNTech COVID-19 vaccine for people aged 16 and older and the Moderna COVID-19 vaccine for people aged 18 and older.

The authors stress the importance of receiving the recommended routine and catch-up immunizations notwithstanding widespread anxiety about visiting medical offices. Last spring, the CDC reported a dramatic drop in child vaccinations after the declaration of the national emergency in mid-March, a drop attributed to fear of COVID-19 exposure.

“ACIP continued to meet and make recommendations during the pandemic,” Dr. Freedman said. “Our recommendation remains that despite challenges caused by the COVID-19 pandemic, adults and their healthcare providers should follow the recommended vaccine schedule to protect against serious and sometimes deadly diseases.”

Regular vaccines can be safely administered even as COVID-19 retains its grasp on the United States. “Healthcare providers should follow the CDC’s interim guidance for the safe delivery of vaccines during the pandemic, which includes the use of personal protective equipment and physical distancing,” Dr. Freedman said.

Dr. Freedman has disclosed no relevant financial relationships. Coauthor Henry Bernstein, DO, is the editor of the Current Opinion in Pediatrics Office Pediatrics Series, is a Harvard School of Public Health faculty member, and is a member of the data safety and monitoring board for a Takeda study on intrathecal enzymes for Hunter and San Filippo syndromes. Coauthor Kevin Ault, MD, has served on the data safety and monitoring committee for ACI Clinical.
 

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

The Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention has updated its recommended immunization schedule for adults for 2021.

A summary of the annual update was published online Feb. 11 in the CDC’s Morbidity and Mortality Weekly Report and is available in Annals of Internal Medicine and on the CDC website.

It features a special section on vaccination during the pandemic as well as interim recommendations on administering the Pfizer-BioNtech and Moderna COVID-19 vaccines.

The authors, led by Mark S. Freedman, DVM, MPH, DACVPM, of the CDC’s National Center for Immunization and Respiratory Diseases, in Atlanta, note that this year’s recommendations for adults – persons aged 19 years and older – are largely the same as last year’s. “There have been very few changes,” Dr. Freedman said in an interview. “Changes to the schedule tables and notes were made to harmonize to the greatest extent possible the adult and child/adolescent schedules.”

Changes in the schedule include new or updated ACIP recommendations for influenza, hepatitis A, hepatitis B (Hep B), and human papillomavirus (HPV) as well as for meningococcal serogroups A, C, W, and Y (MenACYW) vaccines, meningococcal B (MenB) vaccines, and the zoster vaccine.

Vaccine-specific changes

Influenza

The schedule highlights updates to the composition of several influenza vaccines, which apply to components in both trivalent and quadrivalent formulations.

The cover page abbreviation for live attenuated influenza vaccine (LAIV) was changed to LAIV4. The abbreviation for live recombinant influenza vaccine (RIV) was changed to RIV4.

For individuals with a history of egg allergy who experience reactions other than hives, the following procedural warning has been added: “If using an influenza vaccine other than RIV4 or ccIIV4, administer in medical setting under supervision of health care provider who can recognize and manage severe allergic reactions.”

Zoster

The zoster vaccine live (Zostavax) has been removed from the schedule because it is no longer available in the United States. The recombinant zoster vaccine Shingrix remains available as a 2-dose regimen for adults aged 50 years or older.

HPV

As in previous years, HPV vaccination is routinely recommended for persons aged 11-12 years, with catch-up vaccination for those aged 26 or younger. Catch-up vaccination can be considered with shared decision making for those aged 27 through 45. In this year’s schedule, in the pregnancy column, the color pink, which formerly indicated “delay until after pregnancy,” has been replaced with red and an asterisk, indicating “vaccinate after pregnancy.”

HepB

ACIP continues to recommend vaccination of adults at risk for HepB; however, the text overlay has been changed to read, “2, 3, or 4 doses, depending on vaccine or condition.” Additionally, HepB vaccination is now routinely recommended for adults younger than 60 years with diabetes. For those with diabetes who are older than 60, shared decision making is recommended.

Meningococcal vaccine

ACIP continues to recommend routine vaccination with a quadrivalent meningococcal conjugate vaccine (MenACWY) for persons at increased risk for meningococcal disease caused by serogroups A, C, W, or Y. The MenQuadfi (MenACWY-TT) vaccine, which was first licensed in 2020, has been added to all relevant sections of MenACWY vaccines. For MenACWY booster doses, new text addresses special situations, including outbreaks.

Improvements have been made to text and layout, Dr. Freedman said. An example is the minimizing of specialized text. Other changes were made to ensure more consistent text structure and language. Various fine-tunings of color and positioning were made to the cover page and tables, and the wording of the notes sections was improved.

Vaccination in the pandemic

The updated schedule outlines guidance on the use of COVID-19 vaccines approved by the Food and Drug Administration under emergency use authorization, with interim recommendations for the Pfizer-BioNTech COVID-19 vaccine for people aged 16 and older and the Moderna COVID-19 vaccine for people aged 18 and older.

The authors stress the importance of receiving the recommended routine and catch-up immunizations notwithstanding widespread anxiety about visiting medical offices. Last spring, the CDC reported a dramatic drop in child vaccinations after the declaration of the national emergency in mid-March, a drop attributed to fear of COVID-19 exposure.

“ACIP continued to meet and make recommendations during the pandemic,” Dr. Freedman said. “Our recommendation remains that despite challenges caused by the COVID-19 pandemic, adults and their healthcare providers should follow the recommended vaccine schedule to protect against serious and sometimes deadly diseases.”

Regular vaccines can be safely administered even as COVID-19 retains its grasp on the United States. “Healthcare providers should follow the CDC’s interim guidance for the safe delivery of vaccines during the pandemic, which includes the use of personal protective equipment and physical distancing,” Dr. Freedman said.

Dr. Freedman has disclosed no relevant financial relationships. Coauthor Henry Bernstein, DO, is the editor of the Current Opinion in Pediatrics Office Pediatrics Series, is a Harvard School of Public Health faculty member, and is a member of the data safety and monitoring board for a Takeda study on intrathecal enzymes for Hunter and San Filippo syndromes. Coauthor Kevin Ault, MD, has served on the data safety and monitoring committee for ACI Clinical.
 

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

Critical care staff are less likely to acquire COVID-19 infection from ICU patients than they are from areas away from the bedside, a new study has found.

Courtesy NIAID

“Other staff, other areas of the hospital, and the wider community are more likely sources of infection,” said lead author Kate El Bouzidi, MRCP, South London Specialist Virology Centre, King’s College Hospital NHS Foundation Trust, London.

She noted that 60% of critical care staff were symptomatic during the first wave of the coronavirus pandemic and 20% were antibody positive, with 10% asymptomatic. “Staff acquisition peaked 3 weeks before the peak of COVID-19 ICU admission, and personal protective equipment (PPE) was effective at preventing transmission from patients.” Working in other areas of the hospital was associated with higher seroprevalence, Dr. El Bouzidi noted.

The findings were presented at the Critical Care Congress sponsored by the Society of Critical Care Medicine.

The novel coronavirus was spreading around the world, and when it reached northern Italy, medical authorities began to think in terms of how it might overwhelm the health care system in the United Kingdom, explained Dr. El Bouzidi.

“There was a lot of interest at this time about health care workers who were particularly vulnerable and also about the allocation of resources and rationing of care, particularly in intensive care,” she said. “And this only intensified when our prime minister was admitted to intensive care. About this time, antibody testing also became available.”

The goal of their study was to determine the SARS-CoV-2 seroprevalence in critical care staff, as well as look at the correlation between antibody status, prior swab testing, and COVID-19 symptoms.

The survey was conducted at Kings College Hospital in London, which is a tertiary-care teaching center. The critical care department is one of the largest in the United Kingdom. The authors estimate that more than 800 people worked in the critical care units, and between March and April 2020, more than 2,000 patients with COVID-19 were admitted, of whom 180 required care in the ICU.

“There was good PPE available in the ICU units right from the start,” she said, “and staff testing was available.”

All staff working in the critical care department participated in the study, which required serum samples and completion of a questionnaire. The samples were tested via six different assays to measure receptor-binding domain, nucleoprotein, and tri-spike, with one antibody result determined for each sample.

Of the 625 staff members, 384 (61.4%) had previously reported experiencing symptoms and 124 (19.8%) had sent a swab for testing. COVID-19 infection had been confirmed in 37 of those health care workers (29.8%).

Overall, 21% were positive for SARS-CoV-2 antibodies, of whom 9.9% had been asymptomatic.

“We were surprised to find that 61% of staff reported symptoms they felt could be consistent with COVID-19,” she said, noting that fatigue, headache, and cough were the most common symptoms reported. “Seroprevalence was reported in 31% of symptomatic staff and in 5% of those without symptoms.”

Seroprevalence differed by role in a critical care unit, although it did not significantly differ by factors such as age, sex, ethnicity, or underlying conditions. Consultants, who are senior physicians, were twice as likely to test positive, compared with junior doctors. The reason for this finding is not clear, but it may lie in the nature of their work responsibilities, such as performing more aerosol-generating procedures in the ICU or in other departments.

The investigators looked at the timing of infections and found that they preceded peak of patient admissions by 3 weeks, with peak onset of staff symptoms in early March. At this time, Dr. El Bouzidi noted, there were very few patients with COVID-19 in the hospital, and good PPE was available throughout this time period.

“Staff were unlikely to be infected by ICU patients, and therefore PPE was largely effective,” she said. “Other sources of infection were more likely to be the cause, such as interactions with other staff, meetings, or contact in break rooms. Routine mask-wearing throughout the hospital was only encouraged as of June 15.”

There were several limitations to the study, such as the cross-sectional design, reliance on response/recall, the fact that antibody tests are unlikely to detect all previous infections, and no genomic data were available to confirm infections. Even though the study had limitations, Dr. El Bouzidi concluded that ICU staff are unlikely to contract COVID-19 from patients but that other staff, other areas of the hospital, and the wider community are more likely sources of infection.

These findings, she added, demonstrate that PPE was effective at preventing transmission from patients and that protective measures need to be maintained when staff is away from the bedside.

In commenting on the study, Greg S. Martin, MD, professor of medicine in the division of pulmonary, allergy, critical care and sleep medicine, Emory University, Atlanta, noted that, even though the study was conducted almost a year ago, the results are still relevant with regard to the effectiveness of PPE.

“There was a huge amount of uncertainty about PPE – what was most effective, could we reuse it, how to sterilize it, what about surfaces, and so on,” he said. “Even for people who work in ICU and who are familiar with the environment and familiar with the patients, there was 1,000 times more uncertainty about everything they were doing.”

Dr. Martin believes that the situation has improved. “It’s not that we take COVID more lightly, but I think the staff is more comfortable dealing with it,” he said. “They now know what they need to do on an hourly and daily basis to stay safe. The PPE had become second nature to them now, with all the other precautions.”

Critical care staff are less likely to acquire COVID-19 infection from ICU patients than they are from areas away from the bedside, a new study has found.

Courtesy NIAID

“Other staff, other areas of the hospital, and the wider community are more likely sources of infection,” said lead author Kate El Bouzidi, MRCP, South London Specialist Virology Centre, King’s College Hospital NHS Foundation Trust, London.

She noted that 60% of critical care staff were symptomatic during the first wave of the coronavirus pandemic and 20% were antibody positive, with 10% asymptomatic. “Staff acquisition peaked 3 weeks before the peak of COVID-19 ICU admission, and personal protective equipment (PPE) was effective at preventing transmission from patients.” Working in other areas of the hospital was associated with higher seroprevalence, Dr. El Bouzidi noted.

The findings were presented at the Critical Care Congress sponsored by the Society of Critical Care Medicine.

The novel coronavirus was spreading around the world, and when it reached northern Italy, medical authorities began to think in terms of how it might overwhelm the health care system in the United Kingdom, explained Dr. El Bouzidi.

“There was a lot of interest at this time about health care workers who were particularly vulnerable and also about the allocation of resources and rationing of care, particularly in intensive care,” she said. “And this only intensified when our prime minister was admitted to intensive care. About this time, antibody testing also became available.”

The goal of their study was to determine the SARS-CoV-2 seroprevalence in critical care staff, as well as look at the correlation between antibody status, prior swab testing, and COVID-19 symptoms.

The survey was conducted at Kings College Hospital in London, which is a tertiary-care teaching center. The critical care department is one of the largest in the United Kingdom. The authors estimate that more than 800 people worked in the critical care units, and between March and April 2020, more than 2,000 patients with COVID-19 were admitted, of whom 180 required care in the ICU.

“There was good PPE available in the ICU units right from the start,” she said, “and staff testing was available.”

All staff working in the critical care department participated in the study, which required serum samples and completion of a questionnaire. The samples were tested via six different assays to measure receptor-binding domain, nucleoprotein, and tri-spike, with one antibody result determined for each sample.

Of the 625 staff members, 384 (61.4%) had previously reported experiencing symptoms and 124 (19.8%) had sent a swab for testing. COVID-19 infection had been confirmed in 37 of those health care workers (29.8%).

Overall, 21% were positive for SARS-CoV-2 antibodies, of whom 9.9% had been asymptomatic.

“We were surprised to find that 61% of staff reported symptoms they felt could be consistent with COVID-19,” she said, noting that fatigue, headache, and cough were the most common symptoms reported. “Seroprevalence was reported in 31% of symptomatic staff and in 5% of those without symptoms.”

Seroprevalence differed by role in a critical care unit, although it did not significantly differ by factors such as age, sex, ethnicity, or underlying conditions. Consultants, who are senior physicians, were twice as likely to test positive, compared with junior doctors. The reason for this finding is not clear, but it may lie in the nature of their work responsibilities, such as performing more aerosol-generating procedures in the ICU or in other departments.

The investigators looked at the timing of infections and found that they preceded peak of patient admissions by 3 weeks, with peak onset of staff symptoms in early March. At this time, Dr. El Bouzidi noted, there were very few patients with COVID-19 in the hospital, and good PPE was available throughout this time period.

“Staff were unlikely to be infected by ICU patients, and therefore PPE was largely effective,” she said. “Other sources of infection were more likely to be the cause, such as interactions with other staff, meetings, or contact in break rooms. Routine mask-wearing throughout the hospital was only encouraged as of June 15.”

There were several limitations to the study, such as the cross-sectional design, reliance on response/recall, the fact that antibody tests are unlikely to detect all previous infections, and no genomic data were available to confirm infections. Even though the study had limitations, Dr. El Bouzidi concluded that ICU staff are unlikely to contract COVID-19 from patients but that other staff, other areas of the hospital, and the wider community are more likely sources of infection.

These findings, she added, demonstrate that PPE was effective at preventing transmission from patients and that protective measures need to be maintained when staff is away from the bedside.

In commenting on the study, Greg S. Martin, MD, professor of medicine in the division of pulmonary, allergy, critical care and sleep medicine, Emory University, Atlanta, noted that, even though the study was conducted almost a year ago, the results are still relevant with regard to the effectiveness of PPE.

“There was a huge amount of uncertainty about PPE – what was most effective, could we reuse it, how to sterilize it, what about surfaces, and so on,” he said. “Even for people who work in ICU and who are familiar with the environment and familiar with the patients, there was 1,000 times more uncertainty about everything they were doing.”

Dr. Martin believes that the situation has improved. “It’s not that we take COVID more lightly, but I think the staff is more comfortable dealing with it,” he said. “They now know what they need to do on an hourly and daily basis to stay safe. The PPE had become second nature to them now, with all the other precautions.”

Critical care staff are less likely to acquire COVID-19 infection from ICU patients than they are from areas away from the bedside, a new study has found.

Courtesy NIAID

“Other staff, other areas of the hospital, and the wider community are more likely sources of infection,” said lead author Kate El Bouzidi, MRCP, South London Specialist Virology Centre, King’s College Hospital NHS Foundation Trust, London.

She noted that 60% of critical care staff were symptomatic during the first wave of the coronavirus pandemic and 20% were antibody positive, with 10% asymptomatic. “Staff acquisition peaked 3 weeks before the peak of COVID-19 ICU admission, and personal protective equipment (PPE) was effective at preventing transmission from patients.” Working in other areas of the hospital was associated with higher seroprevalence, Dr. El Bouzidi noted.

The findings were presented at the Critical Care Congress sponsored by the Society of Critical Care Medicine.

The novel coronavirus was spreading around the world, and when it reached northern Italy, medical authorities began to think in terms of how it might overwhelm the health care system in the United Kingdom, explained Dr. El Bouzidi.

“There was a lot of interest at this time about health care workers who were particularly vulnerable and also about the allocation of resources and rationing of care, particularly in intensive care,” she said. “And this only intensified when our prime minister was admitted to intensive care. About this time, antibody testing also became available.”

The goal of their study was to determine the SARS-CoV-2 seroprevalence in critical care staff, as well as look at the correlation between antibody status, prior swab testing, and COVID-19 symptoms.

The survey was conducted at Kings College Hospital in London, which is a tertiary-care teaching center. The critical care department is one of the largest in the United Kingdom. The authors estimate that more than 800 people worked in the critical care units, and between March and April 2020, more than 2,000 patients with COVID-19 were admitted, of whom 180 required care in the ICU.

“There was good PPE available in the ICU units right from the start,” she said, “and staff testing was available.”

All staff working in the critical care department participated in the study, which required serum samples and completion of a questionnaire. The samples were tested via six different assays to measure receptor-binding domain, nucleoprotein, and tri-spike, with one antibody result determined for each sample.

Of the 625 staff members, 384 (61.4%) had previously reported experiencing symptoms and 124 (19.8%) had sent a swab for testing. COVID-19 infection had been confirmed in 37 of those health care workers (29.8%).

Overall, 21% were positive for SARS-CoV-2 antibodies, of whom 9.9% had been asymptomatic.

“We were surprised to find that 61% of staff reported symptoms they felt could be consistent with COVID-19,” she said, noting that fatigue, headache, and cough were the most common symptoms reported. “Seroprevalence was reported in 31% of symptomatic staff and in 5% of those without symptoms.”

Seroprevalence differed by role in a critical care unit, although it did not significantly differ by factors such as age, sex, ethnicity, or underlying conditions. Consultants, who are senior physicians, were twice as likely to test positive, compared with junior doctors. The reason for this finding is not clear, but it may lie in the nature of their work responsibilities, such as performing more aerosol-generating procedures in the ICU or in other departments.

The investigators looked at the timing of infections and found that they preceded peak of patient admissions by 3 weeks, with peak onset of staff symptoms in early March. At this time, Dr. El Bouzidi noted, there were very few patients with COVID-19 in the hospital, and good PPE was available throughout this time period.

“Staff were unlikely to be infected by ICU patients, and therefore PPE was largely effective,” she said. “Other sources of infection were more likely to be the cause, such as interactions with other staff, meetings, or contact in break rooms. Routine mask-wearing throughout the hospital was only encouraged as of June 15.”

There were several limitations to the study, such as the cross-sectional design, reliance on response/recall, the fact that antibody tests are unlikely to detect all previous infections, and no genomic data were available to confirm infections. Even though the study had limitations, Dr. El Bouzidi concluded that ICU staff are unlikely to contract COVID-19 from patients but that other staff, other areas of the hospital, and the wider community are more likely sources of infection.

These findings, she added, demonstrate that PPE was effective at preventing transmission from patients and that protective measures need to be maintained when staff is away from the bedside.

In commenting on the study, Greg S. Martin, MD, professor of medicine in the division of pulmonary, allergy, critical care and sleep medicine, Emory University, Atlanta, noted that, even though the study was conducted almost a year ago, the results are still relevant with regard to the effectiveness of PPE.

“There was a huge amount of uncertainty about PPE – what was most effective, could we reuse it, how to sterilize it, what about surfaces, and so on,” he said. “Even for people who work in ICU and who are familiar with the environment and familiar with the patients, there was 1,000 times more uncertainty about everything they were doing.”

Dr. Martin believes that the situation has improved. “It’s not that we take COVID more lightly, but I think the staff is more comfortable dealing with it,” he said. “They now know what they need to do on an hourly and daily basis to stay safe. The PPE had become second nature to them now, with all the other precautions.”

Longer-term survival with immunotherapy for patients with non–small cell lung cancer (NSCLC) is once again being applauded by experts in the field.

This time, the data come from trials that tested immunotherapy in the second-line setting for patients who had experienced disease progression with platinum-based chemotherapy. The latest 5-year follow-up from two landmark trials, one with pembrolizumab, the other with nivolumab, show that the survival benefit can persist for years after treatment is stopped.

“These are unprecedented data,” Fred R. Hirsch, MD, PhD, executive director of the Center for Thoracic Oncology at the Tisch Cancer Institute, New York, said in an interview. He was not involved in either trial and was approached for comment.
 

Pembrolizumab survival data

The new longer-term data on pembrolizumab come from the KEYNOTE-010 trial, which included more than 1,000 patients with advanced NSCLC who had previously undergone treatment with platinum-based chemotherapy. The patients were randomly assigned to receive either pembrolizumab or docetaxel for 2 years.

This is the latest update on data from this trial, which has been described as “really extraordinary.”

The 5-year overall survival rates were more than doubled in the pembrolizumab groups, compared with the docetaxel group, reported Roy Herbst, MD, PhD, department of medical oncology, Yale Comprehensive Cancer Center, New Haven, Conn.. He was presenting the new data at the recent World Conference on Lung Cancer 2020.

Overall results for patients with programmed death-ligand 1 (PD-L1) Tumor Proportion Score (TPS) expression greater than 1% show that 15.6% of the pembrolizumab group were still alive at 5 years versus 6.5% of the docetaxel group.

The results were even better among patients who had high PD-L1 TPS expression (>50%): in this subgroup, 25% of the patients who received pembrolizumab were still alive versus 8.2% of those who received docetaxel.

In addition, at 5 years, 9.4% of patients who received pembrolizumab were disease free versus 0.7% of the patients who received docetaxel, Dr. Herbst reported.

Dr. Hirsch commented that the 5-year survival rate of 25% among patients with high PD-L1 expression who underwent treatment with pembrolizumab is “great progress in lung cancer treatment, there is no doubt about it.”

He noted that the results also show that “numerically,” it matters whether patients have low PD-L1 expression. “We know from first-line studies that pembrolizumab monotherapy is effective in high PD-L1–expressing tumors, so these data fit very well,” he said.

At the meeting, Dr. Herbst summarized his presentation on pembrolizumab for patients with NSCLC who had previously undergone treatment, saying that, “with 5 years of follow-up, we continue to see a clinically meaningful improvement in overall survival and PFS [progression-free survival].

“Pembrolizumab monotherapy is a standard of care in patients with immunotherapy-naive or previously treated PD-L1–positive advanced non–small cell lung cancer,” Herbst stated.

Dr. Hirsch was largely in agreement. He believes that, for patients with a PD-L1 TPS of at least 50%, the standard of care “is practically pembrolizumab monotherapy, unless there are certain circumstances where you would add chemotherapy,” such as for patients with a high tumor volume, “where you want to see a very quick response.”

Dr. Hirsch pointed out, however, that currently most patients with high PD-L1–expressing tumors are given pembrolizumab in the first line, which begs the question as to what to give those who experience disease progression after immunotherapy.

“That is an open space,” he said. “There is a lot of studies going on in what we call the immunotherapy-refractory patients.

“We don’t have clear guidance for clinical practice yet,” he commented. He noted that there are several options: “Do you continue with chemotherapy? Do you continue with chemotherapy plus another immunotherapy? Do you switch to another immunotherapy?”

Commenting on Twitter, Stephen V. Liu, MD, director of thoracic oncology at Georgetown University, Washington, said the results were “very exciting.”

However, he wondered whether the results suggest that patients with high PD-L1 expression “may be able to stop” receiving pembrolizumab, whereas those with disease of lower expression “may need longer therapy.”

H. Jack West, MD, medical director of the thoracic oncology program, Swedish Cancer Institute, Seattle, said on Twitter that, to him, the “most impressive” aspect was the “new insight about patients stopping pembro after 2 years but still having two-thirds with sustained response.”

He added that he would “love to learn which patients can stop therapy and when, or whether we can do infrequent maintenance IO [immunotherapy].”

 

Nivolumab survival data

The data on nivolumab come from a pooled analysis of 5-year data on 854 patients from CheckMate 057 and CheckMate 017. The analysis was published in the Journal of Clinical Oncology on Jan. 15, 2021.

Both of these trials compared nivolumab with docetaxel for patients with NSCLC who had experienced disease progression with platinum-based chemotherapy.

The pooled analysis showed that the 5-year overall survival rate was more than fivefold greater with nivolumab than with docetaxel, at 13.4% versus 2.6%.

Moreover, more than 80% of patients who had not experienced progression with the immunotherapy at 2 years were still alive at 5 years. The percentage rose to more than 90% among those who had not experienced progression at 3 years.

Lead author Julie R. Brahmer, MD, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, and colleagues said the results “demonstrate that nivolumab can provide long-term survival benefit with durable responses and a tolerable safety profile in patients with previously treated, advanced NSCLC.

“Furthermore, some patients appear to maintain prolonged disease control even after stopping systemic therapy,” they noted.

Dr. Hirsch commented that, although the survival rates with nivolumab were slightly lower than reported with pembrolizumab in KEYNOTE-010, they could still be “within the range.” He added that “I wouldn’t conclude that pembrolizumab is better than nivolumab.”

Many factors may account for these differences, he suggested, including differences in the patient populations or simply differences in the numbers of patients included.

For him, the “main point” of the new data from both trials is that immunotherapy has shown “tremendous progress, compared to chemotherapy.”

KEYNOTE-010 was sponsored by Merck Sharp & Dohme. CheckMate 017 and CheckMate057 were sponsored by Bristol-Myers Squibb. Dr. Herbst has relationships with Jun Shi Pharmaceuticals, AstraZeneca, Genentech, Merck, Pfizer, AbbVie, Biodesix, Bristol-Myers Squibb, Eli Lilly, EMD Serono, Heat Biologics, Loxo, Nektar, NextCure, Novartis, Sanofi, Seattle Genetics, Shire, Spectrum Pharmaceuticals, Symphogen, Tesaro, Neon Therapeutics, Infinity Pharmaceuticals, Armo Biosciences, Genmab, Halozyme, and Tocagen. Dr. Brahmer has relationships with Roche/Genentech, Bristol-Myers Squibb, Lilly, Celgene, Syndax, Janssen Oncology, Merck, Amgen, Genentech, AstraZeneca, Incyte, Spectrum Pharmaceuticals, Revolution, and Roche/Genentech.

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

Longer-term survival with immunotherapy for patients with non–small cell lung cancer (NSCLC) is once again being applauded by experts in the field.

This time, the data come from trials that tested immunotherapy in the second-line setting for patients who had experienced disease progression with platinum-based chemotherapy. The latest 5-year follow-up from two landmark trials, one with pembrolizumab, the other with nivolumab, show that the survival benefit can persist for years after treatment is stopped.

“These are unprecedented data,” Fred R. Hirsch, MD, PhD, executive director of the Center for Thoracic Oncology at the Tisch Cancer Institute, New York, said in an interview. He was not involved in either trial and was approached for comment.
 

Pembrolizumab survival data

The new longer-term data on pembrolizumab come from the KEYNOTE-010 trial, which included more than 1,000 patients with advanced NSCLC who had previously undergone treatment with platinum-based chemotherapy. The patients were randomly assigned to receive either pembrolizumab or docetaxel for 2 years.

This is the latest update on data from this trial, which has been described as “really extraordinary.”

The 5-year overall survival rates were more than doubled in the pembrolizumab groups, compared with the docetaxel group, reported Roy Herbst, MD, PhD, department of medical oncology, Yale Comprehensive Cancer Center, New Haven, Conn.. He was presenting the new data at the recent World Conference on Lung Cancer 2020.

Overall results for patients with programmed death-ligand 1 (PD-L1) Tumor Proportion Score (TPS) expression greater than 1% show that 15.6% of the pembrolizumab group were still alive at 5 years versus 6.5% of the docetaxel group.

The results were even better among patients who had high PD-L1 TPS expression (>50%): in this subgroup, 25% of the patients who received pembrolizumab were still alive versus 8.2% of those who received docetaxel.

In addition, at 5 years, 9.4% of patients who received pembrolizumab were disease free versus 0.7% of the patients who received docetaxel, Dr. Herbst reported.

Dr. Hirsch commented that the 5-year survival rate of 25% among patients with high PD-L1 expression who underwent treatment with pembrolizumab is “great progress in lung cancer treatment, there is no doubt about it.”

He noted that the results also show that “numerically,” it matters whether patients have low PD-L1 expression. “We know from first-line studies that pembrolizumab monotherapy is effective in high PD-L1–expressing tumors, so these data fit very well,” he said.

At the meeting, Dr. Herbst summarized his presentation on pembrolizumab for patients with NSCLC who had previously undergone treatment, saying that, “with 5 years of follow-up, we continue to see a clinically meaningful improvement in overall survival and PFS [progression-free survival].

“Pembrolizumab monotherapy is a standard of care in patients with immunotherapy-naive or previously treated PD-L1–positive advanced non–small cell lung cancer,” Herbst stated.

Dr. Hirsch was largely in agreement. He believes that, for patients with a PD-L1 TPS of at least 50%, the standard of care “is practically pembrolizumab monotherapy, unless there are certain circumstances where you would add chemotherapy,” such as for patients with a high tumor volume, “where you want to see a very quick response.”

Dr. Hirsch pointed out, however, that currently most patients with high PD-L1–expressing tumors are given pembrolizumab in the first line, which begs the question as to what to give those who experience disease progression after immunotherapy.

“That is an open space,” he said. “There is a lot of studies going on in what we call the immunotherapy-refractory patients.

“We don’t have clear guidance for clinical practice yet,” he commented. He noted that there are several options: “Do you continue with chemotherapy? Do you continue with chemotherapy plus another immunotherapy? Do you switch to another immunotherapy?”

Commenting on Twitter, Stephen V. Liu, MD, director of thoracic oncology at Georgetown University, Washington, said the results were “very exciting.”

However, he wondered whether the results suggest that patients with high PD-L1 expression “may be able to stop” receiving pembrolizumab, whereas those with disease of lower expression “may need longer therapy.”

H. Jack West, MD, medical director of the thoracic oncology program, Swedish Cancer Institute, Seattle, said on Twitter that, to him, the “most impressive” aspect was the “new insight about patients stopping pembro after 2 years but still having two-thirds with sustained response.”

He added that he would “love to learn which patients can stop therapy and when, or whether we can do infrequent maintenance IO [immunotherapy].”

 

Nivolumab survival data

The data on nivolumab come from a pooled analysis of 5-year data on 854 patients from CheckMate 057 and CheckMate 017. The analysis was published in the Journal of Clinical Oncology on Jan. 15, 2021.

Both of these trials compared nivolumab with docetaxel for patients with NSCLC who had experienced disease progression with platinum-based chemotherapy.

The pooled analysis showed that the 5-year overall survival rate was more than fivefold greater with nivolumab than with docetaxel, at 13.4% versus 2.6%.

Moreover, more than 80% of patients who had not experienced progression with the immunotherapy at 2 years were still alive at 5 years. The percentage rose to more than 90% among those who had not experienced progression at 3 years.

Lead author Julie R. Brahmer, MD, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, and colleagues said the results “demonstrate that nivolumab can provide long-term survival benefit with durable responses and a tolerable safety profile in patients with previously treated, advanced NSCLC.

“Furthermore, some patients appear to maintain prolonged disease control even after stopping systemic therapy,” they noted.

Dr. Hirsch commented that, although the survival rates with nivolumab were slightly lower than reported with pembrolizumab in KEYNOTE-010, they could still be “within the range.” He added that “I wouldn’t conclude that pembrolizumab is better than nivolumab.”

Many factors may account for these differences, he suggested, including differences in the patient populations or simply differences in the numbers of patients included.

For him, the “main point” of the new data from both trials is that immunotherapy has shown “tremendous progress, compared to chemotherapy.”

KEYNOTE-010 was sponsored by Merck Sharp & Dohme. CheckMate 017 and CheckMate057 were sponsored by Bristol-Myers Squibb. Dr. Herbst has relationships with Jun Shi Pharmaceuticals, AstraZeneca, Genentech, Merck, Pfizer, AbbVie, Biodesix, Bristol-Myers Squibb, Eli Lilly, EMD Serono, Heat Biologics, Loxo, Nektar, NextCure, Novartis, Sanofi, Seattle Genetics, Shire, Spectrum Pharmaceuticals, Symphogen, Tesaro, Neon Therapeutics, Infinity Pharmaceuticals, Armo Biosciences, Genmab, Halozyme, and Tocagen. Dr. Brahmer has relationships with Roche/Genentech, Bristol-Myers Squibb, Lilly, Celgene, Syndax, Janssen Oncology, Merck, Amgen, Genentech, AstraZeneca, Incyte, Spectrum Pharmaceuticals, Revolution, and Roche/Genentech.

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

Longer-term survival with immunotherapy for patients with non–small cell lung cancer (NSCLC) is once again being applauded by experts in the field.

This time, the data come from trials that tested immunotherapy in the second-line setting for patients who had experienced disease progression with platinum-based chemotherapy. The latest 5-year follow-up from two landmark trials, one with pembrolizumab, the other with nivolumab, show that the survival benefit can persist for years after treatment is stopped.

“These are unprecedented data,” Fred R. Hirsch, MD, PhD, executive director of the Center for Thoracic Oncology at the Tisch Cancer Institute, New York, said in an interview. He was not involved in either trial and was approached for comment.
 

Pembrolizumab survival data

The new longer-term data on pembrolizumab come from the KEYNOTE-010 trial, which included more than 1,000 patients with advanced NSCLC who had previously undergone treatment with platinum-based chemotherapy. The patients were randomly assigned to receive either pembrolizumab or docetaxel for 2 years.

This is the latest update on data from this trial, which has been described as “really extraordinary.”

The 5-year overall survival rates were more than doubled in the pembrolizumab groups, compared with the docetaxel group, reported Roy Herbst, MD, PhD, department of medical oncology, Yale Comprehensive Cancer Center, New Haven, Conn.. He was presenting the new data at the recent World Conference on Lung Cancer 2020.

Overall results for patients with programmed death-ligand 1 (PD-L1) Tumor Proportion Score (TPS) expression greater than 1% show that 15.6% of the pembrolizumab group were still alive at 5 years versus 6.5% of the docetaxel group.

The results were even better among patients who had high PD-L1 TPS expression (>50%): in this subgroup, 25% of the patients who received pembrolizumab were still alive versus 8.2% of those who received docetaxel.

In addition, at 5 years, 9.4% of patients who received pembrolizumab were disease free versus 0.7% of the patients who received docetaxel, Dr. Herbst reported.

Dr. Hirsch commented that the 5-year survival rate of 25% among patients with high PD-L1 expression who underwent treatment with pembrolizumab is “great progress in lung cancer treatment, there is no doubt about it.”

He noted that the results also show that “numerically,” it matters whether patients have low PD-L1 expression. “We know from first-line studies that pembrolizumab monotherapy is effective in high PD-L1–expressing tumors, so these data fit very well,” he said.

At the meeting, Dr. Herbst summarized his presentation on pembrolizumab for patients with NSCLC who had previously undergone treatment, saying that, “with 5 years of follow-up, we continue to see a clinically meaningful improvement in overall survival and PFS [progression-free survival].

“Pembrolizumab monotherapy is a standard of care in patients with immunotherapy-naive or previously treated PD-L1–positive advanced non–small cell lung cancer,” Herbst stated.

Dr. Hirsch was largely in agreement. He believes that, for patients with a PD-L1 TPS of at least 50%, the standard of care “is practically pembrolizumab monotherapy, unless there are certain circumstances where you would add chemotherapy,” such as for patients with a high tumor volume, “where you want to see a very quick response.”

Dr. Hirsch pointed out, however, that currently most patients with high PD-L1–expressing tumors are given pembrolizumab in the first line, which begs the question as to what to give those who experience disease progression after immunotherapy.

“That is an open space,” he said. “There is a lot of studies going on in what we call the immunotherapy-refractory patients.

“We don’t have clear guidance for clinical practice yet,” he commented. He noted that there are several options: “Do you continue with chemotherapy? Do you continue with chemotherapy plus another immunotherapy? Do you switch to another immunotherapy?”

Commenting on Twitter, Stephen V. Liu, MD, director of thoracic oncology at Georgetown University, Washington, said the results were “very exciting.”

However, he wondered whether the results suggest that patients with high PD-L1 expression “may be able to stop” receiving pembrolizumab, whereas those with disease of lower expression “may need longer therapy.”

H. Jack West, MD, medical director of the thoracic oncology program, Swedish Cancer Institute, Seattle, said on Twitter that, to him, the “most impressive” aspect was the “new insight about patients stopping pembro after 2 years but still having two-thirds with sustained response.”

He added that he would “love to learn which patients can stop therapy and when, or whether we can do infrequent maintenance IO [immunotherapy].”

 

Nivolumab survival data

The data on nivolumab come from a pooled analysis of 5-year data on 854 patients from CheckMate 057 and CheckMate 017. The analysis was published in the Journal of Clinical Oncology on Jan. 15, 2021.

Both of these trials compared nivolumab with docetaxel for patients with NSCLC who had experienced disease progression with platinum-based chemotherapy.

The pooled analysis showed that the 5-year overall survival rate was more than fivefold greater with nivolumab than with docetaxel, at 13.4% versus 2.6%.

Moreover, more than 80% of patients who had not experienced progression with the immunotherapy at 2 years were still alive at 5 years. The percentage rose to more than 90% among those who had not experienced progression at 3 years.

Lead author Julie R. Brahmer, MD, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, and colleagues said the results “demonstrate that nivolumab can provide long-term survival benefit with durable responses and a tolerable safety profile in patients with previously treated, advanced NSCLC.

“Furthermore, some patients appear to maintain prolonged disease control even after stopping systemic therapy,” they noted.

Dr. Hirsch commented that, although the survival rates with nivolumab were slightly lower than reported with pembrolizumab in KEYNOTE-010, they could still be “within the range.” He added that “I wouldn’t conclude that pembrolizumab is better than nivolumab.”

Many factors may account for these differences, he suggested, including differences in the patient populations or simply differences in the numbers of patients included.

For him, the “main point” of the new data from both trials is that immunotherapy has shown “tremendous progress, compared to chemotherapy.”

KEYNOTE-010 was sponsored by Merck Sharp & Dohme. CheckMate 017 and CheckMate057 were sponsored by Bristol-Myers Squibb. Dr. Herbst has relationships with Jun Shi Pharmaceuticals, AstraZeneca, Genentech, Merck, Pfizer, AbbVie, Biodesix, Bristol-Myers Squibb, Eli Lilly, EMD Serono, Heat Biologics, Loxo, Nektar, NextCure, Novartis, Sanofi, Seattle Genetics, Shire, Spectrum Pharmaceuticals, Symphogen, Tesaro, Neon Therapeutics, Infinity Pharmaceuticals, Armo Biosciences, Genmab, Halozyme, and Tocagen. Dr. Brahmer has relationships with Roche/Genentech, Bristol-Myers Squibb, Lilly, Celgene, Syndax, Janssen Oncology, Merck, Amgen, Genentech, AstraZeneca, Incyte, Spectrum Pharmaceuticals, Revolution, and Roche/Genentech.

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

Health care professionals working in critical care settings have been overburdened because of the plethora of COVID-19 cases, which has led to symptoms of burnout in both physicians and nurses, findings from a new study show.

XiXinXing/ThinkStock

“Overburdening ICU professionals during an extended period of time leads to burnout,” said lead study author Niek Kok, MSc, of IQ healthcare, Radboud University Medical Center, Radboud Institute for Health Sciences, Nijmegen, the Netherlands. “All ICU professionals are at the risk of this, and in our study, the incidence of physicians experiencing burnout was significantly higher than that of nurses in June 2020.”

This burnout can be explained by conditions caused by the pandemic, he noted, such as the scarcity of staff and resources and having to work with colleagues who were not qualified to work in critical care but who were there out of necessity.

Mr. Kok presented the findings of the study at the Critical Care Congress sponsored by the Society of Critical Care Medicine.
 

Burnout highest among critical care physicians

The ICU can be a stressful environment for both patients and health care personnel, and burnout is not uncommon among ICU clinicians. However, COVID-19 has amplified the degree of burnout being experienced by clinicians working in this setting. Critical care physicians now top the list of physicians experiencing burnout, at 51%, up from 44% last year, according to the Medscape report ‘Death by 1000 Thousand Cuts’: Physician Burnout and Suicide Report 2021.

The Medscape Nurse Career Satisfaction Report 2020, while not restricted to those working in critical care, also reported higher rates of burnout, compared with the prepandemic period. The percentage of nurses reporting being “very burned out” prior to the pandemic was 4%. Six months into the pandemic, that percentage soared to 18%.

In this study, Mr. Kok and colleagues examined the prevalence and incidence of burnout symptoms and moral distress in health care professionals working in the ICU, both before and during the COVID-19 pandemic.

“When the COVID-19 pandemic surfaced in the Netherlands, the health care professionals in our hospitals were motivated to do everything they could to provide the best care possible,” said Mr. Kok. “Many of the ICU professionals immediately realized that they would have to work longer hours.”

However, the health care professionals that he spoke with did have mixed feelings. Some were afraid of being infected with the virus, while others said that “it was very interesting times for them and that gave them extra motivation to do the work.

“Some physicians [and] the WHO warned that COVID-19 is not going to weathered by a heroic sprint – it is an arduous marathon that is going to go hand in hand with burnout symptoms,” Mr. Kok added. “It will eat away at our qualified ICU staff.”
 

Before and after data on burnout

It was widely believed that the COVID-19 pandemic would increase burnout symptoms, as had been demonstrated in studies of previous pandemics. However, Mr. Kok emphasized that there are no before and after measurements that transcend cross-sectional designs.

“The claim [has been] that it increases burnout – but there are no assessments of how it progresses in ICU professionals through time,” he said. “So what we really need is a comparison [of] before and after the pandemic.”

It is quite difficult to obtain this type of information because disruptive events like the COVID-19 pandemic cannot be predicted, he said. Thus, it is challenging to get a baseline measurement. But Mr. Kok pointed out that the study has both “before and after” measurements.

“By coincidence really, we had baseline data to measure the impact of the COVID-19 pandemic and had information that was collected before the pandemic,” he said.

In January 2020, a study began looking at the effects of ethics meetings on moral distress in ICU professionals. Data had been collected on moral distress and burnout on ICU professionals in December 2019. The first COVID-19 cases appeared in the Netherlands in February 2020.

A follow-up study was then conducted in May and June 2020, several months into the pandemic.

The longitudinal open cohort study included all ICU personnel who were working in five units within a single university medical center, plus another adult ICU that was based in a separate teaching hospital.

A total of 352 health care professionals responded to a baseline survey in October through December 2019, and then 233 responded to a follow-up survey sent in May and June 2020. The authors measured burnout symptoms and moral distress with the Maslach Burnout Inventory and the Moral Distress Scale, respectively.
 

Findings

The overall prevalence of burnout symptoms was 23.0% prior to the pandemic, and that jumped to 36.1% at post-peak time. Higher rates of burnout were reported by nurses (38.0%) than physicians (28.6%).

However, the incidence rate of new burnout cases was higher among physicians, compared with nurses (26.7% vs 21.9%). Not surprisingly, a higher prevalence of burnout symptoms was observed in the post-peak period for all clinicians (odds ratio, 1.83; 95% confidence interval, 1.32-2.53), and was higher for nurses (odds ratio, 1.77; 95% confidence interval, 1.03-3.04), for those working overtime (OR, 2.11; 95% CI, 1.48-3.02), and for personnel who directly engaged in patient care (OR, 1.87; 95% CI, 1.35-2.60).

Physicians in general were much more likely to develop burnout symptoms related to the pandemic, compared with nurses (OR, 3.56; 95% CI, 1.06-12.21).

When looking at findings on moral distress, Kok pointed out that it often arises in situations when the health care professional knows the right thing to do but is prevented from doing so. “Morally distressful situations all rose from December to June,” said Mr. Kok. “Scarcity was the most distressing. The other was where colleagues were perceived to be less skilled, and this had to do with the recruitment of people from outside of the ICU to provide care.”

Moral distress from scarcity and unskilled colleagues were both significantly related to burnout, he noted.

In the final model, working in a COVID-19 unit, stress from scarcity of resources and people, stress from unskilled colleagues, and stress from unsafe conditions were all related to burnout. “The stress of physicians was significantly higher,” said Kok. “Even though nurses had higher baseline burnout, it became less pronounced in June 2020. This indicates that burnout was significantly higher in physicians.”

Thus, Mr. Kok and colleagues concluded that overburdening ICU professionals during an extended period of time leads to burnout, and all ICU workers are at risk.
 

Burnout rates higher in physicians

Weighing in on the study, Greg S. Martin, MD, FCCP, professor of medicine in the division of pulmonary, allergy, critical care and sleep medicine, Emory University, Atlanta, noted that the differences observed between physicians and nurses may have to do with the fact that “nurses have been smoldering all along and experiencing higher rates of burnout.

“They may have adapted better to the pandemic conditions, since they are more used to working overtime and short staffed, and spending far more time at the bedside,” he said. “Because of the volume of patients, physicians may be spending more hours doing patient care and are experiencing more burnout.”

Health care professionals working in critical care settings have been overburdened because of the plethora of COVID-19 cases, which has led to symptoms of burnout in both physicians and nurses, findings from a new study show.

XiXinXing/ThinkStock

“Overburdening ICU professionals during an extended period of time leads to burnout,” said lead study author Niek Kok, MSc, of IQ healthcare, Radboud University Medical Center, Radboud Institute for Health Sciences, Nijmegen, the Netherlands. “All ICU professionals are at the risk of this, and in our study, the incidence of physicians experiencing burnout was significantly higher than that of nurses in June 2020.”

This burnout can be explained by conditions caused by the pandemic, he noted, such as the scarcity of staff and resources and having to work with colleagues who were not qualified to work in critical care but who were there out of necessity.

Mr. Kok presented the findings of the study at the Critical Care Congress sponsored by the Society of Critical Care Medicine.
 

Burnout highest among critical care physicians

The ICU can be a stressful environment for both patients and health care personnel, and burnout is not uncommon among ICU clinicians. However, COVID-19 has amplified the degree of burnout being experienced by clinicians working in this setting. Critical care physicians now top the list of physicians experiencing burnout, at 51%, up from 44% last year, according to the Medscape report ‘Death by 1000 Thousand Cuts’: Physician Burnout and Suicide Report 2021.

The Medscape Nurse Career Satisfaction Report 2020, while not restricted to those working in critical care, also reported higher rates of burnout, compared with the prepandemic period. The percentage of nurses reporting being “very burned out” prior to the pandemic was 4%. Six months into the pandemic, that percentage soared to 18%.

In this study, Mr. Kok and colleagues examined the prevalence and incidence of burnout symptoms and moral distress in health care professionals working in the ICU, both before and during the COVID-19 pandemic.

“When the COVID-19 pandemic surfaced in the Netherlands, the health care professionals in our hospitals were motivated to do everything they could to provide the best care possible,” said Mr. Kok. “Many of the ICU professionals immediately realized that they would have to work longer hours.”

However, the health care professionals that he spoke with did have mixed feelings. Some were afraid of being infected with the virus, while others said that “it was very interesting times for them and that gave them extra motivation to do the work.

“Some physicians [and] the WHO warned that COVID-19 is not going to weathered by a heroic sprint – it is an arduous marathon that is going to go hand in hand with burnout symptoms,” Mr. Kok added. “It will eat away at our qualified ICU staff.”
 

Before and after data on burnout

It was widely believed that the COVID-19 pandemic would increase burnout symptoms, as had been demonstrated in studies of previous pandemics. However, Mr. Kok emphasized that there are no before and after measurements that transcend cross-sectional designs.

“The claim [has been] that it increases burnout – but there are no assessments of how it progresses in ICU professionals through time,” he said. “So what we really need is a comparison [of] before and after the pandemic.”

It is quite difficult to obtain this type of information because disruptive events like the COVID-19 pandemic cannot be predicted, he said. Thus, it is challenging to get a baseline measurement. But Mr. Kok pointed out that the study has both “before and after” measurements.

“By coincidence really, we had baseline data to measure the impact of the COVID-19 pandemic and had information that was collected before the pandemic,” he said.

In January 2020, a study began looking at the effects of ethics meetings on moral distress in ICU professionals. Data had been collected on moral distress and burnout on ICU professionals in December 2019. The first COVID-19 cases appeared in the Netherlands in February 2020.

A follow-up study was then conducted in May and June 2020, several months into the pandemic.

The longitudinal open cohort study included all ICU personnel who were working in five units within a single university medical center, plus another adult ICU that was based in a separate teaching hospital.

A total of 352 health care professionals responded to a baseline survey in October through December 2019, and then 233 responded to a follow-up survey sent in May and June 2020. The authors measured burnout symptoms and moral distress with the Maslach Burnout Inventory and the Moral Distress Scale, respectively.
 

Findings

The overall prevalence of burnout symptoms was 23.0% prior to the pandemic, and that jumped to 36.1% at post-peak time. Higher rates of burnout were reported by nurses (38.0%) than physicians (28.6%).

However, the incidence rate of new burnout cases was higher among physicians, compared with nurses (26.7% vs 21.9%). Not surprisingly, a higher prevalence of burnout symptoms was observed in the post-peak period for all clinicians (odds ratio, 1.83; 95% confidence interval, 1.32-2.53), and was higher for nurses (odds ratio, 1.77; 95% confidence interval, 1.03-3.04), for those working overtime (OR, 2.11; 95% CI, 1.48-3.02), and for personnel who directly engaged in patient care (OR, 1.87; 95% CI, 1.35-2.60).

Physicians in general were much more likely to develop burnout symptoms related to the pandemic, compared with nurses (OR, 3.56; 95% CI, 1.06-12.21).

When looking at findings on moral distress, Kok pointed out that it often arises in situations when the health care professional knows the right thing to do but is prevented from doing so. “Morally distressful situations all rose from December to June,” said Mr. Kok. “Scarcity was the most distressing. The other was where colleagues were perceived to be less skilled, and this had to do with the recruitment of people from outside of the ICU to provide care.”

Moral distress from scarcity and unskilled colleagues were both significantly related to burnout, he noted.

In the final model, working in a COVID-19 unit, stress from scarcity of resources and people, stress from unskilled colleagues, and stress from unsafe conditions were all related to burnout. “The stress of physicians was significantly higher,” said Kok. “Even though nurses had higher baseline burnout, it became less pronounced in June 2020. This indicates that burnout was significantly higher in physicians.”

Thus, Mr. Kok and colleagues concluded that overburdening ICU professionals during an extended period of time leads to burnout, and all ICU workers are at risk.
 

Burnout rates higher in physicians

Weighing in on the study, Greg S. Martin, MD, FCCP, professor of medicine in the division of pulmonary, allergy, critical care and sleep medicine, Emory University, Atlanta, noted that the differences observed between physicians and nurses may have to do with the fact that “nurses have been smoldering all along and experiencing higher rates of burnout.

“They may have adapted better to the pandemic conditions, since they are more used to working overtime and short staffed, and spending far more time at the bedside,” he said. “Because of the volume of patients, physicians may be spending more hours doing patient care and are experiencing more burnout.”

Health care professionals working in critical care settings have been overburdened because of the plethora of COVID-19 cases, which has led to symptoms of burnout in both physicians and nurses, findings from a new study show.

XiXinXing/ThinkStock

“Overburdening ICU professionals during an extended period of time leads to burnout,” said lead study author Niek Kok, MSc, of IQ healthcare, Radboud University Medical Center, Radboud Institute for Health Sciences, Nijmegen, the Netherlands. “All ICU professionals are at the risk of this, and in our study, the incidence of physicians experiencing burnout was significantly higher than that of nurses in June 2020.”

This burnout can be explained by conditions caused by the pandemic, he noted, such as the scarcity of staff and resources and having to work with colleagues who were not qualified to work in critical care but who were there out of necessity.

Mr. Kok presented the findings of the study at the Critical Care Congress sponsored by the Society of Critical Care Medicine.
 

Burnout highest among critical care physicians

The ICU can be a stressful environment for both patients and health care personnel, and burnout is not uncommon among ICU clinicians. However, COVID-19 has amplified the degree of burnout being experienced by clinicians working in this setting. Critical care physicians now top the list of physicians experiencing burnout, at 51%, up from 44% last year, according to the Medscape report ‘Death by 1000 Thousand Cuts’: Physician Burnout and Suicide Report 2021.

The Medscape Nurse Career Satisfaction Report 2020, while not restricted to those working in critical care, also reported higher rates of burnout, compared with the prepandemic period. The percentage of nurses reporting being “very burned out” prior to the pandemic was 4%. Six months into the pandemic, that percentage soared to 18%.

In this study, Mr. Kok and colleagues examined the prevalence and incidence of burnout symptoms and moral distress in health care professionals working in the ICU, both before and during the COVID-19 pandemic.

“When the COVID-19 pandemic surfaced in the Netherlands, the health care professionals in our hospitals were motivated to do everything they could to provide the best care possible,” said Mr. Kok. “Many of the ICU professionals immediately realized that they would have to work longer hours.”

However, the health care professionals that he spoke with did have mixed feelings. Some were afraid of being infected with the virus, while others said that “it was very interesting times for them and that gave them extra motivation to do the work.

“Some physicians [and] the WHO warned that COVID-19 is not going to weathered by a heroic sprint – it is an arduous marathon that is going to go hand in hand with burnout symptoms,” Mr. Kok added. “It will eat away at our qualified ICU staff.”
 

Before and after data on burnout

It was widely believed that the COVID-19 pandemic would increase burnout symptoms, as had been demonstrated in studies of previous pandemics. However, Mr. Kok emphasized that there are no before and after measurements that transcend cross-sectional designs.

“The claim [has been] that it increases burnout – but there are no assessments of how it progresses in ICU professionals through time,” he said. “So what we really need is a comparison [of] before and after the pandemic.”

It is quite difficult to obtain this type of information because disruptive events like the COVID-19 pandemic cannot be predicted, he said. Thus, it is challenging to get a baseline measurement. But Mr. Kok pointed out that the study has both “before and after” measurements.

“By coincidence really, we had baseline data to measure the impact of the COVID-19 pandemic and had information that was collected before the pandemic,” he said.

In January 2020, a study began looking at the effects of ethics meetings on moral distress in ICU professionals. Data had been collected on moral distress and burnout on ICU professionals in December 2019. The first COVID-19 cases appeared in the Netherlands in February 2020.

A follow-up study was then conducted in May and June 2020, several months into the pandemic.

The longitudinal open cohort study included all ICU personnel who were working in five units within a single university medical center, plus another adult ICU that was based in a separate teaching hospital.

A total of 352 health care professionals responded to a baseline survey in October through December 2019, and then 233 responded to a follow-up survey sent in May and June 2020. The authors measured burnout symptoms and moral distress with the Maslach Burnout Inventory and the Moral Distress Scale, respectively.
 

Findings

The overall prevalence of burnout symptoms was 23.0% prior to the pandemic, and that jumped to 36.1% at post-peak time. Higher rates of burnout were reported by nurses (38.0%) than physicians (28.6%).

However, the incidence rate of new burnout cases was higher among physicians, compared with nurses (26.7% vs 21.9%). Not surprisingly, a higher prevalence of burnout symptoms was observed in the post-peak period for all clinicians (odds ratio, 1.83; 95% confidence interval, 1.32-2.53), and was higher for nurses (odds ratio, 1.77; 95% confidence interval, 1.03-3.04), for those working overtime (OR, 2.11; 95% CI, 1.48-3.02), and for personnel who directly engaged in patient care (OR, 1.87; 95% CI, 1.35-2.60).

Physicians in general were much more likely to develop burnout symptoms related to the pandemic, compared with nurses (OR, 3.56; 95% CI, 1.06-12.21).

When looking at findings on moral distress, Kok pointed out that it often arises in situations when the health care professional knows the right thing to do but is prevented from doing so. “Morally distressful situations all rose from December to June,” said Mr. Kok. “Scarcity was the most distressing. The other was where colleagues were perceived to be less skilled, and this had to do with the recruitment of people from outside of the ICU to provide care.”

Moral distress from scarcity and unskilled colleagues were both significantly related to burnout, he noted.

In the final model, working in a COVID-19 unit, stress from scarcity of resources and people, stress from unskilled colleagues, and stress from unsafe conditions were all related to burnout. “The stress of physicians was significantly higher,” said Kok. “Even though nurses had higher baseline burnout, it became less pronounced in June 2020. This indicates that burnout was significantly higher in physicians.”

Thus, Mr. Kok and colleagues concluded that overburdening ICU professionals during an extended period of time leads to burnout, and all ICU workers are at risk.
 

Burnout rates higher in physicians

Weighing in on the study, Greg S. Martin, MD, FCCP, professor of medicine in the division of pulmonary, allergy, critical care and sleep medicine, Emory University, Atlanta, noted that the differences observed between physicians and nurses may have to do with the fact that “nurses have been smoldering all along and experiencing higher rates of burnout.

“They may have adapted better to the pandemic conditions, since they are more used to working overtime and short staffed, and spending far more time at the bedside,” he said. “Because of the volume of patients, physicians may be spending more hours doing patient care and are experiencing more burnout.”

Science by press release and preprint has cooled clinician enthusiasm for the use of colchicine in nonhospitalized patients with COVID-19, despite a pressing need for early treatments.

Photo by Jimmy Hamelin

As previously reported by this news organization, a Jan. 22 press release announced that the massive ColCORONA study missed its primary endpoint of hospitalization or death among 4,488 newly diagnosed patients at increased risk for hospitalization.

But it also touted that use of the anti-inflammatory drug significantly reduced the primary endpoint in 4,159 of those patients with polymerase chain reaction–confirmed COVID and led to reductions of 25%, 50%, and 44%, respectively, for hospitalizations, ventilations, and death.

Lead investigator Jean-Claude Tardif, MD, director of the Montreal Heart Institute Research Centre, deemed the findings a “medical breakthrough.”

When the preprint released a few days later, however, newly revealed confidence intervals showed colchicine did not meaningfully reduce the need for mechanical ventilation (odds ratio, 0.50; 95% confidence interval, 0.23-1.07) or death alone (OR, 0.56; 95% CI, 0.19-1.66).

Further, the significant benefit on the primary outcome came at the cost of a fivefold increase in pulmonary embolism (11 vs. 2; P = .01), which was not mentioned in the press release.

“Whether this represents a real phenomenon or simply the play of chance is not known,” Dr. Tardif and colleagues noted later in the preprint.

“I read the preprint on colchicine and I have so many questions,” Aaron E. Glatt, MD, spokesperson for the Infectious Diseases Society of America and chief of infectious diseases, Mount Sinai South Nassau, Hewlett, N.Y., said in an interview. “I’ve been burned too many times with COVID and prefer to see better data.

“People sometimes say if you wait for perfect data, people are going to die,” he said. “Yeah, but we have no idea if people are going to die from getting this drug more than not getting it. That’s what concerns me. How many pulmonary emboli are going to be fatal versus the slight benefit that the study showed?”

The pushback to the non–peer-reviewed data on social media and via emails was so strong that Dr. Tardif posted a nearly 2,000-word letter responding to the many questions at play.

Chief among them was why the trial, originally planned for 6,000 patients, was stopped early by the investigators without consultation with the data safety monitoring board (DSMB).

The explanation in the letter that logistical issues like running the study call center, budget constraints, and a perceived need to quickly communicate the results left some calling foul that the study wasn’t allowed to finish and come to a more definitive conclusion.

“I can be a little bit sympathetic to their cause but at the same time the DSMB should have said no,” said David Boulware, MD, MPH, who led a recent hydroxychloroquine trial in COVID-19. “The problem is we’re sort of left in limbo, where some people kind of believe it and some say it’s not really a thing. So it’s not really moving the needle, as far as guidelines go.”

Indeed, a Twitter poll by cardiologist James Januzzi Jr., MD, captured the uncertainty, with 28% of respondents saying the trial was “neutral,” 58% saying “maybe but meh,” and 14% saying “colchicine for all.”

Another poll cheekily asked whether ColCORONA was the Gamestop/Reddit equivalent of COVID.

“The press release really didn’t help things because it very much oversold the effect. That, I think, poisoned the well,” said Dr. Boulware, professor of medicine in infectious diseases at the University of Minnesota, Minneapolis.

“The question I’m left with is not whether colchicine works, but who does it work in,” he said. “That’s really the fundamental question because it does seem that there are probably high-risk groups in their trial and others where they benefit, whereas other groups don’t benefit. In the subgroup analysis, there was absolutely no beneficial effect in women.”

According to the authors, the number needed to treat to prevent one death or hospitalization was 71 overall, but 29 for patients with diabetes, 31 for those aged 70 years and older, 53 for patients with respiratory disease, and 25 for those with coronary disease or heart failure.

Men are at higher risk overall for poor outcomes. But “the authors didn’t present a multivariable analysis, so it is unclear if another factor, such as a differential prevalence of smoking or cardiovascular risk factors, contributed to the differential benefit,” Rachel Bender Ignacio, MD, MPH, infectious disease specialist, University of Washington, Seattle, said in an interview.

Importantly, in this pragmatic study, duration and severity of symptoms were not reported, observed Dr. Bender Ignacio, who is also a STOP-COVID-2 investigator. “We don’t yet have data as to whether colchicine shortens duration or severity of symptoms or prevents long COVID, so we need more data on that.”

The overall risk for serious adverse events was lower in the colchicine group, but the difference in pulmonary embolism (PE) was striking, she said. This could be caused by a real biologic effect, or it’s possible that persons with shortness of breath and hypoxia, without evident viral pneumonia on chest x-ray after a positive COVID-19 test, were more likely to receive a CT-PE study.

The press release also failed to include information, later noted in the preprint, that the MHI has submitted two patents related to colchicine: “Methods of treating a coronavirus infection using colchicine” and “Early administration of low-dose colchicine after myocardial infarction.”

Reached for clarification, MHI communications adviser Camille Turbide said in an interview that the first patent “simply refers to the novel concept of preventing complications of COVID-19, such as admission to the hospital, with colchicine as tested in the ColCORONA study.”

The second patent, she said, refers to the “novel concept that administering colchicine early after a major adverse cardiovascular event is better than waiting several days,” as supported by the COLCOT study, which Dr. Tardif also led.

The patents are being reviewed by authorities and “Dr. Tardif has waived his rights in these patents and does not stand to benefit financially at all if colchicine becomes used as a treatment for COVID-19,” Ms. Turbide said.

Dr. Tardif did not respond to interview requests for this story. Dr. Glatt said conflicts of interest must be assessed and are “something that is of great concern in any scientific study.”

Cardiologist Steve Nissen, MD, of the Cleveland Clinic said in an interview that, “despite the negative results, the study does suggest that colchicine might have a benefit and should be studied in future trials. These findings are not sufficient evidence to suggest use of the drug in patients infected with COVID-19.”

He noted that adverse effects like diarrhea were expected but that the excess PE was unexpected and needs greater clarification.

“Stopping the trial for administrative reasons is puzzling and undermined the ability of the trial to give a reliable answer,” Dr. Nissen said. “This is a reasonable pilot study that should be viewed as hypothesis generating but inconclusive.”

Several sources said a new trial is unlikely, particularly given the cost and 28 trials already evaluating colchicine. Among these are RECOVERY and COLCOVID, testing whether colchicine can reduce the duration of hospitalization or death in hospitalized patients with COVID-19.

Because there are so many trials ongoing right now, including for antivirals and other immunomodulators, it’s important that, if colchicine comes to routine clinical use, it provides access to treatment for those not able or willing to access clinical trials, rather than impeding clinical trial enrollment, Dr. Bender Ignacio suggested.

“We have already learned the lesson in the pandemic that early adoption of potentially promising therapies can negatively impact our ability to study and develop other promising treatments,” she said.

The trial was coordinated by the Montreal Heart Institute and funded by the government of Quebec; the National Heart, Lung, and Blood Institute of the National Institutes of Health; Montreal philanthropist Sophie Desmarais, and the COVID-19 Therapeutics Accelerator launched by the Bill & Melinda Gates Foundation, Wellcome, and Mastercard. CGI, Dacima, and Pharmascience of Montreal were also collaborators. Dr. Glatt reported no conflicts of interest. Dr. Boulware reported receiving $18 in food and beverages from Gilead Sciences in 2018.
 

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

Science by press release and preprint has cooled clinician enthusiasm for the use of colchicine in nonhospitalized patients with COVID-19, despite a pressing need for early treatments.

Photo by Jimmy Hamelin

As previously reported by this news organization, a Jan. 22 press release announced that the massive ColCORONA study missed its primary endpoint of hospitalization or death among 4,488 newly diagnosed patients at increased risk for hospitalization.

But it also touted that use of the anti-inflammatory drug significantly reduced the primary endpoint in 4,159 of those patients with polymerase chain reaction–confirmed COVID and led to reductions of 25%, 50%, and 44%, respectively, for hospitalizations, ventilations, and death.

Lead investigator Jean-Claude Tardif, MD, director of the Montreal Heart Institute Research Centre, deemed the findings a “medical breakthrough.”

When the preprint released a few days later, however, newly revealed confidence intervals showed colchicine did not meaningfully reduce the need for mechanical ventilation (odds ratio, 0.50; 95% confidence interval, 0.23-1.07) or death alone (OR, 0.56; 95% CI, 0.19-1.66).

Further, the significant benefit on the primary outcome came at the cost of a fivefold increase in pulmonary embolism (11 vs. 2; P = .01), which was not mentioned in the press release.

“Whether this represents a real phenomenon or simply the play of chance is not known,” Dr. Tardif and colleagues noted later in the preprint.

“I read the preprint on colchicine and I have so many questions,” Aaron E. Glatt, MD, spokesperson for the Infectious Diseases Society of America and chief of infectious diseases, Mount Sinai South Nassau, Hewlett, N.Y., said in an interview. “I’ve been burned too many times with COVID and prefer to see better data.

“People sometimes say if you wait for perfect data, people are going to die,” he said. “Yeah, but we have no idea if people are going to die from getting this drug more than not getting it. That’s what concerns me. How many pulmonary emboli are going to be fatal versus the slight benefit that the study showed?”

The pushback to the non–peer-reviewed data on social media and via emails was so strong that Dr. Tardif posted a nearly 2,000-word letter responding to the many questions at play.

Chief among them was why the trial, originally planned for 6,000 patients, was stopped early by the investigators without consultation with the data safety monitoring board (DSMB).

The explanation in the letter that logistical issues like running the study call center, budget constraints, and a perceived need to quickly communicate the results left some calling foul that the study wasn’t allowed to finish and come to a more definitive conclusion.

“I can be a little bit sympathetic to their cause but at the same time the DSMB should have said no,” said David Boulware, MD, MPH, who led a recent hydroxychloroquine trial in COVID-19. “The problem is we’re sort of left in limbo, where some people kind of believe it and some say it’s not really a thing. So it’s not really moving the needle, as far as guidelines go.”

Indeed, a Twitter poll by cardiologist James Januzzi Jr., MD, captured the uncertainty, with 28% of respondents saying the trial was “neutral,” 58% saying “maybe but meh,” and 14% saying “colchicine for all.”

Another poll cheekily asked whether ColCORONA was the Gamestop/Reddit equivalent of COVID.

“The press release really didn’t help things because it very much oversold the effect. That, I think, poisoned the well,” said Dr. Boulware, professor of medicine in infectious diseases at the University of Minnesota, Minneapolis.

“The question I’m left with is not whether colchicine works, but who does it work in,” he said. “That’s really the fundamental question because it does seem that there are probably high-risk groups in their trial and others where they benefit, whereas other groups don’t benefit. In the subgroup analysis, there was absolutely no beneficial effect in women.”

According to the authors, the number needed to treat to prevent one death or hospitalization was 71 overall, but 29 for patients with diabetes, 31 for those aged 70 years and older, 53 for patients with respiratory disease, and 25 for those with coronary disease or heart failure.

Men are at higher risk overall for poor outcomes. But “the authors didn’t present a multivariable analysis, so it is unclear if another factor, such as a differential prevalence of smoking or cardiovascular risk factors, contributed to the differential benefit,” Rachel Bender Ignacio, MD, MPH, infectious disease specialist, University of Washington, Seattle, said in an interview.

Importantly, in this pragmatic study, duration and severity of symptoms were not reported, observed Dr. Bender Ignacio, who is also a STOP-COVID-2 investigator. “We don’t yet have data as to whether colchicine shortens duration or severity of symptoms or prevents long COVID, so we need more data on that.”

The overall risk for serious adverse events was lower in the colchicine group, but the difference in pulmonary embolism (PE) was striking, she said. This could be caused by a real biologic effect, or it’s possible that persons with shortness of breath and hypoxia, without evident viral pneumonia on chest x-ray after a positive COVID-19 test, were more likely to receive a CT-PE study.

The press release also failed to include information, later noted in the preprint, that the MHI has submitted two patents related to colchicine: “Methods of treating a coronavirus infection using colchicine” and “Early administration of low-dose colchicine after myocardial infarction.”

Reached for clarification, MHI communications adviser Camille Turbide said in an interview that the first patent “simply refers to the novel concept of preventing complications of COVID-19, such as admission to the hospital, with colchicine as tested in the ColCORONA study.”

The second patent, she said, refers to the “novel concept that administering colchicine early after a major adverse cardiovascular event is better than waiting several days,” as supported by the COLCOT study, which Dr. Tardif also led.

The patents are being reviewed by authorities and “Dr. Tardif has waived his rights in these patents and does not stand to benefit financially at all if colchicine becomes used as a treatment for COVID-19,” Ms. Turbide said.

Dr. Tardif did not respond to interview requests for this story. Dr. Glatt said conflicts of interest must be assessed and are “something that is of great concern in any scientific study.”

Cardiologist Steve Nissen, MD, of the Cleveland Clinic said in an interview that, “despite the negative results, the study does suggest that colchicine might have a benefit and should be studied in future trials. These findings are not sufficient evidence to suggest use of the drug in patients infected with COVID-19.”

He noted that adverse effects like diarrhea were expected but that the excess PE was unexpected and needs greater clarification.

“Stopping the trial for administrative reasons is puzzling and undermined the ability of the trial to give a reliable answer,” Dr. Nissen said. “This is a reasonable pilot study that should be viewed as hypothesis generating but inconclusive.”

Several sources said a new trial is unlikely, particularly given the cost and 28 trials already evaluating colchicine. Among these are RECOVERY and COLCOVID, testing whether colchicine can reduce the duration of hospitalization or death in hospitalized patients with COVID-19.

Because there are so many trials ongoing right now, including for antivirals and other immunomodulators, it’s important that, if colchicine comes to routine clinical use, it provides access to treatment for those not able or willing to access clinical trials, rather than impeding clinical trial enrollment, Dr. Bender Ignacio suggested.

“We have already learned the lesson in the pandemic that early adoption of potentially promising therapies can negatively impact our ability to study and develop other promising treatments,” she said.

The trial was coordinated by the Montreal Heart Institute and funded by the government of Quebec; the National Heart, Lung, and Blood Institute of the National Institutes of Health; Montreal philanthropist Sophie Desmarais, and the COVID-19 Therapeutics Accelerator launched by the Bill & Melinda Gates Foundation, Wellcome, and Mastercard. CGI, Dacima, and Pharmascience of Montreal were also collaborators. Dr. Glatt reported no conflicts of interest. Dr. Boulware reported receiving $18 in food and beverages from Gilead Sciences in 2018.
 

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

Science by press release and preprint has cooled clinician enthusiasm for the use of colchicine in nonhospitalized patients with COVID-19, despite a pressing need for early treatments.

Photo by Jimmy Hamelin

As previously reported by this news organization, a Jan. 22 press release announced that the massive ColCORONA study missed its primary endpoint of hospitalization or death among 4,488 newly diagnosed patients at increased risk for hospitalization.

But it also touted that use of the anti-inflammatory drug significantly reduced the primary endpoint in 4,159 of those patients with polymerase chain reaction–confirmed COVID and led to reductions of 25%, 50%, and 44%, respectively, for hospitalizations, ventilations, and death.

Lead investigator Jean-Claude Tardif, MD, director of the Montreal Heart Institute Research Centre, deemed the findings a “medical breakthrough.”

When the preprint released a few days later, however, newly revealed confidence intervals showed colchicine did not meaningfully reduce the need for mechanical ventilation (odds ratio, 0.50; 95% confidence interval, 0.23-1.07) or death alone (OR, 0.56; 95% CI, 0.19-1.66).

Further, the significant benefit on the primary outcome came at the cost of a fivefold increase in pulmonary embolism (11 vs. 2; P = .01), which was not mentioned in the press release.

“Whether this represents a real phenomenon or simply the play of chance is not known,” Dr. Tardif and colleagues noted later in the preprint.

“I read the preprint on colchicine and I have so many questions,” Aaron E. Glatt, MD, spokesperson for the Infectious Diseases Society of America and chief of infectious diseases, Mount Sinai South Nassau, Hewlett, N.Y., said in an interview. “I’ve been burned too many times with COVID and prefer to see better data.

“People sometimes say if you wait for perfect data, people are going to die,” he said. “Yeah, but we have no idea if people are going to die from getting this drug more than not getting it. That’s what concerns me. How many pulmonary emboli are going to be fatal versus the slight benefit that the study showed?”

The pushback to the non–peer-reviewed data on social media and via emails was so strong that Dr. Tardif posted a nearly 2,000-word letter responding to the many questions at play.

Chief among them was why the trial, originally planned for 6,000 patients, was stopped early by the investigators without consultation with the data safety monitoring board (DSMB).

The explanation in the letter that logistical issues like running the study call center, budget constraints, and a perceived need to quickly communicate the results left some calling foul that the study wasn’t allowed to finish and come to a more definitive conclusion.

“I can be a little bit sympathetic to their cause but at the same time the DSMB should have said no,” said David Boulware, MD, MPH, who led a recent hydroxychloroquine trial in COVID-19. “The problem is we’re sort of left in limbo, where some people kind of believe it and some say it’s not really a thing. So it’s not really moving the needle, as far as guidelines go.”

Indeed, a Twitter poll by cardiologist James Januzzi Jr., MD, captured the uncertainty, with 28% of respondents saying the trial was “neutral,” 58% saying “maybe but meh,” and 14% saying “colchicine for all.”

Another poll cheekily asked whether ColCORONA was the Gamestop/Reddit equivalent of COVID.

“The press release really didn’t help things because it very much oversold the effect. That, I think, poisoned the well,” said Dr. Boulware, professor of medicine in infectious diseases at the University of Minnesota, Minneapolis.

“The question I’m left with is not whether colchicine works, but who does it work in,” he said. “That’s really the fundamental question because it does seem that there are probably high-risk groups in their trial and others where they benefit, whereas other groups don’t benefit. In the subgroup analysis, there was absolutely no beneficial effect in women.”

According to the authors, the number needed to treat to prevent one death or hospitalization was 71 overall, but 29 for patients with diabetes, 31 for those aged 70 years and older, 53 for patients with respiratory disease, and 25 for those with coronary disease or heart failure.

Men are at higher risk overall for poor outcomes. But “the authors didn’t present a multivariable analysis, so it is unclear if another factor, such as a differential prevalence of smoking or cardiovascular risk factors, contributed to the differential benefit,” Rachel Bender Ignacio, MD, MPH, infectious disease specialist, University of Washington, Seattle, said in an interview.

Importantly, in this pragmatic study, duration and severity of symptoms were not reported, observed Dr. Bender Ignacio, who is also a STOP-COVID-2 investigator. “We don’t yet have data as to whether colchicine shortens duration or severity of symptoms or prevents long COVID, so we need more data on that.”

The overall risk for serious adverse events was lower in the colchicine group, but the difference in pulmonary embolism (PE) was striking, she said. This could be caused by a real biologic effect, or it’s possible that persons with shortness of breath and hypoxia, without evident viral pneumonia on chest x-ray after a positive COVID-19 test, were more likely to receive a CT-PE study.

The press release also failed to include information, later noted in the preprint, that the MHI has submitted two patents related to colchicine: “Methods of treating a coronavirus infection using colchicine” and “Early administration of low-dose colchicine after myocardial infarction.”

Reached for clarification, MHI communications adviser Camille Turbide said in an interview that the first patent “simply refers to the novel concept of preventing complications of COVID-19, such as admission to the hospital, with colchicine as tested in the ColCORONA study.”

The second patent, she said, refers to the “novel concept that administering colchicine early after a major adverse cardiovascular event is better than waiting several days,” as supported by the COLCOT study, which Dr. Tardif also led.

The patents are being reviewed by authorities and “Dr. Tardif has waived his rights in these patents and does not stand to benefit financially at all if colchicine becomes used as a treatment for COVID-19,” Ms. Turbide said.

Dr. Tardif did not respond to interview requests for this story. Dr. Glatt said conflicts of interest must be assessed and are “something that is of great concern in any scientific study.”

Cardiologist Steve Nissen, MD, of the Cleveland Clinic said in an interview that, “despite the negative results, the study does suggest that colchicine might have a benefit and should be studied in future trials. These findings are not sufficient evidence to suggest use of the drug in patients infected with COVID-19.”

He noted that adverse effects like diarrhea were expected but that the excess PE was unexpected and needs greater clarification.

“Stopping the trial for administrative reasons is puzzling and undermined the ability of the trial to give a reliable answer,” Dr. Nissen said. “This is a reasonable pilot study that should be viewed as hypothesis generating but inconclusive.”

Several sources said a new trial is unlikely, particularly given the cost and 28 trials already evaluating colchicine. Among these are RECOVERY and COLCOVID, testing whether colchicine can reduce the duration of hospitalization or death in hospitalized patients with COVID-19.

Because there are so many trials ongoing right now, including for antivirals and other immunomodulators, it’s important that, if colchicine comes to routine clinical use, it provides access to treatment for those not able or willing to access clinical trials, rather than impeding clinical trial enrollment, Dr. Bender Ignacio suggested.

“We have already learned the lesson in the pandemic that early adoption of potentially promising therapies can negatively impact our ability to study and develop other promising treatments,” she said.

The trial was coordinated by the Montreal Heart Institute and funded by the government of Quebec; the National Heart, Lung, and Blood Institute of the National Institutes of Health; Montreal philanthropist Sophie Desmarais, and the COVID-19 Therapeutics Accelerator launched by the Bill & Melinda Gates Foundation, Wellcome, and Mastercard. CGI, Dacima, and Pharmascience of Montreal were also collaborators. Dr. Glatt reported no conflicts of interest. Dr. Boulware reported receiving $18 in food and beverages from Gilead Sciences in 2018.
 

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

Airways disorders

Updated guidelines on the use of home O2 in COPD: A much-needed respite

The use of long-term oxygen therapy (LTOT, oxygen prescribed for at least 15 h/day) in patients with COPD and chronic hypoxemia has been standard of care based on trials from the 1980s that conferred a survival benefit with the use of continuous oxygen (Ann Internal Med. 1980;93[3]:391-8). More recently, LTOT has not shown to improve survival or delay time to the hospitalization in patients with stable COPD and resting or exercise-induced moderate desaturation (N Engl J Med. 2016;375[17]:1617-27). Thus far, existing recommendations had been semi-inclusive in patient selection. A fundamental lack of evidence-based clinical practice guidelines prompted additional research into patient selection, portable oxygen technology, advocacy for improved oxygen therapy financing, and updating of policies (Jacobs et al., Ann Am Thorac Soc. 2018;15[12]:1369-81). With over a million patients in the United States being prescribed home oxygen and reported disconnect in-home oxygen needs/experiences across disease processes, lifestyles, and oxygen supply requirements, the 2020 American Thoracic Society (ATS) workshop on optimizing home oxygen therapy sought to answer critical questions in the use of LTOT for COPD patients (AlMutairi, et al. Respir Care. 2018;63[11]:1321-30; Jacobs, et al. Am J Respir Crit Care Med. 2020;202[10]:e121-e141).

Dharani Kumari Narendra, MBBS, FCCP
Steering Committee Member

Chest infections

Eradicating COVID-19 scourge: It is up to all of us— get vaccinated!

2021 brings hope, spurred by the availability of several effective COVID-19 vaccines – unprecedented scientific advances, considering that these vaccines were developed in record time. We have stark choices: while some individuals ignore scientific evidence and refuse to take the vaccine, we from the Chest Infections NetWork urge an alternative and imperative choice. As health providers caring for COVID-19 patients, we first-hand witness the horrors of dying alone in a hospital bed – far away from beloved ones. I have a sticker on my car that says: If you do not like your mask, you will not like my ventilator. With the advent of vaccines, I plan on replacing this sticker: If you do not want to get vaccinated, you will not like my ventilator. When the vaccine became available at my institution, I was the first to roll up my sleeve and feel the pinch in my upper arm. I urge you all to do the same. Make a difference, do your part – get vaccinated.

Marcos I. Restrepo, MD, MSc, PhD
Chair

Clinical pulmonary medicine

COVID-19 vaccines – mRNA and beyond

We currently have two COVID-19 mRNA vaccines with US FDA emergency use authorization (EUA) for use in individuals less than or equal to age 18 years – Pfizer and Moderna. They work by introducing mRNA into a muscle cell that instructs the host cell ribosomes to express Sars-CoV-2 spike proteins, thereby triggering a systemic immune response.

Shyam Subramanian, MD, FCCP
Chair

Clinical research and quality improvement
 

COVID-19 treatment, so far!

COVID-19 has turned rapidly into a fatal illness, causing over 1.8 million deaths worldwide so far. The pandemic has also showed us the power of adaptive trials, multi-arm trials, and the role for collaboration across the global scientific community. A few significant studies are worth mentioning.

Ankita Agarwal, MD
Fellows-in-Training Members
 

Critical care

Awake proning in COVID-19

Prone positioning has been shown to improve pulmonary mechanics in intubated patients with acute respiratory distress syndrome (ARDS). Proposed mechanisms for these benefits include shape matching, reversing the pleural pressure gradient, homogenizing distribution of pleural pressures, reducing the impact of the heart and abdomen on the lungs, and maintaining distribution of perfusion. Application of prone positioning has also been shown to reduce mortality in severe ARDS (Guérin, et al. N Engl J Med. 2013;368(23):2159-68). With the COVID-19 pandemic, clinicians have extrapolated that nonintubated patients with severe hypoxia may benefit from awake proning in the hopes of improving oxygenation and decreasing need for intubation. But, what’s the evidence so far?

Viren Kaul, MD
Steering Committee Members

Home-Based Mechanical Ventilation and Neuromuscular Disease

New horizons in home ventilation

Phasing out a particular ventilator (Philips Respironics Trilogy 100 ventilator) has everyone on a steep learning curve with the replacement (Trilogy EVO). Most features are replicated in the EVO, including volume/pressure control and pressure-supported modes, mouthpiece ventilation, active/passive circuit capability, and portability (11.5 lb). Upgrades include longer battery life (15 hours; 7.5 hours internal/7.5 hours detachable) and use in pediatric patients now greater than or equal to 2.5 kg.

Online resources
EVO e-learning curriculum

Interprofessional team

Interprofessional team approach to palliative extubation

The emotional burden of caring for patients at the end of life affects all members of the care team. Palliative (or compassionate) extubation consists of the withdrawal of mechanical ventilation when the absolute priority in care delivery is to afford comfort and allow for natural death to occur. Rapid withdrawal of ventilatory support may lead to significant respiratory distress, and the critical care team has an obligation to ensure patient comfort during the dying process (Truog RD, et al. Crit Care Med. 2008;36[3]:953). Registered nurses (RN) are primarily responsible for the titration of sedation/analgesia and should be included in discussions regarding medication selection. It is imperative that neuromuscular blockade is absent, and benzodiazepines and/or opioids should be initiated prior to palliative extubation (Lanken PN, et al. Am J Respir Crit Care Med. 2008;177:912). Respiratory therapists (RT) are responsible for endotracheal tube removal despite rare participation in end-of-life discussions (Grandhige AP, et al. Respir Care. 2016;61[7]:891). It is recommended that an experienced physician, RN, and RT be readily available to respond quickly to any signs of distress (Downar J, et al. Intensive Care Med. 2016;42:1003). Regular debriefing sessions exploring team actions and communication dynamics are advised following end-of-life care (Ho A, et al. J Interprof Care. 2016;30[6]:795-803). Palliative extubation demands meticulous planning and clear communication among all team members (physician, RN, RT) and the patient’s family. Poor planning may result in physical and emotional suffering for the patient and difficult bereavement for the family (Coradazi A, et al. Hos Pal Med Int J. 2019;3[1]:10-14). Interprofessional team-based care results from intentional teams that exhibit collective identity and shared responsibility for the patients they serve (Core Competencies for Interprofessional Education Collaborative Practice, 2016). An inclusive and interprofessional approach to withdrawal of mechanical ventilation is key to both quality patient care and provider wellbeing.

Rebecca Anna Gersten, MD
Steering Committee Member

Samantha Davis, MS, RRT
Steering Committee Member

Munish Luthra, MD, FCCP
Vice-Chair Committee

Airways disorders

Updated guidelines on the use of home O2 in COPD: A much-needed respite

The use of long-term oxygen therapy (LTOT, oxygen prescribed for at least 15 h/day) in patients with COPD and chronic hypoxemia has been standard of care based on trials from the 1980s that conferred a survival benefit with the use of continuous oxygen (Ann Internal Med. 1980;93[3]:391-8). More recently, LTOT has not shown to improve survival or delay time to the hospitalization in patients with stable COPD and resting or exercise-induced moderate desaturation (N Engl J Med. 2016;375[17]:1617-27). Thus far, existing recommendations had been semi-inclusive in patient selection. A fundamental lack of evidence-based clinical practice guidelines prompted additional research into patient selection, portable oxygen technology, advocacy for improved oxygen therapy financing, and updating of policies (Jacobs et al., Ann Am Thorac Soc. 2018;15[12]:1369-81). With over a million patients in the United States being prescribed home oxygen and reported disconnect in-home oxygen needs/experiences across disease processes, lifestyles, and oxygen supply requirements, the 2020 American Thoracic Society (ATS) workshop on optimizing home oxygen therapy sought to answer critical questions in the use of LTOT for COPD patients (AlMutairi, et al. Respir Care. 2018;63[11]:1321-30; Jacobs, et al. Am J Respir Crit Care Med. 2020;202[10]:e121-e141).

Dharani Kumari Narendra, MBBS, FCCP
Steering Committee Member

Chest infections

Eradicating COVID-19 scourge: It is up to all of us— get vaccinated!

2021 brings hope, spurred by the availability of several effective COVID-19 vaccines – unprecedented scientific advances, considering that these vaccines were developed in record time. We have stark choices: while some individuals ignore scientific evidence and refuse to take the vaccine, we from the Chest Infections NetWork urge an alternative and imperative choice. As health providers caring for COVID-19 patients, we first-hand witness the horrors of dying alone in a hospital bed – far away from beloved ones. I have a sticker on my car that says: If you do not like your mask, you will not like my ventilator. With the advent of vaccines, I plan on replacing this sticker: If you do not want to get vaccinated, you will not like my ventilator. When the vaccine became available at my institution, I was the first to roll up my sleeve and feel the pinch in my upper arm. I urge you all to do the same. Make a difference, do your part – get vaccinated.

Marcos I. Restrepo, MD, MSc, PhD
Chair

Clinical pulmonary medicine

COVID-19 vaccines – mRNA and beyond

We currently have two COVID-19 mRNA vaccines with US FDA emergency use authorization (EUA) for use in individuals less than or equal to age 18 years – Pfizer and Moderna. They work by introducing mRNA into a muscle cell that instructs the host cell ribosomes to express Sars-CoV-2 spike proteins, thereby triggering a systemic immune response.

Shyam Subramanian, MD, FCCP
Chair

Clinical research and quality improvement
 

COVID-19 treatment, so far!

COVID-19 has turned rapidly into a fatal illness, causing over 1.8 million deaths worldwide so far. The pandemic has also showed us the power of adaptive trials, multi-arm trials, and the role for collaboration across the global scientific community. A few significant studies are worth mentioning.

Ankita Agarwal, MD
Fellows-in-Training Members
 

Critical care

Awake proning in COVID-19

Prone positioning has been shown to improve pulmonary mechanics in intubated patients with acute respiratory distress syndrome (ARDS). Proposed mechanisms for these benefits include shape matching, reversing the pleural pressure gradient, homogenizing distribution of pleural pressures, reducing the impact of the heart and abdomen on the lungs, and maintaining distribution of perfusion. Application of prone positioning has also been shown to reduce mortality in severe ARDS (Guérin, et al. N Engl J Med. 2013;368(23):2159-68). With the COVID-19 pandemic, clinicians have extrapolated that nonintubated patients with severe hypoxia may benefit from awake proning in the hopes of improving oxygenation and decreasing need for intubation. But, what’s the evidence so far?

Viren Kaul, MD
Steering Committee Members

Home-Based Mechanical Ventilation and Neuromuscular Disease

New horizons in home ventilation

Phasing out a particular ventilator (Philips Respironics Trilogy 100 ventilator) has everyone on a steep learning curve with the replacement (Trilogy EVO). Most features are replicated in the EVO, including volume/pressure control and pressure-supported modes, mouthpiece ventilation, active/passive circuit capability, and portability (11.5 lb). Upgrades include longer battery life (15 hours; 7.5 hours internal/7.5 hours detachable) and use in pediatric patients now greater than or equal to 2.5 kg.

Online resources
EVO e-learning curriculum

Interprofessional team

Interprofessional team approach to palliative extubation

The emotional burden of caring for patients at the end of life affects all members of the care team. Palliative (or compassionate) extubation consists of the withdrawal of mechanical ventilation when the absolute priority in care delivery is to afford comfort and allow for natural death to occur. Rapid withdrawal of ventilatory support may lead to significant respiratory distress, and the critical care team has an obligation to ensure patient comfort during the dying process (Truog RD, et al. Crit Care Med. 2008;36[3]:953). Registered nurses (RN) are primarily responsible for the titration of sedation/analgesia and should be included in discussions regarding medication selection. It is imperative that neuromuscular blockade is absent, and benzodiazepines and/or opioids should be initiated prior to palliative extubation (Lanken PN, et al. Am J Respir Crit Care Med. 2008;177:912). Respiratory therapists (RT) are responsible for endotracheal tube removal despite rare participation in end-of-life discussions (Grandhige AP, et al. Respir Care. 2016;61[7]:891). It is recommended that an experienced physician, RN, and RT be readily available to respond quickly to any signs of distress (Downar J, et al. Intensive Care Med. 2016;42:1003). Regular debriefing sessions exploring team actions and communication dynamics are advised following end-of-life care (Ho A, et al. J Interprof Care. 2016;30[6]:795-803). Palliative extubation demands meticulous planning and clear communication among all team members (physician, RN, RT) and the patient’s family. Poor planning may result in physical and emotional suffering for the patient and difficult bereavement for the family (Coradazi A, et al. Hos Pal Med Int J. 2019;3[1]:10-14). Interprofessional team-based care results from intentional teams that exhibit collective identity and shared responsibility for the patients they serve (Core Competencies for Interprofessional Education Collaborative Practice, 2016). An inclusive and interprofessional approach to withdrawal of mechanical ventilation is key to both quality patient care and provider wellbeing.

Rebecca Anna Gersten, MD
Steering Committee Member

Samantha Davis, MS, RRT
Steering Committee Member

Munish Luthra, MD, FCCP
Vice-Chair Committee

Airways disorders

Updated guidelines on the use of home O2 in COPD: A much-needed respite

The use of long-term oxygen therapy (LTOT, oxygen prescribed for at least 15 h/day) in patients with COPD and chronic hypoxemia has been standard of care based on trials from the 1980s that conferred a survival benefit with the use of continuous oxygen (Ann Internal Med. 1980;93[3]:391-8). More recently, LTOT has not shown to improve survival or delay time to the hospitalization in patients with stable COPD and resting or exercise-induced moderate desaturation (N Engl J Med. 2016;375[17]:1617-27). Thus far, existing recommendations had been semi-inclusive in patient selection. A fundamental lack of evidence-based clinical practice guidelines prompted additional research into patient selection, portable oxygen technology, advocacy for improved oxygen therapy financing, and updating of policies (Jacobs et al., Ann Am Thorac Soc. 2018;15[12]:1369-81). With over a million patients in the United States being prescribed home oxygen and reported disconnect in-home oxygen needs/experiences across disease processes, lifestyles, and oxygen supply requirements, the 2020 American Thoracic Society (ATS) workshop on optimizing home oxygen therapy sought to answer critical questions in the use of LTOT for COPD patients (AlMutairi, et al. Respir Care. 2018;63[11]:1321-30; Jacobs, et al. Am J Respir Crit Care Med. 2020;202[10]:e121-e141).

Dharani Kumari Narendra, MBBS, FCCP
Steering Committee Member

Chest infections

Eradicating COVID-19 scourge: It is up to all of us— get vaccinated!

2021 brings hope, spurred by the availability of several effective COVID-19 vaccines – unprecedented scientific advances, considering that these vaccines were developed in record time. We have stark choices: while some individuals ignore scientific evidence and refuse to take the vaccine, we from the Chest Infections NetWork urge an alternative and imperative choice. As health providers caring for COVID-19 patients, we first-hand witness the horrors of dying alone in a hospital bed – far away from beloved ones. I have a sticker on my car that says: If you do not like your mask, you will not like my ventilator. With the advent of vaccines, I plan on replacing this sticker: If you do not want to get vaccinated, you will not like my ventilator. When the vaccine became available at my institution, I was the first to roll up my sleeve and feel the pinch in my upper arm. I urge you all to do the same. Make a difference, do your part – get vaccinated.

Marcos I. Restrepo, MD, MSc, PhD
Chair

Clinical pulmonary medicine

COVID-19 vaccines – mRNA and beyond

We currently have two COVID-19 mRNA vaccines with US FDA emergency use authorization (EUA) for use in individuals less than or equal to age 18 years – Pfizer and Moderna. They work by introducing mRNA into a muscle cell that instructs the host cell ribosomes to express Sars-CoV-2 spike proteins, thereby triggering a systemic immune response.

Shyam Subramanian, MD, FCCP
Chair

Clinical research and quality improvement
 

COVID-19 treatment, so far!

COVID-19 has turned rapidly into a fatal illness, causing over 1.8 million deaths worldwide so far. The pandemic has also showed us the power of adaptive trials, multi-arm trials, and the role for collaboration across the global scientific community. A few significant studies are worth mentioning.

Ankita Agarwal, MD
Fellows-in-Training Members
 

Critical care

Awake proning in COVID-19

Prone positioning has been shown to improve pulmonary mechanics in intubated patients with acute respiratory distress syndrome (ARDS). Proposed mechanisms for these benefits include shape matching, reversing the pleural pressure gradient, homogenizing distribution of pleural pressures, reducing the impact of the heart and abdomen on the lungs, and maintaining distribution of perfusion. Application of prone positioning has also been shown to reduce mortality in severe ARDS (Guérin, et al. N Engl J Med. 2013;368(23):2159-68). With the COVID-19 pandemic, clinicians have extrapolated that nonintubated patients with severe hypoxia may benefit from awake proning in the hopes of improving oxygenation and decreasing need for intubation. But, what’s the evidence so far?

Viren Kaul, MD
Steering Committee Members

Home-Based Mechanical Ventilation and Neuromuscular Disease

New horizons in home ventilation

Phasing out a particular ventilator (Philips Respironics Trilogy 100 ventilator) has everyone on a steep learning curve with the replacement (Trilogy EVO). Most features are replicated in the EVO, including volume/pressure control and pressure-supported modes, mouthpiece ventilation, active/passive circuit capability, and portability (11.5 lb). Upgrades include longer battery life (15 hours; 7.5 hours internal/7.5 hours detachable) and use in pediatric patients now greater than or equal to 2.5 kg.

Online resources
EVO e-learning curriculum

Interprofessional team

Interprofessional team approach to palliative extubation

The emotional burden of caring for patients at the end of life affects all members of the care team. Palliative (or compassionate) extubation consists of the withdrawal of mechanical ventilation when the absolute priority in care delivery is to afford comfort and allow for natural death to occur. Rapid withdrawal of ventilatory support may lead to significant respiratory distress, and the critical care team has an obligation to ensure patient comfort during the dying process (Truog RD, et al. Crit Care Med. 2008;36[3]:953). Registered nurses (RN) are primarily responsible for the titration of sedation/analgesia and should be included in discussions regarding medication selection. It is imperative that neuromuscular blockade is absent, and benzodiazepines and/or opioids should be initiated prior to palliative extubation (Lanken PN, et al. Am J Respir Crit Care Med. 2008;177:912). Respiratory therapists (RT) are responsible for endotracheal tube removal despite rare participation in end-of-life discussions (Grandhige AP, et al. Respir Care. 2016;61[7]:891). It is recommended that an experienced physician, RN, and RT be readily available to respond quickly to any signs of distress (Downar J, et al. Intensive Care Med. 2016;42:1003). Regular debriefing sessions exploring team actions and communication dynamics are advised following end-of-life care (Ho A, et al. J Interprof Care. 2016;30[6]:795-803). Palliative extubation demands meticulous planning and clear communication among all team members (physician, RN, RT) and the patient’s family. Poor planning may result in physical and emotional suffering for the patient and difficult bereavement for the family (Coradazi A, et al. Hos Pal Med Int J. 2019;3[1]:10-14). Interprofessional team-based care results from intentional teams that exhibit collective identity and shared responsibility for the patients they serve (Core Competencies for Interprofessional Education Collaborative Practice, 2016). An inclusive and interprofessional approach to withdrawal of mechanical ventilation is key to both quality patient care and provider wellbeing.

Rebecca Anna Gersten, MD
Steering Committee Member

Samantha Davis, MS, RRT
Steering Committee Member

Munish Luthra, MD, FCCP
Vice-Chair Committee

ANNUAL AWARDS

Master FCCP

Nancy A. Collop MD, Master FCCP



College Medalist Award

Neil R. MacIntyre, MD, FCCP



Distinguished Service Award

Lisa K. Moores, MD, FCCP



Master Clinician Educator

William F. Kelly, MD, FCCP

David A. Schulman, MD, MPH, FCCP



Early Career Clinician Educator

Subani Chandra, MD, FCCP



Alfred Soffer Award for Editorial Excellence

Barbara Anderson, CHEST Staff

Laura Lipsey, CHEST Staff



Presidential Citation

Mangala Narasimhan, DO, FCCP

Renli Qiao, MD, PhD, FCCP
 

HONOR LECTURE AND MEMORIAL AWARDS

Edward C. Rosenow III, MD, Master FCCP/Master Teacher Endowed Honor Lecture Evolving Therapies in ANCA-Associated Vasculitides

Joseph P. Lynch, III, MD, FCCP

The lecture is generously funded by the CHEST Foundation.Distinguished Scientist Honor Lecture in Cardiopulmonary PhysiologyHelping the Dyspneic Patient: Clinical Physiology Matters!

Denis E. O’Donnell, MD, MBBCh, FCCP

The lecture is generously funded by the CHEST Foundation.Presidential Honor LectureCOPD Management: We’ve Come So Far

Darcy D. Marciniuk, MD, Master FCCP



Thomas L. Petty, MD, Master FCCP Memorial LectureReal World Research - What Would Dr. Petty Say?

Mary Hart, RRT, MS, FCCP

The lecture is generously funded by the CHEST Foundation.Margaret Pfrommer Endowed Memorial Lecture in Home-Based Mechanical VentilationNavigating to Home NIV Nirvana: What Would Margaret Do?

Peter C. Gay, MD, MS, FCCP

The Margaret Pfrommer Endowed Memorial Lecture in Home-Based Mechanical Ventilation is generously supported by International Ventilator Users Network of Post-Polio Health International and the CHEST Foundation.Pasquale Ciaglia Memorial Lecture in Interventional MedicineRaising the Bar: The Interventional Pulmonary Outcomes Group

Lonny B. Yarmus, DO, MBA, FCCP

The lecture is generously funded by the CHEST Foundation.

Roger C. Bone Memorial Lecture in Critical CareTo SIRS with Love: Dr. Roger Bone’s Continued Influence on Early Sepsis Care

Emanuel P. Rivers, MD, MPH, FCCP

The lecture is generously funded by the CHEST Foundation.Murray Kornfeld Memorial Founders LectureOur Pneumonia Journey: The Lungs and Beyond

Marcos I. Restrepo, MD, PhD, FCCP

The lecture is generously funded by the CHEST Foundation.

CHEST FOUNDATION GRANT AWARDS

The GlaxoSmithKline Distinguished Scholar in Respiratory Health

Deepa Gotur, MD, FCCP

Cytokine Release in SARS COV2 Viral Illness and Trends of Inflammasome Expression in Acute Respiratory Distress Syndrome Manifestations and ManagementThis grant is supported by an endowed fund from GlaxoSmithKline.CHEST Foundation and the Alpha-1 Foundation Research Grant in Alpha-1 Antitrypsin Deficiency

Paul R. Ellis, MBChB

Cardiovascular Outcomes and Phenotypes in Pulmonary Exacerbations of Alpha-1 AntitrypsinThis grant is jointly supported by the CHEST Foundation and the Alpha-1 Foundation.CHEST Foundation Research Grant in Women’s Lung Health

Shannon E. Kay, MD

Sex-specific Gene Expression in AsthmaThis grant is supported by the CHEST Foundation.CHEST Foundation Research Grant in Chronic Obstructive Pulmonary Disease

Davide Biondini, MD, PhD

Role of the Immune Check Points (CTLA-4 and PD-1) in the Development or Evasion of Smoking-Induced Chronic Obstructive Pulmonary Disease



Andrew J. Gangemi, MD

Are Sleep Health, Nicotine Metabolism, and Airway Inflammation Mechanisms for Differences in Lung Function between African American and Non-Hispanic White Smokers? A Proof-of-Concept ExaminationThese grants are supported by AstraZeneca LP.CHEST Foundation Research Grant in Critical Care

Mounica Vallurupalli, MD

Evaluating the Impact of Clonal Hematopoiesis on Host Immune Response During Sepsis

This grant is supported by the CHEST Foundation.CHEST Foundation Research Grant in Lung Cancer

Stefanie Mason, MD

Implications of Longitudinal Muscle-Mass Trajectories in Lung CancerThis grant is supported by the CHEST Foundation.CHEST Foundation Research Grant in Venous Thromboembolism

Jansen N. Seheult, MD, MBBCh

Untangling the NET: Neutrophil Activation as the Driver of Venous Thromboembolism in Coronavirus Disease 2019This grant is supported by the CHEST Foundation.CHEST Foundation Research Grant in Nontuberculous Mycobacteria Diseases

Bryan A. Garcia, MD

Longitudinal Proteomic Endotyping of Patients with Nontuberculous Mycobacterial Lung InfectionsThis grant is supported by Insmed Incorporated.CHEST Foundation Research Grant in Cystic Fibrosis

Jeffrey Barry, MD

Eosinophilia as a Biomarker for Worse Outcomes in Cystic Fibrosis



Kristina Montemayor, MD

The Association of Sex Hormones and Respiratory Morbidity in Individuals with Cystic FibrosisThese grants are supported by Vertex Pharmaceuticals.John R. Addrizzo, MD, FCCP Research Grant in Sarcoidosis

Changwan Ryu, MD

Extracellular Matrix Proteins as a Biomarker for Stage IV SarcoidosisThis grant is in honor of John R. Addrizzo, MD, FCCP and is jointly supported by the Addrizzo family and the CHEST Foundation.CHEST Foundation Research Grant in Severe Asthma

Isaretta L. Riley, MD, MPH

Coping with Asthma through Life Management (CALM)This grant is funded by AstraZeneca LP.CHEST Foundation Research Grant in Pulmonary Fibrosis

Sarah Beshay, MD

COPA Syndrome-Associated Mutations in Lung Transplant Recipients for Pulmonary Fibrosis



Erica D. Farrand, MD

The Future of Telehealth in Interstitial Lung DiseaseThese grants are supported by Boehringer Ingelheim Pharmaceuticals and Genentech, Inc.CHEST Foundation Research Grant in Sleep Medicine

Tetyana Kendzerska, MD, PhD

The Role of Sleep and Circadian Disturbances in Cancer Development and Progression: A Historical Multicenter Clinical Cohort Study



Nancy Stewart, DO

Improving COPD/OSA Overlap Syndrome Pre-Discharge Care DeliveryThese grants are funded by Jazz Pharmaceuticals, Inc.CHEST Foundation and Association of Critical Care Medicine Program Directors Award Research Grant in Medical Education

Ilana R. Krumm, MD

What’s good about Soul Food? Discovering and Analyzing Elements of an ICU Team Group Discussion Which Improve Provider WellnessThis grant is jointly supported by the CHEST Foundation and APCCMPD.CHEST Foundation and American Thoracic Society Research Grant in Diversity

Thomas S. Valley, MD, MSc

Understanding Differences in Delivery of Care Processes for Respiratory Failure by Race/EthnicityThis grant is jointly supported by the CHEST Foundation and ATS.CHEST Foundation Research Grant in COVID-19

David Furfaro, MD

Subphenotypes, Inflammatory Profiles, and Antibody Response in COVID-19 ARDSThis grant is supported by the CHEST Foundation.CHEST Foundation and American Thoracic Society Grant in COVID-19 and Diversity

Peter D. Jackson, MD

The Effect of the COVID-19 Pandemic on Tuberculosis Care in UgandaThis grant is jointly supported by the CHEST Foundation and ATS.CHEST Foundation Research Grant in Ultrasonography and COVID-19

Marjan M. Islam, MD

Thoracic Ultrasound in COVID-19: A Prospective Study Using Lung and Diaphragm Ultrasound in Evaluating Dyspnea in ICU Survivors with COVID-19 in a Post-ICU Clinic



Siddharth Dugar, MBBS

Spontaneous Echo Contrast in Lower Extremity and Correlation with Venous Velocity and Subsequent Deep Venous Thrombosis in Critically Ill COVID-19 PatientsThis grant is jointly supported by the CHEST Foundation and FUJIFILM SonoSite.

CHEST Foundation Community Service Grant Honoring D. Robert McCaffree, MD, Master FCCP



Ivan Nemorin, MBA, MS, RRT

Healthier Homes for Children-Community Asthma Prevention Program



Joseph Huang, MD

East Africa Training Initiative (EATI)



Aninda Das, MD, MBBS

Screening for Childhood Tuberculosis in Children 0-4 years of Age with Moderate to Severe Malnutrition in a Rural District of West Bengal, India



Trishual Siddharthan, MD

Establishing a Pulmonary and Critical Care Training Program in Uganda



Marina Lima, MD, MSc

Asmaland: The First Gamified Pediatric Asthma Educational Program in Portuguese



Roberta M. Kato, MD

Lung Power



These grants are supported by the CHEST Foundation.Alfred Soffer Research Award Winners

Mazen O. Al-Qadi, MD: RESPIRATORY VARIATION IN RIGHT ATRIAL PRESSURE PREDICTS RIGHT VENTRICULAR DYSFUNCTION IN PATIENTS WITH PRE-CAPILLARY PULMONARY HYPERTENSION

Valerie G. Press, MD: COST SAVING SIMULATION FOR THE TRANSITION FROM NEBULIZER TO COMBINATION OF NEBULIZER AND METERED-DOSE INHALERS (MD)



Young Investigator Award Winners

Gabriel E. Ortiz Jaimes, MD: CORRELATION OF CARDIAC OUTPUT MEASUREMENT BY GOAL-DIRECTED ECHOCARDIOGRAPHY PERFORMED BY INTENSIVISTS VS PULMONARY ARTERY CATHETER

Palakkumar Patel, MD: IMPACT OF HAVING PULMONARY HYPERTENSION IN PATIENTS ADMITTED WITH ACUTE EXACERBATION OF COPD IN THEIR HEALTHCARE UTILIZATION AND READMISSION: A US POPULATION COHORT STUDY

Top 5 Abstract Posters

Winner: Amr Alwakeel, MD: IMPACT OF A PLEURAL CARE PROGRAM ON THE PATHWAY TO DEFINITIVE PALLIATION OF MALIGNANT PLEURAL EFFUSIONS: A PRE-AND POST STUDY

Winner: Konstantinos Zorbas, MD: A SIMPLE PREDICTION SCORE FOR POSTOPERATIVE DEATH AFTER DECORTICATION

Winner: Yichen Wang, MD, MSc: CORONAVIRUS-RELATED HOSPITAL ADMISSIONS IN THE UNITED STATES IN 2016-2017

Runner up: Daniel Ospina-Delgado, MD: CHARACTERIZATION OF LARYNGEAL DISORDERS IN PATIENTS WITH EXCESSIVE CENTRAL AIRWAY COLLAPSE

Runner up: Vishal Vashistha, MD: TREATMENT PATTERNS AMONG LOWER-INCOME INDIAN PATIENTS WITH METASTATIC NON-SMALL CELL LUNG CANCER HARBORING EGFR MUTATIONS OR ALK REARRANGEMENTS



Case Report Poster Winners

Faiza Khalid, MD: FORME FUSTE OF INTERMEDIATE SYNDROME (IMS) IN ORGANOPHOSPHATE POISOING (OPP): EXPERT OPINION GUIDELINE WITHOUT CLEAR END-POINT.

William Meng, MD: VINGT MILLE LIEUES SOUS LES MERS: A POISONOUS GUEST FROM THE BLUE SEA TOXIC INHALATION OF CORAL PALYTOXIN

Dhruv Amratia, MD: PULMONARY BLASTOMA: A RARE FORM OF LUNG CANCER

Melinda Becker, MD: ECMO-ASSISTED BRONCHOSCOPY FOR NEAR-COMPLETE TRACHEAL OBSTRUCTION

Brittany Blass, PA-C: A CASE OF AUTOIMMUNE PULMONARY ALVEOLAR PROTEINOSIS WITH UNDERLYING MONOCLONAL B-CELL LYMPHOCYTOSIS

Abigayle Sullivan, MD: BIRD FANCIER’S LUNG: AN UNDERDIAGNOSED CAUSE OF SHORTNESS OF BREATH

Nitin Gupta, DO: SUCCESSFUL EMERGENT CORONARY ARTERY BYPASS IN A WOMAN WITH POSTPARTUM SPONTANEOUS CORONARY ARTERY DISSECTION

Michelle Miles, DO: GI VARIANT OF LEMIERRE SYNDROME: COMPLETE OCCLUSION OF SUPERIOR MESENTERIC VEIN IN A 30-YEAR-OLD WITH APPENDICEAL ABSCESS

Adarsha Ojha, MD: BLEEDING LUNG AND BLOATING GUT: LANE HAMILTON SYNDROME

Abdul Siddiqui, MD: A CASE OF E-CIGARETTE OR VAPING PRODUCT USE-ASSOCIATED LUNG INJURY IN AN INFREQUENT VAPE USER

James Dugan, MD: EMPHYSEMA WITH PLACENTAL TRANSMOGRIFICATION AND LIPOMATOUS CHANGE

Daniel Condit, MD: DUPLICATE INFERIOR VENA CAVA AS A POTENTIAL PATHWAY FOR RECURRENT PULMONARY EMBOLISM


 

CHEST 2020 CHEST Challenge

1st Place



Case Western Reserve University (MetroHealth)



Enambir Josan, MD

Ishan Lalani, MD, MPH

Faisal Qadir, MD



Program Director: Ziad Shaman, MD, FCCP







2nd Place





SUNY Downstate



Suchit Khanijao, MD

Chetana Pendkar, MBBS

Ayla Zubair, MBBS



Program Director: Robert Foronjy, MD



3rd Place



NYP Brooklyn Methodist Hospital



John Gorski, MD

Sandi Khin, MD

Kinjal Patel, MD


 

Program Director: Anthony Saleh, MD, FCCP

ANNUAL AWARDS

Master FCCP

Nancy A. Collop MD, Master FCCP



College Medalist Award

Neil R. MacIntyre, MD, FCCP



Distinguished Service Award

Lisa K. Moores, MD, FCCP



Master Clinician Educator

William F. Kelly, MD, FCCP

David A. Schulman, MD, MPH, FCCP



Early Career Clinician Educator

Subani Chandra, MD, FCCP



Alfred Soffer Award for Editorial Excellence

Barbara Anderson, CHEST Staff

Laura Lipsey, CHEST Staff



Presidential Citation

Mangala Narasimhan, DO, FCCP

Renli Qiao, MD, PhD, FCCP
 

HONOR LECTURE AND MEMORIAL AWARDS

Edward C. Rosenow III, MD, Master FCCP/Master Teacher Endowed Honor Lecture Evolving Therapies in ANCA-Associated Vasculitides

Joseph P. Lynch, III, MD, FCCP

The lecture is generously funded by the CHEST Foundation.Distinguished Scientist Honor Lecture in Cardiopulmonary PhysiologyHelping the Dyspneic Patient: Clinical Physiology Matters!

Denis E. O’Donnell, MD, MBBCh, FCCP

The lecture is generously funded by the CHEST Foundation.Presidential Honor LectureCOPD Management: We’ve Come So Far

Darcy D. Marciniuk, MD, Master FCCP



Thomas L. Petty, MD, Master FCCP Memorial LectureReal World Research - What Would Dr. Petty Say?

Mary Hart, RRT, MS, FCCP

The lecture is generously funded by the CHEST Foundation.Margaret Pfrommer Endowed Memorial Lecture in Home-Based Mechanical VentilationNavigating to Home NIV Nirvana: What Would Margaret Do?

Peter C. Gay, MD, MS, FCCP

The Margaret Pfrommer Endowed Memorial Lecture in Home-Based Mechanical Ventilation is generously supported by International Ventilator Users Network of Post-Polio Health International and the CHEST Foundation.Pasquale Ciaglia Memorial Lecture in Interventional MedicineRaising the Bar: The Interventional Pulmonary Outcomes Group

Lonny B. Yarmus, DO, MBA, FCCP

The lecture is generously funded by the CHEST Foundation.

Roger C. Bone Memorial Lecture in Critical CareTo SIRS with Love: Dr. Roger Bone’s Continued Influence on Early Sepsis Care

Emanuel P. Rivers, MD, MPH, FCCP

The lecture is generously funded by the CHEST Foundation.Murray Kornfeld Memorial Founders LectureOur Pneumonia Journey: The Lungs and Beyond

Marcos I. Restrepo, MD, PhD, FCCP

The lecture is generously funded by the CHEST Foundation.

CHEST FOUNDATION GRANT AWARDS

The GlaxoSmithKline Distinguished Scholar in Respiratory Health

Deepa Gotur, MD, FCCP

Cytokine Release in SARS COV2 Viral Illness and Trends of Inflammasome Expression in Acute Respiratory Distress Syndrome Manifestations and ManagementThis grant is supported by an endowed fund from GlaxoSmithKline.CHEST Foundation and the Alpha-1 Foundation Research Grant in Alpha-1 Antitrypsin Deficiency

Paul R. Ellis, MBChB

Cardiovascular Outcomes and Phenotypes in Pulmonary Exacerbations of Alpha-1 AntitrypsinThis grant is jointly supported by the CHEST Foundation and the Alpha-1 Foundation.CHEST Foundation Research Grant in Women’s Lung Health

Shannon E. Kay, MD

Sex-specific Gene Expression in AsthmaThis grant is supported by the CHEST Foundation.CHEST Foundation Research Grant in Chronic Obstructive Pulmonary Disease

Davide Biondini, MD, PhD

Role of the Immune Check Points (CTLA-4 and PD-1) in the Development or Evasion of Smoking-Induced Chronic Obstructive Pulmonary Disease



Andrew J. Gangemi, MD

Are Sleep Health, Nicotine Metabolism, and Airway Inflammation Mechanisms for Differences in Lung Function between African American and Non-Hispanic White Smokers? A Proof-of-Concept ExaminationThese grants are supported by AstraZeneca LP.CHEST Foundation Research Grant in Critical Care

Mounica Vallurupalli, MD

Evaluating the Impact of Clonal Hematopoiesis on Host Immune Response During Sepsis

This grant is supported by the CHEST Foundation.CHEST Foundation Research Grant in Lung Cancer

Stefanie Mason, MD

Implications of Longitudinal Muscle-Mass Trajectories in Lung CancerThis grant is supported by the CHEST Foundation.CHEST Foundation Research Grant in Venous Thromboembolism

Jansen N. Seheult, MD, MBBCh

Untangling the NET: Neutrophil Activation as the Driver of Venous Thromboembolism in Coronavirus Disease 2019This grant is supported by the CHEST Foundation.CHEST Foundation Research Grant in Nontuberculous Mycobacteria Diseases

Bryan A. Garcia, MD

Longitudinal Proteomic Endotyping of Patients with Nontuberculous Mycobacterial Lung InfectionsThis grant is supported by Insmed Incorporated.CHEST Foundation Research Grant in Cystic Fibrosis

Jeffrey Barry, MD

Eosinophilia as a Biomarker for Worse Outcomes in Cystic Fibrosis



Kristina Montemayor, MD

The Association of Sex Hormones and Respiratory Morbidity in Individuals with Cystic FibrosisThese grants are supported by Vertex Pharmaceuticals.John R. Addrizzo, MD, FCCP Research Grant in Sarcoidosis

Changwan Ryu, MD

Extracellular Matrix Proteins as a Biomarker for Stage IV SarcoidosisThis grant is in honor of John R. Addrizzo, MD, FCCP and is jointly supported by the Addrizzo family and the CHEST Foundation.CHEST Foundation Research Grant in Severe Asthma

Isaretta L. Riley, MD, MPH

Coping with Asthma through Life Management (CALM)This grant is funded by AstraZeneca LP.CHEST Foundation Research Grant in Pulmonary Fibrosis

Sarah Beshay, MD

COPA Syndrome-Associated Mutations in Lung Transplant Recipients for Pulmonary Fibrosis



Erica D. Farrand, MD

The Future of Telehealth in Interstitial Lung DiseaseThese grants are supported by Boehringer Ingelheim Pharmaceuticals and Genentech, Inc.CHEST Foundation Research Grant in Sleep Medicine

Tetyana Kendzerska, MD, PhD

The Role of Sleep and Circadian Disturbances in Cancer Development and Progression: A Historical Multicenter Clinical Cohort Study



Nancy Stewart, DO

Improving COPD/OSA Overlap Syndrome Pre-Discharge Care DeliveryThese grants are funded by Jazz Pharmaceuticals, Inc.CHEST Foundation and Association of Critical Care Medicine Program Directors Award Research Grant in Medical Education

Ilana R. Krumm, MD

What’s good about Soul Food? Discovering and Analyzing Elements of an ICU Team Group Discussion Which Improve Provider WellnessThis grant is jointly supported by the CHEST Foundation and APCCMPD.CHEST Foundation and American Thoracic Society Research Grant in Diversity

Thomas S. Valley, MD, MSc

Understanding Differences in Delivery of Care Processes for Respiratory Failure by Race/EthnicityThis grant is jointly supported by the CHEST Foundation and ATS.CHEST Foundation Research Grant in COVID-19

David Furfaro, MD

Subphenotypes, Inflammatory Profiles, and Antibody Response in COVID-19 ARDSThis grant is supported by the CHEST Foundation.CHEST Foundation and American Thoracic Society Grant in COVID-19 and Diversity

Peter D. Jackson, MD

The Effect of the COVID-19 Pandemic on Tuberculosis Care in UgandaThis grant is jointly supported by the CHEST Foundation and ATS.CHEST Foundation Research Grant in Ultrasonography and COVID-19

Marjan M. Islam, MD

Thoracic Ultrasound in COVID-19: A Prospective Study Using Lung and Diaphragm Ultrasound in Evaluating Dyspnea in ICU Survivors with COVID-19 in a Post-ICU Clinic



Siddharth Dugar, MBBS

Spontaneous Echo Contrast in Lower Extremity and Correlation with Venous Velocity and Subsequent Deep Venous Thrombosis in Critically Ill COVID-19 PatientsThis grant is jointly supported by the CHEST Foundation and FUJIFILM SonoSite.

CHEST Foundation Community Service Grant Honoring D. Robert McCaffree, MD, Master FCCP



Ivan Nemorin, MBA, MS, RRT

Healthier Homes for Children-Community Asthma Prevention Program



Joseph Huang, MD

East Africa Training Initiative (EATI)



Aninda Das, MD, MBBS

Screening for Childhood Tuberculosis in Children 0-4 years of Age with Moderate to Severe Malnutrition in a Rural District of West Bengal, India



Trishual Siddharthan, MD

Establishing a Pulmonary and Critical Care Training Program in Uganda



Marina Lima, MD, MSc

Asmaland: The First Gamified Pediatric Asthma Educational Program in Portuguese



Roberta M. Kato, MD

Lung Power



These grants are supported by the CHEST Foundation.Alfred Soffer Research Award Winners

Mazen O. Al-Qadi, MD: RESPIRATORY VARIATION IN RIGHT ATRIAL PRESSURE PREDICTS RIGHT VENTRICULAR DYSFUNCTION IN PATIENTS WITH PRE-CAPILLARY PULMONARY HYPERTENSION

Valerie G. Press, MD: COST SAVING SIMULATION FOR THE TRANSITION FROM NEBULIZER TO COMBINATION OF NEBULIZER AND METERED-DOSE INHALERS (MD)



Young Investigator Award Winners

Gabriel E. Ortiz Jaimes, MD: CORRELATION OF CARDIAC OUTPUT MEASUREMENT BY GOAL-DIRECTED ECHOCARDIOGRAPHY PERFORMED BY INTENSIVISTS VS PULMONARY ARTERY CATHETER

Palakkumar Patel, MD: IMPACT OF HAVING PULMONARY HYPERTENSION IN PATIENTS ADMITTED WITH ACUTE EXACERBATION OF COPD IN THEIR HEALTHCARE UTILIZATION AND READMISSION: A US POPULATION COHORT STUDY

Top 5 Abstract Posters

Winner: Amr Alwakeel, MD: IMPACT OF A PLEURAL CARE PROGRAM ON THE PATHWAY TO DEFINITIVE PALLIATION OF MALIGNANT PLEURAL EFFUSIONS: A PRE-AND POST STUDY

Winner: Konstantinos Zorbas, MD: A SIMPLE PREDICTION SCORE FOR POSTOPERATIVE DEATH AFTER DECORTICATION

Winner: Yichen Wang, MD, MSc: CORONAVIRUS-RELATED HOSPITAL ADMISSIONS IN THE UNITED STATES IN 2016-2017

Runner up: Daniel Ospina-Delgado, MD: CHARACTERIZATION OF LARYNGEAL DISORDERS IN PATIENTS WITH EXCESSIVE CENTRAL AIRWAY COLLAPSE

Runner up: Vishal Vashistha, MD: TREATMENT PATTERNS AMONG LOWER-INCOME INDIAN PATIENTS WITH METASTATIC NON-SMALL CELL LUNG CANCER HARBORING EGFR MUTATIONS OR ALK REARRANGEMENTS



Case Report Poster Winners

Faiza Khalid, MD: FORME FUSTE OF INTERMEDIATE SYNDROME (IMS) IN ORGANOPHOSPHATE POISOING (OPP): EXPERT OPINION GUIDELINE WITHOUT CLEAR END-POINT.

William Meng, MD: VINGT MILLE LIEUES SOUS LES MERS: A POISONOUS GUEST FROM THE BLUE SEA TOXIC INHALATION OF CORAL PALYTOXIN

Dhruv Amratia, MD: PULMONARY BLASTOMA: A RARE FORM OF LUNG CANCER

Melinda Becker, MD: ECMO-ASSISTED BRONCHOSCOPY FOR NEAR-COMPLETE TRACHEAL OBSTRUCTION

Brittany Blass, PA-C: A CASE OF AUTOIMMUNE PULMONARY ALVEOLAR PROTEINOSIS WITH UNDERLYING MONOCLONAL B-CELL LYMPHOCYTOSIS

Abigayle Sullivan, MD: BIRD FANCIER’S LUNG: AN UNDERDIAGNOSED CAUSE OF SHORTNESS OF BREATH

Nitin Gupta, DO: SUCCESSFUL EMERGENT CORONARY ARTERY BYPASS IN A WOMAN WITH POSTPARTUM SPONTANEOUS CORONARY ARTERY DISSECTION

Michelle Miles, DO: GI VARIANT OF LEMIERRE SYNDROME: COMPLETE OCCLUSION OF SUPERIOR MESENTERIC VEIN IN A 30-YEAR-OLD WITH APPENDICEAL ABSCESS

Adarsha Ojha, MD: BLEEDING LUNG AND BLOATING GUT: LANE HAMILTON SYNDROME

Abdul Siddiqui, MD: A CASE OF E-CIGARETTE OR VAPING PRODUCT USE-ASSOCIATED LUNG INJURY IN AN INFREQUENT VAPE USER

James Dugan, MD: EMPHYSEMA WITH PLACENTAL TRANSMOGRIFICATION AND LIPOMATOUS CHANGE

Daniel Condit, MD: DUPLICATE INFERIOR VENA CAVA AS A POTENTIAL PATHWAY FOR RECURRENT PULMONARY EMBOLISM


 

CHEST 2020 CHEST Challenge

1st Place



Case Western Reserve University (MetroHealth)



Enambir Josan, MD

Ishan Lalani, MD, MPH

Faisal Qadir, MD



Program Director: Ziad Shaman, MD, FCCP







2nd Place





SUNY Downstate



Suchit Khanijao, MD

Chetana Pendkar, MBBS

Ayla Zubair, MBBS



Program Director: Robert Foronjy, MD



3rd Place



NYP Brooklyn Methodist Hospital



John Gorski, MD

Sandi Khin, MD

Kinjal Patel, MD


 

Program Director: Anthony Saleh, MD, FCCP

ANNUAL AWARDS

Master FCCP

Nancy A. Collop MD, Master FCCP



College Medalist Award

Neil R. MacIntyre, MD, FCCP



Distinguished Service Award

Lisa K. Moores, MD, FCCP



Master Clinician Educator

William F. Kelly, MD, FCCP

David A. Schulman, MD, MPH, FCCP



Early Career Clinician Educator

Subani Chandra, MD, FCCP



Alfred Soffer Award for Editorial Excellence

Barbara Anderson, CHEST Staff

Laura Lipsey, CHEST Staff



Presidential Citation

Mangala Narasimhan, DO, FCCP

Renli Qiao, MD, PhD, FCCP
 

HONOR LECTURE AND MEMORIAL AWARDS

Edward C. Rosenow III, MD, Master FCCP/Master Teacher Endowed Honor Lecture Evolving Therapies in ANCA-Associated Vasculitides

Joseph P. Lynch, III, MD, FCCP

The lecture is generously funded by the CHEST Foundation.Distinguished Scientist Honor Lecture in Cardiopulmonary PhysiologyHelping the Dyspneic Patient: Clinical Physiology Matters!

Denis E. O’Donnell, MD, MBBCh, FCCP

The lecture is generously funded by the CHEST Foundation.Presidential Honor LectureCOPD Management: We’ve Come So Far

Darcy D. Marciniuk, MD, Master FCCP



Thomas L. Petty, MD, Master FCCP Memorial LectureReal World Research - What Would Dr. Petty Say?

Mary Hart, RRT, MS, FCCP

The lecture is generously funded by the CHEST Foundation.Margaret Pfrommer Endowed Memorial Lecture in Home-Based Mechanical VentilationNavigating to Home NIV Nirvana: What Would Margaret Do?

Peter C. Gay, MD, MS, FCCP

The Margaret Pfrommer Endowed Memorial Lecture in Home-Based Mechanical Ventilation is generously supported by International Ventilator Users Network of Post-Polio Health International and the CHEST Foundation.Pasquale Ciaglia Memorial Lecture in Interventional MedicineRaising the Bar: The Interventional Pulmonary Outcomes Group

Lonny B. Yarmus, DO, MBA, FCCP

The lecture is generously funded by the CHEST Foundation.

Roger C. Bone Memorial Lecture in Critical CareTo SIRS with Love: Dr. Roger Bone’s Continued Influence on Early Sepsis Care

Emanuel P. Rivers, MD, MPH, FCCP

The lecture is generously funded by the CHEST Foundation.Murray Kornfeld Memorial Founders LectureOur Pneumonia Journey: The Lungs and Beyond

Marcos I. Restrepo, MD, PhD, FCCP

The lecture is generously funded by the CHEST Foundation.

CHEST FOUNDATION GRANT AWARDS

The GlaxoSmithKline Distinguished Scholar in Respiratory Health

Deepa Gotur, MD, FCCP

Cytokine Release in SARS COV2 Viral Illness and Trends of Inflammasome Expression in Acute Respiratory Distress Syndrome Manifestations and ManagementThis grant is supported by an endowed fund from GlaxoSmithKline.CHEST Foundation and the Alpha-1 Foundation Research Grant in Alpha-1 Antitrypsin Deficiency

Paul R. Ellis, MBChB

Cardiovascular Outcomes and Phenotypes in Pulmonary Exacerbations of Alpha-1 AntitrypsinThis grant is jointly supported by the CHEST Foundation and the Alpha-1 Foundation.CHEST Foundation Research Grant in Women’s Lung Health

Shannon E. Kay, MD

Sex-specific Gene Expression in AsthmaThis grant is supported by the CHEST Foundation.CHEST Foundation Research Grant in Chronic Obstructive Pulmonary Disease

Davide Biondini, MD, PhD

Role of the Immune Check Points (CTLA-4 and PD-1) in the Development or Evasion of Smoking-Induced Chronic Obstructive Pulmonary Disease



Andrew J. Gangemi, MD

Are Sleep Health, Nicotine Metabolism, and Airway Inflammation Mechanisms for Differences in Lung Function between African American and Non-Hispanic White Smokers? A Proof-of-Concept ExaminationThese grants are supported by AstraZeneca LP.CHEST Foundation Research Grant in Critical Care

Mounica Vallurupalli, MD

Evaluating the Impact of Clonal Hematopoiesis on Host Immune Response During Sepsis

This grant is supported by the CHEST Foundation.CHEST Foundation Research Grant in Lung Cancer

Stefanie Mason, MD

Implications of Longitudinal Muscle-Mass Trajectories in Lung CancerThis grant is supported by the CHEST Foundation.CHEST Foundation Research Grant in Venous Thromboembolism

Jansen N. Seheult, MD, MBBCh

Untangling the NET: Neutrophil Activation as the Driver of Venous Thromboembolism in Coronavirus Disease 2019This grant is supported by the CHEST Foundation.CHEST Foundation Research Grant in Nontuberculous Mycobacteria Diseases

Bryan A. Garcia, MD

Longitudinal Proteomic Endotyping of Patients with Nontuberculous Mycobacterial Lung InfectionsThis grant is supported by Insmed Incorporated.CHEST Foundation Research Grant in Cystic Fibrosis

Jeffrey Barry, MD

Eosinophilia as a Biomarker for Worse Outcomes in Cystic Fibrosis



Kristina Montemayor, MD

The Association of Sex Hormones and Respiratory Morbidity in Individuals with Cystic FibrosisThese grants are supported by Vertex Pharmaceuticals.John R. Addrizzo, MD, FCCP Research Grant in Sarcoidosis

Changwan Ryu, MD

Extracellular Matrix Proteins as a Biomarker for Stage IV SarcoidosisThis grant is in honor of John R. Addrizzo, MD, FCCP and is jointly supported by the Addrizzo family and the CHEST Foundation.CHEST Foundation Research Grant in Severe Asthma

Isaretta L. Riley, MD, MPH

Coping with Asthma through Life Management (CALM)This grant is funded by AstraZeneca LP.CHEST Foundation Research Grant in Pulmonary Fibrosis

Sarah Beshay, MD

COPA Syndrome-Associated Mutations in Lung Transplant Recipients for Pulmonary Fibrosis



Erica D. Farrand, MD

The Future of Telehealth in Interstitial Lung DiseaseThese grants are supported by Boehringer Ingelheim Pharmaceuticals and Genentech, Inc.CHEST Foundation Research Grant in Sleep Medicine

Tetyana Kendzerska, MD, PhD

The Role of Sleep and Circadian Disturbances in Cancer Development and Progression: A Historical Multicenter Clinical Cohort Study



Nancy Stewart, DO

Improving COPD/OSA Overlap Syndrome Pre-Discharge Care DeliveryThese grants are funded by Jazz Pharmaceuticals, Inc.CHEST Foundation and Association of Critical Care Medicine Program Directors Award Research Grant in Medical Education

Ilana R. Krumm, MD

What’s good about Soul Food? Discovering and Analyzing Elements of an ICU Team Group Discussion Which Improve Provider WellnessThis grant is jointly supported by the CHEST Foundation and APCCMPD.CHEST Foundation and American Thoracic Society Research Grant in Diversity

Thomas S. Valley, MD, MSc

Understanding Differences in Delivery of Care Processes for Respiratory Failure by Race/EthnicityThis grant is jointly supported by the CHEST Foundation and ATS.CHEST Foundation Research Grant in COVID-19

David Furfaro, MD

Subphenotypes, Inflammatory Profiles, and Antibody Response in COVID-19 ARDSThis grant is supported by the CHEST Foundation.CHEST Foundation and American Thoracic Society Grant in COVID-19 and Diversity

Peter D. Jackson, MD

The Effect of the COVID-19 Pandemic on Tuberculosis Care in UgandaThis grant is jointly supported by the CHEST Foundation and ATS.CHEST Foundation Research Grant in Ultrasonography and COVID-19

Marjan M. Islam, MD

Thoracic Ultrasound in COVID-19: A Prospective Study Using Lung and Diaphragm Ultrasound in Evaluating Dyspnea in ICU Survivors with COVID-19 in a Post-ICU Clinic



Siddharth Dugar, MBBS

Spontaneous Echo Contrast in Lower Extremity and Correlation with Venous Velocity and Subsequent Deep Venous Thrombosis in Critically Ill COVID-19 PatientsThis grant is jointly supported by the CHEST Foundation and FUJIFILM SonoSite.

CHEST Foundation Community Service Grant Honoring D. Robert McCaffree, MD, Master FCCP



Ivan Nemorin, MBA, MS, RRT

Healthier Homes for Children-Community Asthma Prevention Program



Joseph Huang, MD

East Africa Training Initiative (EATI)



Aninda Das, MD, MBBS

Screening for Childhood Tuberculosis in Children 0-4 years of Age with Moderate to Severe Malnutrition in a Rural District of West Bengal, India



Trishual Siddharthan, MD

Establishing a Pulmonary and Critical Care Training Program in Uganda



Marina Lima, MD, MSc

Asmaland: The First Gamified Pediatric Asthma Educational Program in Portuguese



Roberta M. Kato, MD

Lung Power



These grants are supported by the CHEST Foundation.Alfred Soffer Research Award Winners

Mazen O. Al-Qadi, MD: RESPIRATORY VARIATION IN RIGHT ATRIAL PRESSURE PREDICTS RIGHT VENTRICULAR DYSFUNCTION IN PATIENTS WITH PRE-CAPILLARY PULMONARY HYPERTENSION

Valerie G. Press, MD: COST SAVING SIMULATION FOR THE TRANSITION FROM NEBULIZER TO COMBINATION OF NEBULIZER AND METERED-DOSE INHALERS (MD)



Young Investigator Award Winners

Gabriel E. Ortiz Jaimes, MD: CORRELATION OF CARDIAC OUTPUT MEASUREMENT BY GOAL-DIRECTED ECHOCARDIOGRAPHY PERFORMED BY INTENSIVISTS VS PULMONARY ARTERY CATHETER

Palakkumar Patel, MD: IMPACT OF HAVING PULMONARY HYPERTENSION IN PATIENTS ADMITTED WITH ACUTE EXACERBATION OF COPD IN THEIR HEALTHCARE UTILIZATION AND READMISSION: A US POPULATION COHORT STUDY

Top 5 Abstract Posters

Winner: Amr Alwakeel, MD: IMPACT OF A PLEURAL CARE PROGRAM ON THE PATHWAY TO DEFINITIVE PALLIATION OF MALIGNANT PLEURAL EFFUSIONS: A PRE-AND POST STUDY

Winner: Konstantinos Zorbas, MD: A SIMPLE PREDICTION SCORE FOR POSTOPERATIVE DEATH AFTER DECORTICATION

Winner: Yichen Wang, MD, MSc: CORONAVIRUS-RELATED HOSPITAL ADMISSIONS IN THE UNITED STATES IN 2016-2017

Runner up: Daniel Ospina-Delgado, MD: CHARACTERIZATION OF LARYNGEAL DISORDERS IN PATIENTS WITH EXCESSIVE CENTRAL AIRWAY COLLAPSE

Runner up: Vishal Vashistha, MD: TREATMENT PATTERNS AMONG LOWER-INCOME INDIAN PATIENTS WITH METASTATIC NON-SMALL CELL LUNG CANCER HARBORING EGFR MUTATIONS OR ALK REARRANGEMENTS



Case Report Poster Winners

Faiza Khalid, MD: FORME FUSTE OF INTERMEDIATE SYNDROME (IMS) IN ORGANOPHOSPHATE POISOING (OPP): EXPERT OPINION GUIDELINE WITHOUT CLEAR END-POINT.

William Meng, MD: VINGT MILLE LIEUES SOUS LES MERS: A POISONOUS GUEST FROM THE BLUE SEA TOXIC INHALATION OF CORAL PALYTOXIN

Dhruv Amratia, MD: PULMONARY BLASTOMA: A RARE FORM OF LUNG CANCER

Melinda Becker, MD: ECMO-ASSISTED BRONCHOSCOPY FOR NEAR-COMPLETE TRACHEAL OBSTRUCTION

Brittany Blass, PA-C: A CASE OF AUTOIMMUNE PULMONARY ALVEOLAR PROTEINOSIS WITH UNDERLYING MONOCLONAL B-CELL LYMPHOCYTOSIS

Abigayle Sullivan, MD: BIRD FANCIER’S LUNG: AN UNDERDIAGNOSED CAUSE OF SHORTNESS OF BREATH

Nitin Gupta, DO: SUCCESSFUL EMERGENT CORONARY ARTERY BYPASS IN A WOMAN WITH POSTPARTUM SPONTANEOUS CORONARY ARTERY DISSECTION

Michelle Miles, DO: GI VARIANT OF LEMIERRE SYNDROME: COMPLETE OCCLUSION OF SUPERIOR MESENTERIC VEIN IN A 30-YEAR-OLD WITH APPENDICEAL ABSCESS

Adarsha Ojha, MD: BLEEDING LUNG AND BLOATING GUT: LANE HAMILTON SYNDROME

Abdul Siddiqui, MD: A CASE OF E-CIGARETTE OR VAPING PRODUCT USE-ASSOCIATED LUNG INJURY IN AN INFREQUENT VAPE USER

James Dugan, MD: EMPHYSEMA WITH PLACENTAL TRANSMOGRIFICATION AND LIPOMATOUS CHANGE

Daniel Condit, MD: DUPLICATE INFERIOR VENA CAVA AS A POTENTIAL PATHWAY FOR RECURRENT PULMONARY EMBOLISM


 

CHEST 2020 CHEST Challenge

1st Place



Case Western Reserve University (MetroHealth)



Enambir Josan, MD

Ishan Lalani, MD, MPH

Faisal Qadir, MD



Program Director: Ziad Shaman, MD, FCCP







2nd Place





SUNY Downstate



Suchit Khanijao, MD

Chetana Pendkar, MBBS

Ayla Zubair, MBBS



Program Director: Robert Foronjy, MD



3rd Place



NYP Brooklyn Methodist Hospital



John Gorski, MD

Sandi Khin, MD

Kinjal Patel, MD


 

Program Director: Anthony Saleh, MD, FCCP

In the year of COVID-19, we saw unprecedented changes in our environment and social interactions. Almost nothing was as it should be—sports championships in a “bubble,” social distancing, limited travel, economic hardships, and, of course, the devastating effects on the health of people all over the world. CHEST did not shy away from the challenges of COVID-19. Instead, we accelerated our focus on education, patient care, research, and advocacy to assist clinicians caring for affected patients. The CHEST Foundation, the philanthropic arm of CHEST, contributed to this effort by funding research and community service grants and distributing over 14,000 pieces of PPE to health workers and the public.

Amid social protests, CHEST issued statements supporting inclusion and diversity and called for improving health care disparities. To better understand how these important issues interact, the CHEST Foundation began conducting listening tours across the country

to learn what is important to patients and what barriers they face. These lessons will influence how the foundation implements its current programs and designs future programs. Over the next few months, the CHEST Foundation will set in motion a course of action to support valuable programs in these areas. We will focus on three main themes.

First, we will utilize the strength of CHEST by inviting fellows to participate in CHEST Foundation activities and serve on our committees. By creating an atmosphere of inclusion and collegiality, we believe that fellows will better understand the CHEST Foundation’s goals and commit themselves to strengthening the foundation for years to come.

Second, we want to establish relationships with organizations outside of CHEST. Although our partnerships with health care industry organizations are strong, we have few robust alliances in the non-endemic space. Corporations espouse wellness, and we have experts all over the world who can address the needs and concerns of these companies. Preliminary exploration tells us that non-endemic corporations have an interest in what we can offer.

Third, we want to grow the corpus of the CHEST Foundation. Dreams without funding become only aspirations, but dreams with funding become reality. Without a solid corpus, we operate on a short-term plan. CHEST has some of the most influential leaders in the fields of pulmonary, critical care, and sleep medicine. Together, we can develop programs that can significantly impact the lives of the people we serve.

The CHEST Foundation looks forward to building on past successes and tackling new challenges. On behalf of CHEST’s Board of Trustees and the gifted staff, I invite you to join us to reach these goals.

In the year of COVID-19, we saw unprecedented changes in our environment and social interactions. Almost nothing was as it should be—sports championships in a “bubble,” social distancing, limited travel, economic hardships, and, of course, the devastating effects on the health of people all over the world. CHEST did not shy away from the challenges of COVID-19. Instead, we accelerated our focus on education, patient care, research, and advocacy to assist clinicians caring for affected patients. The CHEST Foundation, the philanthropic arm of CHEST, contributed to this effort by funding research and community service grants and distributing over 14,000 pieces of PPE to health workers and the public.

Amid social protests, CHEST issued statements supporting inclusion and diversity and called for improving health care disparities. To better understand how these important issues interact, the CHEST Foundation began conducting listening tours across the country

to learn what is important to patients and what barriers they face. These lessons will influence how the foundation implements its current programs and designs future programs. Over the next few months, the CHEST Foundation will set in motion a course of action to support valuable programs in these areas. We will focus on three main themes.

First, we will utilize the strength of CHEST by inviting fellows to participate in CHEST Foundation activities and serve on our committees. By creating an atmosphere of inclusion and collegiality, we believe that fellows will better understand the CHEST Foundation’s goals and commit themselves to strengthening the foundation for years to come.

Second, we want to establish relationships with organizations outside of CHEST. Although our partnerships with health care industry organizations are strong, we have few robust alliances in the non-endemic space. Corporations espouse wellness, and we have experts all over the world who can address the needs and concerns of these companies. Preliminary exploration tells us that non-endemic corporations have an interest in what we can offer.

Third, we want to grow the corpus of the CHEST Foundation. Dreams without funding become only aspirations, but dreams with funding become reality. Without a solid corpus, we operate on a short-term plan. CHEST has some of the most influential leaders in the fields of pulmonary, critical care, and sleep medicine. Together, we can develop programs that can significantly impact the lives of the people we serve.

The CHEST Foundation looks forward to building on past successes and tackling new challenges. On behalf of CHEST’s Board of Trustees and the gifted staff, I invite you to join us to reach these goals.

In the year of COVID-19, we saw unprecedented changes in our environment and social interactions. Almost nothing was as it should be—sports championships in a “bubble,” social distancing, limited travel, economic hardships, and, of course, the devastating effects on the health of people all over the world. CHEST did not shy away from the challenges of COVID-19. Instead, we accelerated our focus on education, patient care, research, and advocacy to assist clinicians caring for affected patients. The CHEST Foundation, the philanthropic arm of CHEST, contributed to this effort by funding research and community service grants and distributing over 14,000 pieces of PPE to health workers and the public.

Amid social protests, CHEST issued statements supporting inclusion and diversity and called for improving health care disparities. To better understand how these important issues interact, the CHEST Foundation began conducting listening tours across the country

to learn what is important to patients and what barriers they face. These lessons will influence how the foundation implements its current programs and designs future programs. Over the next few months, the CHEST Foundation will set in motion a course of action to support valuable programs in these areas. We will focus on three main themes.

First, we will utilize the strength of CHEST by inviting fellows to participate in CHEST Foundation activities and serve on our committees. By creating an atmosphere of inclusion and collegiality, we believe that fellows will better understand the CHEST Foundation’s goals and commit themselves to strengthening the foundation for years to come.

Second, we want to establish relationships with organizations outside of CHEST. Although our partnerships with health care industry organizations are strong, we have few robust alliances in the non-endemic space. Corporations espouse wellness, and we have experts all over the world who can address the needs and concerns of these companies. Preliminary exploration tells us that non-endemic corporations have an interest in what we can offer.

Third, we want to grow the corpus of the CHEST Foundation. Dreams without funding become only aspirations, but dreams with funding become reality. Without a solid corpus, we operate on a short-term plan. CHEST has some of the most influential leaders in the fields of pulmonary, critical care, and sleep medicine. Together, we can develop programs that can significantly impact the lives of the people we serve.

The CHEST Foundation looks forward to building on past successes and tackling new challenges. On behalf of CHEST’s Board of Trustees and the gifted staff, I invite you to join us to reach these goals.

What’s in a name?

Bronchiolitis, a group of diseases also referred to as “small airways diseases,” is characterized by inflammation and/or fibrosis in airways less than 2 mm in diameter. In pediatric patients, it is most commonly related to acute viral infections, while in adults, it is often associated with chronic diseases. Bronchiolitis is a well-recognized complication in a significant number of patients who have undergone lung or stem cell transplantation. Common associations also include connective tissue diseases, environmental or occupational inhalation exposures, aspiration, drug toxicity, and infections. Diagnosing bronchiolitis can be challenging for clinicians, and few treatment options exist apart from treating identifiable underlying etiologies. More research is needed into noninvasive diagnostic techniques and treatment modalities.

The terminology used to describe bronchiolitis has evolved over time. Bronchiolitis is now used to describe conditions where the primary pathologic condition is damage to the bronchiolar epithelium not attributable to a larger parenchymal disease (such as hypersensitivity pneumonitis). This change in nomenclature explains why the condition formerly known as “bronchiolitis obliterans organizing pneumonia” (BOOP) is now simply recognized as “organizing pneumonia.” Despite several proposed classification schemes focusing on histopathology, there is no consensus regarding the different subtypes of bronchiolitis, leading to confusion in some cases. Recently, authors have attempted to distinguish cases based on three main histologic patterns (Urisman A, et al. Surg Pathol Clin. 2020;13[1]:189).

• Obliterative/constrictive bronchiolitis (OB) – the terms “obliterative” and “constrictive” are used interchangeably throughout pulmonary literature. It is characterized by fibroblast-rich tissue accumulation in the sub-epithelium of bronchioles leading to progressive narrowing of the lumen. In addition to the transplant setting, it is often seen in patients with rheumatoid arthritis or other connective tissue diseases, inhalational exposures, or acute respiratory infections. More recently, clinicians have recognized diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) as a rare condition causing OB with potentially effective treatment.
• Follicular bronchiolitis (FB) – features peribronchiolar inflammation with subepithelial lymphoid deposits leading to luminal obstruction. FB is chiefly associated with conditions of impaired immunity or chronic airway infection, such as autoimmune connective tissues diseases (especially rheumatoid arthritis and Sjogren’s), severe combined immunodeficiency, HIV, cystic fibrosis, and primary ciliary dyskinesia. 
• Diffuse panbronchiolitis (DBP) – features bilateral bronchiolar lesions with lymphocytic inflammation of the bronchiolar wall, as well as peribronchiolar inflammation and accumulation of interstitial foamy macrophages. Patients afflicted with DBP may suffer repeated bacterial colonization or infection. There is a higher prevalence of DBP in Asia where it was first identified in the 1960s, potentially due to several HLA alleles that are more common in Asia. 

In addition to the above terminology, the transplant-setting diagnosis “bronchiolitis obliterans syndrome” (BOS) is used to denote progressive obstructive lung disease for which there is not another cause aside from chronic graft rejection. For these patients, clinicians assume the underlying disease entity is OB, but they often lack histopathologic confirmation. 
 

Diagnosis is challenging

Symptoms of bronchiolitis are typically dyspnea and cough, and patients may often be diagnosed with asthma or COPD initially. Pulmonary function testing may show signs of obstruction, restriction, or mixed disease with or without a reduction in Dlco. Chest radiography often appears normal, but high-resolution CT may show expiratory air trapping and centrilobular nodules. Advanced imaging modalities may augment or replace CT imaging in diagnosing bronchiolitis: investigators are evaluating pulmonary MRI and fluoroscopy with computerized ventilation analysis in clinical trials (NCT04080232).

Currently, open or thoracoscopic lung biopsy is typically required to make a definitive diagnosis. Because bronchiolitis is a patchy and heterogeneous process, transbronchial biopsy may provide insufficient yield, with a sensitivity of 29% to 70% reported in lung transplant literature (Urisman A, et al. Surg Pathol Clin. 2020;13[1]:189).

Recent studies have demonstrated transbronchial cryobiopsy to be a promising alternative to surgical biopsy, owing to larger tissue samples than conventional transbronchial lung biopsies. For example, in a recent case series four patients underwent transbronchial cryobiopsy. The procedure yielded adequate tissue for diagnosis of a chronic bronchiolitis in each case (Yamakawa H, et al. Internal Med Advance Publication. doi: 10.2169/internalmedicine.6028-20.
 

Treatment options are growing

Evidence for treatment of bronchiolitis remains limited. Options are extrapolated from lung transplant patients, where incidence of BOS ranges from 50% at 5 years to 76% at 10 years post transplant. Guidelines recommend a 3-month minimum trial of azithromycin, which has been shown to slow or reverse decline of lung function in some patients. Modification of immunosuppression is also recommended. In patients who have continued lung function decline, a systematic review concluded that extracorporeal photopheresis had the most robust evidence for efficacy with stabilized lung function and improved overall survival (Benden C, et al. J Heart Lung Transplant. 2017;36[9]:921). Other salvage therapies that have lower-quality evidence of benefit include total lymphoid irradiation, montelukast, and aerosolized cyclosporine.

In patients who have undergone hematopoietic stem cell transplant, steroids are typically the first line treatment for OB as it is thought to be a form of chronic graft-vs-host disease (GVHD). Ruxolitinib, a selective JAK1/2 inhibitor, demonstrated significant improvement overall in patients with steroid-refractory acute GVHD in a recent randomized clinical trial, although the trial did not examine its effect on pulmonary manifestations (Zeiser R, et al. N Engl J Med. 2020;382[19]:1800). To date, retrospective observational studies of ruxolitinib in patients with lung GVHD have shown conflicting results regarding benefit. Investigators are currently studying ruxolitinib in a phase II trial for patients with BOS following stem cell transplant (NCT03674047).

DIPNECH is unique from other bronchiolitis entities, as small airways dysfunction develops as a result of neuroendocrine cell proliferation in the airway mucosa, ultimately leading to bronchial narrowing. It most commonly presents in middle-aged nonsmoking women with years of chronic cough and dyspnea. While it has an indolent course in many patients, some patients develop progressive symptoms and obstructive lung disease. DIPNECH is considered a precursor to other pulmonary neuroendocrine tumors. The lesions demonstrate somatostatin receptor expression in many cases, prompting the use of somatostatin analogues as treatment. In the largest published case series, 42 patients from three different institutions were identified who were treated with somatostatin analogues for a mean of 38.8 months at the time of review. Symptomatic improvement was seen in 33 of the 42 (79%), and of the 15 with posttreatment PFT data, 14 (93%) showed improvement in PFTs (Al-Toubah, T, et al. Chest. 2020;158[1]:401). Other small studies have demonstrated varying results with symptomatic improvement in 29% to 76% of patients and improvement or stability of PFTs in 50% to 100% of patients (Samhouri BF, et al. ERJ Open Res. 2020;6[4]:527).

For patients who have not undergone lung transplant, and who do not have an identifiable exposure or underlying rheumatologic condition, a similar 3-month minimum trial of macrolide antibiotics is reasonable. Macrolides have been shown to double long-term survival rates to over 90% in patients with DPB. Evidence in this patient population is quite limited, and further research is needed to determine effective therapies for patients.
 

What’s next for bronchiolitis

While clinicians currently have few tools for diagnosing and treating these uncommon diseases, in the coming years, we should learn whether novel imaging modalities or less invasive procedures can aid in the diagnosis. Physicians hope these advances will preclude the need for invasive biopsies in more patients going forward. We should also learn whether newer, targeted agents like ruxolitinib are effective for BOS in patients with stem cell transplant. If so, this finding may open it and similar agents to investigation in other forms of bronchiolitis.
 

Dr. Poole and Dr. Callahan are with University of Utah Health, Salt Lake City, Utah.

What’s in a name?

Bronchiolitis, a group of diseases also referred to as “small airways diseases,” is characterized by inflammation and/or fibrosis in airways less than 2 mm in diameter. In pediatric patients, it is most commonly related to acute viral infections, while in adults, it is often associated with chronic diseases. Bronchiolitis is a well-recognized complication in a significant number of patients who have undergone lung or stem cell transplantation. Common associations also include connective tissue diseases, environmental or occupational inhalation exposures, aspiration, drug toxicity, and infections. Diagnosing bronchiolitis can be challenging for clinicians, and few treatment options exist apart from treating identifiable underlying etiologies. More research is needed into noninvasive diagnostic techniques and treatment modalities.

The terminology used to describe bronchiolitis has evolved over time. Bronchiolitis is now used to describe conditions where the primary pathologic condition is damage to the bronchiolar epithelium not attributable to a larger parenchymal disease (such as hypersensitivity pneumonitis). This change in nomenclature explains why the condition formerly known as “bronchiolitis obliterans organizing pneumonia” (BOOP) is now simply recognized as “organizing pneumonia.” Despite several proposed classification schemes focusing on histopathology, there is no consensus regarding the different subtypes of bronchiolitis, leading to confusion in some cases. Recently, authors have attempted to distinguish cases based on three main histologic patterns (Urisman A, et al. Surg Pathol Clin. 2020;13[1]:189).

• Obliterative/constrictive bronchiolitis (OB) – the terms “obliterative” and “constrictive” are used interchangeably throughout pulmonary literature. It is characterized by fibroblast-rich tissue accumulation in the sub-epithelium of bronchioles leading to progressive narrowing of the lumen. In addition to the transplant setting, it is often seen in patients with rheumatoid arthritis or other connective tissue diseases, inhalational exposures, or acute respiratory infections. More recently, clinicians have recognized diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) as a rare condition causing OB with potentially effective treatment.
• Follicular bronchiolitis (FB) – features peribronchiolar inflammation with subepithelial lymphoid deposits leading to luminal obstruction. FB is chiefly associated with conditions of impaired immunity or chronic airway infection, such as autoimmune connective tissues diseases (especially rheumatoid arthritis and Sjogren’s), severe combined immunodeficiency, HIV, cystic fibrosis, and primary ciliary dyskinesia. 
• Diffuse panbronchiolitis (DBP) – features bilateral bronchiolar lesions with lymphocytic inflammation of the bronchiolar wall, as well as peribronchiolar inflammation and accumulation of interstitial foamy macrophages. Patients afflicted with DBP may suffer repeated bacterial colonization or infection. There is a higher prevalence of DBP in Asia where it was first identified in the 1960s, potentially due to several HLA alleles that are more common in Asia. 

In addition to the above terminology, the transplant-setting diagnosis “bronchiolitis obliterans syndrome” (BOS) is used to denote progressive obstructive lung disease for which there is not another cause aside from chronic graft rejection. For these patients, clinicians assume the underlying disease entity is OB, but they often lack histopathologic confirmation. 
 

Diagnosis is challenging

Symptoms of bronchiolitis are typically dyspnea and cough, and patients may often be diagnosed with asthma or COPD initially. Pulmonary function testing may show signs of obstruction, restriction, or mixed disease with or without a reduction in Dlco. Chest radiography often appears normal, but high-resolution CT may show expiratory air trapping and centrilobular nodules. Advanced imaging modalities may augment or replace CT imaging in diagnosing bronchiolitis: investigators are evaluating pulmonary MRI and fluoroscopy with computerized ventilation analysis in clinical trials (NCT04080232).

Currently, open or thoracoscopic lung biopsy is typically required to make a definitive diagnosis. Because bronchiolitis is a patchy and heterogeneous process, transbronchial biopsy may provide insufficient yield, with a sensitivity of 29% to 70% reported in lung transplant literature (Urisman A, et al. Surg Pathol Clin. 2020;13[1]:189).

Recent studies have demonstrated transbronchial cryobiopsy to be a promising alternative to surgical biopsy, owing to larger tissue samples than conventional transbronchial lung biopsies. For example, in a recent case series four patients underwent transbronchial cryobiopsy. The procedure yielded adequate tissue for diagnosis of a chronic bronchiolitis in each case (Yamakawa H, et al. Internal Med Advance Publication. doi: 10.2169/internalmedicine.6028-20.
 

Treatment options are growing

Evidence for treatment of bronchiolitis remains limited. Options are extrapolated from lung transplant patients, where incidence of BOS ranges from 50% at 5 years to 76% at 10 years post transplant. Guidelines recommend a 3-month minimum trial of azithromycin, which has been shown to slow or reverse decline of lung function in some patients. Modification of immunosuppression is also recommended. In patients who have continued lung function decline, a systematic review concluded that extracorporeal photopheresis had the most robust evidence for efficacy with stabilized lung function and improved overall survival (Benden C, et al. J Heart Lung Transplant. 2017;36[9]:921). Other salvage therapies that have lower-quality evidence of benefit include total lymphoid irradiation, montelukast, and aerosolized cyclosporine.

In patients who have undergone hematopoietic stem cell transplant, steroids are typically the first line treatment for OB as it is thought to be a form of chronic graft-vs-host disease (GVHD). Ruxolitinib, a selective JAK1/2 inhibitor, demonstrated significant improvement overall in patients with steroid-refractory acute GVHD in a recent randomized clinical trial, although the trial did not examine its effect on pulmonary manifestations (Zeiser R, et al. N Engl J Med. 2020;382[19]:1800). To date, retrospective observational studies of ruxolitinib in patients with lung GVHD have shown conflicting results regarding benefit. Investigators are currently studying ruxolitinib in a phase II trial for patients with BOS following stem cell transplant (NCT03674047).

DIPNECH is unique from other bronchiolitis entities, as small airways dysfunction develops as a result of neuroendocrine cell proliferation in the airway mucosa, ultimately leading to bronchial narrowing. It most commonly presents in middle-aged nonsmoking women with years of chronic cough and dyspnea. While it has an indolent course in many patients, some patients develop progressive symptoms and obstructive lung disease. DIPNECH is considered a precursor to other pulmonary neuroendocrine tumors. The lesions demonstrate somatostatin receptor expression in many cases, prompting the use of somatostatin analogues as treatment. In the largest published case series, 42 patients from three different institutions were identified who were treated with somatostatin analogues for a mean of 38.8 months at the time of review. Symptomatic improvement was seen in 33 of the 42 (79%), and of the 15 with posttreatment PFT data, 14 (93%) showed improvement in PFTs (Al-Toubah, T, et al. Chest. 2020;158[1]:401). Other small studies have demonstrated varying results with symptomatic improvement in 29% to 76% of patients and improvement or stability of PFTs in 50% to 100% of patients (Samhouri BF, et al. ERJ Open Res. 2020;6[4]:527).

For patients who have not undergone lung transplant, and who do not have an identifiable exposure or underlying rheumatologic condition, a similar 3-month minimum trial of macrolide antibiotics is reasonable. Macrolides have been shown to double long-term survival rates to over 90% in patients with DPB. Evidence in this patient population is quite limited, and further research is needed to determine effective therapies for patients.
 

What’s next for bronchiolitis

While clinicians currently have few tools for diagnosing and treating these uncommon diseases, in the coming years, we should learn whether novel imaging modalities or less invasive procedures can aid in the diagnosis. Physicians hope these advances will preclude the need for invasive biopsies in more patients going forward. We should also learn whether newer, targeted agents like ruxolitinib are effective for BOS in patients with stem cell transplant. If so, this finding may open it and similar agents to investigation in other forms of bronchiolitis.
 

Dr. Poole and Dr. Callahan are with University of Utah Health, Salt Lake City, Utah.

What’s in a name?

Bronchiolitis, a group of diseases also referred to as “small airways diseases,” is characterized by inflammation and/or fibrosis in airways less than 2 mm in diameter. In pediatric patients, it is most commonly related to acute viral infections, while in adults, it is often associated with chronic diseases. Bronchiolitis is a well-recognized complication in a significant number of patients who have undergone lung or stem cell transplantation. Common associations also include connective tissue diseases, environmental or occupational inhalation exposures, aspiration, drug toxicity, and infections. Diagnosing bronchiolitis can be challenging for clinicians, and few treatment options exist apart from treating identifiable underlying etiologies. More research is needed into noninvasive diagnostic techniques and treatment modalities.

The terminology used to describe bronchiolitis has evolved over time. Bronchiolitis is now used to describe conditions where the primary pathologic condition is damage to the bronchiolar epithelium not attributable to a larger parenchymal disease (such as hypersensitivity pneumonitis). This change in nomenclature explains why the condition formerly known as “bronchiolitis obliterans organizing pneumonia” (BOOP) is now simply recognized as “organizing pneumonia.” Despite several proposed classification schemes focusing on histopathology, there is no consensus regarding the different subtypes of bronchiolitis, leading to confusion in some cases. Recently, authors have attempted to distinguish cases based on three main histologic patterns (Urisman A, et al. Surg Pathol Clin. 2020;13[1]:189).

• Obliterative/constrictive bronchiolitis (OB) – the terms “obliterative” and “constrictive” are used interchangeably throughout pulmonary literature. It is characterized by fibroblast-rich tissue accumulation in the sub-epithelium of bronchioles leading to progressive narrowing of the lumen. In addition to the transplant setting, it is often seen in patients with rheumatoid arthritis or other connective tissue diseases, inhalational exposures, or acute respiratory infections. More recently, clinicians have recognized diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) as a rare condition causing OB with potentially effective treatment.
• Follicular bronchiolitis (FB) – features peribronchiolar inflammation with subepithelial lymphoid deposits leading to luminal obstruction. FB is chiefly associated with conditions of impaired immunity or chronic airway infection, such as autoimmune connective tissues diseases (especially rheumatoid arthritis and Sjogren’s), severe combined immunodeficiency, HIV, cystic fibrosis, and primary ciliary dyskinesia. 
• Diffuse panbronchiolitis (DBP) – features bilateral bronchiolar lesions with lymphocytic inflammation of the bronchiolar wall, as well as peribronchiolar inflammation and accumulation of interstitial foamy macrophages. Patients afflicted with DBP may suffer repeated bacterial colonization or infection. There is a higher prevalence of DBP in Asia where it was first identified in the 1960s, potentially due to several HLA alleles that are more common in Asia. 

In addition to the above terminology, the transplant-setting diagnosis “bronchiolitis obliterans syndrome” (BOS) is used to denote progressive obstructive lung disease for which there is not another cause aside from chronic graft rejection. For these patients, clinicians assume the underlying disease entity is OB, but they often lack histopathologic confirmation. 
 

Diagnosis is challenging

Symptoms of bronchiolitis are typically dyspnea and cough, and patients may often be diagnosed with asthma or COPD initially. Pulmonary function testing may show signs of obstruction, restriction, or mixed disease with or without a reduction in Dlco. Chest radiography often appears normal, but high-resolution CT may show expiratory air trapping and centrilobular nodules. Advanced imaging modalities may augment or replace CT imaging in diagnosing bronchiolitis: investigators are evaluating pulmonary MRI and fluoroscopy with computerized ventilation analysis in clinical trials (NCT04080232).

Currently, open or thoracoscopic lung biopsy is typically required to make a definitive diagnosis. Because bronchiolitis is a patchy and heterogeneous process, transbronchial biopsy may provide insufficient yield, with a sensitivity of 29% to 70% reported in lung transplant literature (Urisman A, et al. Surg Pathol Clin. 2020;13[1]:189).

Recent studies have demonstrated transbronchial cryobiopsy to be a promising alternative to surgical biopsy, owing to larger tissue samples than conventional transbronchial lung biopsies. For example, in a recent case series four patients underwent transbronchial cryobiopsy. The procedure yielded adequate tissue for diagnosis of a chronic bronchiolitis in each case (Yamakawa H, et al. Internal Med Advance Publication. doi: 10.2169/internalmedicine.6028-20.
 

Treatment options are growing

Evidence for treatment of bronchiolitis remains limited. Options are extrapolated from lung transplant patients, where incidence of BOS ranges from 50% at 5 years to 76% at 10 years post transplant. Guidelines recommend a 3-month minimum trial of azithromycin, which has been shown to slow or reverse decline of lung function in some patients. Modification of immunosuppression is also recommended. In patients who have continued lung function decline, a systematic review concluded that extracorporeal photopheresis had the most robust evidence for efficacy with stabilized lung function and improved overall survival (Benden C, et al. J Heart Lung Transplant. 2017;36[9]:921). Other salvage therapies that have lower-quality evidence of benefit include total lymphoid irradiation, montelukast, and aerosolized cyclosporine.

In patients who have undergone hematopoietic stem cell transplant, steroids are typically the first line treatment for OB as it is thought to be a form of chronic graft-vs-host disease (GVHD). Ruxolitinib, a selective JAK1/2 inhibitor, demonstrated significant improvement overall in patients with steroid-refractory acute GVHD in a recent randomized clinical trial, although the trial did not examine its effect on pulmonary manifestations (Zeiser R, et al. N Engl J Med. 2020;382[19]:1800). To date, retrospective observational studies of ruxolitinib in patients with lung GVHD have shown conflicting results regarding benefit. Investigators are currently studying ruxolitinib in a phase II trial for patients with BOS following stem cell transplant (NCT03674047).

DIPNECH is unique from other bronchiolitis entities, as small airways dysfunction develops as a result of neuroendocrine cell proliferation in the airway mucosa, ultimately leading to bronchial narrowing. It most commonly presents in middle-aged nonsmoking women with years of chronic cough and dyspnea. While it has an indolent course in many patients, some patients develop progressive symptoms and obstructive lung disease. DIPNECH is considered a precursor to other pulmonary neuroendocrine tumors. The lesions demonstrate somatostatin receptor expression in many cases, prompting the use of somatostatin analogues as treatment. In the largest published case series, 42 patients from three different institutions were identified who were treated with somatostatin analogues for a mean of 38.8 months at the time of review. Symptomatic improvement was seen in 33 of the 42 (79%), and of the 15 with posttreatment PFT data, 14 (93%) showed improvement in PFTs (Al-Toubah, T, et al. Chest. 2020;158[1]:401). Other small studies have demonstrated varying results with symptomatic improvement in 29% to 76% of patients and improvement or stability of PFTs in 50% to 100% of patients (Samhouri BF, et al. ERJ Open Res. 2020;6[4]:527).

For patients who have not undergone lung transplant, and who do not have an identifiable exposure or underlying rheumatologic condition, a similar 3-month minimum trial of macrolide antibiotics is reasonable. Macrolides have been shown to double long-term survival rates to over 90% in patients with DPB. Evidence in this patient population is quite limited, and further research is needed to determine effective therapies for patients.
 

What’s next for bronchiolitis

While clinicians currently have few tools for diagnosing and treating these uncommon diseases, in the coming years, we should learn whether novel imaging modalities or less invasive procedures can aid in the diagnosis. Physicians hope these advances will preclude the need for invasive biopsies in more patients going forward. We should also learn whether newer, targeted agents like ruxolitinib are effective for BOS in patients with stem cell transplant. If so, this finding may open it and similar agents to investigation in other forms of bronchiolitis.
 

Dr. Poole and Dr. Callahan are with University of Utah Health, Salt Lake City, Utah.